HK1162903B - Body-associated receiver - Google Patents

Description

Body-associated receiver

Cross Reference to Related Applications

According to 35u.s.c. § 119(e), the present application claims priority from the filing date of U.S. provisional patent application serial No. 61/122,723 filed 12/15/2008, U.S. provisional patent application No. 61/160,289 filed 3/13/2009, U.S. provisional patent application No. 61/240,571 filed 9/8/2009, and U.S. provisional patent application No. 61/251,088 filed 10/13/2009, the disclosures of which are incorporated herein by reference. This application is also a continuation-in-part application of U.S. patent application serial No. 11/912,475 filed on 28.2006 and a continuation-in-part application of U.S. patent application serial No. 12/324,798 filed on 26.11.2008, the disclosures of which are incorporated herein by reference.

Technical Field

The present invention relates to receivers in communication systems, and more particularly to receivers that detect data transmission encoded in the current flowing through a conductive solution and are capable of managing power and controlling dosage.

Background

In medical and non-medical applications, in many cases, it is desirable to record personal events, i.e. events for a given individual. Examples of medical applications where one may wish to record events for a given individual include, but are not limited to, the occurrence of one or more physiological parameters of interest, including disease symptoms, drug delivery, etc. Examples of non-medical applications where one wishes to record an event for a given individual include, but are not limited to, ingestion of a certain type of food (e.g., for an individual controlling a diet), initiation of an exercise program, and the like.

Because in many cases, people wish to record personal events, a variety of different methods and techniques have been developed to make such recording possible. For example, logbooks and techniques have been developed in which individuals, such as patients and/or their healthcare providers, may record the time and date of an event by, for example, manual writing or data entry. However, there is still a need for improvements in personal event monitoring. For example, manual recording when an event occurs can be time consuming and error prone.

Disclosure of Invention

The present invention provides a receiver that may be external, implantable, semi-implantable, or the like. Aspects of the receiver of the present invention include the presence of one or more of the following: a high-low power module; an intermediate module; a power module configured to activate and deactivate one or more power supplies of the high power processing block; a serial peripheral interface bus connecting the master block and the slave block; and a multi-purpose connector. The receiver of the present invention may be configured to receive conductively transmitted signals. The invention also provides a system comprising the receiver and a method of using the receiver.

Drawings

Fig. 1 is a schematic diagram of a receiver for detecting data transmission through a living subject.

Fig. 1A is a block diagram of the receiver of fig. 1 in accordance with the teachings of the present invention.

Fig. 1B is a block diagram of a power management module of the receiver of fig. 1A in accordance with the teachings of the present invention.

Fig. 2 is a functional block diagram of a demodulation circuit that performs coherent demodulation that may be present in a receiver according to one aspect.

Fig. 3A shows a beacon switching module that provides a sniff period that is longer than the transmit signal repetition period.

Fig. 3B shows that a beacon switching module with a short but frequent sniff period is provided, as well as long transmission packets.

Fig. 3C illustrates a flow diagram of a sniffing process performed by a sniffing module, according to one aspect.

Fig. 3D illustrates a functional block diagram of a beacon module within a receiver in accordance with an aspect.

Figure 4 shows a beacon function that correlates beacons with one frequency and associates messages with another frequency.

Fig. 5 illustrates a functional block diagram of an ECG sensing module that may be present in a receiver according to one aspect.

Fig. 6 illustrates a functional block diagram of an accelerometer module that may be present in a receiver of the present invention according to an aspect.

Fig. 7 is a functional block diagram of different functional modules that may be present in a receiver according to one aspect.

Fig. 8 is a block diagram of a receiver in accordance with an aspect.

Fig. 9 provides a block diagram of a high frequency signal chain in a receiver according to one aspect.

Fig. 10 is a three-dimensional view of an external signal receiver according to one aspect.

Fig. 11 provides an exploded view of the signal receiver shown in fig. 10, according to one aspect.

Fig. 12 provides an exploded view of the patch component of the signal receiver shown in fig. 10 and 11, according to one aspect.

Fig. 13A-13E provide various views of a two-electrode external signal receiver according to one aspect.

Fig. 14A-14D provide block diagrams of hardware configurations that may be present in the signal receivers shown in fig. 13A-13E, according to one aspect.

Fig. 15A provides a schematic diagram of how a system including a signal receiver and an ingestible event marker may be employed, according to one aspect.

Fig. 15B provides a drug delivery system that receives control information from a receiver and controls dosage delivery.

Fig. 16 provides a block diagram illustrating a receiver connected to a patient.

Fig. 17 provides a block diagram showing a receiver connected to an external charger.

Fig. 18 provides a block diagram illustrating a receiver connected to an external control and data communication device.

19A-19B illustrate schematic diagrams of a router according to an aspect of the invention that discriminates signals based on voltage levels.

Fig. 20A-20C show schematic diagrams of a router according to an aspect of the invention that discriminates signals based on frequency.

Fig. 21 shows a schematic diagram of a router according to an aspect of the invention that discriminates signals by employing active switches.

Figures 22A-C (generally referred to as figure 22) provide circuit diagrams of multi-purpose electrode connections according to one aspect of the present invention.

23A-B (collectively FIG. 23) provide circuit schematic diagrams of an internal power supply block of an external receiver in accordance with an aspect of the present invention.

24A-C (collectively FIG. 24) provide circuit schematic diagrams of an internal power supply block of an external receiver in accordance with an aspect of the present invention.

Fig. 25 provides a schematic illustration of the component/functional relationship.

Figures 26A-B (collectively figure 26) provide a circuit diagram for controlling power to various components of a receiver including a multi-purpose connector, according to one aspect.

FIG. 27 provides a circuit diagram for modeling a drive scheme in an electrode impedance measurement module, according to one aspect.

FIG. 28 provides a circuit diagram of an electrode impedance measurement module using a three-wire ohmmeter according to one aspect of the present invention.

Fig. 29 shows a state flow diagram of the power management module and operation of the receiver.

FIG. 30 provides a block diagram of a hardware accelerator module in accordance with an aspect.

Detailed Description

The present invention provides a receptacle which may be external or implantable. Aspects of the receiver of the present invention include the presence of one or more of the following: a high-low power module; an intermediate module; a power module configured to activate and deactivate one or more power supplies of the high power processing block; a serial peripheral interface bus connecting the master block and the slave block; and a multipurpose connector. The receiver of the present invention may be configured to receive conductively transmitted signals. The invention also provides a system comprising the receiver and a method of using the receiver.

The receiver of the present invention is an electrical device comprising circuitry and logic residing in a housing, wherein the device is configured to perform one or more medical functions. The term "medical" is used broadly to refer to any type of function performed against the health of a living subject, such as a patient. Thus, if a device implements the functionality of receiving data relating to one or more parameters of a subject, the device is considered a medical device regardless of whether the subject is in a healthy or diseased state. Parameters of interest include those described in more detail below, such as physiological parameters, signals from other medical devices such as Ingestible Event Marker (IEM) devices, and the like. Thus, the medical devices of interest are those that can be used in therapeutic applications or non-therapeutic applications, such as those described in more detail below.

In certain embodiments of the present invention, the receiver is a device sized to be stably associated with a living subject, such as a patient, in a manner that does not substantially affect movement of the living subject and also provides a desired function, such as a signal receiving function, during an extended period of time. The term "patient" as used herein broadly refers to subjects suspected or diagnosed as diseased or abnormal as well as healthy subjects. A receptacle according to the teachings of the present invention may be associated with the body of a patient in any convenient manner, such as with tape or using a clip, collar or strap to attach the device to the body or clothing of the patient. Alternatively, the device may be placed in a compartment of a garment worn by the patient, such as the patient's pocket. When desired, the device may be configured to be continuously associated with the patient for an extended period of time, such as minutes to months. In one embodiment, the apparatus may be configured to be continuously associated with the patient for a week or more. In some examples, the apparatus is configured to be directly associated with a localized skin site of the subject. In other aspects, the device is configured to be implantable. Since the device is a device sized to be stably associated with a living subject in a manner that does not substantially affect the movement of the living subject, when used with a subject, such as a human subject, the dimensions of the various aspects of the device will not cause the subject to perceive any difference in their ability to move. Thus, in these aspects, the device is sized and shaped so that its size and shape do not interfere with the subject's ability to move. The device of the invention may be sized to provide a function when applied to a local body location, for example as described above. In such examples, the device may have a 50cm³Or less, e.g. 30cm³Or less, including 25cm³Or less, e.g. 20cm³Or smaller. In some aspectsThe face, the device has a small size, wherein in certain aspects the device occupies about 5cm³Or a smaller volume, e.g. about 3cm³Or less, including about 1cm³Or smaller. The device of the invention may have a longest dimension of 30cm or less, such as 20cm or less, including 15cm or less.

Despite the small receiver size, the device can operate for extended periods of time. As such, the receiver may operate for a week or more, such as two weeks or more, including one month or more, three months or more, six months or more, including twelve months or more. To provide such operation for extended periods of time and in view of the small size of the receiver, the apparatus is configured for low power consumption. By low power consumption is meant that the average power consumption of the device during a 24 hour period is mA or less, such as 100 μ A or less, and including 10 μ A or less. The average current consumption of the receiver when in standby mode (described in more detail below) is 100 μ A or less, such as 10 μ A or less, including μ A or less. The average current consumption of the receiver when in the storage mode (described in more detail below) is 10 μ A or less, such as 1 μ A or less, and includes 0.1 μ A or less. In some examples, the current consumption of the receiver when in the active state (described in more detail below) is in the range of 3 μ A to 30mA, such as 30 μ A to 3mA, and including 30 μ A to 300 μ A.

In certain aspects, the receiver of the present invention is a signal receiver. A signal receiver is a device configured to receive a signal, e.g., a conductively transmitted signal, from another device, e.g., across a body (trans-body), as will be described in more detail below. Where the receiver is a signal receiver, the receiver may be configured to receive a signal emitted by an ingestible event marker, as described in more detail below.

The receiver of the present invention may comprise various modules configured to perform one or more functions of the apparatus, e.g., by hardware and/or software implementation. A module is made up of one or more functional blocks that cooperate to perform a particular function that is the purpose of the module. A given module may be implemented as hardware, software, or a combination thereof. The modules that may be present in the receiver of the present invention are described in more detail below.

Aspects of the device include a high-low power module. A high power-low power module is a module that includes a high power functional block and a low power functional block. The low power functional block refers to a functional block that performs processing and requires low current consumption and low power consumption. The low power functional block performs at least one independent function, e.g., a function requiring non-high performance processing, where examples of such functions include holding a standby state, monitoring a bus, waiting for a signal such as an interrupt signal to occur, and the like. Of interest as low power functional blocks are those that consume 10 μ A or less and include 1 μ A or less of current. The high power functional block refers to a functional block that performs higher performance processing requiring greater current consumption and power consumption than the low power functional block. The high power functional block performs at least one independent function, such as processing conductively transmitted signals, processing received physiological data, and the like. The greater computational processing may involve, for example, performing digital signal processing algorithms such as Finite Impulse Response (FIR) filters, Fast Fourier Transforms (FFTs), and the like. Examples of high power functional blocks are functional blocks that consume a current of 30 μ A or more, e.g., 50 μ A or more, in order to perform their designated function.

The low power functional block and the high power functional block may be implemented in a variety of different ways. For example, the low power functional blocks and the high power functional blocks may be implemented on separate processors or may be implemented as separate circuit elements of a system-on-a-chip (SOC) architecture, among other configurations. Further details regarding the hardware implementation of interest are provided below. The receiver of interest includes at least one low power functional block and at least one high power functional block. In some instances, the receiver will include additional low power functional blocks and/or high power functional blocks to implement a particular receiver as desired.

The receiver of the present invention may further comprise an intermediate module configured to cycle the high power functional block between an active state and an inactive state. An active state refers to a state in which a functional block performs a specified function or functions, such as demodulating and/or processing received signals, processing physiological data, and so forth. An inactive state refers to a state in which the functional block is not performing a specified function or functions, where the inactive state may be a standby or sleep state, such as a shutdown state in which the functional block consumes minimal current (e.g., 1 μ A or less, including 0.1 μ A or less) or in which the functional block does not consume current. "cycling" refers to the intermediate module transitioning the high power functional block between an active state and an inactive state. In other words, the intermediate module changes the state of the high-power functional block from active to inactive or vice versa. The intermediate module may cycle the high power functional block between the active and inactive states according to various inputs, such as a predetermined schedule (e.g., provided by programming of the receiver) or applied stimuli. In some examples, the intermediate module may cycle the high power functional block between the active state and the inactive state according to a predetermined schedule. For example, the intermediate module may cycle the high power functional block between the active state and the inactive state every 20 seconds, for example every 10 seconds and including every 5 seconds. In some instances, the intermediate module may cycle the high power functional block between the active state and the inactive state in accordance with an applied stimulus, such as receiving a conductively transmitted signal, responding to one or more predetermined physiological parameters, responding to a user instruction (e.g., by pressing an operating button on the receiver or sending an instruction signal to the receiver), and so forth.

The receiver may be configured to have various states, such as a standby state or one or more active states. Accordingly, the intermediate module may cycle the high power functional block between the active and inactive states as needed depending on the desired function of the device at a given time. In the active state, the receiver performs one or more active functions, such as receiving signals, processing signals, transmitting signals, acquiring physiological data, processing physiological data, and the like. In the standby state, the receiver consumes minimal current, for example as described above. In the standby state, the receiver may perform minimal functions to minimize current consumption, such as maintaining configuration, maintaining sleep mode, and the like. However, in the standby state, the receiver does not perform a function requiring more than the minimum current consumption. The intermediate module may cycle the receiver between the active and standby states according to different inputs, such as a predetermined schedule (e.g., provided by programming of the receiver) or applied stimuli as described above.

The receiver of interest may be configured to perform a cross-body conductive signal (such as an IEM or smart parenteral device signal) detection protocol. Such devices may be considered signal receivers. The cross-body conductive signal detection protocol is the following process: the signal receiver is in a state capable of receiving the signal emitted by the IEM or smart parenteral device and processing the signal as needed, e.g., by performing one or more tasks, such as decoding the signal, storing the signal, time stamping the signal, and retransmitting the signal, as described in more detail below.

The receiver of interest, such as a signal receiver, may also be configured to, for example, execute a physiological data detection protocol while in an active state in order to acquire ECG data, accelerometer data, temperature data, and the like, as described in more detail below.

Referring now to fig. 1, fig. 1A and 1B illustrate one embodiment of a receiver of the present invention. The receiver 100 is shown on a living subject 102. The receiver 100 is shown attached to the left side of the middle of the subject 102. However, the scope of the present invention is not limited to the location of the receiver 100 on the subject 102.

Referring now to fig. 1A, receiver 100 includes a power supply unit or power supply 200, an operating unit 202 including electrodes 202A, an operating or processing unit 204, and a memory unit 206. Receiver 100 also includes a power management module 208 that controls power consumption. The receiver 100 is able to communicate with other devices in the vicinity using the transmission module 210. Additionally, the receiver 100 may include various features, such as an accelerometer for detecting the orientation of the receiver 100. In the case where the subject is lying down or in a horizontal position, the receiver 100 is able to detect this position and the duration of time the subject remains in this position.

In addition, receiver 100 may also include one or more different physiological parameter sensing capabilities. Physiological parameter sensing capability refers to the capability to sense physiological parameters or biomarkers including, but not limited to, heart rate, respiration rate, temperature, pressure, chemical composition of fluids such as analyte detection in blood, flow regime, blood flow velocity, accelerometer motion data, IEGM (intracardiac electrogram) data, and the like.

Accordingly, the receiver 100 may include a physiological parameter measurement tool that enables the receiver to determine whether the subject is merely lying down or whether the subject has suffered a certain illness such that it is in that position. For example, the subject may have a heart attack and the receiver 100 can detect the condition and, in conjunction with the information from the accelerometer 212, the receiver 100 can determine that the patient has a potentially serious illness. Another example would include the moment a patient is afflicted with a seizure. The accelerometer 212 will provide information to the receiver 100 that, in combination with the measured physiological parameters, will enable the receiver 100 to determine that a disease is occurring that will need immediate treatment.

Referring now to FIG. 1B, the power management module 208 includes a high power operation module 300, an intermediate power operation module 302, and a low power operation module 304. Power management module 208 controls power provided to components of receiver 100 via beacon switch module 306. The beacon switching module 306 generates such signals: the signal enables the power management module 208 to transition the state of the receiver from an active state to an active-inactive state to an inactive state based on information provided by various modules and units of the receiver 100.

As described above, in the embodiment illustrated in fig. 1, receiver 100 may transition from one state to another depending on the information provided by the environment. In the standby or inactive state, receiver 100 does not perform any active functions and remains in standby. Receiver 100 may transition between the inactive state and the other state depending on the function that is desired to be performed. Depending on the function, the intermediate power operation module may cycle the receiver 100 between an inactive (e.g., standby) state and an active state. For example, when receiver 100 transitions from an inactive state to a detect or active inactive state in order to collect ECG and/or accelerometer data, the intermediate module cycles receiver 100 from an inactive (e.g., standby) state to an active state. When the receiver 100 is finished collecting ECG and accelerometer data, the intermediate module cycles the receiver 100 back to an inactive state (e.g., a standby state) and the receiver 100 returns to the inactive state.

The intermediate module cycles the receiver 100 from an inactive (e.g., standby) state to an active inactive state when the receiver 100 transitions from the inactive state to a sniff (sniff) state for an active inactive condition in order to scan for detection of data transmission signals (e.g., using a sniff module, as described in more detail below) associated with ion emission for generating current with data transmission encoded as part thereof or data transmission associated with wireless communications. If the receiver 100 receives a signal during this scanning or sniffing, the receiver 100 enters an active operating state and the high power operational module 300 of fig. 1B provides high power to all the operational units 202, processing units 204 and memory units 206 of fig. 1A. Receiver 100 then processes the signal in an active operating state, e.g., demodulates the signal, time stamps the signal, and stores the signal, as described in more detail below. When receiver 100 completes processing the signal, power management module 208 cycles receiver 100 back to an inactive state (e.g., a standby state) and receiver 100 returns to the inactive state.

In some aspects, scanning for data transmission signals from a communication module within the subject 102 of fig. 1, such as the active inactive state 130, the receiver 100 does not require high power to cycle to the active inactive state. In such cases, there is no high power requirement until the signal for demodulation and decoding is detected.

In accordance with the teachings of the present invention, the signal receiver aspect of receiver 100 may be configured to receive conductively transmitted signals. The conductively transmitted signal may be a signal conductively transmitted by any physiological part of the body, or a signal from a device that conductively transmits a signal through the body using ionic emission of a controlled delivered mass from a solid to a conductive solution or fluid. The signal may be generated by an ion emission module or an Ingestible Event Marker (IEM) or an intelligent parenteral delivery system. Ingestible event markers of interest include those described in the following patent documents: PCT application Ser. No. PCT/US2006/016370 published as WO/2006/116718; PCT application Ser. No. PCT/US2007/082563, published as WO/2008/052136; PCT application Ser. No. PCT/US2007/024225, published as WO/2008/063626; PCT application Ser. No. PCT/US2007/022257, published as WO/2008/066617; PCT application Ser. No. PCT/US2008/052845, published as WO/2008/095183; PCT application Ser. No. PCT/US2008/053999, published as WO/2008/101107; PCT application Ser. No. PCT/US2008/056296, published as WO/2008/112577; PCT application Ser. No. PCT/US2008/056299, published as WO/2008/112578; and PCT application serial No. PCT/US2008/077753 published as WO/2009/042812; the disclosures of these patent applications are incorporated herein by reference. Intelligent parenteral delivery systems are described in PCT application Ser. No. PCT/US2007/015547, published as WO 2008/008281; the disclosure of each of the foregoing applications is hereby incorporated by reference in its entirety.

Because the receiver of these aspects is configured to receive data encoded in the current flowing through the conductive fluid, the receiver and the device that transmits the signal (e.g., the IEM) use the living body associated therewith as a communication medium. In order to employ the body as a communication medium for signals, the body fluid functions as a conductive fluid, and the body of the patient serves as a conductive medium for communication. Thus, signals transmitted between the ion emitting device and any other signal emitting device and a receiver, such as receiver 100 of fig. 1, pass through the body of subject 102. The conductively transmitted signal of interest may be transmitted through and received from the skin and other body tissue of the subject's body in the form of an alternating current (a.c.) signal that is electrically conductive through the body tissue. Thus, there is no need for a signal to be transmitted between the device and the receiver, and such a receiver does not require any additional cables or hard wire connections.

Because the signal receiver is configured to receive the conductively transmitted signal, the signal receiver may include a cross-body conductive communication module. The cross-body conductive communication module is a functional module configured to receive conductively conveyed signals, such as signals emitted by the IEM. The cross-body conductive communication module may be implemented by a high power functional block as described above, if desired. In some instances, the signal that the cross-body conductive communication module is configured to receive is an encoded signal, which refers to a signal that has been modulated in some manner (e.g., using a protocol such as Binary Phase Shift Keying (BPSK), Frequency Shift Keying (FSK), Amplitude Shift Keying (ASK), etc.). In such examples, the receiver and its conductive communication module across the body are configured to decode the received encoded signal, e.g., the signal transmitted by the ingestible event marker. The receiver may be configured to decode the encoded signal in, for example, a low signal-to-noise ratio (SNR) environment where there may be substantial noise in addition to the signal of interest, e.g., an environment having an SNR of 7.7dB or less. The receiver may also be configured to decode the encoded signal substantially without errors. In certain aspects, the signal receiver has a high coding gain, for example, a coding gain in the range of 6dB to 12dB, such as a coding gain in the range of 8dB to 10dB, including a coding gain of 9 dB. The signal receiver of aspects of the present invention is capable of decoding an encoded signal substantially without errors, e.g., with 10% or less errors.

In these aspects of encoding the received signal, such as where the received signal is an encoded IEM signal, the cross-body conductive communication module may be configured to process the received signal in at least one demodulation protocol, where the cross-body conductive communication module may be configured to process the received signal with two or more, three or more, four or more, etc. different demodulation protocols as desired. When two or more different demodulation protocols are employed to process a given encoded signal, these protocols may be performed simultaneously or sequentially as desired. The received signal may be processed using any convenient demodulation protocol. Demodulation protocols of interest include, but are not limited to: costas Loop demodulation (e.g., as described in PCT application serial No. PCT/US07/024225, published as WO 2008/063626, the disclosure of which is incorporated herein by reference); coherent demodulation (e.g., as described in PCT application Ser. No. PCT/US07/024225, published as WO 2008/063626, the disclosure of which is incorporated herein by reference); accurate low-overhead iterative demodulation (e.g., as described in PCT application serial No. PCT/US07/024225, published as WO 2008/063626, the disclosure of which is incorporated herein by reference); non-coherent demodulation; and differential coherent demodulation.

In some examples, a coherent demodulation protocol is employed. Coherent demodulation modules that may be employed in aspects of the receiver include, but are not limited to, those described in PCT application serial No. PCT/US2007/024225, the disclosure of which is incorporated herein by reference.

In some examples, a differential coherent demodulation protocol is employed. Differential coherent demodulation compares the phases of adjacent bits in a Binary Phase Shift Keying (BPSK) modulated signal. For example, an 8-bit binary code of 11001010 would produce a differential signal of 0101111. Because this technique utilizes the phase difference between adjacent bits, it is inherently more robust to signal frequency instability and frequency shift than coherent demodulation schemes.

Coherent demodulation

In some embodiments, BPSK demodulation in the presence of AWGN (additive white gaussian noise) is performed to minimize BER (bit error rate) using coherent demodulation.

In these embodiments, the intra-body transmitter facilitates the coherent demodulation process of the receiver by sending the preamble carrier in the "front porch" of each burst of BPSK modulation. This protocol provides a stable carrier of full amplitude and a reference phase corresponding to the transmission of 0 bits. The presence of the leading edge gives the receiver a useful detection mark and a large number of carrier periods for accurately estimating the carrier frequency and phase.

Other practical applications are the use of carrier frequencies to simplify the derivation of data rates. The transmitted signal is formatted such that the data clock frequency is divided by the carrier frequency. Thus, once carrier acquisition is completed, easy and fast data clock acquisition can be achieved.

In some embodiments, the receiver samples the incoming signal at a rate of about 4 times the carrier frequency. This signal is mixed with a DDS (direct digital synthesizer) set to the nominal carrier frequency to produce complex baseband (real and imaginary components). The output of the mixer is low pass filtered and decimated (decimated). The low pass filter bandwidth must be wide enough to capture frequencies in the frequency band due to carrier oscillator uncertainty and frequency hopping jitter (frequency hopping). The frequency of the subsequent BPSK is around 0Hz with a frequency accuracy of +/-20%.

The receiver squares the complex baseband BPSK signal to produce a strong frequency-multiplied line. The leading edge signal and subsequent BPSK modulation all contribute to the formation of this line. The squared complex time domain signal is transformed to the frequency domain using an FFT (fast fourier transform). The peak energy interval is identified as 2 x the carrier frequency. This frequency is divided by 2 to provide an estimate of the carrier offset frequency with an accuracy of about 0.1% using a 1024-point FFT.

The complex baseband signal is then mixed again with the determined offset frequency. The result after narrow-band low-pass filtering is a complex BPSK signal centered at 0Hz with an accuracy of 0.1%. The bandwidth of the narrow band low pass filter corresponds to half the bandwidth of the BPSK signal.

The leading edge signal is then extracted. The frequency offset is determined by first calculating the phase (phi) of all sample points in the leading edge (imaginary/real), and then estimating the slope of phi over time using a least mean square fit to a straight line. The slope of the line corresponds to the residual frequency offset. The complex baseband signal is then mixed a third time to remove this frequency offset and with an accuracy higher than 0.01%.

The complex signal leading edge is then averaged to determine the average imaginary and real values. arctan (mean imaginary part/mean real part) yields the leading edge phase. Based on this phase, a rotation coefficient is calculated to rotate BPSK 270 degrees on the imaginary axis of the leading edge.

The entire rotated BPSK signal is then averaged a second time to identify the 90 degree center of gravity (data 1), and BPSK is rotated in a similar manner to place this center of gravity on the imaginary axis. The imaginary signal is then clipped (sliced) to extract the data.

The clipped data is gated using a data clock derived from a predetermined determination of the carrier frequency and a priori knowledge of integer coefficients relating the carrier frequency to the data clock frequency.

In the embodiment of the protocol described above, it is assumed that the carrier frequency maintains sufficient accuracy in frequency and phase throughout the duration of the entire burst.

Aspects of coherent demodulation modules that may be employed in the implementation of a receiver include, but are not limited to, those described in PCT application serial No. PCT/US 2007/024225; the disclosure of which is incorporated herein by reference. Accurate low-overhead iterative decoding

In some embodiments, the receiver includes an accurate low overhead interactive decoder (also referred to herein as a communication decoder). A communication decoder provides highly accurate communication in a simple, elegant and cost-effective manner despite significant signal distortion due to noise and other factors. The communication decoder uses an error correction code and a simple iterative process to obtain a decoding result. Communication decoders can be used in a variety of applications to achieve high coding gain at low cost.

Broadly speaking, one embodiment of a communication decoder provides decoding capabilities for data communication. One embodiment of a communication decoder provides high coding gain with minimal overhead. In some instances, the communication decoder helps to bring the data transmission rate close to the theoretical maximum, the Shannon Limit (Shannon Limit), while minimizing processing overhead. The low overhead ensures a cost-effective implementation. Various embodiments of the invention include hardware, software, and circuitry.

Various embodiments of the inventive communication decoder of the present invention use error correction codes and a simple and unique process to "force" the measurement signals associated with the erroneous bits towards the measurement signals associated with the correct original bits, thereby increasing the probability of identifying destination data that matches the data encoded at the originating point, and significantly increasing the data accuracy at the destination. This simple and unique process facilitates efficient implementation. The low overhead associated with a simple and unique process minimizes costs. By using the iterative communication decoder of the present invention, LDPC decoding is much less complex.

In general, the decoder module generates decoded data through a variation of the following technique. For each bit group of encoded data, a set of measured signals associated with the encoded data is rounded to the closest most likely measurement, e.g., to the closest transmission symbol, if no noise is present. The set of transmission symbols is converted into a set of hard-coded decision values. Error detection is performed on the set of hard-code decision values. The set of measured signals is adjusted based on the results of the error detection on the set of hard-code decision values. The foregoing steps are performed in turn in all measured signal sets of the encoded data until a predetermined stop condition is met. Aspects of accurate low-overhead iterative decoding modules that may be employed in embodiments of the receiver include, but are not limited to, those accurate low-overhead iterative decoding modules described in PCT application serial number PCT/US 2007/024225; the disclosure of which is incorporated herein by reference.

Forward error correction

In some embodiments, the receiver is configured for use with an intra-body transmitter that employs FEC (forward error correction) to provide additional gain against interference from other unwanted signals and noise. Error correction is simple in both the transmitter and receiver and provides high coding gain. This function is implemented using single parity check product codes and a novel SISO (soft-in soft-out) iterative decoding algorithm.

The transmitter encodes the message by arranging the message in rows and columns. Each row has additional parity bits and likewise each column has additional parity bits. For example, 100 bit messages may be arranged in a 10 x 10 bit array. Parity bits are added to create the final 11 x 11 bit array to be subsequently transmitted over the channel using BPSK. To obtain additional gain, additional dimensions may be used, for example, if a cube is created to arrange messages and check bits, three dimensions are used.

The receiver decodes the message through an iterative process to achieve high coding gain. Each bit is sampled and stored in a "soft" form. Assuming that the ideal samples (i.e., hard decision points) are normalized to-1 and +1, the received bits will fall in a range between say-2.0 and + 2.0. Hard decisions are performed on all samples and parity checks are performed. If a row or column has a parity error, samples of the row or column are rejected from the corresponding hard decision point in small increments. If a row or column has no parity error, samples of the row or column are absorbed into the corresponding hard decision point in small increments. With an appropriately chosen delta, ten iterations are often sufficient to achieve a coding gain of 8dB to 10dB for AWGN (additive white gaussian noise) based on the required channel SNR (signal to noise ratio). This method is easily implemented as stored program DSP or FPGA/ASIC logic. It also falls within 1dB or 2dB of the shannon limit of forward error correction given a particular coding rate.

Aspects of forward error correction modules that may be employed in embodiments of the receiver include, but are not limited to, those described in PCT application serial No. PCT/US2007/024225, published as WO 2008/063626; the disclosure of which is incorporated herein by reference.

Beacon function module

Various aspects may employ a beacon function module. In various aspects, the beacon function sub-module may employ one or more of the following: a beacon wakeup module, a beacon signal module, a wave/frequency module, a multiple frequency module, and a modulated signal module.

The beacon function may be associated with beacon communications, e.g., a beacon communications channel, a beacon protocol, etc. For purposes of this disclosure, a beacon is generally a signal transmitted as part of a message or a signal transmitted to augment a message (sometimes referred to herein as a "beacon signal"). These beacons may have well defined characteristics, such as frequency. Beacons can be easily detected in noisy environments and can be used by the trigger of a sniff circuit, such as those described above.

In one aspect, the beacon function module may include a beacon wakeup module having a wakeup function. The wake-up function generally includes a function of operating in a high power mode only during a specific time, for example, a short period for a specific purpose, for example, to receive a signal or the like. An important consideration for the receiver portion of the system is that it should be low power. This feature may be advantageous in an implanted receiver to support small size while maintaining long term power supply of the battery. The beacon wakeup module may achieve these advantages by operating the receiver in a high power mode for a very limited period of time. Such short duty cycles can provide optimal system size and energy consumption characteristics.

In practice, the receiver may "wake up" periodically and with low power consumption, in order to perform a "sniff function" by means of, for example, a sniff circuit. For the purposes of this application, the term "sniff function" generally refers to a short-lived low power function for determining whether a transmitter is present. If the sniff function detects the transmitter signal, the device may switch to a higher power communication coding mode. If no transmitter signal is present, the receiver may return, for example, to an immediate return to sleep mode. In this way, when there is no transmitter signal, then energy may be saved during a relatively long period of time, while when there is a transmitter signal, high power capacity may be used for efficient coding mode operation during a relatively short period of time.

For operating the sniff circuit, a variety of modes and combinations thereof are available. By matching the requirements of a particular system with the sniff circuit configuration, an optimized system can be achieved.

Still other examples of beacon function modules are described in PCT application Ser. No. PCT/US 08/85048; the disclosure of which is incorporated herein by reference.

Frequency hopping function module

Various aspects may employ a frequency hopping function. The frequency hopping function may be associated with a particular communication channel, frequency hopping protocol, etc. Thus, various aspects may employ one or more frequency hopping protocols. For example, the receiver may search for a specified frequency range, e.g., two or more different frequencies, at which the transmission may fall. When a correct decoding is achieved, the in-vivo transmitter has completed its task of transmitting its digital information payload to the receiver.

In some instances, the frequency uncertainty of the transmission provided by random frequency hopping, e.g., via a random module, may yield a number of benefits. An example of such a communication protocol is frequency hopping spread spectrum communication (FHSS). FHSS is a method of transmitting radio signals by rapidly switching carriers between multiple frequency channels using a pseudo-random sequence known to both the transmitter and the receiver. For example, one such benefit, for example, can be easily realized on a small die. For example, the intra-body transmitter carrier frequency oscillator may be an inaccurate free-running oscillator that is easily implemented on a fraction of a 1mm bare chip. An accuracy of about +/-20 is readily available. This is because the receiver employs a frequency search algorithm.

Another benefit of this is that the useful life of the battery can be extended. By way of example, during the lifetime of the transmitter battery, e.g. 3 to 10 minutes, the probability of the transmitter transmitting on a clear channel that can be received by a frequency agile receiver can be significantly increased due to random frequency hopping.

Another benefit is minimizing collision events in high capacity environments. For example, the probability of collision is minimized when multiple in-vivo transmitters, such as ingestible event markers, may transmit simultaneously, such as in the case where multiple ingestible event markers are ingested at the same time or in close proximity. In other words, without the frequency hopping function, the probability that ingestible event markers of similar batches will transmit on the same (or nearly the same) frequency resulting in multiple collisions may be high.

In certain aspects, the available frequency spectrum for use in volume conduction applications is in the range from about 3kHz to 150 kHz. Through detailed animal studies, it has been found that in some environments, in-vivo transmitters (see above) with received signal levels ranging from 1 to 100 μ V can compete in the same spectrum with narrowband interfering signals on the order of hundreds to thousands of μ V. To mitigate the destructive nature of interfering signals, a frequency hopping channel or protocol may be employed in which the in-vivo transmitter randomly hops the narrowband transmitted signal, e.g., a modulated signal such as a Binary Phase Shift Keying (BPSK) signal or FSK signal, output on each transmission.

Further examples of frequency hopping modules are described in PCT application Ser. No. PCT/US 08/85048; the disclosure of which is incorporated herein by reference.

Collision avoidance function module

Various aspects may employ a collision avoidance function. The collision avoidance function may be associated with a particular communication channel, collision avoidance protocol, etc. Thus, various aspects may utilize various collision avoidance protocol techniques associated with a particular communication channel. Collision avoidance techniques are particularly useful in environments where, for example, there are two or more in-vivo transmitters (e.g., an individual ingests multiple IEMs). In such an environment, if individual in-vivo transmitters continue to transmit their signals, the transmission of one transmitter may mask the transmissions of all other in-vivo transmitters. Therefore, the failure to detect a signal may increase significantly.

Various aspects may include various collision avoidance methodologies, alone or in various combinations.

One such method employs multiple transmit frequencies. By using frequency selective filtering, the transmitter transmitting on f1 can be distinguished from the transmitter transmitting on f2 even in the case of simultaneous transmission.

Still other examples of collision avoidance modules are described in PCT application Ser. No. PCT/US 08/85048; the disclosure of which is incorporated herein by reference.

Physiological sensing

In addition to receiving conductively transmitted signals, such as signals emitted by an identifier of an ingestible event marker, the signal receiver may also include one or more different physiological parameter sensing capabilities. Physiological parameter sensing capability refers to the ability to sense a physiological parameter or biomarker as follows, but not limited to: electrocardiographic data includes heart rate, Electrocardiogram (ECG), and the like; respiration rate, temperature; pressure; chemical composition of the fluid such as analyte detection in blood, flow regime, blood flow velocity, accelerometer motion data, etc. Where the signal receiver has a physiological parameter or biomarker sensing capability, the number of different parameters or biomarkers that the signal receiver can sense may be different, e.g., 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 10 or more, etc. The term "biomarker" refers to an anatomical, physiological, biochemical or molecular parameter that correlates with the presence and severity of a particular disease state. Biomarkers are detectable and measurable by a variety of methods, including physical examination, laboratory assays, and medical imaging. Depending on the particular embodiment, the signal receiver may implement one or more of these sensing functions using signal receiving elements, e.g., using electrodes of the receiver for signal receiving and sensing applications, or the signal receiver may include one or more different sensing elements different from the signal receiving elements. The number of different sensing elements that may be present on (or at least connected to) the signal receiver may be different and may be 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 10 or more, etc.

In certain embodiments, the signal receiver comprises a set of 2 or more electrodes, such as 2 or 3, that provide dual functions of signal reception and sensing. For example, the electrodes may have additional sensing functions in addition to receiving signals. In certain embodiments, electrodes are used to generate electrocardiographic data. From the above data, a variety of processes can be performed, such as detecting various cardiac events, such as tachycardia, ventricular fibrillation, heart rate, and the like. The obtained electrocardiographic data can be used to titrate drugs or to give alerts when significant changes or significant abnormalities in heart rate or rhythm are detected. This data may also be helpful in certain embodiments in monitoring heart rate for patients without pacemakers, or alternatively for patients who may typically require a Holter monitor or cardiac event monitor for a portable or other device that continuously monitors the electrical activity of the heart for 24 hours. An extended recording period is helpful for finding occasional arrhythmias that are difficult to identify in a shorter period of time.

As described above, two or more different demodulation protocols may be employed to decode a given received signal. In some instances, a coherent demodulation protocol and a differential coherent demodulation protocol may be employed simultaneously. Fig. 2 provides a functional block diagram of how a receiver may perform a coherent demodulation protocol in accordance with an aspect of the present invention. It should be noted that only a portion of the receiver is shown in fig. 2. Fig. 2 shows the process of mixing down the signal to baseband once the carrier frequency (and carrier signal mixed down to the carrier offset) is determined. The carrier signal 221 is mixed with a second carrier signal 222 at mixer 223. A narrow low pass filter 220 is applied at a suitable bandwidth to reduce the effect of out-of-boundary noise. In accordance with the coherent demodulation scheme of the present invention, demodulation occurs at block 225. The unwrapped phase of the complex signal is determined 230. An optional third mixer stage may be applied where the phase evolution is used to estimate the frequency difference between the calculated carrier frequency and the actual carrier frequency. The structure of the packet (packet) is then utilized at block 240 to determine the start of the coded domain of the BPSK signal. Primarily, the presence of a synchronization header, an FM edge in the amplitude signal that appears as a complex demodulated signal, is utilized to determine the starting boundary of the packet. Once the start point of the packet is determined, the signal is rotated at block 250 on the IQ plane and standard bit identity and finally decoded at block 260.

In addition to demodulation, the cross-body communication module may also include a forward error correction module that provides additional gain to combat interference from other unwanted signals and noise. Forward error correction functional modules of interest include those described in PCT application serial number PCT/US 2007/024225; the disclosure of which is incorporated herein by reference. In some examples, the forward error correction module may employ any convenient protocol, such as Reed-Solomon, Golay, Hamming, BCH, and Turbo protocols, to identify and correct (within-boundary) decoding errors.

The receiver of the present invention may also employ a beacon function module. In various aspects, the beacon switching module 306 may employ one or more of the following: the device comprises a beacon awakening module, a beacon signal module, a wave/frequency module, a multi-frequency module and a modulation signal module.

The beacon switching module 306 of fig. 1B may be associated with beacon communications, e.g., a beacon communications channel, a beacon protocol, etc. For purposes of this disclosure, a beacon is generally a signal transmitted as part of a message or a signal transmitted to augment a message (sometimes referred to herein as a "beacon signal"). These beacons may have well-defined characteristics, such as frequency. Beacons can be easily detected in noisy environments and can be used as triggers for sniffing circuits, as described below.

In one aspect, the beacon switching module 306 may include a beacon wakeup module having a wakeup function. The wake-up function generally includes a function of operating in a high power mode only during a specific time (e.g., a short period for a specific purpose) in order to receive a signal or the like. An important consideration for the receiver portion of the system is that it should be low power. This feature may be advantageous in an implanted receiver to support small size while maintaining long-term power supply of the battery. The beacon switching module 306 may achieve these advantages by operating the receiver in a high power mode for a very limited period of time. Such short duty cycles can provide optimal system size and energy consumption characteristics.

In practice, the receiver 100 may "wake up" periodically and with low power consumption, in order to perform a "sniff function" by means of, for example, a sniff circuit. For the purposes of this application, the term "sniff function" generally refers to a short-lived low power function for determining whether a transmitter is present. If the sniff function detects the transmitter signal, the device may switch to a higher power communication coding mode. If no transmitter signal is present, the receiver may return, for example, to an immediate return to sleep mode. In this way, when no transmitter signal is present, then energy may be saved during a relatively long period of time, while when a transmitter signal is present, high power capacity may be used for efficient coding mode operation during a relatively short period of time. Various modes and combinations thereof may be used to operate the sniff circuit. By matching specific system requirements with sniff circuit configurations, an optimized system can be achieved.

Fig. 3A shows a beacon switching module 306 in which the sniff period 301 is longer than the transmission signal repetition period 303. The time function is provided on the X-axis. As shown, the transmit signal is repeated periodically while the sniff function is also running. In practice, the sniff period 301 may be longer than the transmit signal repetition period 303. In various aspects, there may be relatively long periods of time between sniff periods. In this way it is ensured that each time the sniffing circuit is started, the sniffing function, which is for example implemented as a sniffing circuit, ensures that at least one transmission takes place.

Referring now to fig. 3B, fig. 3B shows a beacon switch module 306 provided with short but frequent sniff periods 305 and long transmission packets 307. The sniffing circuit will start at some point during transmission. In this way, the sniff circuit can detect the transmitted signal and switch to a high power decoding mode.

An additional beacon wakeup aspect is to provide a "sniff" function in a continuous mode. In comparison to the approach provided above, this aspect of the cross-body beacon transmission channel may exploit the fact that: the total energy consumption is the product of the average power consumption and time. In this regard, the system can minimize the total energy consumption by having a very short active period, in which case the active period average is reduced to a small value. Alternatively, a low continuous sniffing activity is provided. In this case, the configuration provides sufficiently low power to keep the transceiver running continuously while the total energy consumption is at a level appropriate for these parameters of the particular system.

A functional flow diagram of the beacon switch module 306 of fig. 1B is shown in fig. 3C. In fig. 3C, the beacon switching module is shown as a sniffing module 310. The sniffing module 310 is configured to scan data encoded in the current generated by ion emission. The data is received at the receiver as a conductive signal on a set schedule, for example every 20 seconds. At step 315, a time period, e.g., 300 milliseconds, during sniff of the activity is defined. This relatively low duty cycle allows for a lower average power functionality to achieve an extended system lifetime. At step 320, the receiver determines whether a signal is present and whether the signal has a valid ID. If no signal with a valid ID is detected during active sniffing (as illustrated by arrow 320), the process returns to step 315 and active sniffing is stopped until the next predetermined activity period. If at step 320 a signal with a valid ID is received, the process moves to step 322. At step 322, the receiver determines whether the received signal is from a previously detected ion emitter. If the signal is from a previously detected ion emitter, the process moves to step 326. At step 326, the receiver determines whether the count (in other words, the number of valid detections of individuals with the same ID) in the current wake-up period (a specified time, such as 10 minutes, since the last reported ID) is greater than a specified number (such as 50) as measured by a threshold counter. If the count exceeds this threshold as determined by the threshold counter, the receiver returns to sniff mode. If the count does not exceed the threshold, the process moves to step 330 and the receiver operates in 100% detection mode to analyze the received data encoded in the current generated by the ion emission. Once the received data is decoded and analyzed, the process returns to step 315. If at step 322 the receiver determines that the data encoded in the current is from a valid source that is different from the previously detected source, then the process moves to step 328. At step 328, the threshold counter is reset.

Another view of the beacon module is provided in the functional block diagram shown in fig. 3D. The scheme summarized in fig. 3D outlines a technique to identify valid beacons. Incoming signal 360 represents a signal that is received by the electrodes, bandpass filtered (such as from 10KHz to 34KHz) through a high frequency signaling chain (containing the carrier frequency), and then converted from analog to digital. The signal 360 is then decimated at block 361 and mixed at a nominal drive frequency (e.g., 12.5KHz, 20KHz, etc.) at mixer 362. The resulting signal is decimated at block 364 and low pass filtered (e.g., 5KHz BW) at block 365 to produce a carrier signal, signal 369, which is mixed down to a carrier offset. Signal 369 is further processed (fast fourier transformed and then the two strongest peaks are detected) by block 367 to provide a true carrier frequency signal 368. This protocol allows the carrier frequency of the transmitted beacon to be determined accurately.

Fig. 4 illustrates a beacon function in which a beacon is associated with one frequency, e.g., a beacon channel, and a message is associated with another frequency, e.g., a message channel. This configuration is advantageous, for example, when the system is processing multiple transmitted signals. The solid line represents the beacon transmitting signal 1. The dashed line represents the beacon transmitting signal 2. In various transmission scenarios, the beacon transmitting signal 2 may overlap with the beacon transmitting signal 1, as shown. Message signal 1 and message signal 2 may be on different frequencies than their respective beacons. One advantage may be that the beacon transmitting signal 2 does not interfere at all with the message transmitting signal 1, even if they are transmitted simultaneously. Although fig. 4 is shown to contain two emitters, it will be apparent to those skilled in the art that the system may be modified to expand it into more emitters. The specific system requirements determine to some extent the specific architecture of the system.

Still other examples of beacon function modules are described in PCT application Ser. No. PCT/US 08/85048; the disclosure of which is incorporated herein by reference.

Various aspects may employ a frequency hopping function. The frequency hopping function may be associated with a particular communication channel, frequency hopping protocol, etc. Thus, various aspects may utilize one or more frequency hopping protocols. For example, the receiver may search for a specified frequency range, e.g., two or more different frequencies, within which the transmission falls. When a single correct decoding is achieved, the in-vivo transmitter has completed the task of transmitting its digital information payload to the receiver.

In some instances, the transmit frequency uncertainty provided by, for example, random frequency hopping via the random module, may yield a number of benefits. For example, one benefit of this is ease of implementation on a small die. To illustrate, the intra-body transmitter carrier frequency oscillator may be an imprecise and free-running oscillator that is easily implemented on a small portion of a 1mm bare chip. On the order of +/-20 is readily acceptable because the receiver employs a frequency search algorithm.

Another benefit of this is extended battery life. By way of example, during the lifetime of the transmitter battery, e.g. 3 to 10 minutes, the probability of the transmitter transmitting on a clear channel that can be received by a frequency agile receiver can be significantly increased due to random frequency hopping.

Another benefit is minimizing collision events in high capacity environments. To illustrate, the probability of collision is minimized when multiple in-vivo transmitters, such as ingestible event markers, may transmit simultaneously, such as where multiple ingestible event markers are ingested at the same time or in close proximity. In other words, without the frequency hopping function, there is a high likelihood that similar batches of ingestible event markers transmit on the same (or nearly the same) frequency, resulting in multiple collisions.

In certain aspects, the available spectrum for use in bulk conductive applications is in the range from about 3kHz to 150 kHz. Through detailed animal studies, it has been found that in some environments in-vivo transmitters (see above) with received signal levels ranging from 1 to 100 μ V can compete with narrowband interfering signals on the order of hundreds to thousands of μ V in the same spectrum. To mitigate the destructive nature of interfering signals, a frequency hopping channel or protocol may be employed in which the in-vivo transmitter randomly hops each time it transmits an outgoing narrowband transmit signal, e.g., a modulated signal such as a Binary Phase Shift Keying (BPSK) signal or an FSK signal.

Further examples of frequency hopping modules are described in PCT application Ser. No. PCT/US 08/85048; the disclosure of which is incorporated herein by reference.

Various aspects of the receiver may employ collision avoidance functionality. The collision avoidance function may be associated with a particular communication channel, collision avoidance protocol, etc. Thus, various aspects may utilize various collision avoidance protocol techniques associated with a particular communication channel. Collision avoidance techniques are particularly useful in environments where, for example, there are two or more in-vivo transmitters, e.g., an individual ingests multiple IEMs. In such an environment, if the individual in-vivo transmitters continue to transmit their signals, the transmission of one in-vivo transmitter may mask the transmissions of all other in-vivo transmitters. Therefore, the failure to detect a signal may increase significantly.

Various aspects may include various collision avoidance methodologies, alone or in various combinations.

One such method employs multiple transmit frequencies. By using frequency selective filtering, transmitters broadcasting on f1 can be distinguished from transmitters broadcasting on f2 even when transmitted simultaneously.

Still other examples of collision avoidance modules are described in PCT application Ser. No. PCT/US 08/85048; the disclosure of which is incorporated herein by reference.

Other functional modules that may be included in the cross-body communication module of the receiver of the present invention include a clock function module that correlates a particular time with a given signal, for example, as described in one or more of the following PCT applications: PCT application Ser. No. PCT/US 08/85048; PCT application Ser. Nos. PCT/US2007/024225 disclosed as WO 2008/095183 and PCT application Ser. No. PCT/US2007/024225 disclosed as WO 2008/063626; the disclosures of these patent applications are incorporated herein by reference.

As noted above, the trans-body conductive signal may also be a signal generated by an intelligent parenteral delivery system, such as described in PCT application Ser. No. PCT/US2007/015547, published as WO 2008/008281; the disclosure of which is incorporated herein by reference. In these examples, a medical device associated with the body may be configured to derive a plurality of different types of information about the fluid delivery event from the received signals. Types of information that may be derived include, but are not limited to: a fluid delivery event that will occur or has occurred, what the amount of fluid once administered is, the nature of the fluid once administered, etc. For those instances where the receiver is configured to determine what the amount of fluid has been administered, the device may be configured to receive a variety of volumetric dosing data, so as to configure it to receive different values for this data field.

The receiver may provide an additional communication path via which the collected data can be transferred from the receiver to another device, such as, but not limited to, a smart phone, a hospital information system, and the like. This additional communication path is provided by the "extra-corporeal communication" module. The extracorporeal communication module may employ a number of different protocols. Protocols of interest include wired communication protocols and wireless communication protocols. For example, the receiver may comprise conventional RF circuitry (e.g. operating in the 405MHz medical device band) with which medical personnel can communicate, for example by using a communication interface with a data retrieval device such as a bar code reader (wand) or similar device. Of interest in some aspects are low power wireless communication protocols, such as BLUETOOTH^TM(bluetooth) wireless communication protocol. Also of interest are communication protocols that employ multi-purpose connectors, as described in more detail below.

Where the receiver comprises at least a part outside the living body during use, said part may have output means for providing, for example, audio and/or visual feedback; examples of such output devices include audible alarms, LEDs, display screens, and the like. The external portion may also include an interface port via which components can be connected to a computer to read data stored therein. Furthermore, the outer part may comprise one or more operating elements, such as buttons or similar structures, to enable a user to manually interact with the body-associated medical device in some way, for example to test operability, to open the device, to reset the device, etc.

In some examples, an extracorporeal communication module is employed to reconfigure various parameters of the receiver. Thus, the communication module may be a bi-directional communication module. Reconfigurable parameters include the "duty cycle" of data acquisition, such as how frequently the receiver sniffs IEMs, how frequently and for how long the receiver collects ECG or activity data, and so forth.

In one aspect, the extracorporeal communication module may be implemented with its own power supply so that it can be turned on and off independently of other components of the device, e.g., by a microprocessor.

A receiver according to the teachings of the present invention may include one or more different physiological sensing modules. Physiological sensing module refers to the ability or function to sense one or more physiological parameters or biomarkers of interest, such as but not limited to: electrocardiographic data including heart rate, Electrocardiogram (ECG), etc.; respiration rate, temperature; pressure; chemical composition of the fluid such as analyte detection in blood, flow regime, blood flow velocity, accelerometer motion data, etc. Where the receiver has physiological parameter or biomarker sensing capability, the number of different parameters or biomarkers that the signal receiver can sense may be different, e.g., one or more, two or more, three or more, four or more, five or more, ten or more, etc. The term "biomarker" refers to an anatomical, physiological, biochemical or molecular parameter that is associated with the presence and severity of a health state, such as a particular disease state. According to particular aspects, the device may implement one or more of these sensing functions using its signal receiving elements, e.g., using electrodes of a receiver for signal receiving and sensing applications, or the receiver may include one or more different sensing elements (such as microneedles described below) that are different from the signal receiving elements. The number of different sensing elements that may be present on (or at least connected to) the signal receiver may be different, may be one or more, two or more, three or more, four or more, five or more, ten or more, etc.

In certain aspects, the receiver includes a set of two or more electrodes, such as two or three, that provide dual functions of signal reception and sensing. For example, the electrodes may have additional sensing functions in addition to receiving signals. In certain aspects, electrocardiogram data is generated using the electrodes. From the data, a variety of processes can be accomplished, such as detecting individual cardiac events such as tachycardia, ventricular fibrillation, heart rate, etc., detecting neurological symptoms such as seizures (e.g., such as possibly epileptic seizures (see, e.g., the apparatus and modules for seizure detection described in more detail below)), and so forth. The obtained electrocardiographic data can be used to titrate the drug, or can be used to alert when a significant change or significant abnormality in heart rate or rhythm is detected. In certain aspects, this data is also helpful when used to monitor heart rate for patients without a pacemaker, or alternatively for patients who may typically require a Holter monitor or cardiac event monitor, a portable device or other device for continuously monitoring electrical activity of the heart for 24 hours. An extended recording period is helpful for finding occasional arrhythmias that are difficult to identify over a shorter period of time.

As described above, one or more additional physiological sensors, different from the electrodes, may be included in the receiver. For example, temperature sensors such as thermistors, CMOS temperature sensors, Resistance Temperature Detectors (RTDs) may be employed to obtain an accurate measurement of temperature. An additional physiological sensor may include an LED and photodiode combined in a pulse oximeter that can be used to measure blood oxygen and also provide information about pulse pressure. Further, aspects of the signal receiver include a pressure sensor, for example, where the signal receiver is implanted alongside an artery to make a measurement of arterial blood pressure. In certain aspects, a strain gauge is present to measure pressure deflection, and then connected to a signal receiver.

The receiver may also include an analyte detection sensor. For example, specific chemical sensors may be incorporated into the signal receiver to detect the presence of various agents, such as alcohol, glucose, BNP (B-type natriuretic peptide, which is associated with cardiac disease), and the like. Sensors of interest include those configured to detect the presence of chemical analytes in a biological fluid sample, including but not limited to: blood glucose (glucose), cholesterol, bilirubin, sarcosine, various metabolic enzymes, hemoglobin, heparin, hematocrit, vitamin K or other coagulation factors, uric acid, carcinoembryonic antigen or other tumor antigens, various reproductive hormones such as those associated with ovulation or pregnancy, drugs of abuse, and/or metabolites thereof; blood alcohol concentration, etc. In certain aspects, the substances or properties to be detected by the receiver are configured to include lactate (important for athletes), oxygen, pH, alcohol, tobacco metabolites, and illegal drugs (important for medical diagnostics and law enforcement). Where the receiver includes an analyte that detects the sensing element, the sensing element can be configured in the receiver in a variety of different ways. For example, a sensor may be provided that includes a permselective membrane that is permeable to the agent to be detected, wherein the membrane is followed by a separate compartment and the agent penetrates the membrane. The change in a characteristic of the chamber, such as an electrical characteristic, is then measured. In some aspects, a small reservoir with a membrane spanning it on the side of the receiver is employed and the circuit located behind it is measured. Also of interest are ChemFET sensors, which are based on binding of an analyte to the sensor causing a change in conductivity. In certain aspects, when a material, such as a protein analyte, is employed to bind to the sensor, the electrical properties (or other properties) of the material are altered. The blood alcohol concentration may be determined in a variety of ways, including but not limited to: sensors for analyzing fluid samples such as sweat, optical spectroscopic sensors, and the like.

Of interest is a receiver comprising at least one Electrocardiogram (ECG) sensor module. The ECG sensor module is a module configured to acquire ECG data, and if desired, further performs one or more of the following operations: data processing, storing and forwarding is performed in some manner. The receiver may employ the ECG data to derive a number of different metrics, including but not limited to: r-wave, heart rate variability, respiration rate, etc. Where the receiver includes one or more physiological sensing functions, the apparatus may further include a sensing module configured to acquire and process data from these sensing functions. For example, where the receiver includes ECG sensing functionality, the device may include a suitable functional module (e.g. in the form of programming) capable of operating and processing raw data from these sensors. An example of a physiological sensing module of interest is the ECG sensing module shown in fig. 5.

Referring now to FIG. 5, an example of an ECG sensing module implementing the improved Hamilton and Tompkins algorithms is shown. Fig. 5 illustrates one possible implementation of an R-wave detection algorithm in accordance with an aspect of the present invention. As shown in fig. 5, the ECG sensing module receives the signals via the electrodes and band-pass filters the signals (e.g., 0.3 to 150Hz) at filter 501 before converting the signals to digital signals at a/D converter 502. The signal is then sent to the microprocessor 503 and the digital signal processor 504 for processing. For example, the data signal received by the DSP 504 is band pass filtered (e.g., at 10-30Hz) at block 505, and differentiated at block 510 and further filtered at block 515 to enhance and ultimately identify the window in which the QRS complex (QRS complex) exists at block 520. Logic is then applied to identify the R-waves within each window. At logic block 525, a determination is made whether the window width is greater than, for example, 140 ms. The peaks and valleys in the window are determined, as indicated by logic block 530. If the peak is greater than twice the valley, the R-wave is equal to the peak. If the valley is greater than twice the peak, then the R-wave is equal to the valley. Otherwise, the R-wave is equal to the ratio of the peak to the first occurring valley. Logic block 535 illustrates this. Thereafter, the R-wave amplitude and time-to-peak are sent to memory (e.g., flash memory), as indicated by logic block 540.

Also of interest are accelerometer modules. The accelerometer module is a module configured to acquire accelerometer data, and if desired, to perform one or more of the following operations: data processing, storing and retransmitting data is performed in some manner. The receiver may employ the accelerometer module to derive a number of different metrics, including but not limited to the following data: data about patient activity, average activity, position and angle of the patient, type of activity such as walking, sitting, resting (where this data can be acquired using a 3-axis accelerometer); the acquired data is then saved. Of interest are analog accelerometers and digital accelerometers. One example of an accelerometer module of interest is shown in figure 6.

Referring now to fig. 6, a functional block diagram of a 3-axis accelerometer module configured to acquire and process accelerometer data from three different axes is shown, according to one aspect of the invention. Each axis of the accelerometer is processed to determine a mean (as shown at block 601), a standard deviation (as shown at block 602), and an autocorrelation (as shown at block 603). The mean reflects the orientation of the accelerometer with respect to gravity, while the standard deviation and autocorrelation are important metrics describing the amplitude and frequency of the observed motion, e.g., peak correlation, associated frequency, correlation between axes. To perform step counting, the three axes are combined at block 630 and filtered at block 635. The total acceleration is constructed as shown in block 640. Using the total acceleration makes the system more robust to handle different orientations of the receiver relative to the subject. Once the total acceleration is calculated, the standard deviation and autocorrelation are calculated, as shown in block 645. These values are then thresholded (e.g., standard deviation > 0.1, autocorrelation > 0.25) to determine if significant cyclic motion is present, as shown in block 650. Then, as shown in block 655, if the threshold is exceeded, the number of steps is determined as the number of zero crossings of the average corrected total acceleration.

In some receivers, the apparatus may include an ambient function module. An environmental function module is a module configured to or obtaining data related to the environment of the receiver, such as environmental conditions, whether the receiver is connected to a skin surface, etc. For example, the environmental function module may be configured to obtain receiver ambient temperature data. The environmental function module may be configured to determine the electrode connections by, for example, impedance measurements. The environmental function module may be configured to determine a battery voltage. The particular functionality of the environment function module described above is merely exemplary and not limiting.

The receiver may be configured to process the received data in various ways. In some aspects, the receiver simply forwards the data to an external device (e.g., using conventional RF communication). In other aspects, the receiver processes the received data to determine whether some action is to be taken, such as operating an effector under its control, activating a visual or audible alarm, sending a control signal to an effector located elsewhere in the body, and so forth. In still other aspects, the receiver stores the received data for subsequent forwarding to an external device or for use in processing subsequent data (e.g., detecting a change in a parameter over time). The receivers may perform any combination of these operations and/or other operations using the received data.

In certain aspects where the receiver is an IEM signal receiver, the data recorded on the data storage element comprises at least one, if not all, of the following: the time, date, and identifier (e.g., a globally unique serial number) of each IEM is administered to the patient, where the identifier can be the generic name of the composition or an encoded version thereof. The data recorded on the data storage element of the receiver may also contain medical record information, e.g., identifying information, of the subject with which the receiver is associated, such as, but not limited to, the following: name, age, treatment record, etc. In certain aspects, the data of interest comprises hemodynamic measurements. In certain aspects, the data of interest includes cardiac tissue characteristics. In certain aspects, the data of interest includes pressure or volume measurements, temperature, activity, respiration rate, pH, and the like.

The receiver may include a variety of different types of power supplies that provide operational power to the device in some manner. The characteristics of the power supply block modules may differ. In some examples, the power block may include a battery. When present, the battery may be a single use battery or a rechargeable battery. For rechargeable batteries, any convenient protocol may be used to charge the battery. Of interest are protocols that facilitate the multitasking implementation of the elements of the receiver. For example, a receiver of the present invention may include one or more electrodes for performing a variety of functions, such as receiving conductively transmitted signals, sensing physiological data, and the like. One or more electrodes (when present) may also be employed as a power receiver that may be used to charge a rechargeable battery, as further described in the multipurpose connection module section below. Alternatively, the power block may be configured to receive a power signal, for example the power block comprises a coil capable of imparting power to the device when a suitable magnetic field is applied to the receiver. In other examples, the device may include a body-powered power block, such as the power block described in U.S. patent application serial No. 11/385,986, the disclosure of which is incorporated herein by reference.

The receiver may include a power supply module that controls when the device assumes certain conditions, for example, to minimize power usage of the device. For example, the power supply module may perform a duty cycle for data acquisition based on a period of the day or activity of the patient or other events, where the performed duty cycle may be based on a signal factor or factors. For example, the power supply module may cause the receiver to acquire activity data of the patient (e.g., via the accelerometer module) while the patient is ambulatory, rather than while the patient is at rest. In other aspects, the power management module may have the receiver acquire ECG data only during the night, for example using a real time clock in the receiver to acquire an ECG only during a predetermined time range (e.g., from 9PM to 7 AM).

As previously mentioned, the receiver may be configured to have various states, such as a standby state or one or more active states, with the intermediate module cycling the high power functional block between the active and inactive states as required for each desired receiver state. In addition, other receiver elements may also be cycled on and off by the power module during different states of the receiver. The power supply module may be configured to control power to various circuit blocks within the medical device, such as circuit blocks associated with the power supply to the processor, circuit blocks associated with various peripheral components (e.g., wireless communication modules, etc.), their power supplies, and the like. Thus, during each state of the receiver, power to various components of the receiver can be independently cycled on and off as needed to achieve power efficiency (as well as independently cycling the high power functional block between active and inactive states, as previously discussed). For example, in some instances, a receiver may be configured to exist in two or more different activity states, where a different task or set of tasks is performed in each different activity state. The receiver of interest may be configured to execute an IEM signal detection protocol when present in the first active state and a physiological data detection protocol when present in the second active state. In these types of receivers, the various components of the receiver can be independently cycled on and off as needed to achieve power efficiency (as well as independently cycling the high power functional block between active and inactive states, as previously discussed).

The power supply module may include one or more individual power supplies to activate and deactivate power to these various components. For example, in one aspect, the power supply module may include: a high power processing input/output power supply supplying an input/output power supply to the high power processing block; and a high power processing core power supply supplying the core power to the high power processing block. In addition, the power supply module may further include: a wireless communication input/output power supply supplying an input/output power to the wireless communication module; and a wireless communication core power supply supplying the core power supply to the wireless communication module.

It should be understood that a single power supply may be used to power multiple components. For example, a single power supply may supply input/output power to the high power processing block and the wireless communication module. In one aspect, the power supply module receives control signals from a low power processing block (e.g., a microprocessor) that determines which power supplies to turn on/off.

Referring now to fig. 26, a circuit diagram of a portion of a circuit of a receiver in accordance with the teachings of the present invention is provided. Circuitry 2600 is responsible for controlling the power to the various components of the receiver. Fig. 26 is connected to fig. 24 at a signal line "VCC _ EN _ BAT" shown in both figures, and works together with a part of the circuit in fig. 24 to control power supply. As shown in fig. 26, where the translator 2610 is shown electrically coupled to a switch 2620, the switch 2620 is electrically coupled to voltage references 2630 and 2640. Converter 2610 translates the data signal VC _ ENA on its A bus to the signal VC _ EN _ BAT on its B bus. The signal VCC _ EN _ BAT is connected to the enable pins of regulators 24155, 24157, and 24159 (shown in fig. 24) that power the various components. Accordingly, the data signal VCC _ EN _ BAT may enable/disable power supplies to various components of the receiver. For example, regulators 24155, 24157, and 24159 provide power to the DSP core, the DSP and wireless communication I/O, and the wireless communication core, respectively. Thus, each of these components can be turned on and off with a respective enable/disable data signal (VCC _ EN _ BT) from circuit 2600.

The receiver may include a multi-purpose connector module. The multi-purpose connector module includes living subject contacts, such as the electrodes described herein (hereinafter also referred to as "multi-purpose connector"), and may be used to periodically charge the power source of the device, to reprogram the control functions of the device, and/or to reprogram the data retrieval of the device. This configuration is different from those that include separate connectors for each of these functions, such as different patient connectors, power connectors, and device configuration connectors.

A receiver including a multi-purpose connector module enables a variable connection between a target subject, such as a patient or patient-related device, and a second external device, such as an external programming device and an external charger device. The connections may be used to facilitate communication of signals, such as electrical signals, digital signals, optical signals, combinations of various types of signals, and the like. The term "variable connection" as used herein refers to the ability of the multi-purpose connector to receive a connection component connected to one of a living subject, such as a patient, and a second external device and to form a connection based on a particular connection component, such as the connection component connected to the patient or the connection component connected to the second external device. The receiver also includes a multi-function block to control signals related to communication of the signals via the connection. In various aspects, the second external device comprises an external programming device and the second functional block comprises a controller functional block to control signals related to communication between the external programming device and the receiver. When the receiver is connected to the external programming device via the multipurpose connector, the external programming device may be used to programmatically control the receiver. In various aspects, the second external device comprises an external charger device and the second functional block comprises a power functional block to control signals related to communication between the external charger device and the receiver. When the receiver is connected to the external charger via the multipurpose connector, the external charger may be used to charge the receiver. In various aspects, the second function block comprises a patient interaction function block. When the receiver is connected to the patient or to the patient-related device via the multi-purpose connector, the device may be used to interactively communicate with the patient or patient-related device. For example, the receiver may be configured with electrodes to stimulate or sense a variety of patient parameters and physically connected to the patient to facilitate various functional goals, such as delivering pacing stimulation to the patient; receive physiological information from the patient, and the like.

In some aspects, at least one of the multifunction blocks is configured as a signal director. The signal director may be any component, subcomponent or combination thereof, that is capable of performing the described function. In one embodiment, the receiver is physically connected to the signal director, for example, the receiver is configured to include the signal director. Such a configuration may include one or more circuits, and the like. In another embodiment, the signal director is physically separate from the receiver. Such configurations may include routers or other network devices capable of facilitating the signal functions described herein. The signal director may include a control element configured to control a signal, such as an authentication signal. In various aspects, the signal director includes at least one of software and circuitry.

Signal control or discrimination may be based on various criteria such as voltage, frequency, manual control, programmed control, etc. The control element configuration is correspondingly different. For example, the control element based on voltage discrimination may be implemented as one or more diodes, thermistors, or the like. The control element based on frequency discrimination may be implemented as a high-pass filter or a low-pass filter. The control elements providing manual control and/or programmed control may be implemented as analog switches, relays, multiplexers, etc. Various other implementations may be based on various parameters such as light, temperature, time, etc.

As mentioned above, the multipurpose connector is a connector element configured to provide a connection to a patient and one or more second external devices, such as an external programming device, an external charger device, or an external data processor. Accordingly, the multi-purpose connector is configured such that it can provide for connection of the receiver to the patient and to another device, either directly or through another device (as described below). Accordingly, the receiver is capable of connecting to a patient via the multi-purpose connector at a first time and to another device via the same multi-purpose connector at a second time different from the first time, such that the receiver is connected to different entities at different times using the same multi-purpose connector. Thereby, one or more physical realizations of the functional blocks of the device may be connected to the patient and to at least one or more additional external devices, such as an external charger, an external programming device, or an external data processor, at different times using the multipurpose connector.

The structure of the multipurpose connector may vary as desired, with connector structures of interest including, but not limited to: IS-1 connectors, medical device advanced association electrocardiogram (AAMI ECG) wire connectors, and medical grade shielded multi-pin connectors. In some examples, the connector includes one or more electrodes, such as two to ten electrodes, including three electrodes or four electrodes.

If desired, the multi-purpose connector may be configured to connect directly with the patient or other external device, such that no additional connector device is required to provide a connection between the multi-purpose connector of the receptacle and the patient or other external device. Alternatively, the multipurpose connector may be configured to connect to a patient or other external device via a physically different connector device, such as a cable or wire. The physically distinct electrical connector may have one terminal configured to mate with the multi-purpose connector and another terminal configured to perform a specific purpose, such as connecting to a patient or an external device, such as a battery charger or an external programming device, for example. It should be noted that the device is still considered a receiver when the receiver is connected to the patient via a different connector, such as a wire.

In the receptacle of the present invention, the multi-purpose connector is operatively connected (e.g., electrically connected, optically connected, etc.) to a multi-functional block (e.g., two or more, three or more, four or more, five or more, seven or more, ten or more functional blocks), as described elsewhere in this application.

In addition to being configured to connect to a patient, the multi-purpose connector of interest may be configured to connect the receiver to other external devices including, but not limited to, external charger devices, external programming devices, data processing devices, modems, keyboards, displays, and/or external storage devices, and the like. By connecting the receiver to the patient and other devices using the same connector, it is avoided that the patient is connected to the receiver at the same time as the medical device is connected to another device, such as a charger. This configuration enhances patient safety as it eliminates the possibility that signals from other external devices, such as chargers, programming devices, data processors, etc., will be transmitted to the patient and may harm the patient. The use of a single connector for multiple functions also makes it easier to waterproof the device because there are fewer openings in the housing of the device.

The receiver of interest may include a router functionally disposed between the multi-purpose connector and one or more of the multi-function blocks of the device. "functionally disposed between …" means that a signal, such as an incoming signal, an outgoing signal, or a bi-directional signal, passes through the multi-purpose connector before entering one of the multi-function blocks and then passes through the router. The router may be configured to selectively allow signals to pass through to certain functional blocks according to one or more parameters. For example, a router may be configured to discriminate between signals based on voltage, e.g., only allowing signals above or below a certain threshold voltage (or within a certain voltage band) to pass through; discriminating signals based on frequency, e.g., allowing only signals above or below a threshold frequency (or within a certain frequency band) to pass; or an authentication signal based on a mode of operation, such as a charging mode, a data transfer mode, a patient interaction mode, etc. In some instances, a router may be functionally disposed between the multi-purpose connector and only some of the multi-function blocks. In other words, there may be one or more functional blocks that are not separated from the multi-purpose connector by a router.

In some instances, the router may be configured to authenticate the signal based on a characteristic of the signal of interest that is unique to the device. The signal measured from the body may be a relatively low voltage, for example 500mV or less, such as 100mV or less, or 50mV or less. Similarly, the signal measured from the body may be of a relatively low frequency, for example 20kHz or less, such as 5kHz or less, or 1kHz or less. In contrast, typical power supply signals used to charge internal batteries of devices, such as external medical devices, may be relatively high voltages, such as 1V or higher, 2V or higher, or 5V or higher. Typical signals for data transmission may have a relatively higher frequency than the body measurement signal, for example 100kHz or higher, such as 1MHz or higher, or 10MHz or higher. Thus, by differentiating based on frequency and voltage, a router can selectively route signals to one or more appropriate functional blocks. The router may discriminate the signal based on any characteristic of the signal including, but not limited to, voltage, frequency, and a combination of the two. In other embodiments, the router is capable of routing incoming signals based on the operating mode of the device, which may be set by other circuitry, software, or manual switches or instructions.

In some instances, a router is configured to route certain types of signals to a particular functional block while isolating signals of one or more other functional blocks. For example, if a high impedance measurement of the patient's signal is desired, it may be important to isolate the low impedance of the power block. In this case, a router may be provided between the power functional block and the multipurpose connector, which allows only signals above a certain voltage to pass. Thus, the relatively low voltage signal measured from the patient's body will be isolated from the power function and the patient interaction function will be able to correctly measure the signal.

However, in some instances, it may not be important to isolate a particular block from other functional blocks that are not in use. Thus, in some instances, a router may not be configured to disconnect one or more particular functional blocks from a signal. That is, in these examples, the incoming signal will always pass through a particular functional block. However, in some cases, the functional block may only respond to certain types of signals, such as a range of frequency or voltage signals, and will not be damaged when exposed to other signals. Such selective response may be effective as a routing means.

A router as used herein may itself be made up of a plurality of functional routing blocks, each functionally disposed between one or more device functional blocks and a multi-purpose connector. Thus, a single router block may discriminate signals based on different parameters, allowing different types of signals to reach the corresponding device function blocks.

A router may route signals to appropriate circuitry either inherently, actively, or through a combination of inherent and active techniques. In some instances, the router may discriminate incoming signals based on voltage. For example, a router functionally disposed between the multipurpose connector and one or more functional blocks may only allow signals above a certain voltage threshold to pass through to reach those functional blocks. In some instances, this may be accomplished with one or more diodes. In some examples, the diodes may be provided as rectifiers, such as half-wave rectifiers, full-wave rectifiers, three-phase rectifiers, and the like. In other instances, a router may only allow signals below a certain threshold voltage to pass through to the associated functional block.

In other instances, the router may route signals based on frequency. For example, a router functionally disposed between the multipurpose connector and one or more functional blocks may only allow signals above a certain frequency to pass through to those associated functional blocks. In other instances, a router may only allow signals below a certain frequency, within a certain frequency band, or outside a certain frequency band to pass through. The router that discriminates based on frequency may contain a filter, such as a low pass filter, a high pass filter, or a band pass filter. The filter may be of any convenient design and the filter characteristics may be different depending on the characteristics of the signal to be distinguished.

In some aspects, a router may contain one or more controlled switches that route signals to the appropriate functional blocks. The switches may include, but are not limited to, analog switches, multiplexers, relays, and the like, or any combination thereof. The switches may be controlled by other circuitry that detects the presence of a signal and routes it accordingly. Alternatively, the switch may be controlled by software. In other aspects, the switch may be controlled by a user. For example, there may be a user interface on the housing of the device or on an external controller. The user interface may include, but is not limited to, one or more switches, one or more buttons, a touch screen, etc., through which a user can select an appropriate operating mode and can set the router switch accordingly. In some examples, the operating mode of the device may be modified by internal circuitry or software based on signals input from the multipurpose connector. Possible operating modes may include, but are not limited to: patient interaction mode, charging mode, data transfer mode, etc. These switches can then be routed according to the operating mode.

In some instances where data or processing instructions are to be sent via the multi-purpose connector, it may be desirable to select a signaling protocol that is compatible with the patient connection circuitry. To comply with regulatory requirements, the patient's electrical connection may have a safety capacitor connected to the electrical connection to protect the patient from DC voltage. In these aspects, it may be desirable to select a communication protocol that does not represent data bits, i.e., 1 or 0, based on a DC level. Instead, a data communication protocol may be selected that represents data based on conversion or frequency modulation. In other examples, the use of a DC data protocol need not be avoided, and any convenient data protocol may be used.

A block diagram of a receiver including a multi-purpose connector is shown in fig. 16, with the device shown in a patient interaction mode. The receiver 1601 is connected to the patient 1603 via a multi-purpose connector 1605. A multi-purpose connector 1605 is located on the housing 1607 and connected to the router 1609. The router 1609 is connected to an internal power supply 1611, a signal acquisition block 1613, an energy output block 1615, and/or a controller and data input/output block 1617. As shown, the receiver 1601 is connected to the patient 1603, so the router 1609 passes the signal to the signal acquisition block 1613 via connection 1619. The energy output block 1615 can deliver energy to the patient via connection 1621. Connection 1621 may or may not share the same wire with connection 1619.

The same receiver is shown in fig. 17, where the device is shown in a charging mode. The external power source 1723 is connected to the receiver 1701 via the multipurpose connector 1705. The multipurpose connector 1705 is connected to a router 1709. The router 1709 recognizes that the incoming signal is a charging signal and accordingly routes the signal to the internal power supply 1711 via the connection 1725, thereby charging the internal power supply 1711.

Fig. 18 shows a receiver 1801 when the device is in a data communication mode. An external control and data communication device 1827 is connected to the receiver 1801 via the multipurpose connector 1805. The multipurpose connector 1805 is connected to the router 1809. The router 1809 recognizes the incoming signals as control and/or data communication signals and routes the signals to the control and data input/output block 1817 via connection 1829 accordingly. The external control and data communication device 1827 may then send control signals and/or data packets to the control and data input/output block 1817 or send signals requesting data from the control and data input/output block 1817. The control and data input/output block 1819 may transmit data to the external control and data communications device 1827 through the same connection 1829 or through a different connection, including a wireless connection.

An embodiment of a router that can be employed in the receiver of the present invention is shown in fig. 19A and 19B. Fig. 19A depicts a router that discriminates signals based on voltage levels. Only signals that exceed the threshold voltage of the router 1931 are communicated from the bus 1933 to the bus 1935. A simple embodiment of this principle is shown in fig. 19B, where diode 1937 is used as a signal director, such as router 1909. Only signals greater than the threshold voltage of diode 1937 pass from bus 1939 to bus 1941.

Fig. 20A and 20B illustrate embodiments of a router that discriminates based on the frequency of an incoming signal. Fig. 20A shows the principle of a router by means of an incoming signal bus 2043 and functional block buses 2045 and 2047 on a frequency basis. Element 2049 has an impedance that increases with increasing frequency and forms a high pass filter with resistor 2050. Only signals above the design frequency of the high pass filter pass from bus 2043 to bus 2045. The element 2051 has an impedance that decreases with decreasing frequency and forms a low pass filter with a resistor 2052. Only signals below the design frequency of the low pass filter pass from bus 2043 to bus 2047. The high pass filter and the low pass filter may or may not have different design frequencies. Fig. 20B shows a simple embodiment of this principle. Capacitor 2053 and resistor 2054 form a high pass filter between bus 2057 and bus 2059, and inductor 2055 and resistor 2056 form a low pass filter between bus 2057 and bus 2061. Only those signals above the cutoff frequency are allowed to pass from bus 2057 to bus 2059 and only those signals below the cutoff frequency are allowed to pass from bus 2057 to bus 2061.

Fig. 20C illustrates another embodiment of a router based on frequency discrimination of incoming signals. The high pass filter 2056 has a gain that decreases below a certain design frequency. Only signals above the design frequency will pass from bus 2058 to bus 2060. The low pass filter 2062 has a gain that decreases above the second design frequency. Only signals above the design frequency will pass from bus 2058 to bus 2064.

Fig. 21 illustrates an aspect of a router employing an active switch. Bus 2163 is separated from buses 2165, 2167, and 2169 by switches 2171, 2173, and 2175. Buses 2165, 2167 and 2169 each connect to one or more functional blocks of an external receiver. Switches 2171, 2173, and 2175 may be controlled by other circuitry, software, and/or by a user to open or close as needed to connect or disconnect bus 2163 with the respective functional block.

The receiver of the present invention may incorporate circuitry connected to the multi-purpose connector that inherently routes the applied AC voltage above a certain threshold to a rectifying device, a power conversion device, and then to a battery charger circuit that uses the energy to charge an internal battery. The data acquisition circuitry within the receiver is not affected by the specified applied AC voltage. The receiver also detects the presence of this voltage and can change its operating mode based on this information.

Fig. 22-24 illustrate embodiments of a circuit for one aspect of a receiver. Fig. 22 shows multi-purpose electrode connections SNAP _ E12277, SNAP _ E22279 and SNAP _ E32281, and switches 22113, 22115 and 22117 connecting the electrodes to the signal receiving block via signal receiving amplifier inputs 22121 and 22123. Diodes 2283, 2285, and 2287 protect the circuit from damage due to electrostatic discharge (ESD). Inductors 2289, 2291, and 2293 reduce electromagnetic interference (EMI). Capacitors 2295, 2297, and 2299 protect the patient by preventing any DC voltage from being applied to electrodes 2277, 2279, and 2281. Lines ChargeInACI 22101, ChargeInAC 222103 and ChargeInAC 322105 connect the inputs to an internal power supply shown in subsequent figures. Capacitors 22107, 22109, and 22111 prevent any DC voltage from being applied to the signal receiving amplifier. Any combination of the three electrodes 2277, 2279, and 2281 is selected for connection to the two signal receiving amplifier inputs V + diff 22121 and V-diff 22123 using switches 22113, 22115, 22117, and 22119.

In the apparatus shown in fig. 22, it is impossible to completely disconnect the signal receiving block. If a charge signal is applied to the electrodes, the charge signal will pass through the switch and onto the amplifier input. However, the amplifier input is designed to be immune to relatively large voltages, so it is not necessary to switch off the signal receiving block.

In an alternative configuration, the signal receiving block may be switched off when a signal other than the data signal is received on the electrode. This may be achieved, for example, by using other switches and/or a different switch arrangement.

Fig. 23 shows the battery charger input of the internal power supply function. Lines ChargeInACI 22101, ChargeInAC 222103 and ChargeInAC 322103 of fig. 22 are connected to the power supply function block at ChargeInACI 23125, ChargeInAC 223127 and ChargeInAC 323129, respectively. Diode 23131 and 23136 form a three-phase rectifier. When the device is connected to an external charger, the rectifier receives a charging signal, which may be an alternating current, e.g., a square wave at 100kHz, and converts it to a direct current on the network ChargerIn 23139. When these voltages present on the inputs are less than about 0.6V, such as when the device is connected to a patient, the signal does not pass through the rectifier and the ChargerIn node 23139 is disconnected from the inputs 23125, 23127 and 23129. The low impedance of the ChargerIn node 23139 is isolated from the electrodes when a high impedance measurement of the signal to the patient is required. The boost converter 23141 increases the voltage across the net ChargerIn 23139 to a desired charging voltage, for example, about 5V. The increased voltage is transferred to the battery charger via node 23143. Diode 23145 protects the circuit when a higher than desired voltage is placed on the ChargerIn node 23139.

One aspect of the battery charger circuit is shown in fig. 24. The output node 23143 of fig. 23 is connected to the battery charger circuit of fig. 24 at the battery charger input node 24147. The battery charger input 24147 is connected to a battery charger integrated circuit 24149. In this regard, the battery charger input 24147 is configured to charge a battery, such as a lithium battery, at the battery pads 24151 and 24153. The remainder of the circuit shown in fig. 24 includes regulators 24155, 24157, and 24159 that regulate the battery voltage for use by the remainder of the circuitry in the device.

During use, the receiver may be operatively connected to a living subject, such as a patient or another external device, via the multi-purpose connector. Other external devices that may be connected include, but are not limited to, external charger devices, external programming devices, external data processing devices. The receiver may also be operatively connected to another medical device via a multi-purpose connector, including an external proximal end connected to an implanted medical device. When connecting a patient or another device to an external medical device via the multipurpose connector, the router (when present) may open and close the signal path based on the type of signal or characteristics of the signal. As discussed above, routing may be performed inherently, proactively, or by a combination of these and other techniques.

Fig. 25 provides a schematic illustration of the component/functional relationships that can be achieved in connection with having a multi-purpose connector. A schematic illustration provides, for example, a signal director 2500. Signal director 2500 includes a control element 2502. Control element 2502 may control or respond to voltage 2504, frequency 2506, manual/programmed instructions 2508, and other criteria 2510. The voltage 2504 may be discriminated via one or more diodes 2512, thermistors 2514, and the like. Frequency 2506 may be discriminated by a high pass filter 2516, a low pass filter 2518, and the like. Signals may be controlled manually and/or programmatically by manual/programmatic instructions 2508 issued via analog switches 2520, relays 2522, multiplexers 2524, and the like. Other criteria for signal control/response 2510 may include, for example, light, temperature, time, etc.

The method of using the device with the multipurpose connector of the invention further comprises disconnecting the receiver from either the patient or one of the other devices described above and operatively coupling the device to either the patient or one of the other devices via the multipurpose connector. A router in the receiver (when present) may route signals from the second connected device in a different manner than signals from the first connected device. Further, the mode of operation of the external medical device may be changed in response to a signal from the second connected device.

Further details regarding receptacles that may include the multi-purpose connectors of the present invention and methods of using them may be found in U.S. provisional patent application serial No. 61/122,723 filed on 12/15 of 2008; the disclosure of which is incorporated herein by reference.

Impedance (EZ) measurement module

The receiver of the present invention may comprise an impedance measurement module, for example wherein the devices are configured to measure the impedance across at least one pair of electrodes of the device. The impedance measurement module may be configured to determine a loop impedance of a series combination of the two electrodes and a resistive load (e.g., provided by tissue therebetween). The impedance measurement module includes a current source block that provides a current across the electrode, and a voltage processing block that measures a voltage signal across the resistive load and determines the impedance of the electrode. For example, the receiver may be configured to apply a square wave current of 2 μ App (RMS amplitude of 1 μ Arms) across the two electrodes. This is sufficient to detect the detached electrode. Applications may include, but are not limited to: receiver diagnostic applications, for example, where measured impedance is employed to determine whether an electrode is disconnected from a patient and/or whether an electrode is operational; patient monitoring applications, such as where impedance is employed to determine one or more physiological parameters, and the like.

FIG. 27 provides a circuit diagram modeling a drive scheme 2700 implemented by a current source block in accordance with an aspect of the present invention. As shown in this aspect, the bipolar current can be derived from unipolar logic driving, where there is no "DC" component in the driving scheme. Two currents, "EZ _ Carrier" 2720 and "EZ _ Balance" 2730 are generated and an electrode current lez 2710 is provided across the two electrodes. "EZ _ Carrier" 2720 and "EZ _ Balance" 2730 may be generated by, for example, a low power processor (e.g., a microprocessor) and implemented in series with capacitor 2740 and resistor 2750 (unknown electrode impedance).

The voltage processing block measures a voltage signal 2760 across the electrodes (i.e., across the resistive load-resistor 2710) generated by the electrode current lez 2710. The voltage processing block may then use the voltage signal 2710 to determine the electrode impedance. For example, the voltage signal 2710 may be first amplified by [ gain ═ 287], band-limited by 5KHz HPF and 33KHz LPF to reduce noise, and applied to an a/D converter input (e.g., a 12-bit a/D converter sampled at 500 KHz) to provide a digital data stream from the voltage signal. For example, the DSP may process the digital data stream to determine the electrode impedance. For example, the DSP may mix the incoming data stream with a sine wave at an EZ carrier frequency (e.g., 20KHz), use a Hogenauer ("CIC") filter in the low pass filter, and decimate (e.g., decimate by 16) the data stream. This shifts the fundamental of the carrier energy to 0 Hz. The DSP can then calculate the absolute value (magnitude) of the data stream, average it over a 1 second period, and then convert it to impedance using the following formula:

zelectrode ═ (Vc/(lez × gain)) -300

Wherein: vc is the amplitude measured at the a/D converter at lez carrier frequency (20 KHz). Gain setting G3... G0 ═ 0000; the calculation is performed using 287 as a gain value. This results in a 300 ohm Tare resistance (electrode impedance) in series with the electrode being measured.

FIG. 28 provides a circuit diagram of electrode impedance measurement using a 3-wire ohmmeter according to one aspect of the present invention. The current source block generates EZ carrier line 2820 and EZ balance line 2830 to provide electrode current (lez)2810 flowing through the resistive load (electrode resistance En 2850). With a kelvin connection, and no current flowing through the electrode (impedance) Em 2860, the voltage observed by the first stage 2870 would be lez × (300+ En). Electrode current lez 2810 may be, for example, 2 μ App ═ 1 μ ARMS.

The impedance measurement module comprises a control module, a processing module and an electrode. Impedance measurements are an example of sensing capabilities that can be achieved with any two electrodes of the receiver. In addition to determining the function of the device and its deployment, e.g., whether the electrodes are working and/or connected to the subject as needed, physiological data of interest can be derived from the measured impedance. For example, the measured impedance will have some component related to breathing determined by the transthoracic impedance. In this way, impedance data can be employed to obtain the respiration rate of the subject. The electrodes 2860 may also serve as sensors of the fluid state of the subject. Over time, especially for heart failure patients with diuretics, fluid status is a very important quantity. The obtained flow regime can be used for titration measurements of the drug and/or for issuing an alarm. In addition to measuring flow regime, impedance measurements can also be used to measure body fat.

Module implementation

In various aspects, the aforementioned modules, e.g., high-low power module, intermediate module, conductive communication module across the body, physiological sensing module, power module, memory module, extracorporeal communication module, etc., and/or one or a combination of their components, may be implemented as software, such as digital signal processing software; hardware, such as circuitry; or a combination thereof. Thus, other elements that may be present in a signal receiver include, but are not limited to: a signal demodulator, e.g., for decoding signals transmitted from the IEM; a signal transmitter, e.g., for transmitting a signal from the signal receiver to an external location; a data storage element, e.g., for storing data relating to the received signal, physiological parameter data, medical record data, etc.; a clock element, for example, for associating a particular time with an event (e.g., receipt of a signal); a preamplifier; a microprocessor, for example for coordinating one or more different functions of the signal receiver, band pass filter, etc.

In certain aspects, the modules of the inventive receiver reside on an integrated circuit, wherein the integrated circuit comprises a plurality of different functional blocks. Within a given receiver, at least some, e.g., two or more, up to and including all, of the modules may be present in a single integrated circuit in the receiver (e.g., in the form of a system on a chip or SOC). A single integrated circuit refers to a single circuit structure that contains all the different functional blocks. Thus, an integrated circuit is a monolithic integrated circuit (also known as an IC, microcircuit, microchip, silicon chip, computer chip or chip) that is a miniaturized electronic circuit (which may contain semiconductor devices as well as passive components) fabricated on the surface of a thin substrate of semiconductor material. The integrated circuits of certain aspects of the present invention may be hybrid integrated circuits, which are miniaturized electronic circuits composed of individual semiconductor devices and passive components bonded to a substrate or circuit board.

Fig. 7 provides a functional block diagram of integrated circuit components of a signal receiver in accordance with an aspect of the present invention. In fig. 7, receiver 700 includes an electrode input 710. Electrically coupled to the electrode input 710 is a cross-body conductive communication module 720 and a physiological sensing module 730. In one aspect, the cross-body conductive communication module 720 is implemented as a High Frequency (HF) signal chain and the physiological sensing module 730 is implemented as a Low Frequency (LF) signal chain. Also shown are a CMOS temperature sensing module 740 (for detecting ambient temperature) and a 3-axis accelerometer 750. Receiver 700 also includes a processing engine 760 (e.g., a microcontroller and digital signal processor), non-volatile memory 770 (for data storage), and a wireless communication module 780 (for transmitting data to another device, such as in a data upload action).

Fig. 8 provides a more detailed block diagram of circuitry configured to implement the functional block diagram of the receiver shown in fig. 7 in accordance with an aspect of the present invention. In fig. 8, receiver 800 includes electrodes e1, e2, and e3(811, 812, and 813) that receive conductively transmitted signals emitted by IEMs, for example, and/or sense a physiological parameter or biomarker of interest. Signals received by electrodes 811, 812, and 813 are multiplexed by multiplexer 820, multiplexer 820 being electrically coupled to the electrodes.

Multiplexer 820 is electrically coupled to high bandpass filter 830 and low bandpass filter 840. The high frequency signal chain and the low frequency signal chain provide programmable gain to cover a desired level or range. In this particular aspect, high band pass filter 830 passes frequencies in the 10KHz to 34KHz frequency band, while filtering out noise from out-of-band frequencies. This high frequency band may vary and may include, for example, a range of 3KHz to 300 KHz. The passed frequency is amplified by an amplifier 832 before it is converted into a digital signal by a converter 834 for input to a high power processor 880 (shown as a DSP), the high power processor 880 being electrically coupled to the high frequency signal chain.

Low band pass filter 840 is shown passing lower frequencies in the range of 0.5Hz to 150Hz, while filtering out-of-band frequencies. The frequency band may vary and may comprise, for example, frequencies less than 300Hz, such as less than 200Hz, including less than 150 Hz. The passed frequency signal is amplified by an amplifier 842. An accelerometer 850 is also shown electrically coupled to the second multiplexer 860. Multiplexer 860 multiplexes the signal from the accelerometer and the amplified signal from amplifier 842. The multiplexed signal is then converted to a digital signal by a converter 864, which is also electrically coupled to the low power processor 870.

In one aspect, accelerometer 850 may be replaced with a digital accelerometer, such as those manufactured by Analog Devices, Inc. Various advantages may be realized using a digital accelerometer. For example, because the signal generated by the digital accelerometer is already in digital format, the digital accelerometer may turn on the converter 864 and be electrically coupled to the low power microcontroller 870 — in which case the multiplexer 860 is no longer required. The digital signal may also be configured to turn itself on when motion is detected, thereby further saving power. Furthermore, continuous step counting may also be performed. The digital accelerometer may include a FIFO buffer to help control the flow of data sent to the low power processor 870. For example, data may be buffered in a FIFO until full, at which point the processor may be triggered to wake up from a standby state and receive data.

Low power processor 870 may be, for example, an MSP430 microcontroller by Texas Instruments. The low power processor 870 of the receiver 800 remains in a standby state, which, as previously mentioned, requires a minimum current consumption-e.g., 10 μ A or less, or 1 μ A or less.

High power processor 880 may be, for example, a Texas instruments VC5509 digital signal processor. The high power processor 880 performs signal processing actions during the active state. As previously mentioned, these actions require a larger amount of current than in the standby state, e.g. 30 μ Α or more, such as 50 μ Α or more, and may include actions such as scanning the conductively transmitted signal, processing the conductively transmitted signal when received, acquiring and/or processing physiological data, etc.

The receiver may include a hardware accelerator module to process the data signal. A hardware accelerator module may be used instead of, for example, a DSP. As a more specialized computational unit, it performs some aspects of the signal processing algorithm with fewer transistors (lower cost and power) than a more general purpose DSP. These hardware blocks may be used to "speed up" the execution of certain functions of interest. Some configurations of the hardware accelerator may be "programmable" by microcode or VLIM components. During use, their functions may be accessed through calls to a function library.

A hardware accelerator (HWA) module includes a HWA input block to receive an input signal to be processed and instructions for processing the input signal; and a HWA processing block to process the input signal according to the received instructions and generate a resultant output signal. The resulting output signal may be sent by the HWA output block as needed.

Fig. 30 provides a block diagram of a HWA module in accordance with an aspect of the present invention. As shown, input block 3001 is coupled to processing block 3002, and processing block 3002 is coupled to output block 3003. Input block 3001 receives input signals 3001 and/or instructions 3015. HWA module 300 may receive the cross-body conductive communication signal, e.g., from a cross-body conductive communication module, and/or the physiological data signal from one or more physiological sensing modules.

The HWA module may receive an analog signal and include an a/D converter to convert the signal to a digital signal, or may receive a digital input signal (e.g., from an a/D converter or microprocessor). For example, the HWA module may be electrically coupled to an a/D converter and a microprocessor, which has a state machine that collects data directly from the a/D converter. In another embodiment, the hardware accelerator may be connected only to a microprocessor that processes data as instructed by the microprocessor.

The instructions 3015 may be received, for example, from an internal memory, an external memory, or by a microprocessor. In an aspect, the HWA module shares memory with the microprocessor (e.g., via a dual port memory or multiplexer). In another aspect, the HWA module exchanges data via the DMA port.

HWA processing block 3002 processes input signal 3010 according to received instruction 3015. Functions like DCO (digitally controlled oscillator), DDC (digital down converter), FIR filter, CIC decimating samples can be implemented by such a hardware accelerator. These functions are optimal for IEM-related signal processing and may also be applicable to general data acquisition, impedance measurements, ECG signal processing (Hamilton and Tomkins), accelerometers, etc. The resulting output signal 3020 generated by the HWA processing block 3002 may be sent by the HWA output block 3003 as needed.

The HWA module 3000 may also include an HWA power block 3030 to enable/disable power to the HWA module 3000. For example, the HWA module 3000 may be configured to be powered off and on, or configured to gate (clock) the clock driving it to be disabled, etc. The number of transistors required to implement it is relatively small (in the range of about 10k to 100k gates), where most of the static power is consumed by the associated memory/buffer. The hardware accelerator is thus able to achieve low power consumption.

Fig. 8 also shows a flash memory 890 electrically coupled to high power processor 880. In an aspect, flash memory 890 may be electrically coupled to low power processor 870, which may provide better power efficiency.

Wireless communication element 895 is shown electrically coupled to high power processor 880 and may comprise, for example, BLUETOOTH^TMA wireless communication transceiver. In an aspect, the wireless communication element 895 is electrically coupled to the high power processor 880. In another aspect, the wireless communication element 895 is electrically coupled to the high power processor 880 and the low power processor 870. WhileAlso, the wireless communication element 895 may be implemented with its own power supply so that it can be switched on and off independently of the other components of the receiver, e.g., by a microprocessor.

Fig. 9 provides an illustration of a block diagram of hardware associated with a high frequency signal chain in a receiver in accordance with an aspect of the present invention. In fig. 9, receiver 900 includes a receiver probe (e.g., in the form of electrodes 911, 912, and 913) electrically coupled to multiplexer 920. A high pass filter 930 and a low pass filter 940 are also shown to provide a band pass filter that eliminates any out of band frequencies. In the aspect shown, a 10KHz to 34KHz bandpass is provided to pass carrier signals that fall within this band. Exemplary carrier frequencies may include, but are not limited to, 12.5KHz and 20 KHz. There may be one or more carriers. In addition, receiver 900 includes an analog-to-digital converter 950, such as an analog-to-digital converter sampled at 500 KHz. Thereafter, the DSP can process the digital signal. A DMA to DSP device 960 is shown in this aspect that sends the digital signal to the DSP's dedicated memory. Direct memory access provides the benefit of allowing the rest of the DSP to remain in a low power mode.

Exemplary configuration of various states

As previously mentioned, for each receiver state, the high power functional block may be cycled between an active state and an inactive state accordingly. For each receiver state, the various receiver elements of the receiver (e.g., circuit blocks, power domains within the processor, etc.) may also be configured to be cycled on and off independently by the power module. Thus, the receiver may have different configurations for each state in order to achieve power efficiency. For example, fig. 29 shows that the receiver has a standby state and an active state-e.g., a standby state 110, a sniff state 130, a demodulate and decode state 140, an acquire ECG and accelerometer state 120, and a transmit state 160. It should be noted that as mentioned previously, the beacon signal module may implement multiple types of sniff signals to achieve low power efficiency, and thus the sniff states have been grouped into inactive states for the following embodiments.

Considering the state shown in fig. 29, the following paragraphs provide an exemplary configuration of the receiver component shown in fig. 8 during various states of the receiver, according to an aspect of the present invention. It should be understood that alternative configurations may be implemented depending on the desired application.

In state 110, the receiver consumes the least current. Receiver 800 is configured such that low power processor 870 is in an inactive state (e.g., a standby state) and high power processor 880 is in an inactive state (e.g., a standby state), and circuit blocks associated with peripheral circuits and their power required during various active states remain off (e.g., wireless communication module 895 and the analog front end). For example, the low power processor may have a 32KHz oscillator active and may consume a few μ A of current or less, including 0.5 μ A or less. In the standby state, low power processor 870 may, for example, wait for a signal to transition to an active state. The signal may be external, such as an interrupt signal, or internally generated by one of the peripherals of the device, such as a timer. During the standby state of the high power processor, the high power processor may run off of a 32KHz clock crystal, for example. The high power processor may, for example, wait for a signal to transition to an active state.

When the receiver is in the sniff state, the low power processor 870 is in a standby state and the high power processor 880 is in a standby state. Furthermore, the circuit block including the a/D converter is on (in other words, a high frequency signal chain) in relation to the analog front end required for the sniff function. As previously mentioned, the beacon signal module may implement multiple types of sniff signals to achieve low power efficiency.

When a transmitted signal is detected, a higher power demodulation and decoding state may be entered. When the receiver is in the demodulation and decoding states, the low power processor 870 is in an active state and the high power processor 880 is in an active state. The high power processor 880 may run, for example, from a crystal oscillator at or near 12MHz and a PLL based clock multiplier to provide a clock speed of 108MHz for the device. The low power processor 870 may, for example, run off of an internal R-C oscillator ranging from 1MHz to 20MHz, and consume power ranging from 250 to 300uA per MHz clock speed during the active state. The active state allows processing and any possible subsequent transmissions. The desired transmission may trigger the wireless communication module to cycle from off to on.

When the receiver is in the acquire ECG and accelerometer states, circuit blocks associated with the accelerometer and/or ECG signal conditioning chain are on. During acquisition, the high power processor 880 is in a standby state, while during processing and transmission, the high power processor 880 is in an active state (e.g., running from a crystal oscillator at or near 12MHz, and a PLL-based clock multiplier provides the device with a clock speed of 108 MHz). During this state, low power processor 870 is in an active state and may run off of an internal R-C oscillator ranging from 1MHz to 20MHz, and each MHz clock speed consumes power ranging from 250 to 300 uA.

Other states of the receiver

In addition to the operational state in which the receiver cycles between the standby state and the active state, the receiver may include other operational states. The receiver may comprise a storage state, e.g. exhibiting a very low current consumption of 10 muA or less, such as 1 muA or less and including 0.1 muA or less. In the stored state, the receiver may be configured, for example, such that the low power processor is in a standby state, the high power processor is off, and other receiver elements such as circuit blocks associated with peripheral circuitry required during the active state are off. Fig. 29 shows the storage state 170 of the receiver. The receiver may transition from the storage state to the non-storage state based on a plurality of inputs, such as a predetermined schedule or applied stimulus, for example in response to manual operation of the receiver (e.g., pressing an "on" button or pulling a tab (tab) from the receiver or in response to an "on" signal transmitted to the receiver, as shown in fig. 1, the receiver may transition from the storage state 170 to the standby state 110.

The receiver may also be configured to include a charging state, shown in fig. 29 as charging state 150. When the receiver is in the charging state, only the low power processor is on, e.g., in a standby state. Circuit blocks associated with the power supplies of the high power processor and all peripherals are shut down.

The receiver may also be configured to include a transmission state 160 in which data may be transmitted to and/or from the receiver and another extracorporeal device, for example, by using a wireless communication protocol. The high power processor is in an active state and the low power processor is in an active state while other receiver elements, such as circuit blocks associated with the wireless communication module, are on.

The receiver may also be configured to include a "diagnostic" state. In the diagnostic state, the receiver may test the operation of one or more functions of the receiver, such as signal reception, physiological data acquisition and/or processing, etc., in order to determine whether the functions are being performed correctly. The receiver may also be configured to report the results of the test to a user, e.g., via a signal (which may be audible, visual, forwarded to a third device, etc.). For example, the receiver may be configured to report to the user that all functions are working properly or that one or more functions are having a problem. In some aspects, the receiver transitions to and from the diagnostic state based on various inputs, such as a predetermined schedule (e.g., provided by programming of the receiver) or applied stimuli, as described above.

Communication via a serial peripheral interface bus

The low power processor (e.g., MSP shown in fig. 8) and the high power processor (e.g., DSP shown in fig. 8) may communicate with each other using any convenient communication protocol. In some examples, these two elements (when present) communicate with each other via a serial peripheral interface bus (hereinafter "SPI bus"). The following description describes signaling and messaging schemes implemented to enable the high and low power processors to communicate and send messages back and forth along the SPI bus. For the following description of communication between processors, "LPP" and "HPP" are used instead of "low power processor" and "high power processor", respectively, to remain consistent with FIG. 8. However, the discussion thereof may be applicable to other processors besides those shown in fig. 8.

The interface is configured such that the LPP is the master and the HPP is the slave, and the link is driven only by the LPP side. The HPP can only respond to the LPP via the SPI. In addition, SPI requires HPP to respond immediately to LPP. If the LPP sends data but the HPP is not waiting for the data, the data is lost. In accordance with one aspect of the present invention, the following describes signaling and messaging configurations of an interface in order to overcome these limitations.

Signaling

To overcome the above limitations, three "out-of-band" signals are implemented in the signaling protocol. The LPP has an "attention" signal that it can assert and de-assert, and the HPP has "attention" and "grant" signals.

For LPPs to send data (e.g., LPP-initiated messages) to HPPs, LPPs assert their LPP attention signals. It then waits until the HPP responds by asserting the HPP grant signal. This ensures that both sides are ready for SPI interaction and data is not lost. At this time, the HPP can receive messages from the LPP. Enabling the HPP to receive the LPP-initiated message if the LPP-initiated message cannot currently be received from the LPP. The HPP remains "on-line" until the LPP deasserts its LPP attention signal. The HPP responds to this deassertion by deasserting its HPP grant signal. At this time, the HPP cannot receive messages from the LPP. Because LPP-initiated messages can be received from LPPs, HPPs are disabled from receiving LPP-initiated messages. In this case, the system responds to the level changes of these signals and the levels themselves. In other words, the system treats the asserted signal as a request for action, and the system treats the level of the signal as an indication to continue action. The HPP may enter a low power standby state because the HPP need not perform any operations until the LPP asserts its LPP attention signal. In this case, the LPP attention signal not only requests the SPI link, but also wakes up the HPP.

For an HPP to send data (e.g., an HPP initiated message) to an LPP, the HPP asserts its HPP attention signal. The assertion informs the LPP that the HPP has data. The assertion of the HPP attention signal is to prompt the assertion of the LPP, not the deassertion of the HPP attention signal. The HPP need only deassert this signal, and it can then assert the signal again. Once the LPP sees the HPP's attention signal asserted, it will eventually respond according to 1) below. No LPP immediate response is required. In this case, only the assertion of the signal is important. The system never takes into account the existing level of the signal.

And (3) message sending:

the HPP can only respond to LPP messages because of the master/slave designation of the SPI bus. It cannot ask questions of the LPP. To enable bi-directional data flow, the above-described signaling is implemented in combination with two types of messaging, as described below.

For LPP-initiated messages destined for HPPs, case 1) above may be employed to send messages to HPPs. Such messages never require the response message of the HPP. An example of a message may be the instruction "process this ECG". The message tells the HPP that ECG data is expected, and then the LPP sends a series of messages containing ECG data to the HPP. Another example may be when the LPP sends an instruction to the HPP telling it to sniff for the IEM signal delivered.

For HPP-initiated message sending, these messages must still originate from the LPP. To enable communication in this direction, case 2) above is used to tell the LPP to query the HPP to retrieve the message. Before the HPP asserts the HPP attention signal, the HPP prepares a query message (i.e., an HPP-initiated message) so that it can respond to the LPP immediately. The LPP sends a series of messages to get queries from the HPPs. The LPP queries the query length and performs this by sending a "query length" message to the HPP. The LPP then uses this length to request HPP initiated messages. Because the LPP queries the query length, the LPP knows exactly how much data to extract from the HPP. The LPP answers the HPP's "question" by sending an inquiry response message to the HPP. Since the HPP is implemented with only one outstanding query at a time, it knows to expect this response.

It should also be noted that for the above sequence, since the LPP "clocks" the SPI link, the LPP always knows exactly how much data to extract from the HPP. In addition, in this regard, since the LPP always asks a problem, and the HPP is always ready to answer any problem from the LPP, there is no guarantee that the HPP will always get a "query length" message from the LPP when the HPP wants to send a query.

In an aspect, error detection and correction may be implemented, for example, using a Fletcher checksum algorithm. Because the retransmission is performed upon detection of an error, for any message that requires an action to be performed, such as a pill sniff (pill sniff), etc., the action is not performed until the entire scenario 1 above is completed. This is important because HPPs appear to be the correct data while LPPs may detect errors. The final confirmation is complete and the correct data transfer is the completion of case 1) above.

Global Positioning System (GPS) module

The receiver of the present invention may include a Global Positioning System (GPS) module. A GPS module as used herein is a module that receives signals from the global positioning system of satellites and determines a geographic location. Any convenient GPS module may be employed.

Receiver arrangement

Medical devices associated with the body of interest include external devices and implantable devices. Externally, the receptacle is external, which means that the device is present outside the body during use. Where the receivers are external, they may be configured in any convenient manner, where in some aspects they are configured to be associated with a desired skin location. Thus, in certain aspects, the external receiver is configured to be brought into contact with a localized skin location of the subject. Configurations of interest include, but are not limited to: patches, wristbands, jewelry (such as watches, earrings, and bracelets), clothing, accessories such as belts and shoes, glasses, and the like. In some examples, the receptacles are configured to be adhered to the skin site, for example, by using a suitable adhesive, as described below. In some examples, the receivers are configured to contact, but not adhere to, a skin site, for example, wherein the device is configured as a wristband, jewelry (e.g., watches, earrings, and bracelets), clothing, accessories (e.g., belts and shoes), and a pair of eyeglasses. In still other examples, the receivers may be configured to remain within a certain defined distance of the skin surface, such as within 1cm, including within 0.5 cm.

In certain aspects, the receiver is an implantable component. Implantable means that the receiver is designed, i.e., configured, to be implanted, e.g., semi-permanently or permanently, into a subject. In these aspects, the receiver is in vivo during use. Implantable means that the receivers are configured to remain functional when present in a physiological environment, including a high salt, high humidity environment common in the body, for more than two days, such as about one week or more, about four weeks or more, about six months or more, about one year or more, such as about five years or more. In certain aspects, the implantable receiver is configured to remain functional when implanted at the physiological site for a period of time ranging from about 1 year to about 80 years or more, such as from about 5 years to about 70 years or more, including a period of time ranging from about 10 years to about 50 years or more. For the implantable aspect, the receptacle may have any convenient shape, including but not limited to: capsule shape, disc shape, etc. The receiver may be configured to be placed in a variety of different locations, such as the abdomen, the low back, the shoulders (e.g., where the implantable pulse generator is placed), and so forth. In certain implantable aspects, the receiver is a separate device in that it is not physically connected to any other type of implantable device. In still other aspects, the receiver may be physically connected to a second implantable device, such as a device that serves as a platform for one or more physiological sensors, where the device may be a lead, such as a cardiovascular lead, where in some of these aspects the cardiovascular lead includes one or more different physiological sensors, such as where the lead is a multisensor lead (MSL). Implantable devices of interest also include, but are not limited to: implantable pulse generators (e.g., ICDs), neurostimulators, implantable loop recorders, and the like.

The receiver may include a signal receiver element for receiving a conductively transmitted signal, such as a signal emitted by a marker of an ingestible event marker. The signal receiver may comprise various different types of signal receiver elements, wherein the properties of the receiver elements necessarily differ according to the properties of the signal generated by the signal generating element. In certain aspects, the signal receiver element may include one or more electrodes, such as two or more electrodes, three or more electrodes, etc., for detecting the signal emitted by the signal generating element. In certain aspects, the receiver device will be provided with two or three electrodes that are dispersed at a distance from each other. This distance enables the electrodes to detect a differential voltage. The distance can vary, and in some aspects ranges from 0.1cm to 1.0m, such as 0.1cm to 5cm, such as 0.5cm to 2.5cm, with the distance being 1cm in some examples.

An embodiment of the external signal receiver aspect of the receiver of interest is shown in fig. 10. Fig. 10 shows a receiver 1000 configured to be placed on an external local location of a subject, such as a chest region. The receiver includes an upper housing plate 1010 (such as may be made of a suitable polymeric material) and includes manually depressible operating buttons 1020 and a status identifier LED 1030, the status identifier LED 1030 may be used to relay to an observer that the receiver is operating. The manually depressible operating button 1020 may be manually manipulated to transition the receptacle from the storage mode to the non-storage mode. When the receiver is in the storage mode, the microcontroller of the receiver may remain in an active state at all times with a low duty cycle to process inputs from the on/off button and power down the Digital Signal Processor (DSP) of the receiver. When the on/off button is pressed to power on the receiver, the microcontroller controls the input to be debounced and powers on the DSP to enter its standby state. In the storage mode, the device may consume less than 10 μ A of current, including 5 μ A of current or less, such as 1 μ A or less, including 0.1 μ A or less. This configuration enables the device to maintain greater than 90% of the available battery life (assuming 250mAH of battery is present) when stored for one month. This button can also be used for other functions. This button may be employed, for example, to instruct the receiver to acquire certain types of data. Additionally or alternatively, this button may be employed to manually instruct the receiver to transmit data to another device.

Fig. 11 provides an exploded view of the receiver shown in fig. 10. As shown in fig. 11, the receiver 1000 includes an upper housing plate 1010, a rechargeable battery 1100, an integrated circuit component 1120, and a lower housing plate 1130. The lower housing plate 1130 snaps into the upper housing plate 1010 to seal the battery and integrated circuit components 1100 and 1120 in a fluid tight enclosure. While snap-fit interaction is shown, any convenient mating scheme may be employed such that the upper and lower skin plates may interact through interlocking slots, may be secured together by a suitable adhesive, may be welded together, etc. In some examples, the electrical components may be molded into the upper and/or lower shell. Also shown is an adhesive patch 1140 which is snapped to the upper housing plate 1010 and includes conductive posts 1141-1143 which serve as electrodes for contact with the body during use of the receiver. In the receiver, the posts 1141-1143 are in electrical contact with the integrated circuit component 1120 via, for example, wires or other conductive members associated with the upper housing 1010. In one example, the upper housing plate 1010 includes conductive members configured to receive posts 1141-1143 coupled to wires (not shown) that in turn provide electrical connections to the integrated circuit component 1120.

Fig. 12 provides an exploded view of the adhesive patch 1140. The adhesive patch 1140 includes upper posts 1141, 1142, and 1143, as described above. These posts are in electrical contact with skin contact posts 1151, 1152 and 1153. Located on the skin-side surface of skin contact posts 1151, 1152, and 1153 is a conductive hydrogel layer 1154. Located around each post 1151, 1152, and 1153 are a non-conductive hydrogel 1155 and pressure sensitive adhesive 1156 component. In this section, any convenient physiologically acceptable adhesive may be employed. In some examples, adhesives are employed that change their tack in response to an applied stimulus. For example, adhesives that become less adhesive upon application of light (e.g., UV light) or chemicals may be employed in order to require the receptor to remain associated with the body while maintaining strong adhesion, but which tend to become less adhesive as needed to facilitate removal of the receptor from the body. Located on the non-skin side of each skin contact post is a layer of dry electrode material such as Ag/AgCl. Located on the upper surface of this layer of dry electrode material is a porous layer, such as a carbon vinyl layer. An upper backing layer 1180 is also shown. Although not shown, the upper posts 1141-1143 are in electrical contact with dry electrode and skin contact posts, which are located below each upper post, through a backing layer 1180 (e.g., polyurethane and polyethylene). As shown, the posts are off-center with respect to their dry electrode layers in the direction of the outer edge of the patch in a manner sufficient to increase the dipole size between any two given posts. Further, a conductive gradient may be associated with each pillar as desired, for example, by changing the pattern of the porous layer 1170 and/or modifying the composition of the dry electrode layer. Of interest in such aspects is where the conductivity gradient increases in conductivity along the direction of the outer edge of the patch.

Fig. 13A through 13E provide various views of an alternative outer patch configuration 1300, the outer patch configuration 1300 including two electrodes 1310 and 1320 in a flexible structure with an adhesive bandage configuration. The patch 1300 includes an upper flexible outer support 1330 and a lower flexible support 1350 that are assembled together as shown in fig. 13E so as to enclose an integrated circuit/battery component 1360 and electrodes 1310 and 1320. As shown in fig. 13D, the bottom surfaces of the electrodes 1310 and 1320 are exposed. As shown in fig. 13E, electrodes 1310 and 1320 include lead elements 1375 and 1370, with lead elements 1375 and 1370 providing electrical contact between the electrodes and integrated circuit/cell component 1360. Any convenient adhesive means, such as those described above, may be employed.

Fig. 14A-14B provide block diagrams of exemplary hardware configurations that may be present in the receivers shown in fig. 13A-13E. However, it should be understood that these exemplary hardware configurations are not limited to the aspects illustrated in fig. 13A through 13E.

Fig. 14A provides a block diagram of an exemplary hardware configuration that may be included in a receiver, such as receiver 1300, in accordance with an aspect of the subject invention. As shown, hardware system 1400 includes a first electrode 1310 and a second electrode 1320 electrically coupled to an analog ASIC 1410. ASIC 1410 may include, for example, an analog front end (e.g., a high frequency signal chain, a low frequency signal chain, etc.) of hardware system 1400. If the analog front end can be implemented in an ASIC, custom logic can be substituted for the DSP. Digital ASIC 1420 is shown electrically coupled to analog ASIC 1410 and performs digital signal conditioning and processing. An accelerometer 1430, such as a three-axis accelerometer, is shown electrically coupled to the digital ASIC 1420. In an aspect, accelerometer 1430 is electrically coupled to analog ASIC 1410. It is also understood that a digital accelerometer may be implemented. Microprocessor 1440 is shown electrically coupled to digital ASIC 1410 and flash memory 1450. Additionally, the microprocessor 1440 is shown electrically coupled to a radio 1460, such as a wireless transceiver.

Fig. 14B provides a block diagram of another exemplary hardware configuration that may be included in a receiver, such as receiver 1300, in accordance with an aspect of the subject invention. Within hardware system 1490, electrodes 1310 and 1320 are shown electrically coupled to an optional Low Noise Amplifier (LNA) 1461. The analog ASIC1462 is shown electrically coupled to the LNA 1461, and the analog ASIC1462 may comprise, for example, an analog front end of the hardware system 1490. Digital ASIC1463 is shown electrically coupled to analog ASIC1462 and performs digital signal conditioning and processing. In this regard, digital ASIC1463 further includes a microprocessor unit 1464, and microprocessor unit 1464 may be any convenient microprocessor unit, such as CORTEX-M3 from ARM, Inc^TMA micro-processing unit. Accelerometer 1430 is electrically coupled to analog ASIC1462, but as previously mentioned, accelerometer 1430 may be implemented to be electrically coupled to digital ASIC1463 as well as a digital accelerometer. Electrically coupled to the digital ASIC1463 is a radio 1460.

Fig. 14C provides a block diagram of another exemplary hardware configuration that may be included in a receiver, such as receiver 1300, in accordance with an aspect of the subject innovation. Within the hardware system 1480, a single system on a chip (SOC)1470 replaces both ASICs in fig. 14A and 14B. For example, SOC 1470 would replace ASICs 1410 and 1420 shown in fig. 14A or ASICs 1462 and 1463 shown in fig. 14B (optional LNA 1460 not shown in this case). In this case, radio 1460 is electrically coupled to SOC 1470.

Fig. 14D provides a block diagram of another exemplary hardware configuration that may be included in a receiver, such as receiver 1300, in accordance with an aspect of the subject innovation. Within hardware system 1499, an optional LNA 1461 is electrically coupled to electrodes 1310 and 1320. SOC 1482 is shown electrically coupled to optional LNA 1461, accelerometer 1430, temperature sensor 1494, and radio 1498 (e.g., a wireless communication module including a transceiver). SOC 1492 includes processor 1492, electrode inputs 1484, analog front end 1486 (e.g., a cross-body conductive communication module and a physiological sensing module), and a software-defined radio 1488. Additionally, the temperature sensor 1496 may also be included in a single ASIC 1470 and/or radio 1498 (sensors not shown).

If desired, one or more components of the receiver may be coated with a conformal non-porous sealing layer such as described in U.S. patent application serial No. 12/296,654, the disclosure of which is incorporated herein by reference. The conformal non-porous sealing layer can be characterized as a "thin film" coating because it is of such a thickness that it does not significantly increase the overall volume of the structure associated therewith, wherein any increase in volume of the device that may be caused by the layer is about 10% or less by volume, such as about 5% or less by volume, including about 1% or less by volume. According to aspects of the invention, the conformal non-porous sealing layer has a thickness in the range of 0.1 to 10.0 μm thickness, such as in the range of 0.3 to 3.0 μm thickness, and included in the range of 1.0 to 2.0 μm thickness. According to aspects of the invention, the conformal non-porous sealing layer may be applied using planar processing protocols such as plasma enhanced chemical vapor deposition, physical vapor deposition, sputtering, evaporation, cathodic arc deposition (see, e.g., U.S. patent application serial No. 12/305,894, the disclosure of which is incorporated herein by reference), low pressure chemical vapor deposition, and other such processes. When present, the conformal non-porous sealing layer may comprise a variety of different materials. In one aspect, the layer comprises silicon carbide to create a high corrosion resistant seal. Alternatively, the layer may comprise silicon dioxide, carbon oxides, carbon nitrogen oxides, metals such as noble metals and alloys thereof, e.g. platinum, rhodium, iridium and alloys thereof, metal suicides, nitrides such as silicon nitride, carbon nitrogen compounds, aluminium nitride, titanium nitride, tungsten carbide or other carbides. The layer may be a single layer or be composed of multiple layers of the same material or different materials. When multiple materials are employed, the coefficients of thermal expansion can also be calculated and designed so that the materials do not adversely affect the receiver components associated therewith. In some examples, the conformal non-porous sealing layer covers at least a portion of the outer surface of the receptacle (if not the entire outer surface). In such instances, electrical connections may be present in the sealing layer to provide electrical communication between components within the receptacle and the environment external to the receptacle.

Active agent delivery

The receptacle of the present invention may comprise an active agent delivery means. The active agent delivery means (when present) may vary. In some examples, the active agent delivery component may be a different component of the receptacle, wherein the component may include a source of the active agent composition. The active agent composition may vary and includes one or more active agents in combination with a carrier composition, where the carrier composition may be a liquid or solid composition and may be configured to provide controlled delivery characteristics as desired. Active agent delivery devices of interest include, but are not limited to: solid delivery forms, such as patch and ointment delivery forms, and fluid introduction forms, such as ionophoresis forms and forms employing microneedle components, as described in more detail below. For implantable receivers, any convenient form of active agent delivery may be employed. Examples of active agent delivery forms of interest include, but are not limited to: 11/897,931 to those described in the list; the disclosure of which is incorporated herein by reference. Depending on the particular form, the delivery means may comprise a device means that provides delivery of an amount of the active agent composition from a source of medicament to the patient. The device components may vary over a wide range, with examples of device components including selective membranes, pumps, electric field sources, microneedles, and the like. In some instances, the active agent delivery component may be combined with other components of the receiver. For example, where the receptacle includes an adhesive component, the adhesive composition of the adhesive component may include one or more active agents as desired, wherein the adhesive composition may be formulated to provide any desired active agent delivery characteristics. Where active agent delivery is included, the receiver may be configured to deliver the active agent according to a predetermined dosage regimen in response to a received dosage signal, in response to one or more detected physiological parameters (e.g., the device is configured as a closed-loop active agent delivery device), and/or the like.

Microneedle

The receivers of the present invention may include a microneedle component that may be configured for analyte detection and/or active agent delivery, such as described in more detail below. Microneedle components of interest are configured for use in transferring biological fluids from a physiological source to another location (e.g., an external location) in a minimally invasive, painless, and convenient manner. The microneedle component can be configured to allow in vivo sensing or extraction of biological fluids from the body, such as from or through the skin, with minimal or no damage, pain, or irritation to the tissue.

The microneedle component can include one or more microneedles (where a plurality of microneedles can be configured in any convenient form, such as a three-dimensional array), a substrate to which the one or more microneedles are attached, a fluid chamber in communication with the one or more microneedles, and/or a sensor.

The microneedles may be configured to function as catheters, sensing elements, or a combination thereof. The catheter microneedles may have porous or hollow shafts. As used herein, the term "porous" means having pores or cavities through at least a portion of the microneedle structure that are sufficiently large and interconnected to allow the transport of liquid and/or solid materials through the microneedle. As used herein, the term "hollow" means having one or more generally annular holes or channels through the interior of the microneedle structure that have a diameter large enough to allow for the transport of liquids and/or solids through the microneedle. If desired, the annular bore may extend through the entire needle body or a portion thereof in the needle tip to base direction, extend in a direction parallel to the needle body or branch off or form an outlet at the side of the needle body. Solid or porous microneedles may be hollow. One or more microneedles may be coated (if solid, porous, or hollow) and/or at least partially filled (if porous or hollow) with a susceptible or diffusion-modifying material, as desired.

Microneedles may be constructed from a variety of materials, including metals, ceramics, semiconductors, organics, polymers, and composites. Materials of construction of interest include, but are not limited to: pharmaceutical grade stainless steel, gold, titanium, nickel, iron, tin, chromium, copper, palladium, platinum, alloys of these or other metals, silicon, silica, and polymers. Biodegradable polymers of interest include, but are not limited to: hydroxy acid polymers such as lactic acid and glycolic acid polylactic acid, polyglycolide, polylactic acid-polyglycolide copolymers and copolymers with PEG, polyanhydrides, polyorthoesters, polyurethanes, polybutanoic acid, polypentanoic acid, and lactide-caprolactone copolymers. Non-biodegradable polymers of interest include, but are not limited to: polycarbonate, polymethacrylic acid, ethylene vinyl acetate, polytetrafluoroethylene, and polyester.

The microneedles may be configured to have a cross-section that is circular in the vertical direction or the cross-section may be non-circular. For example, the microneedles can be polygonal (e.g., star, square, triangular), elliptical, or other shapes in cross-section. The rod may have one or more holes. The cross-sectional dimensions may vary, and in some examples range between 1 μm and 500 μm, such as between 10 μm and 100 μm. Its outer and inner diameters may also vary, with its outer diameter ranging between 10 μm and 100 μm in some examples, and its inner diameter ranging between 3 μm and 80 μm in some examples. The length of the microneedles may also vary, in some examples ranging between 10 μm and 1mm, such as between 100 μm and 500 μm, including between 150 μm and 350 μm.

The substrate of the device may be constructed of a variety of materials including metals, ceramics, semiconductors, organics, polymers, and composites. The substrate includes a base to which the microneedles are attached or integrally formed with the microneedles. The substrate of the microneedle component may be bonded to another component of the receiver structure, as desired.

The fluid chamber (configured as a fluid collection chamber or an active agent reservoir) and/or the sensor may be attached to the substrate or formed (e.g., as part of the substrate) in direct communication with the base of the microneedle.

The fluid chamber (when present) can be selectively coupled to the bore or aperture of the microneedle to enable biological fluid to flow from tissue surrounding the microneedle, through the microneedle, and into the fluid chamber, or the active agent composition can flow from the chamber, through the microneedle, and into the subject. The fluid chamber is attached to or incorporated into the substrate as desired. The fluid chamber may be substantially rigid or easily deformable. The fluid chamber may be formed from one or more polymers, metals, ceramics, semiconductors, or combinations thereof. In one aspect, the fluid chamber contains a porous or absorbent material such as a sponge, gel or paper, or a polymeric tape. The fluid chamber may include a fluid active agent composition comprising one or more active agents in combination with a carrier formulation. Thus, this fluid chamber may be initially empty, or may contain one or more reagents or active agents, etc., in gas or any form (e.g., liquid or solid particles), as desired.

The microneedle component can include one or more sensors, as desired. These sensors may be located in the microneedles or in the device body (e.g., in the fluid chamber). These sensors may be in or attached to one or more microneedles, incorporated into a substrate, or located within or in communication with a fluid chamber. Sensors of interest include pressure sensors, temperature sensors, chemical sensors, pH sensors, and/or electromagnetic field sensors. Sensors of interest include those configured to detect the presence of chemical analytes in a biological fluid sample, including but not limited to: blood glucose (glucose), cholesterol, bilirubin, sarcosine, various metabolic enzymes, hemoglobin, heparin, hematocrit, vitamin K or other coagulation factors, uric acid, carcinoembryonic antigen or other tumor antigens, various reproductive hormones such as those associated with ovulation or pregnancy, drugs of abuse, and/or metabolites thereof; blood alcohol concentration, etc. In certain aspects, the substances or properties that the receiver is configured to detect include lactate (important for athletes), oxygen, pH, alcohol, tobacco metabolites, and illegal drugs (important for medical diagnostics and law enforcement). The sensor (when present) may be in communication with a microneedle sensor functional module, which may include software and/or hardware components and be present only in the microneedle component and/or incorporated at least to some extent into other portions of the receiver.

System for controlling a power supply

In certain aspects, the receiver is part of a body-associated system or network of devices, such as sensors, signal receivers, and optionally other devices that may be internal and/or external, that provide various different types of information that is ultimately collected and processed by a processor, such as an external processor, which is then able to provide contextual data about a living subject, such as a patient, as an output. For example, the receiver may be a member of an in-vivo network of devices that is capable of providing an output including data regarding IEM ingestion, one or more physiological sensing parameters, implantable device operation, and the like, to an external collector of data. An external collector of data, for example in the form of a medical web server or the like, then combines the data provided by this receiver with other relevant data about the patient, such as weight, climate, medical record data, etc., and can process this heterogeneous data to provide highly targeted and contextual patient-specific data.

In certain aspects, the system of the present invention includes a signal receiver aspect of a receiver and one or more IEMs. IEMs of interest include those described in the following patent documents: PCT application Ser. No. PCT/US2006/016370 published as WO/2006/116718; PCT application Ser. No. PCT/US2007/082563, published as WO/2008/052136; PCT application Ser. No. PCT/US2007/024225, published as WO/2008/063626; PCT application Ser. No. PCT/US2007/022257, published as WO/2008/066617; PCT application Ser. No. PCT/US2008/052845, published as WO/2008/095183; PCT application Ser. No. PCT/US2008/053999, published as WO/2008/101107; PCT application Ser. No. PCT/US2008/056296, published as WO/2008/112577; PCT application Ser. No. PCT/US2008/056299, published as WO/2008/112578; and PCT application serial No. PCT/US2008/077753 published as WO/2009/042812; the disclosures of these applications are incorporated herein by reference.

In certain aspects, the system includes an external device distinct from the receiver (which in certain aspects may be implanted or applied locally), wherein the external device provides multiple functions. Such external devices can include the ability to provide feedback and appropriate clinical adjustments to the patient. Such devices can take any of a variety of forms. For example, the device can be configured to be positioned on a bed beside a patient, such as a bedside monitor. Other forms include, but are not limited to, PDAs, smart phones, home computers, and the like.

One embodiment of the system of the present invention is shown in FIG. 15A. In fig. 15A, system 1500 includes a pharmaceutical composition 1510 comprising an IEM. Also present in system 1500 is a signal receiver 1520, such as the signal receivers shown in fig. 10-12. Signal receiver 1520 is configured to detect signals emitted from the markers of IEM 1510. The signal receiver 1520 also includes physiological sensing capabilities, such as ECG, as well as motion sensing capabilities. The signal receiver 1520 is configured to transmit data to a patient's external device or PDA 1530 (e.g., a smart phone or other wireless communication enabled device), which external device or PDA 1530 then transmits the data to the server 1540. The server 1540 can be configured as desired, for example, to provide patient consent permissions. For example, the server 1540 may be configured to allow the home caregiver 1550 to participate in the patient's treatment plan, e.g., via an interface (e.g., a network interface), thereby allowing the home caregiver 1550 to monitor alarms and trends generated by the server 1540 and provide support to the patient, as illustrated by arrow 1560. The server 1540 can also be configured to provide responses directly to the patient, e.g., in the form of patient alerts, patient stimuli, etc., as indicated by arrow 1565, which are forwarded to the patient via the PDA 1530. Server 1540 can also interact with a medical professional (e.g., RN, physician) 1555, which medical professional 1555 can use data processing algorithms to obtain measurements of patient health and compliance, e.g., health index reports, alerts, cross-patient benchmarks (cross-patient benchmarks), etc., and provide informed clinical communications and support to the patient, as shown by arrow 1580.

Another embodiment of the system of the present invention is shown in FIG. 15B. FIG. 15B depicts a system comprising a syringe 15107, a receiver 15105, a blood glucose meter 15110, a wireless communication device 15115, communication links 15150B-E, and a dose manager 15160. The system generally provides an intelligent mechanism for controlling dose delivery through a syringe 15107, such as a hypodermic needle or a bayonet coupling (luer connection) of an intravenous access device. The control may include, for example, detecting whether the syringe 15107 is near the patient, measuring the dose administered by the syringe 15107, transmitting the measurement information to other devices such as a receiver 15105, a blood glucose meter 15110, a wireless device 15115, and/or a dose manager 15160, and providing feedback information to one or more of these devices. In some implementations, the feedback information can prevent dose administration to the patient, for example, using an interlock on the syringe 15107 to avoid supplying a dose. The injector 15107 may output a visual indication (e.g., a Light Emitting Diode (LED)) or an audible signal based on the feedback to indicate that the dose should not be administered to the patient. For example, an interlock mechanism, LED, and/or sound on the syringe 15107 may signal that the patient is receiving the wrong type of medication, receiving a dose at the wrong time, and/or receiving the wrong amount of medication.

In some implementations, the syringe 15107 may be configured in an interlock mode as a default state to prevent administration until the dose manager 15160 provides feedback to unlock the syringe 15107 to allow administration of the medicament or drug.

Additionally, in some embodiments, the syringe 15107 may include a measurement mechanism to provide measurement information indicative of the dose. When this is the case, the dose manager 160 may use this measurement information along with other patient information, such as blood pressure, blood glucose levels, heart rate, Ingestible Event Marker (IEM) data, etc., to control when and/or how many doses to provide to the patient. Additionally, when the syringe 15107 is in proximity to (e.g., in or near) the patient's body, the syringe 15107 may activate a measurement mechanism (which provides measurement information) at which time the measurement information and other information, such as an identifier associated with the syringe 15107, a patient identifier, etc., are carried by a signal to other devices, such as a receiver 15105, a blood glucose meter 15110, and/or a wireless device 15115, for transmission to the dose manager 15160. In addition, these other devices may monitor the time of administration through syringe 15107. Thus, the dose manager 15160 may receive the precise time when to administer the drug rather than relying on the user-provided time of administration. Thus, the system may be used to assess a particular fluid delivery event between an injectable fluid delivery device, such as syringe 15107, and a patient.

In some aspects of the system of the present invention, the receptacle of the present invention, including the multipurpose connector, is operatively connected to a patient or another device via the multipurpose connector. As noted above, other devices to which the receiver is operatively connected include, but are not limited to, external charger devices, external programming devices, external data processing devices, and the like. In some examples, the system may include a receiver operably connected directly to the patient or operably connected to an external proximal end of a device associated with the patient, such as an implanted medical device.

In the case where the receiver is operatively connected to an external device, it may be connected directly to the external device, or via one or more different connector devices, such as cables, wires or the like. An example of an external device is an external programming device. The programming device may be configured to alter the settings of the receiver. For example, the programming device may alter the operational settings of the receiver, such as parameters of signal measurements related to the patient, the frequency of the measurements, the duration of the measurements, the electrodes used for the measurements, and so forth. The programming device may also alter the operating mode of the receiver. The programming device can also transmit data to the receiver, such as medical records or other data about the patient. The programming means may be any means suitable for the purpose. Programming devices of interest include, but are not limited to, computers with built-in or peripheral monitors (such as may be found in bedside monitors or health information systems), Personal Digital Assistants (PDAs), smart phones, messaging devices or other handheld devices, and the like.

The system of the present invention may further comprise an external data processor configured to receive data from the receiver. The external data processor may receive the electrical signal data directly from the receiver or via a data forwarding device, such as a device that receives data from a signal receiver associated with the body and then forwards the received data to the extracorporeal data processor. The external data processor may be configured to receive data via any convenient wired or wireless protocol, as desired. Some external data processors of interest may receive data from the receiver by connecting to the multi-purpose connector. External data processors of interest are those capable of receiving electrical signal data and processing that data to produce useful information. The external data processor may also simply store the data for subsequent processing or viewing. The processed data may be output to the user through any convenient medium, such as writing the data on paper, displaying the processed data to the user via a graphical user interface, and so forth. The data may be arranged in any useful form such as a graph, table or signal. The external data processor of the system of the present invention may take on a variety of configurations, such as a computer with built-in or peripheral monitors (e.g., embedded in a bedside monitor or health information system), a Personal Digital Assistant (PDA), a smart phone, a messaging device, and so forth.

The system of the present invention allows for dynamic feedback and treatment cycles that track medication times and levels, measure treatment response, and give recommendations for altering dosages based on the physiological and molecular characteristics of individual patients. For example, patients with symptomatic heart failure take multiple medications daily, with the primary purpose of reducing the workload on the heart and improving the quality of life of the patient. The primary therapeutic agents include Angiotensin Converting Enzyme (ACE) inhibitors, beta-blockers and diuretics. In order for a drug treatment to be effective, it is critical that the patient follow their prescribed treatment plan and take the required dosage at the appropriate time. Several studies in the clinical literature have shown that: more than 50% of patients with class II and class III heart failure do not receive the guidelines recommend treatment; and for some of the patients who had been properly titrated, only 40-60% of the patients followed the treatment plan. With the subject system, compliance of heart failure patients with therapy can be monitored, and compliance performance can be correlated with key physiological measures to help physicians optimize treatment regimens.

In certain aspects, the system of the present invention may be employed to obtain a collection of information including sensor data and administration data. For example, one can combine heart rate, respiration rate, multi-axis acceleration data, information about flow regime, and information about temperature together and then derive an indicator that will inform about the overall activity of the subject, which can be used to generate a physiological indicator, such as an activity indicator. For example, when the temperature rises, the heart rate rises a little and breathing accelerates, which can be used as an indication that the person is active. By calibrating such information, the amount of calories burned by the person at that instant can be determined. In another embodiment, a particular set of rhythmic pulse or multi-axis acceleration data may indicate that a person is walking up a flight of stairs, and thus one can infer how much energy they are consuming. In another aspect, a body fat measurement (e.g., from impedance data) may be combined with an activity index generated by a combination of measured biomarkers to generate a physiological index for use in managing a weight or cardiovascular health plan. This information can be combined with cardiac performance indicators to get overall health integrity, which can be combined with medication administration data. On the other hand, one may find that, for example, a particular drug is associated with a small rise in body temperature or changes in the electrocardiogram. One can develop a pharmacodynamic model for drug metabolism and use the information from the receiver to fit the free parameters in the model as necessary to provide a more accurate estimate of the levels actually present in the serum of the subject. This information can be fed back to the dose treatment plan. On the other hand, for use as a high risk pregnancy monitor, one may incorporate information from sensors that measure uterine contractions (e.g., using strain gauge measurements) and also monitor fetal heart rate.

In certain aspects, subject-specific information acquired using the system of the invention may be transmitted to a location where the information is combined with data from one or more other individuals to provide a data set that is a composite of data acquired from two or more individuals, e.g., five or more, ten or more, twenty-five or more, fifty or more, one hundred or more, one thousand or more, etc. The aggregated data may then be processed, such as by being sorted according to different criteria and made available to one or more different types of groupings, such as patient groupings, healthcare worker groupings, and the like, where the processing of the data may restrict access to any given grouping to the types of data that the grouping can access. For example, data may be collected from one hundred different individuals who have the same condition and are taking the same medication. This data can be processed and used to develop an easily compliable display of patient compliance with the medication plan and overall health. The patient members of the group can access this information and see how their compliance compares to other patient members of the group, and whether they enjoy the benefits that others are experiencing. In another aspect, doctors may also be granted access to integrated data processing to see their patients compared to those of other doctors and to obtain useful information about the real patient's response to a given treatment plan. Additional functionality may be provided for packets having access to the integrated data, where such functionality may include, but is not limited to: the ability to annotate data, chat functionality, privacy privileges, etc.

These receivers may be part of the system described in the following patent applications: PCT application Ser. No. PCT/US 08/85048; PCT application Ser. No. PCT/US2007/024225, published as WO 2008/095183; PCT application Ser. Nos. PCT/US2007/024225 disclosed as WO 2008/063626 and US2006/016370 disclosed as WO 2006/116718; the disclosures of these patent applications are incorporated herein by reference.

According to another aspect of the invention, the receiver may be implemented in a variety of ways, including implantable devices, semi-implantable devices such as subcutaneous devices, and externally applied or positioned devices (e.g., personal signal receivers), and each device may be used with a dosage delivery system. Examples of receiver configurations of interest include, but are not limited to, the receiver configurations described in the following patent applications: PCT application Ser. No. PCT/US08/85048, published as WO 2009/070773; PCT application Ser. No. PCT/US2007/052845, published as WO 2008/095183; PCT application Ser. Nos. PCT/US2007/024225 disclosed as WO 2008/063626 and US2006/016370 disclosed as WO 2006/116718; the disclosures of these patent applications are incorporated herein by reference. One example of a personal signal receiver for use with a dosage delivery system is a "patch" receiver that is removably adhered to the skin or clothing of a user. Other implementations include a wristband or IV access device. In some implementations, the receiver may be implemented as a personal health signal receiver associated with the body (e.g., located within or in close proximity to the body) and may be configured to receive and decode signals from an in-vivo transmitter located within the body.

Receivers according to the teachings of the present invention may also be configured to receive information from other sources, such as Intelligent Event Marker (IEM) data. In this case, the receiver 105 may detect data related to an IEM event, such as administration of a medication containing a radio frequency identifier (rfld) -like, and may process the data and forward it to another device, such as the blood glucose meter 110 and/or the wireless device 115, for further processing and forwarding to the dose manager 160.

In certain aspects, the system further comprises an element for storing data, i.e., a data storage element. The data storage element may be a computer readable medium. The term "computer-readable medium" as used herein refers to any physical storage or transmission medium that participates in providing instructions and/or data to a computer for execution and/or processing. Examples of storage media include floppy disks, magnetic tape, CD-ROMs, hard drives, ROMs, or integrated circuits, magneto-optical disks, or computer-readable cards (e.g., PCMCIA cards, etc.), whether such devices are internal or external to the computer. A file containing information may be "stored" on a computer-readable medium, where "storing" refers to recording the information so that it may be later accessed and retrieved by a computer. With respect to computer-readable media, "persistent storage" refers to storage that is persistent. The persistent memory is not erased due to the termination of power to the computer or processor. Computer hard drives ROM (i.e., ROM that is not used as virtual memory), CD-ROM, floppy disks, and DVD are all examples of permanent storage. Random Access Memory (RAM) is an example of volatile memory. The files in persistent storage may be editable and rewritable.

The present invention also provides computer-executable instructions (i.e., programming) for performing the above-described methods. Computer-executable instructions reside on physical computer-readable media. Accordingly, the present invention provides computer readable media containing programming for detecting and processing signals generated by compositions of the invention (e.g., as repeated above).

As repeated above, in certain aspects of interest, the receiver includes a semiconductor support member. Any of a variety of different protocols may be employed in the manufacture of the receiver structure and its components. For example, molding, deposition, and material removal, e.g., planar processing techniques such as micro-electromechanical system (MEMS) fabrication techniques, including surface micromachining techniques and bulk micromachining techniques, may be employed. Deposition techniques that may be employed in fabricating certain aspects of these structures include, but are not limited to: electroplating, cathodic arc deposition, ion spraying, sputtering, electron beam evaporation, physical vapor deposition, chemical vapor deposition, plasma enhanced chemical vapor deposition, and the like. Material removal techniques include, but are not limited to: reactive ion etching, anisotropic chemical etching, isotropic chemical etching, planarization (e.g., by chemical mechanical polishing), laser ablation, Electrical Discharge Machining (EDM), and the like. Also of interest is the photolithography protocol (lithographic protocol). Of interest in certain aspects is the use of planar processing protocols, wherein structures are built up and/or removed on one or more surfaces of an initially planar substrate using a plurality of different material removal protocols and deposition protocols applied to the substrate in a sequential manner. Exemplary manufacturing methods of interest are described in more detail in co-pending PCT application Ser. No. PCT/US 2006/016370; the disclosure of which is incorporated herein by reference.

In certain aspects, the receivers or components thereof may be manufactured using off-the-shelf components. For example, off-the-shelf instrumentation amplifiers for amplifying the input, for example in the form of bare chips, may be employed. Custom logic, FPGA or ASIC, performing the demodulator, memory, microprocessor functions and all interface functions may be used. The transmitter may be a chip of an off-the-shelf product, such as in a hybrid communication band, that is approved for medical implantation. The clock may be a separate clock or the device may have a microprocessor with a built-in clock.

Aspects of the invention also include methods of using a receiver. In the receiver approach, the receiver receives the input signal in some way, where the input signal may be different. Examples of input signals include, but are not limited to: signals received conductively across the body (as may be received from the IEM or smart parenteral delivery device), signals acquired by device sensors such as physiological parameters and/or environmental signals, and the like. Aspects of the invention also include the device acting in some manner in response to receiving an input signal, such as forwarding a signal to a second device, delivering an active agent to a subject associated with the device, and the like.

In some methods of the present invention, as an optional step, a signal is first conductively transmitted from an in-vivo transmitter (e.g., an IEM). The transmitted signal is then received by the receiver, where it may be stored in memory, retransmitted to another receiver, e.g., output to a user, either directly or via a third device, such as an external PDA, etc. In the methods of the invention wherein the in vivo emitter is an IEM, the IEM is administered by ingestion as needed.

The methods of the invention find use in the treatment of a variety of different conditions, including symptomatic applications. The particular condition that can be treated with the compositions of the present invention will vary depending on the type of active agent that may be present in the compositions of the present invention. Thus, symptoms include, but are not limited to: cardiovascular diseases, cell proliferative diseases (such as neoplastic diseases), autoimmune diseases, hormonal abnormalities, infectious diseases, pain management, neurological diseases (such as epilepsy) and the like.

Treatment refers to at least an improvement in the symptoms associated with the symptoms afflicting the subject, where improvement is used broadly to mean that the parameters associated with the pathological condition being treated, e.g., symptoms, are at least reduced in magnitude. Thus, treatment also includes where the pathological state or symptoms associated therewith are completely inhibited, e.g., prevented from occurring or ceasing (e.g., terminating), such that the subject is no longer afflicted with the pathological state or at least the symptoms characteristic of the pathological state. Accordingly, "treatment" of a disease includes preventing the disease from occurring in an animal that may be predisposed to the disease but does not yet experience or exhibit symptoms of the disease (prophylactic treatment), inhibiting the disease (slowing or arresting its development), alleviating symptoms or side effects of the disease (including palliative treatment), and alleviating the disease (causing regression of the disease).

Various subjects can be treated according to the methods of the invention. Generally, such subjects are "mammals" or "mammals," where these terms are used broadly to describe organisms belonging to the class mammalia, including the orders carnivore (e.g., dogs and cats), rodentia (e.g., rats, guinea pigs, and mice), and primates (e.g., humans, chimpanzees, and monkeys). In representative aspects, the subject will be a human.

In certain aspects, as described above, the methods of the invention are methods of managing symptoms over, e.g., an extended period of time, such as one week or more, one month or more, six months or more, one year or more, two years or more, five years or more, etc. The methods of the present invention may be employed in conjunction with one or more other disease management protocols, including, for example, electrical stimulation-based protocols in cardiovascular disease management, such as pacing protocols, cardiac resynchronization protocols, and the like; lifestyle, such as diet and/or exercise treatment programs for a variety of different symptoms; and so on.

In certain aspects, the methods include adjusting a treatment plan based on data acquired from the composition. For example, data may be obtained that includes information regarding patient compliance with a prescribed treatment plan. Data with or without additional physiological data (e.g., using one or more sensors, such as may be acquired using the sensors described above) may be employed, e.g., as needed, using appropriate decision tools, in order to make a determination as to whether a given treatment plan should be maintained or modified in some manner, e.g., by modifying a drug treatment plan and/or an implant activity treatment plan. Thus, the methods of the present invention include methods of modifying a treatment plan based on signals obtained from a composition.

In certain aspects, methods of determining the history of a composition of the invention are also provided, wherein the composition comprises an active agent, an identifier element, and a pharmaceutically acceptable carrier. In certain aspects, the identifier emits a signal in response to an interrogation, such as by a bar code reader or other suitable interrogation device interrogating the identifier to obtain the signal. The acquired signals are then used to determine historical information about the composition, such as source, chain of custody, and the like. In certain aspects, this determining step may include accessing a database or similar compilation of stored histories of the composition.

The receiver of the present invention may be used in a variety of different applications. The medical aspect of the present invention provides clinicians with an important new tool in their suite of treatment devices: the pharmaceutical agent actually delivered into the body is automatically detected and identified. The applications of this new information device and system are multiple. Applications include, but are not limited to: (1) monitoring patient compliance with a prescribed treatment plan; (2) customizing a treatment plan based on patient compliance; (3) monitoring patient compliance in a clinical trial; (4) monitoring the use of controlled substances, and the like. Each of these various exemplary applications is described in more detail in the following patent applications: PCT application Ser. No. PCT/US 08/85048; PCT application Ser. No. PCT/US2007/024225, published as WO 2008/095183; PCT application Ser. Nos. PCT/US2007/024225 disclosed as WO 2008/063626 and US2006/016370 disclosed as WO 2006/116718; the disclosures of these patent applications are incorporated herein by reference.

It has also been found that the receiver of interest can be used in conjunction with the delivery of therapeutic fluids to a subject. Of interest is the use of a receiver in conjunction with a smart injection delivery device, as described in PCT patent application serial No. PCT/US2007/015547, published as WO 2008/008281; the disclosure of which is incorporated herein by reference. When used in conjunction with such fluid delivery devices (e.g., smart injection devices), the receiver may be configured to receive data regarding the actual amount of therapeutic fluid that has been administered. The receiver may be configured to combine this particular data with other relevant data (e.g., analyte test data, physiological data, etc.), wherein the receiver or another type of test (e.g., a specialized home-use analyte test device, etc.) may be employed to acquire these additional types of data. Additionally, the receiver may be configured to perform one or more actions based on the received information, including but not limited to: forward data to a second device, modify a treatment plan, etc.

Also of interest are applications in which no receiver is used to receive signals from an IEM or smart parenteral delivery system. Such an application of interest in the receiver of the present invention is in the detection of epileptic seizures. Such apparatus includes an epileptic seizure detection module configured to employ one or more types of received data to determine whether a subject is about to, or is suffering from, an epileptic seizure. Accordingly, in these applications, a receiver is employed to acquire one or more types of physiological data and process the data to determine whether the subject is about to be, or is suffering from, an epileptic seizure. In other words, the receiver employs the acquired physiological data to make an episode prediction or detect the occurrence of an episode. Physiological data that may be acquired and used in these applications include electroencephalography (EEG) data, accelerometer data, heart rate (ECG) data, and the like. One type of data may be acquired or two or more different types of data may be acquired and processed to determine whether the subject is about to be afflicted with an epileptic seizure or is suffering from an epileptic seizure. In some instances, the determination may be made by combining data acquired by the receiver with data from other sources and processing such data. The data may include, for example, an accelerometer or a unique signature of the rate of change of heart rate. Sensor data may be integrated from the EEG as part of the system or as an auxiliary input as desired. With multiple data streams, one can detect a "primer," a set of events that cause an episode. In such instances, medical treatments may be adjusted as needed based on the episode status. Neuromodulation devices may accommodate these needs — measuring EEG or adjusting a treatment regimen.

The receiver may be configured to make this determination using any convenient protocol. One or more algorithms may be employed that use the acquired physiological data to make a decision as to whether an episode is about to occur or is occurring. Examples of such algorithms include, but are not limited to: algorithms for implementing automated episode alert (ASWA) (such as described in published U.S. patent No. 20070213786); algorithms for detecting chirp-like temporal frequency changes in EEG signals (e.g., computational and mathematical methods in medicine by Sen et al, "Analysis of Seizure EEG in modulated epigenetic rates", published 12/4 of 2007, Vol. 8, pages 225 to 234, etc.).

In this application, the prediction or detection of an epileptic seizure may result in a number of additional actions. In some instances, the receiver may be configured to generate and transmit an alarm signal. The alert signal may or may not be detectable to the subject. For example, the alarm signal may be in the form of an audible or visual signal that can be detected by the subject. The alarm signal may also be a signal sent to medical or other personnel via, for example, a wireless communication protocol. The alert signal can be employed in a number of different ways, for example to prompt medical personnel to provide assistance to the subject, to encourage or modify a treatment plan, or the like.

In some examples, the receiver is configured as a "closed loop" epilepsy treatment apparatus, where the receiver includes an epilepsy treatment component, such as a medication treatment component or an electrical treatment component. In these examples, the receiver may employ prediction or detection of an epilepsy episode (e.g., by delivering an active agent and/or electrical stimulation or by directing another device to perform one or more of such actions) to encourage epilepsy therapy. Alternatively, existing epilepsy treatment protocols may be modified in terms of, for example, dosage, duration, etc., based on predicted or detected seizures.

The receiver of the present invention is also used in tracking applications, where one or more persons, such as patients, soldiers, etc., are monitored over a given period of time. The receiver employed in these aspects may include a plurality of different physiological and/or environmental sensing modules, such as the accelerometers and ECG sensing modules described above, in order to monitor the health status of the subject over time. This data can be combined with location data provided by, for example, a GPS module, in order to track the subject's position relative to the location as a function of time.

One particular type of tracking application of interest is tracking personnel, such as personnel in an active work environment, such as military personnel in a battlefield environment, fire and rescue personnel in a fire environment, medical personnel in a hospital, and the like. In such applications, the receiver of the present invention may include functional modules for determining certain physiological states that are common in the environment of interest. For example, there may be functional modules for determining certain physiological states of common battlefield conditions. Examples of such functional modules include the accelerometer and ECG functional modules described above, as these particular functional modules provide useful data about movement and vital activity. When one or more physiological states of interest reach one or more critical limits (e.g., the soldier is no longer moving and/or vital sign activity is no longer sufficient), the receiver may be configured to send an alarm signal to the commander/medic unit indicating that the soldier needs immediate care. For example, if the temperature sensor of the receiver indicates that the weather is cold and the soldier's body temperature has begun to fall below a specified minimum, the receiver may automatically signal the commander/medic unit and the commander unit that the soldier may be suffering from hypothermia. The commander or the medic operating the commander/medic unit or the person operating the central control unit can then inform other soldiers or medical personnel in the area that the soldier should be treated for the condition as soon as possible. Similarly, the injured soldier can be monitored for symptoms, and the severity of the injury or syncope following blood loss.

In these applications, each receiver may be customized to a particular wearer. Thus, a given receiver may contain information about an individual, such as drug allergies and other medical information that may be important to medical personnel treating the individual. In addition, the receiver may maintain a short physiological history, such as body temperature, heart rate, posture, blood pressure, blood oxygen saturation, and movement over the last four hours or some other period of time. This information can be forwarded to the on-site commander/medic unit or commander unit as required. This may be achieved by a remote communication system of the receiver or by a direct connection between the receiver and the commander/medico unit when the medico of the commander/medico unit arrives to treat the user.

In these applications, the receiver or commander/medico unit may include software/firmware for providing guidance and medical decision support. In addition, a microprocessor provided therein or in the receiver can be programmed to control the patient's fluid replacement, drug delivery and ventilator support to enable effective treatment even in battlefield situations. The receiver may communicate with, for example, a commander/military unit or a commander unit, continuously or in short bursts, through a number of predetermined schemes, in order to prevent an enemy combat unit from tracking the communication to find the soldier. These bursts may occur periodically based on a schedule or as directed by a commander/medico-unit or commander unit.

In these applications, the commander/officer unit may be a portable device worn by officers and other commanders to enable each to monitor the person for whom they are responsible. The commander/medic unit may contain a communication system for communicating with the receiver and the commander unit, and/or may contain a display that enables the user to graphically monitor the location of personnel on the battlefield and/or view the physiological condition of each soldier within the commander's command structure. The commander/medic unit can receive information about the location of the injured soldier and can receive medical information when the medic is deployed to the soldier's site. When used by a military medical practitioner, this unit enables the military medical practitioner to view vital signs and other information of the injured soldier prior to actually inspecting the soldier. Thus, the military medical practitioner can derive an initial assessment of the injured soldier en route to the soldier's location. Furthermore, because the receiver is also in communication with the command unit, medical personnel at the central command post can instruct the medic as to the diagnosis and treatment options while en route to the temporary rescue. By continuously monitoring the position and state of the soldier, the casualty rate can be greatly reduced. Furthermore, the techniques used in the present invention may be modified slightly to maintain a high level of care in civilian medical applications while greatly reducing costs.

While the above description has been provided in terms of tracking military personnel, these receivers may be employed in tracking any type of personnel, particularly personnel in an active work environment where personnel are located at fixed locations for extended periods of time.

Non-worker tracking applications are also provided. The receiver may be employed in a hospital environment for patient tracking and management. Rather than requiring a nurse to track the patient for their vital signs, the nurse or other medical personnel can employ the receiver to determine the patient's location and their vital signs. If the received information indicates that a problem exists, the location of the patient can be easily determined. Thus, a smaller number of nurses may be used while providing a higher level of care.

Kits for carrying out the methods of the invention are also provided. The kit may comprise one or more receptors of the invention, as described above. In addition, the kit may include one or more dosage compositions, for example in the form of IEM compositions. The dosage of one or more pharmaceutical formulations provided in the kit may be sufficient for one application or more applications. Accordingly, in certain aspects of the kits of the invention, there is a single dose of the pharmaceutical formulation, and in certain other aspects, there may be multiple doses of the pharmaceutical formulation in the kit. In those aspects having multiple doses of a pharmaceutical formulation, the pharmaceutical formulation may be packaged in a single container, e.g., a single tube, bottle, vial, etc., or one or more doses may be packaged separately, such that a certain kit may have more than one container of pharmaceutical formulation.

In certain aspects, the kit can further include an external monitoring device, e.g., as described above, which can provide communication with a remote location (e.g., a physician's office, a central facility, etc.) that acquires and processes the acquired data regarding the use of the composition.

The kit of the invention may also comprise instructions for use of the kit components to perform the method of the invention. These instructions may be recorded on a suitable recording medium or substrate. For example, the instructions may be printed on a substrate such as paper or plastic or the like. Thus, instructions for use may be placed in the kit as a package insert, in a container label (i.e., associated with a package or sub-package) for the kit or components thereof, and the like. In other aspects, the instructions reside as an electronically stored data file on a suitable computer readable storage medium, such as a CD-ROM, diskette, or the like. In some other aspects, the actual instructions are not placed in the kit, but a means is provided for obtaining the instructions from a remote source, such as over the Internet. An example of this is a kit comprising a web address where instructions for use can be viewed and/or from which instructions for use can be downloaded. As with the instructions, the means for obtaining the instructions are recorded on a suitable substrate.

Some or all of the components of the kits of the invention may be packaged in suitable packaging to maintain sterility. In many aspects of the kits of the invention, the components of the kit may be packaged in a kit containment element, such as a cassette or similar structure, which may or may not be a sealed container, to form a single, easily handled unit, for example to further maintain the sterility of some or all of the components of the kit.

It is to be understood that the invention is not limited to the specific aspects described and that it may be varied accordingly. It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only, and is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims. Where a range of values is provided, it is understood that up to one tenth of the unit of the lower limit, intermediate values between the upper and lower limits of that range, and any other stated values or intermediate values in that stated range are encompassed within the invention unless the context clearly dictates otherwise. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges, except where any explicitly excluded limit in the stated range is also encompassed within the invention. Where a stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the invention. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present invention, the exemplary methods and/or materials are now described. All publications and patent applications cited in this application are herein incorporated by reference as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference and were set forth in its entirety herein to disclose and describe the methods and/or materials in connection with which the publications were cited. Any reference to a publication is made prior to the filing date and should not be construed as an admission that the invention is not entitled to antedate such publication by virtue of prior invention. Moreover, the dates of publication provided may be different from the actual publication dates which may need to be independently confirmed.

It should be noted that, as used herein and in the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. It is also noted that the claims may be intended to exclude any optional elements. Accordingly, this statement is intended to serve as antecedent basis for use of such exclusive terminology as "solely," "only," and the like in connection with the recitation of claim elements, or use of a "negative" limitation. It will be apparent to those skilled in the art upon reading this disclosure that each of the individual aspects described and illustrated herein has discrete components and structures, which may be readily separated from or combined with the structures of any of the other several aspects without departing from the scope or spirit of the present invention. Any referenced method may be implemented in the order in which events are referenced, or in any other order that is logically possible. Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, it will be readily apparent to those of ordinary skill in the art in light of the teachings of this invention that certain changes and modifications may be made thereto without departing from the spirit or scope of the appended claims. Thus, the foregoing merely illustrates the principles of the invention. It will thus be appreciated that those skilled in the art will be able to devise various arrangements which, although not explicitly described or shown herein, embody the principles of the invention and are included within its spirit and scope. Moreover, all examples and conditional language recited herein are principally intended to aid the reader in understanding the principles of the invention and the concepts contributed by the inventor to furthering the art, and are to be construed as being without limitation to such specifically recited examples and conditions. Moreover, all statements herein reciting principles, aspects, and specific examples thereof, are intended to encompass both structural and functional equivalents thereof. Further, it is intended that such equivalents include both currently known equivalents as well as equivalents developed in the future, i.e., any elements developed that perform the same function, regardless of structure. Thus, the scope of the present invention is not intended to be limited to the exemplary aspects shown and described herein. Rather, the scope and spirit of the invention is embodied by the appended claims.

Claims (14)

1. A physiological communications receiver removably securable to the skin of a subject, the receiver comprising:

a housing;

a power source secured within the housing;

a processing unit electrically coupled to the power source and secured within the housing; and

at least two electrodes electrically coupled to the processing unit and secured to a perimeter of the housing such that the electrodes will be in contact with the skin of the subject,

wherein the processing unit is configured to receive data encoded in the form of an alternating current conducted through the subject's body tissue in a frequency range of 3kHz to 300kHz, wherein the at least two electrodes are configured to detect a differential voltage therebetween that corresponds to the alternating current conducted through the subject's body tissue between the at least two electrodes, and wherein the alternating current is generated by a device internal to the subject.

2. The receiver of claim 1, wherein the processing unit is configured to also receive the encoded physiological information in the form of a physiological signal of a frequency in the range of 0.5Hz to 150Hz that is electrically conductive through the subject's body tissue, and wherein the physiological signal is associated with a physiological function of the subject.

3. The receiver of claim 2, further comprising a communication module electrically coupled to the processing unit, wherein the communication module allows wireless communication between the receiver and a device external to the subject such that the receiver can provide physiological information to the device external to the subject.

4. The receiver of claim 3, wherein the communication module is configured to communicate using a frequency hopping spread spectrum communication protocol.

5. The receiver of claim 2, further comprising a communication module electrically coupled to the processing unit, wherein the communication module allows wireless communication between the receiver and a device external to the subject, such that the receiver can provide control information to the device external to the subject, and wherein the control information is derived from data encoded in alternating current provided with the device internal to the subject.

6. The receptacle according to claim 5, wherein the device external to the subject is a control device associated with a drug delivery system comprising a drug product and capable of varying a delivered dose of the drug product.

7. The receiver of claim 6, wherein the drug delivery system comprises a fluid containing unit having a chamber configured to contain a fluid and a piston secured to the fluid containing unit, wherein the piston is controlled by the control unit based on control information provided by the receiver.

8. The receptacle according to claim 7, wherein the fluid containing unit is an intravenous bag containing fluid.

9. The receiver of claim 1, further comprising a power management module electrically coupled to the power source and the processing unit such that the power management module controls power output from the power source to the processing unit, and wherein the receiver uses a beacon switching module configured to identify an alternating current of encoded data and generate a signal such that the power management module switches the processing unit from an inactive state to an active state when the beacon switching module identifies the alternating current of encoded data.

10. The receiver of claim 9, wherein the power management module comprises:

a high power operation module that controls high power output from the power supply to the processing unit when the processing unit is in an active state;

an intermediate power operation module that controls intermediate power output from the power supply to the processing unit when the processing unit is in an active and inactive state; and

a low power operation module that controls low power output from the power supply when the processing unit is in an inactive state.

11. The receiver of claim 10, wherein the beacon switching module is configured to signal the intermediate power operating module to allow the processing unit to switch to the active inactive state.

12. The receiver of claim 9, wherein the power management module comprises the beacon switching module, and wherein the beacon switching module comprises:

a counter;

a beacon signal generator coupled to the counter for generating a plurality of beacon signals; and

a memory unit coupled to the beacon signal generator, wherein the memory unit is configured to store an algorithm, and wherein the beacon signal generator is configured to execute the algorithm to determine a time lag between each of the plurality of beacon signals.

13. The receiver of claim 1, further comprising:

a router coupled to the power supply; and

a multi-purpose connector electrically coupled to the router, wherein the router is configured to control an electrical connection path between a device external to the subject and the power source, and wherein the multi-purpose connector is configured to connect to the receiver and a device external to the subject.

14. The receiver of claim 13, wherein the electrical signal of the device external to the subject is from an external power source that charges a power source in the receiver.