HK1152162A - Transbody communication systems employing communication channels - Google Patents

Description

Through body communication system using communication channel

Cross Reference to Related Applications

In accordance with 35u.s.c. § 119(e), the present application claims priority to the filing date of the following U.S. provisional patent applications: serial No. 60/990562 filed on day 11-27 of 2007, serial No. 60/990567 filed on day 11-27 of 2007 and serial No. 60/990572 filed on day 11-27 of 2007; these applications are incorporated herein by reference for all purposes.

Background

Communication plays an important role in today's world. Transbody communication is for example increasingly used in medical applications. The term "through-body communication" generally refers to the transmission of a signal from an in vivo (in vivo) location to a receiver location (e.g., a second in vivo location), the receiver location being associated with a body (body), or the like, that is extracorporeally.

However, communications may be susceptible to errors. In particular, noisy (noise) transmission environments may distort and corrupt communication data. Noisy transmission environments include the body. In addition, the communication device may be subject to errors in signal generation and measurement related to the communicated data.

Moreover, various devices and combinations of devices may require high power consumption, resulting in relatively short life cycles of the devices within the body. Such short life cycles may lead to replacement surgery and other inconvenient, expensive and/or high risk procedures.

As such, there is a continuing need for error-free data and accurate communications provided via persistent devices. Of particular interest is the development of communication channels that can be readily deployed to reliably communicate information from an intra-body location to a receiver located in or in close physical proximity to the body.

Disclosure of Invention

The system comprises: an in-vivo transmitter to transmit the encoded signal; a transbody function module to facilitate communication of the encoded signal; and a receiver to receive the encoded signal to at least facilitate accurate trans-body communication and save power consumption. The system further includes at least one of a beacon (beacon) function, a frequency hopping function, and a collision avoidance function. Related methods and apparatus are also provided.

Drawings

Fig. 1 illustrates a communication environment including a wearable communication system having a wearable functional module.

Fig. 2 illustrates the transbody function module of fig. 1 in more detail.

Fig. 3A illustrates a beacon wakeup (wakeup) module that provides a listening (sniff) period that is longer than a transmission signal repetition period.

Fig. 3B illustrates a beacon wakeup module that provides short but frequent listening periods and provides long transmission packets.

Fig. 4A illustrates a resonant narrow band analog circuit.

Fig. 4B illustrates a classical power detection circuit.

Fig. 5 illustrates a beacon function with long-term continuous wave tones.

Fig. 6 illustrates a beacon function in which a beacon is associated with one frequency and a message is associated with another frequency.

Fig. 7 illustrates a beacon function associated with a two beacon scheme.

Fig. 8 illustrates a beacon function associated with a beacon signal where frequency is a function of time.

Fig. 9 also illustrates a beacon function associated with a beacon signal where frequency is a function of time.

Fig. 10 illustrates a collision avoidance function with one collision avoidance technique.

11A-11D illustrate a collision avoidance function with another approach to collision avoidance.

Fig. 12A and 12B illustrate a collision avoidance function with a technique for detecting low amplitude signals in a noisy environment.

Detailed Description

A transbody communication system employing a communication channel is provided. The various aspects facilitate accurate communication in noisy environments and provide enhanced power saving features. More specifically, the various aspects may be associated with a transbody communication system, such as an in-vivo transmitter and signal receiver (sometimes referred to herein as a "receiver") associated with the body. The receiver may be configured to receive and decode signals from the in-vivo transmitter. Various aspects of the invention feature employing a particular communication channel having a transbody function, e.g., via a transbody function module. Related methods are also provided.

The invention can be widely applied to the medical and non-medical fields. The medical field includes, for example, transbody communication systems associated with various medical and therapeutic devices (e.g., cardiac devices, ingestible devices, etc.). Non-medical areas include, for example, body related devices, such as gaming devices that incorporate physiological sensing functionality, and the like.

Fig. 1 illustrates a communication environment 100 including a through-body communication system 102. The transbody communication system 102 includes, for example, an in-body transmitter 104, a transbody function module 106, and a receiver 108. In various aspects, the in-vivo transmitter 104 transmits a signal (e.g., an encoded signal) to the receiver 108 via the through-body communication module 104, as described in detail below.

1.0 in vivo emitter

The implementation of the in-vivo transmitter may vary widely. In general, in-vivo transmitter 102 comprises any in-vivo device capable of transmitting a signal (e.g., an encoded signal).

In various aspects, the in-vivo transmitter 102 may be associated with various devices (e.g., cardiac-related devices, ingestible devices, neurostimulation-related devices), drugs, and so forth. The in-vivo transmitter 102 may be fully or partially integrated with such devices, drugs, etc., for example.

One example of such a device is a pharmaceutical informatics-supporting pharmaceutical composition (composition) described in PCT application serial number US 2006/016370. Another example is the Ingestible Event Marker (IEM) and personal receiver described in U.S. provisional patent application serial No. 60/949223. Yet another example is the intelligent parenteral device described in PCT/US 2007/15547. Yet another example is the intelligent implantable fluid delivery device described in U.S. provisional patent application serial No. 60/989078. Other examples include implantable physiologic event recorders described in U.S. patent nos. 5919210, 5989352, 6699200, and 6895275; various systems and methods are described in PCT application WO 2006/116718. Other examples include PCT application Ser. Nos. PCT/US2007/022257, PCT/US07/24225, PCT/US08/56296, PCT/US2008/56299 and PCT/US08/77753, and US provisional application Nos. 61/034085 and 61/105346. Each of the foregoing is incorporated by reference herein in its entirety. +

The signals transmitted by the device generally include any signals, data, identifiers (identifiers) and their representatives, etc. The signal comprises an encoded signal, e.g. encoded at the source and decoded at the destination. Examples of signals include identifiers of drugs, parenteral delivery devices, ingestible event markers, and the like (supra).

2.0 wearable functional Module

Signals may be transmitted from in-vivo transmitter 104 to receiver 108 via transbody function module 106. Transbody function module 106 typically uses protocol(s), communication channels, etc., that can facilitate accurate reception of signals, data, etc., and/or facilitate low power consumption. Such a transbody function module 106 includes a beacon function, a frequency hopping function, and a collision avoidance function. Each of the foregoing functions is discussed in detail below.

In various aspects, one or a combination of the transbody function module 106 and/or its sub-modules (described below) may be implemented as: software, such as digital signal processing software; hardware, such as circuitry; or a combination thereof.

The communication medium used for transmission may vary. In one aspect, the patient's body may be used as a conductive medium for signals. As such, signals are conducted between the in vivo transmitter and receiver via bodily fluids or the like. In another aspect, the signal is communicated via Radio Frequency (RF) transmission. Those skilled in the art will appreciate that other communication media are possible.

Fig. 2 illustrates the transbody function module 106 of fig. 1 in more detail. In various aspects, the transbody function includes a beacon function 200, a frequency hopping function 202, and a collision avoidance function 204.

2.1 Beacon function Module

Various aspects may employ a beacon function module 200. In various aspects, the beacon function module 200 may employ one or more of the following: beacon wakeup module 200A, beacon signal module 200B, wave/frequency module 200C, multi-frequency module 200D, and modulated signal module 200E.

Beacon function 200 may be associated with beacon communications, e.g., a beacon communications channel, a beacon protocol, etc. For purposes of this disclosure, a beacon is typically a signal (sometimes referred to herein as a "beacon signal") that is transmitted as part of a message or used to enhance a message. Beacons may have well-defined characteristics, such as frequency. Beacons can be easily detected in noisy environments and can be used as triggers to a listening circuit, such as those described above.

In one aspect, the beacon function module 200 may include a beacon wakeup module 200A having a wakeup function. The wake-up function generally includes a function that operates in a high power mode only during certain times, such as short periods for certain purposes (e.g., to receive signals, etc.). An important consideration with respect to the receiver portion of the system is that it has low power. This feature may be advantageous in an implanted receiver to provide a power source that is small in size and maintains long-term operation from a battery. The beacon wakeup module 200A may achieve these advantages by having the receiver operate in a high power mode for a very limited period of time. Such a short duty cycle may provide optimal system size and energy draw characteristics.

In practice, the receiver may "wake up" periodically and be at low power consumption to perform a "snoop function" via, for example, a snoop circuit. For purposes of this application, the term "listening function" generally refers to a short, low power function for determining whether a transmitter is present. If the listening function detects a transmitter signal, the device may transition to a higher power communication decoding mode. If no transmitter signal is present, the receiver may return, for example, to an immediate return to sleep mode. In this way, energy is saved during relatively long periods when there is no transmitter signal present, while high power capability remains available for efficient decoding mode operation during relatively few periods when there is a transmit signal present.

Several modes and combinations thereof may be available to operate the snoop circuit. By matching the needs of a particular system with the snoop circuit configuration, an optimized system can be obtained.

Fig. 3A illustrates a beacon wakeup module 200A in which the listening period 300 is longer than the transmission signal repetition period 302. The time function is provided on the x-axis. As shown, the transmit signal is repeated periodically and so is the listen function. In practice, the listening period 300 is typically longer than the transmission signal repetition period 302. In various aspects, there may be relatively long periods of time between listening periods. In this way it is ensured that the listening function, e.g. implemented as a listening circuit, causes at least one transmission to take place each time the listening circuit is active.

Fig. 3B illustrates the beacon wakeup module 200A, where short but frequent listening periods 306 and long transmission packets 308 are provided. The sniffer circuit will be active at some point during the transmission time. In this way, the listening circuit may detect the transmitted signal and switch to a high power decoding mode.

A further beacon wakeup aspect is to provide a "listen" function in a continuous mode. This aspect of the transbody beacon transmission channel may take advantage of the fact that total energy consumption is the product of average power consumption times time, as compared to the approach provided above. In this regard, the system can minimize the total energy consumption by having very short active periods, in which case the active periods are averaged down to fractions. Optionally, low continuous listening activity is provided. In this case, the configuration provides sufficiently low power so that the transmit receiver operates continuously and the total energy consumption is at an appropriate level for the particular system parameters.

The system may be passive. Two examples of circuit implementations are provided.

Fig. 4A illustrates a resonant narrowband analog circuit 400 that includes an input antenna 402, an inductor 404, and a capacitor 406. In various aspects, the resonant narrowband analog circuit 400 can have a high impedance. An LC resonator may be provided that is tuned to the frequency of the transmitted signal. The voltage across the LC circuit may be measured and flow into the comparator. The gate may be triggered when the voltage measurement exceeds a certain value. The circuit then enters a high power mode.

Fig. 4B illustrates a classical power detection circuit 408. The power detection circuit 408 may be those known in the art, such as those used in AM radios to give a received optical signal indicative of a radio signal. In one aspect, the power detection circuit 408 is an LC resonant circuit, i.e., a tank circuit. The LC tank circuit 'rings up' when a signal at the LC resonant frequency is present. Because the circuit has a high Q, its voltage increases sharply. The voltage is rectified by a diode. When this voltage exceeds a threshold set by Vref, the comparator is triggered. The comparator informs the microprocessor of the presence of the signal/circuit and directs it to enter a high power mode.

Each of the above circuits may be very low powered and may include only passive components, except for the comparator. The comparator may also have a very low power. Each circuit may operate continuously. Each circuit may inform the microprocessor when a transmitter is present (e.g., a signal is transmitted) to enter a high power mode. For each of these circuits, a useful prerequisite may be a well-defined transmitter frequency.

One type of beacon signal associated with the current transbody communication channel is a continuous wave, single frequency tone. In this case, when the circuit in fig. 4A or 4B is tuned to the correct frequency, consecutive single-frequency tones trigger either of them.

Beacon signal module 200B may provide digitally detected beacon signals as shown in fig. 3A or 3B. This can be done by sampling the beacon signal with an a- > D converter. The beacon signal is placed in a digital processing system. The beacon signal is detected by a single frequency tone having strong characteristics.

An example of such a system is provided in fig. 5.

Fig. 5 illustrates a beacon function with a long period of continuous wave tones, e.g., via wave/frequency module 200C. In one aspect, the beacon signal is comprised of a continuous wave tone for a long period of time. This continuous wave tone has both modulated and unmodulated portions that hold information. In this frequency domain, there is typically a well-defined segment of frequencies. This modulation tends to smear the spectrum (smear). This portion of the wave tone serves as a beacon. It has a single tone in the frequency domain and is easily discernible in spectrograms.

Any of the methods shown above may detect a single frequency tone. This frequency tone alert processing circuit: a message is about to come. It then moves to a decoding mode so that the message can be understood. In fig. 5, this is shown as one packet.

Fig. 6 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). Such a configuration may be advantageous, for example, when the system is processing multiple transmission signals. The solid line represents the beacon from transmission signal 1. The dashed line represents the beacon from transmission signal 2. In various transmission scenarios, the beacon transmitting signal 2 may overlap with the beacon transmitting signal 1, as depicted.

Message signal 1 and message signal 2 may be at different frequencies than their respective beacons. One advantage may be that the beacon from transmission signal 2 does not interfere at all with the message from transmission signal 1 even if they are transmitted simultaneously. In contrast, if an approach were taken in the example shown in fig. 5, the beacon from the second transmission signal would likely obscure the message from the first transmission signal (obscure).

In this case, the beacon channel is a well-defined frequency band. The message is provided in a channel in which data is actually transmitted. Interference between different messages in the message channel can be handled by collision avoidance as described below. Although fig. 6 is shown with two transmitters, it will be apparent to one of ordinary skill in the art that the system can be modified to extend it to more transceivers. The requirements of a particular system may, to some extent, dictate the particular architecture of the system.

Fig. 7 illustrates beacon functionality associated with a two beacon scheme (e.g., beacon 1 and beacon 2). In this case, there is a well-defined mathematical relationship between the frequency of the beacon channel and the frequency of the message channel. If the beacon is a continuous wave signal or a signal with very simple modulation, it would be a simple matter to detect the carrier frequency of the beacon signal. In one case, for example, the beacon is at frequency 2f and the message is at frequency f, as shown in fig. 7. In this case, the value of f may be determined from the beacon channel. As a result, if the message is to be demodulated, the frequency is known exactly.

This aspect may be used, inter alia, to resolve frequency uncertainty. This approach may provide a workable system for message channel modulation without a well-defined carrier frequency.

One example of such a message channel modulation is spread spectrum modulation. Attempting to determine the frequency of the spread spectrum modulation by itself and by itself can be difficult because there are no well-defined peaks in the spectrum. However, having the beacon channel accompany the message channel with a well-defined mathematical relationship allows the message channel frequency to be accurately determined from the beacon channel. The message channel may then be demodulated based on this information.

The beacons are described above as being continuous single frequency tones. However, in another aspect, the beacon may have a simple modulation thereon. Examples of such aspects are the use of on-off keying (OOK) or simple frequency modulation. In various aspects, a Frequency Shift Keyed (FSK) two-tone beacon signal generated by two different division ratios of a master silicon oscillator has particular utility. This may provide a unique spectral signature and the frequency ratio of the two tones is invariant to frequency drift of a silicon oscillator, such as an IEM silicon oscillator. The frequency ratio metric may provide a high probability that the detected signal originates from a preferred source device (e.g., IEM). This approach gives the beacon a unique feature that can be uniquely identified with other interfering signals. In this way, the system does not run the risk of confusing the beacon with other jammers (jammers) from the environment. One of the main properties of frequency is that it stands out uniquely and still has a well-defined mathematical relationship in terms of carrier frequency.

Fig. 8 illustrates a beacon function associated with a beacon signal where frequency is a function of time. One problem that may occur with transmitters is that the carrier frequency is set by a silicon oscillator and not by a crystal oscillator. This introduces a large uncertainty into the characteristic frequency. The determination of this frequency can be a major challenge in terms of both decoding the packet and detecting the beacon frequency.

The circuitry provided in fig. 4A and 4B provides an example of such an approach. If these circuits have a high power (Q), the frequency uncertainty can cause the beacon to fall outside of the response function of the listening circuit. Thus, as shown in fig. 8 and 9, another type of beacon may be employed. The frequency 700 is ramped (ramp) over a certain range to provide a message. Two narrow band filters are provided. Signal from f_{Height of}Is ramped to f_{Is low in}. The two narrowband filters are tuned to frequencies f1 and f2, for example, via the multifrequency module 200D. Frequencies f1 and f2 fall at f_{Height of}And f_{Is low in}In the meantime.

The output of the filter at f1 shows no power, a power spike as the beacon frequency ramps through f1 at time t1, and then no power. Similarly, the output of the filter at f2 will show no power, a power spike as the beacon frequency ramps through f2 at time t2, and then no power.

By establishing a timing window comparator, an analog snoop circuit is employed that triggers on the time difference between t1 and t 2. This may be implemented digitally or in an analog way. In this case, when the circuit is set at time t1, if time t2 falls within some defined window t0, it indicates that a signal is present.

This ramping is a very unique feature. The frequency f1 start (ringing) will be detected and (by way of example) a 10ms later f2 start is detected. If these two events occur within a defined time interval t0 plus or minus t', it indicates that a signal is present. The wake-up circuit is then triggered. The resulting design provides very low power analog circuitry. An important application of this circuit is the determination of the frequency as shown in fig. 8.

The beacon may be modulated, for example, via modulated signal module 200E to ensure that its characteristics will be unique. One way of this approach is to have the beacon alternate between two frequencies. When such an alternation is detected with a well-defined frequency difference and a well-defined time period, the confidence level that a beacon has been detected instead of a certain background signal may be high. Similar results can be obtained with on-off keying in a frequency modulation keying approach.

Any standard modulation technique may be applied to the beacon to give it unique characteristics. In various aspects, the data may be imprinted on the beacon to avoid it being confused with any other signal. In various aspects, the snoop circuit triggers only turning on the beacon.

There are a variety of beacon approaches that can be used to avoid interference. In the idea related to fig. 6, if there are two beacons transmitted simultaneously, the transmitter 1 may have beacons at multiple frequencies via the multi-frequency module 200D to avoid the influence from interference. In a related approach, this aspect is simply to have the beacons at different frequencies to avoid contention between beacons.

In various aspects, the frequency of the beacon and data channels is invariant to frequency errors in the ingestible event marker system to provide additional assurance of detection of the encoded signal.

2.2 frequency hopping function module

Various aspects may employ a frequency hopping function. The frequency hopping function 202 may be associated with a particular communication channel(s), frequency hopping protocol, and so forth. As such, the various aspects may utilize one or more frequency hopping protocols. For example, the receiver may search for a specified frequency range in which the transmission may fall. When a single correct decode is obtained, the in-vivo transmitter performs its task of transmitting its digital information payload to the receiver.

The uncertainty in the transmission frequency, such as provided by random frequency hopping via the randomization module 202A, may yield a number of benefits. One such benefit may be, for example, ease of implementation on a die. For illustration, the intra-body transmitter carrier frequency oscillator may be an inaccurate free running oscillator, which is easily implemented on a small portion of a 1mm die. Accuracies on the order of +/-20 are easily tolerated. This is because the receiver employs a frequency search algorithm.

Another such benefit may be extended battery life. To illustrate, the probability of a transmitter transmitting on a clear channel that can be received by a frequency agile receiver may be significantly enhanced due to random frequency hopping over the transmitter battery life, e.g., three to ten minutes.

Yet another benefit may be minimized collision events in high volume environments. To illustrate, the probability of collision is minimized when multiple in-vivo transmitters, e.g., ingestible event markers, are potentially transmitting simultaneously, such as where multiple ingestible event markers are ingested simultaneously (or in close temporal proximity). In other words, without the frequency hopping function, there may be a high probability that a similar batch of ingestible event markers will transmit on the same (or nearly the same) frequency, resulting in multiple collisions.

In certain aspects, the useful frequency spectrum for volume conduction applications varies from about 3kHz to 150 kHz. Through detailed animal studies, it has been observed that the above-described in-vivo transmitter, which in some environments has a received signal level in the range of 1 to 100 μ V, may 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 frequency hops a narrowband transmit signal (e.g., a modulated signal such as a Binary Phase Shift Keying (BPSK) signal or an FSK signal) output on each transmission.

2.3 Collision avoidance function Module

Various aspects may employ a collision avoidance function. The collision avoidance functionality may be associated with a particular communication channel(s), collision avoidance protocol, and so forth. As such, various aspects may utilize various collision avoidance protocol techniques associated with a particular communication channel(s). Collision avoidance techniques may be particularly useful, for example, in environments where there are two or more in-vivo transmitters, e.g., where an individual ingests multiple IEMs. In such an environment, if each in-vivo transmitter continuously transmits its signal, the transmission of one may obscure the transmissions from all other in-vivo transmitters. As a result, detection signal failure may increase significantly.

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

One such approach employs multiple transmission frequencies. By using frequency selective filtering, transmitters broadcasting at f1 can be distinguished from transmitters broadcasting at f2 even if they are transmitting at the same time. An alternative to this approach is illustrated in fig. 9.

Fig. 10 illustrates a first collision avoidance technique, e.g., via transmitter module 204A, with transmitter 1 broadcasting on f 1. Transmitter 2 broadcasts at f 2. A receiver and two band pass filters are provided, for example, via a plurality of band pass filter modules 204E. Band pass filter 1 is sensitive to f1 and band pass filter 2 is sensitive to f 2. Once the signals from the transmitters (e.g., the two IEMs associated with pill (pill)1 and pill 2) pass through their respective band pass filters, the signals go to a demodulator. In various aspects, these demodulators may be implemented as separate analog circuits or in the digital domain. In this way, collisions may be avoided.

FIGS. 11A-11D illustrate another collision avoidance approach. In various aspects, the particular communication channel(s) may employ duty cycle modulation, e.g., via duty cycle modulation module 204B, wherein the transmitter need not transmit all the time. If two transmitters, e.g., xmtr1 and xmtr2, do not transmit at the same time, they will not interfere with each other. For example, if two transmitters with low duty cycles (such as 10% time broadcast and 90% time off) are used, there is only a 20% chance that the signals will overlap each other in probability. In this way, collisions may be avoided.

Referring to fig. 11A, there is a transmitter 1, e.g., xmtr1, that is only 10% of the time on. There is a transmitter 2 such as xmtr2 that is also only 10% of the time on. Of course, there is some probability that they will be transmitted simultaneously. However, the probability can be controlled by varying the duty cycle and the frequency spread. As a result, if the two transmission periods are slightly different, they will reach and leave interference (see in and out of interference other) with each other. The overlap may be controlled, however, by dithering the duty cycle and frequency spreading, e.g., via the dither (dither) module 204F and the spread spectrum module 204D, respectively. In this way, collisions that would otherwise occur can be avoided.

Referring to fig. 11B, dashed line emitter xmtr2 has a slightly shorter period than solid line emitter xmtr 1. Even if the transmitters start broadcasting at the same time, after some number of transmissions, the transmitters are not aligned with each other. As a result, they are now different from each other and collisions that would otherwise occur can be avoided.

Referring to fig. 11C, a similar effect can be obtained by having an extension of the oscillator frequency. In practice, the silicon oscillators used for these transmitters have a spread of a few percent in frequency. A 1% difference in frequency means: after 100 transmissions, the two oscillators 1008, 1010 that begin to be in phase with each other are no longer in phase with each other. Aspects may be based on a frequency distribution or the frequencies may also be programmed to be distinct, e.g. with a certain period range. Noise that dithers the frequency of the voltage controlled oscillator may also create this frequency spread.

Referring to fig. 11D, the retry period is randomized. In this example, xmtr1 is factory broadcast and then waits for some random period of time before broadcasting again. Xmtr1 then waits another random period of time before broadcasting again, and so on. Xmtr2 begin broadcasting at the same time. However, in this case it waits a random time before the next transmission and another random time before the next transmission, and so on. In this way, the probability of two transmitters broadcasting simultaneously can be controlled by affecting the standard deviation of the retry period.

This approach may be based on a pseudo-random sequence that is pre-programmed into the chip. It may also be based on a true physical random number generator (thermal noise) or on a serial number on the chip. Since each transmitter has a unique serial number, some of the lower bits of the serial number can be used to program this randomization time, either directly or through the use of a linear shift register.

Additional aspects of the transbody transmission channel use spread spectrum transmission to modulate the transmitted message. This approach may be direct spread spectrum or frequency hopping spread spectrum. By way of example, any of the Code Division Multiple Access (CDMA) technologies developed for cellular telephones may be employed in this universe that allows multiple cellular telephones to broadcast on the same frequency without interference. This aspect may also be based on any known Code in the spread spectrum, such as the Gold Code or Kasami Code.

Probabilistically addresses the challenge to be met. The code is chosen such that there are enough cases: the probability of two transmitters with the same code broadcasting simultaneously is sufficiently small. This approach is linked to the idea of using beacons to find the carrier frequency, since spread spectrum transmissions generally do not have a well-defined carrier frequency. The information is determined, for example, from the beacons.

In some applications, it is useful to combine different technologies. Pursuant to an example, extended frequency transmission may be particularly valuable when there is a long duty cycle. In this case, the probability of collision is the probability of a long duty cycle times the probability of spread spectrum. There is no constraint on the combining technique.

In the calculations, it was shown that the duty cycle is very suitable for two or more transmitters operating simultaneously. However, for some applications, the duty cycle method fails when there are more than five transmitters providing data in overlapping time frames.

The simplest way to support the duty cycle is to add the retransmission randomization, e.g., via the retransmission randomization module 204C. This effect is made less noticeable immediately by adding a few bits of retransmission randomization. In this respect, the system can easily distinguish between five and ten simultaneous transmissions.

To obtain more than ten transmissions, spread spectrum is an interesting approach. As the system becomes many simultaneous transmitters, even if one has a short duty cycle, the total time of transmission by multiple transmitters becomes a significant portion of the time and collisions become unavoidable.

In systems requiring only a few transmitters, the system design may rely on using simpler approaches, such as long duty cycles. When the frequency of the transmitter is known, multiple transmission frequencies may be employed in a controlled environment. Retransmission randomization works well for three to ten transmitters. Beyond ten transmitters, spread spectrum is one approach that can be taken and it can combine spread spectrum with other techniques.

The plot for a long duty cycle shows that for three simultaneous transmitters there is a probability of approximately 1% that the transmitter is not detected due to a collision. This is during the one minute transmission interval. An important feature of some transmitter systems is that the transmitter has a limited lifetime. In systems where the transmitter has a very long lifetime, these problems may not exist.

For other kinds of implanted sensors, there are still important considerations for power consumption. If the system must wait an hour before a window is available that is clear enough for the transmitted signal, the transmitter is using power for that entire time.

Another possibility is presented when the system has more complex transmitters. The transmitter may listen to a silent channel, e.g. wait until it does not hear anything to transmit and then transmit.

The spread spectrum approach is quantifiable depending on how many different codes are used. When the Kasami code set is used, there are 32000 different codes. In this case, the probability of two transmitters transmitting on the same code is 1/(32000)². The probability rises geometrically with the number of emitters. Even if nothing is done to select transmitters with different codes and depending on the randomization of the code selection, it supports dozens (if not hundreds) of transmitters.

In certain aspects, a receiver of the system is configured to selectively receive signals in silent portions of a given spectrum. Fig. 12A illustrates aspects for addressing the problem of detecting low amplitude signals in noisy environments. One way to solve this problem is to find silent places in the noise spectrum. The detector of the receiver is programmed to this frequency band. The transmitter periodically broadcasts in this frequency band.

Fig. 12A and 12B illustrate techniques for detecting low amplitude signals in noisy environments. Referring to fig. 12A, in the case where the receiver is looking for the noise spectrum, the power is a function of frequency. There are noise zones, silence zones, followed by noise zones. The broadcast is provided in the silent region because there is the least amount of interference in that region.

In fig. 12B, transmission is performed at a plurality of different frequencies, e.g., in a ramping scheme. In various aspects, other schemes, such as frequency hopping or random schemes, may be used. Typically, the chosen scheme will densely cover the frequency band of interest. In practice, the transmitter will eventually jump into and eventually transmit in the silent band. By having the receiver listen only in the silent band, there is a good chance of receiving/decoding the signal due to excellent signal-to-noise ratio (SNR).

The above configuration, in which the receiver is employed to receive only the silent bands, is not limited to systems having collision avoidance channels as described elsewhere in this application. Instead, a receiver as described in any of the following applications may be configured to receive only silent channels: PCT application Ser. No. US2007/024225, filed on 19.11.2007 and entitled "Active Signal Processing Personal Health Signal Receivers"; WO 2006/116718; 60/866581, respectively; 60/945251, respectively; 60/956694, 60/887780, and 2006/116718; the disclosures of these applications are incorporated herein by reference.

To illustrate some of the foregoing concepts, in one aspect a transmission is decomposed into two channels. The first channel is used to broadcast data. A one or two percent duty cycle is performed. Immunity to collisions is enhanced by randomizing the rebroadcast rate. The second channel is used to broadcast a wakeup beacon. A one or two percent duty cycle is performed. The packet rate is in the 10 millisecond range. When collisions are not of interest, the beacon transmissions are short, in the range of 100 to 200 microseconds. The beacon and the data channel carrier are generated from the same oscillator, so the data carrier can be calculated from the beacon. The receiver will turn on every 10 to 30 seconds for a duration of 10 milliseconds. If a beacon is observed, the receiver will remain on to perform full demodulation and decoding. Otherwise, the receiver will go back to sleep.

In certain aspects, the above system is modified to include frequency dithering to packet interval dithering.

In certain aspects, the above system is modified to include a longer duration transmission of 16 carrier periods of 25kHz (640 microseconds), 1-2% duty cycle. This is consistent with narrow band filter compatibility.

In certain aspects, the above system is modified such that, for example, BPSK or OOK is modulated on a lower channel.

In certain aspects, the above system is modified such that OOK bursts, for example, are modulated on higher beacon channels.

In some aspects, the above system is modified such that a simple multi-dimensional parity code is used for FEC (forward error correction).

3.0 receiver

A signal receiver, sometimes referred to herein as a "receiver," generally includes any device or component capable of receiving, e.g., conductively receiving, a signal via one or more particular communication channels.

An example of such a receiver is the personal receiver described above. Another example of a receiver is described in the following applications: PCT application Ser. No. PCT/US2006/016370 published as WO 2006/116718; PCT application Ser. No. PCT/2007/24225, published as WO 2008/063626; PCT application Ser. No. PCT/US2008/52845, published as US 2008/052845; the disclosures of these applications are incorporated herein by reference.

Various aspects include a moving configuration of a receiver sized to be stably associated with a living subject in a manner that does not substantially affect movement of the living subject. In certain aspects, the receiver has a small size. For illustration, the receiver may occupy about 5cm³Or less (such as about 3 cm)³Or less, including about 1cm³Or less) of the volume of space. In certain aspects, the receiver has a width of approximately from 10mm²To 2cm²Chip size of (2).

Receivers of interest may include both external and implantable receivers.

3.1External receiver

Externally, the receiver may be extracorporeal (ex vivo), i.e. present outside the body during use. The external receiver may be configured in any convenient manner. For example, in certain aspects, the external receiver may be configured to be associated with a desired skin location. As such, in various aspects, the external receiver may be configured to contact a local skin location of the subject. Configurations of interest include, but are not limited to, a patch (patch), a wristband (wrist), a belt (belt), and the like. For example, a watch or belt worn externally and equipped with suitable receiving electrodes may be used as a receiver according to an aspect of the invention. The receiver may provide other communication paths via which the patient or healthcare practitioner can extract the collected data. For example, the implantable collector may include conventional RF circuitry that the physician may communicate with, for example, operating in the 405MHz medical device band. The physician may communicate, for example, via a data acquisition device, such as a wand (wand) or the like.

Where the receiver includes an external component, the component may have an output device for providing, for example, audio and/or visual feedback. Examples include audible alarms, LEDs, display screens, etc. The external component may also include an interface port via which the component may be connected to a computer for reading out data stored therein. According to other examples, the device may be positioned by a fixation strap (harness) worn outside the body and having one or more electrodes attached to the skin at different locations.

In certain external aspects, the receiver may be configured to be in contact with or associated with the patient only temporarily, i.e., instantaneously. For example, the receiver may be associated/attached/in contact when a pill, ingestible event marker, or the like, is actually being ingested.

For illustration, the receiver may be configured as an external device with two finger electrodes or handles. After ingesting a pill supporting pharmaceutical informatics, the patient touches the electrodes or grasps the handle to complete the conductive circuit with the receiver. The signal emitted by the pill's identifier is picked up by the receiver when the signal is emitted from the pill, for example when the pill dissolves in the stomach.

In certain aspects, the external receiver may include a miniaturized electronic component integrated with the electrodes to form a bandage-type patch having electrodes that contact the skin upon application. The bandage-type patch may be removably attached, for example, via an adhesive layer or other construction. Batteries and electronics may also be included. The bandage-type patch may be configured to be positioned on a desired target skin site of the subject, such as the chest, back, sides of the torso, and the like. In these aspects, the bandage circuitry may be configured to receive a signal from a device within the subject, such as a marker from a pharmaceutical composition supporting pharmaceutical informatics, and then relay this information to an external processing device, such as a PDA, smartphone, mobile phone, handheld device, computer, or the like, as described in more detail elsewhere. Bandage-type devices that may be readily adapted for use with the present system include, but are not limited to, those described in U.S. patent No. 6315719, et al, the disclosures of which are incorporated herein by reference.

3.2Implantable receiver

In certain aspects, the receptacle may be implantable, i.e. designed and/or configured for implantation into a subject. Implantation may be temporary or permanent. In these aspects, the receiver is in the body during use. In general, the implantable receiver can maintain function for various periods of time when present in a physiological environment, including high salt, high humidity environments found within the body. The time period includes, for example, several minutes to eighty years. More specific time periods include, for example, one or more hours, one or more days, one or more weeks, one or more months, and one or more years.

For implantable aspects, the receptacle may have any convenient shape, including but not limited to a capsule shape, a disc shape, and the like. The various receivers may have relatively small dimensions. These small dimensions can be obtained, for example, by introducing a rechargeable battery. In one aspect, the rechargeable battery has a life of about two weeks. In another aspect, a rechargeable battery automatically charges a coil in, for example, a patient's bed from various sources. The receiver may be configured to be placed at a plurality of different locations. Examples of locations include, for example, the abdomen, the small of the back, the shoulders (e.g., where an implantable pacemaker is placed), etc.

In some implantable aspects, the receiver is a stand-alone device, i.e., not physically connected to any other type of implantable device. In other aspects, the receiver may be physically coupled to a second implantable device, such as a device that serves as a platform for one or more physiological sensors. Such a device may be a lead such as a cardiovascular lead (lead). To illustrate, a cardiovascular lead may include one or more different physiological sensors, for example, where the lead is a multi-sensor lead (MSL). Implantable devices of interest also include, but are not limited to, implantable pacemakers, neurostimulator devices, implantable loop recorders, and the like.

The receiver may further comprise a receiver element for receiving the signal of interest. The receiver may comprise various different types of receiver elements, wherein the properties of the receiver elements necessarily vary depending on the properties of the signal produced by the signal generating element. In certain aspects, the receiver may include one or more electrodes for detecting the signal emitted by the signal generating element. For the sake of illustration, the receiver device may be provided with two electrodes dispersed at a predetermined distance. The predetermined distance may allow the electrodes to detect a differential voltage. The distance may vary, and in some aspects varies from about 0.1 to about 5cm, such as from about 0.5 to about 2.5cm, for example about 1 cm. In certain aspects, the first electrode is in contact with an electrically conductive body element (e.g., blood), and the second electrode is in contact with an electrically insulating body element (e.g., adipose tissue (fat)) relative to the electrically conductive body element. In an alternative aspect, a receiver utilizing a single electrode is employed. In certain aspects, the signal detection component may include one or more coils for detecting the signal emitted by the signal generating element. In certain aspects, the signal detection component includes an acoustic detection element for detecting the signal emitted by the signal generating element.

The receiver may process the received data in various ways. In some aspects, the receiver simply retransmits the data to the external device, e.g., via 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 visible or audible alarm, transmitting a control signal to an effector located elsewhere within the body, and so forth. In other aspects, the receiver stores the received data for subsequent retransmission to another device or for processing of subsequent data, such as detecting a change in a parameter over time. The receiver may perform any combination of these and/or other operations using the received data

In certain aspects, the data recorded on the data storage element includes at least one, if not all, of the time, date, and identifier (e.g., a globally unique serial number) of each composition administered to the patient. The identifier may be the usual name for the composition or a coded version thereof. The data recorded on the data storage element of the receiver may also include medical record information, e.g., identification information, such as but not limited to name, age, treatment record, etc., of the subject with which the receiver is associated. In certain aspects, the data of interest comprises a hemodynamic metric. In certain aspects, the data of interest includes cardiac tissue properties. In certain aspects, the data of interest includes various physiological metrics or parameters, such as pressure or volume, temperature, activity, respiration rate, pH, and the like.

As outlined above, the receiver may be configured to have a small size. In certain aspects, the desired functionality of the receiver is achieved with one or more integrated circuits and a battery. Aspects of the invention include a receiver having at least one receiver element, for example in the form of one or more electrodes (such as two spaced apart electrodes) and a power generating element (e.g. a battery, wherein the battery may be rechargeable), or the like, as mentioned above. As such, in some aspects, the power generating element is converted to wirelessly receive power from an external location.

Additional elements that may be present in the receiver include, but are not limited to: a signal demodulator, for example, for decoding a signal transmitted from a marker supporting pharmacy informatics; a signal transmitter, for example, 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 such as the receipt of a signal; a preamplifier; a microprocessor, for example, for coordinating one or more different functions of the receiver.

Aspects of an implantable version of the receiver will have a biocompatible housing, two or more sensing electrodes, a power source which may be a primary or rechargeable battery or a power source powered by inductively broadcasting to a coil (broadcase induced to a coil). The receiver may also have circuitry comprising: a demodulator for decoding the transmitted signal; a storage device for recording events; a clock; and a path to travel outside the body. In some aspects, the clock and transfer functions may be omitted. The transmitter may be an RF link or conductive link for moving information from a local data storage device to an external data storage device.

For an external receiver, aspects include a structure having an electrode opposite the skin, a demodulator, a storage device, and a power source. Communication may be wireless or performed over one or more conductive media (e.g., wires, optical fibers, etc.).

In certain aspects, the same electrodes are used for receiving and transmitting signals. One mode may be a watch, which is in conductive contact with the body. To move data from the implant to the watch, current may be sent from the pad and received by the watch. There are a variety of RF techniques that may be employed to facilitate transmission out of the body, such as inductive schemes (protocols) that use coils. Alternatively, an electric field may be employed, for example using insulated electrodes.

In some embodiments, the components or functional blocks of the present receiver are present on an integrated circuit, wherein the integrated circuit comprises a plurality of different functional blocks, i.e. modules. Within a given receiver, at least some (e.g., two or more up to and including all) of the functional blocks may be present in a single integrated circuit in the receiver. A single integrated circuit means a single circuit structure comprising all the different functional blocks. As such, 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 include semiconductor devices as well as passive components) that has been fabricated in the surface of a thin substrate of semiconductor material. The integrated circuit of certain aspects of the present invention may be a hybrid integrated circuit, which is a miniaturized electronic circuit composed of individual semiconductor devices and passive components bonded to a substrate or circuit board.

As described above, the receiver exhibits reliable decoding of the encoded signal even in the presence of a large amount of noise and a low SNR. This functional aspect of the receiver of the present invention may be provided via various schemes. Some such schemes include, for example, coherent demodulation, such as Costas loop demodulation, accurate low-overhead iterative decoding, Forward Error Correction (FEC), and noise cancellation, such as described in PCT application serial No. PCT/US2007/024225, filed on 19.11.2007 and entitled "Active Signal Processing Personal Health Receivers," the disclosure of which is incorporated herein by reference. Other receivers of interest include, but are not limited to, those described in the following applications: WO 2006/116718; 60/866581, respectively; 60/945251, respectively; 60/956694, 60/887780 and WO 2006/116718; the disclosures of these applications are incorporated herein by reference.

Method

Various aspects include, for example: transmitting the encoded signal via an in-vivo transmitter; facilitating communication of signals via the transbody function module; and receiving the encoded signal via a receiver, as previously described.

In one aspect, the method provides a characteristic of the encoded signal, wherein the characteristic optimizes power consumption to facilitate at least one of: spending maximum time in the inactive mode, waking up quickly, and waking up during periods when there is a high probability of a transmitter being present.

Moreover, various aspects may alternatively or optionally include such steps in connection with beacon functionality, such as: facilitating communication of the encoded signals via the beacon function; facilitating communication of the encoded signal via a frequency hopping function; and facilitating communication of the encoded signal via a collision avoidance function. Some functions may include, for example, providing a beacon wake-up function; providing beacon signal functionality; generating a continuous wave, single frequency tone; providing a first frequency different from the data signal at the second frequency; and modulating the encoded signal.

Further, the various aspects can alternatively or optionally include the step of generating random frequency hopping on the narrowband transmitted signal in connection with frequency hopping.

Also, the various aspects may alternatively or optionally include steps related to collision avoidance, such as: transmitting via the first in-body transmitter and the second in-body transmitter at different frequencies; modulating the duty cycle; randomly retransmitting; and spread over the spectrum. Modulating the duty cycle may include dithering the duty cycle and spreading among frequencies. Transmitting at different frequencies may include providing, by different devices, a plurality of band pass filters, wherein respective signals associated with the different frequencies are filtered by respective band pass filters.

Article

Various aspects may include an article comprising, for example, a storage medium having instructions that when executed by a computing platform result in performing a method of providing transbody communication employing a communication channel. The method may comprise, for example, individual steps and/or combinations of steps such as: transmitting the encoded signal via an in-vivo transmitter; facilitating communication of signals via the transbody function module; and receiving the encoded signal via a receiver. Various other steps are previously described.

Further system aspects

In certain aspects, the receiver is part of a body-related system or network of sensors, receivers, and optionally other devices, both internal and external, that provides a variety of different types of information that is ultimately collected and processed by a processor, such as an external processor, which may then provide contextual data about the patient as output. For example, the sensor may be a component of an in-body network of the device that is capable of providing output to an external collector of data, including data regarding pill ingestion, one or more physiological sensing parameters, implantable device operation, and the like. An external collector of data (e.g. in the form of a healthcare web server or the like) then combines the data provided by the receiver with further relevant data about the patient, such as weight, weather, medical record data or the like, and may process this very different data to provide highly specific and contextual patient-specific data.

In certain aspects, the systems of the invention comprise a receiver and one or more pharmaceutical informatics-supporting active agents comprising a composition. Pharmaceutical compositions supporting pharmaceutical informatics are active agents comprising compositions having a marker stably associated therewith. In certain aspects, the composition is split after administration to a subject. As such, in certain aspects, the composition is physically disrupted, e.g., dissolved, degraded, eroded, etc., upon delivery to the body, e.g., via ingestion, injection, etc. The compositions of these aspects are distinguished from devices that are configured to be ingested and undergo substantially, if not completely, transport through the gastrointestinal tract. The composition comprises a marker and an active agent/carrier component, both of which are present in a pharmaceutically acceptable excipient (vehicle).

The identifiers of the compositions may vary depending on the particular aspect and intended application of the composition, so long as they are activated (i.e., turned on) upon contact with the target physiological site (e.g., stomach). As such, the marker may be one that emits a signal when it contacts a target body (i.e., physiological) site. Additionally or alternatively, the marker may be one that emits a signal when interrogated after it has been activated. The marker may be any component or device capable of providing a detectable signal after activation, for example upon contact with a target site. In certain aspects, the marker emits a signal upon contact of the composition with a physiological target site as outlined above. For example, a patient may ingest a pill that generates a detectable signal upon contact with gastric fluid.

The composition includes an active agent/carrier component. By "active agent/carrier component" is meant a composition that can be a solid or a fluid (e.g., a liquid) having an amount, e.g., a dose, of active agent present in a pharmaceutically acceptable carrier. The active agent/carrier component may be referred to as a "dosage formulation".

An "active agent" includes any compound or mixture of compounds that produces a physiological result (e.g., a beneficial or useful result) when contacted with a living organism (e.g., a mammal such as a human). Active agents can be distinguished from components such as excipients, carriers, diluents, lubricants, binders, and other formulating aids (formulating aids), as well as from encapsulating or other protective components. The active agent can be any molecule and binding moiety or fragment thereof that is capable of modulating a biological process in a living subject. In certain aspects, the active agent may be a substance for the diagnosis, treatment or prevention of a disease or a component for use as a medicament. In certain aspects, the active agent may be a chemical substance, such as an anesthetic or hallucinogen, that affects the central nervous system and causes a change in behavior.

An active agent (i.e., a drug) is capable of interacting with a target in a living subject. The target may be a number of different types of naturally occurring structures, wherein the target of interest includes both intracellular and extracellular targets. Such targets may be proteins, phospholipids, nucleic acids, etc., of particular interest. Specific protein targets of interest include, but are not limited to: enzymes such as kinases, phosphatases, reductases, cyclooxygenases, proteases, etc., targets including domains involved in protein-protein interactions (domains) such as SH2, SH3, PTB and PDZ domains, structural proteins such as actin, tubulin, etc., membrane receptors such as immunoglobulins of IgE, cell adhesion receptors such as integrin (integrin), etc., ion channels, transmembrane pumps, transcription factors (transcription factors), signal proteins, etc.

The active agent (i.e., drug) may include one or more functional groups necessary for structural interaction with the target, such as groups necessary for hydrophobic, hydrophilic, electrostatic, or even covalent interactions, depending on the particular drug and its intended target. Where the target is a protein, the drug moiety may include functional groups necessary for structural interaction with the protein (such as hydrogen bonding, hydrophobic-hydrophobic interactions, electrostatic interactions, etc.), and may include at least amine, amide, thiol, carbonyl, hydroxyl, or carboxyl groups, such as at least two of these functional chemical groups.

Drugs of interest may include cyclic carbons or heterocyclic structures and/or aromatic or polycyclic aromatic structures substituted with one or more of the functional groups described above. Also of interest as drug moieties are structures found in biomolecules, including peptides, carbohydrates, fatty acids, steroids, purines, pyrimidines and their derivatives, structural analogs or combinations thereof. Such compounds can be screened to identify those of interest, where various screening protocols are known in the art.

Drugs may be derived from naturally occurring or synthetic compounds that may be obtained from a variety of sources, including libraries of synthetic or natural compounds. For example, a number of approaches are available for the random and directed synthesis of a wide variety of organic compounds and biomolecules (including the preparation of randomized oligonucleotides and oligopeptides). Alternatively, libraries of natural compounds in the form of bacterial, fungal, plant and animal extracts (extracts) are available or readily produced. In addition, natural or synthetically produced libraries and compounds are readily modified by conventional chemical, physical and biochemical means and can be used to generate combinatorial libraries. Known agents may be subjected to directed or random chemical modifications such as acylation, alkylation, esterification, amination (amidification), etc. to produce structural analogs.

As such, drugs can be obtained from libraries of naturally occurring or synthetic molecules (including libraries of compounds produced by combinatorial approaches, i.e., compound diversity combinatorial libraries). When obtained from such a library, the drug moiety employed will have some desired activity demonstrated in an appropriate screening assay for activity. Combinatorial libraries and methods for generating and screening such libraries are known in the art and described in the following patent documents: 5741713, respectively; 5734018, respectively; 5731423, respectively; 5721099, respectively; 5708153, respectively; 5698673, respectively; 5688997, respectively; 5688696, respectively; 5684711, respectively; 5641862, respectively; 5639603, respectively; 5593853, respectively; 5574656, respectively; 5571698, respectively; 5565324, respectively; 5549974, respectively; 5545568, respectively; 5541061, respectively; 5525735, respectively; 5463564, respectively; 5440016, respectively; 5438119, respectively; 5223409, the disclosures of which are incorporated herein by reference.

A broad class of active agents of interest includes, but is not limited to: a cardiovascular agent; pain relief agents, such as analgesics, anesthetics, anti-inflammatory agents, and the like; (ii) a neuroactive agent; chemotherapeutic (anti-tumor) agents; and so on.

As outlined above, the compositions of the invention also comprise a pharmaceutically acceptable excipient (i.e. carrier). Of interest are common carriers and adjuvants (excipients) such as corn starch or gelatin, lactose, dextrose, sucrose, microcrystalline cellulose, kaolin, mannitol, dicalcium phosphate, sodium chloride, and alginic acid. Disintegrants (disintegrants) which are often used in the formulations of the invention include croscarmellose, microcrystalline cellulose, corn starch, sodium starch glycolate and alginic acid.

Further details regarding aspects of pharmaceutical compositions that support pharmaceutical informatics may be found in the following applications: pending PCT application PCT/US2006/16370, filed on 28.4.2006 and entitled "Pharma-information systems"; and U.S. provisional application serial No. 60/807060 entitled "academic Pharma-information systems," filed on 11.7.2006; 60/862925 entitled "Controlled Activation pharmacy-information System" filed on 25.10.2006; and 60/866581 entitled "In-Vivo Transmission Decoder" filed on 21.11.2006; the disclosures of these applications are incorporated herein by reference.

In certain aspects, the system includes an external device different from the receiver (which in certain aspects may be implanted or applied locally), wherein the external device provides multiple functions. Such devices may include the ability to provide feedback and appropriate clinical adjustments to the patient. Such devices may take any of a number of forms. According to an example, the device may be configured to sit on a bed beside the patient, such as a bedside monitor. Other forms include, but are not limited to, PDAs, smart phones, home computers, and the like. The device can read out information described in more detail in other parts of the patent application, such as information generated internally by the pacemaker device or a dedicated implant for detecting pills, both from the medical uptake reports and from the physiological sensing device. The purpose of the external device is to derive data from the patient and input it to an external device. One feature of the external device is its ability to provide medication and physiological information to a remote location, such as a clinician or central monitoring facility (agency), in a form that can be transmitted over a transmission medium, such as a telephone line.

The system of the present invention enables the following dynamic feedback and treatment loops (loops): drug timing and levels are tracked, responses to treatment are measured, and altered doses are recommended based on the physiological and molecular profile of the individual patient. For example, symptomatic heart failure patients take a variety of drugs daily, primarily with the goal of reducing heart load and improving the quality of life of the patient. Treatment relies primarily on (mainstay) including Angiotensin Converting Enzyme (ACE) inhibitors, beta blockers and diuretics. For medical treatment to be effective, patients must adhere to their prescribed regimen and take the required dose at the appropriate time. Various studies conducted in the clinical literature have shown that more than 50% of patients with class II and class III heart failure do not receive guidelines (guideline) recommending treatment, and that only 40-60% of those patients with properly titrated class II and class III heart failure adhere to this regimen. With the present system, heart failure patients can be monitored to let the patients adhere to treatment, and adherence performance can be linked to key physiologic metrics to facilitate treatment optimization by physicians.

In certain aspects, the system of the present invention may be used to obtain an aggregation of information including sensor data and administration data. For example, heart rate, respiration rate, multi-axis acceleration data, something about fluid state, and something about temperature may be combined and an index that informs about the overall activity of the subject may be derived, which may be used to generate a physiological index, such as an activity index. For example, as the temperature rises, the heart rate goes a little up and the breathing rate accelerates, which can be used as an indication that the person is active. By calibrating this, the amount of calories burned by the person at that moment can be determined. In another example, a particular pulse rhythm set or multi-axis acceleration data may indicate that a person is walking up a set of steps, and as such may infer how much energy they are using. In another aspect, body fat metrics (e.g., from impedance data) may be combined with activity indices generated from a combination of measured biomarkers to generate physiological indices useful for managing weight loss or cardiovascular health care programs. This information may be combined with cardiac performance indicators to get a good picture of overall health, which may be combined with medical treatment administration data. In another aspect, it may be found that, for example, a particular drug is associated with a slight increase in body temperature or a change in electrocardiogram. A pharmacodynamic model can be established for drug metabolism and information from the receiver used to substantially fit free parameters into the model to give a more accurate estimate of the levels actually present in the subject's serum. This information can be fed back to the dosage regimen. In another aspect, information from sensors measuring contractions (e.g., using strain gauges) and also monitoring fetal heart rate, which are used as high risk pregnancy monitors, may be combined.

In certain aspects, subject-specific information collected using the system of the invention may be conveyed to a location where it is combined with data from one or more additional individuals to provide a data set that is a composite of data collected from 2 or more (e.g., 5 or more, 10 or more, 25 or more, 50 or more, 100 or more, 1000 or more, etc.) individuals. The composite data may then be manipulated, e.g., sorted, according to different criteria and made available to one or more different types of groups, e.g., patient groups, healthcare practitioner groups, etc., where the manipulation of the data may be such as to limit access to any given group to the types of data that the group may access. For example, data may be collected from 100 different individuals subjected to the same conditions and taking the same medication. The data can be processed and used to develop easy to follow (easy to follow) displays regarding patient compliance with drug dosage regimens and overall health. Patient members of the group can access this information and see how well their compliance matches other patient members in the group and whether they enjoy the benefits that other members are experiencing. In another aspect, physicians may also be authorized to manipulate the composite data to see how well their patients match the patients of other physicians and to obtain useful information about how the actual patient responds to a given treatment regimen. Additional functionality may be provided for groups that are granted access to the composite data, where such functionality may include, but is not limited to, the ability to annotate data, chat functionality, security privileges, and the like.

Computer readable medium and programming

In certain aspects, the system further comprises an element for storing data, i.e. a data storage element, wherein the element is present on an external device such as a bedside monitor, a PDA, a smart phone, etc. Typically, the data storage element is a computer readable medium. The term "computer-readable medium" as used herein refers to any 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 a computer-readable card, such as a PCMCIA card or the like, whether or not such devices are internal or external to the computer. Files containing information may be "stored" on a computer-readable medium, where "storing" means recording information so that it can be accessed and retrieved by a computer at a later date. With respect to computer-readable media, "persistent storage" refers to persistent storage. The persistent memory is not erased by terminating 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 water-based memory. Random Access Memory (RAM) is an example of non-persistent 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 a computer-readable medium. Accordingly, the present invention provides a computer readable medium containing programming for detecting and processing signals generated by the compositions of the present invention, e.g., as described above.

As such, in certain aspects, the system includes one or more of: a data storage element, a data processing element, a data display element, a data transmission element, a notification mechanism, and a user interface. These additional elements may be incorporated into the receiver and/or reside on an external device, such as a device configured to process data and make decisions, forward data to a remote location (which provides such activity), and so forth.

The above system is commented on the communication between the marker and the receiver on the pharmaceutical composition. However, the system is not limited thereto. In a broader sense, the system consists of two or more different modules communicating with each other, e.g. using the transmitter/receiver functionality described above, e.g. using the monopole transmitter (e.g. antenna) structure described above. As such, the above-described marker elements may be incorporated into any of a number of different devices, for example to provide a communication system between two self-powered devices within the body, where the self-powered devices may be sensors, data receiver and storage elements, effectors, and the like. In an exemplary system, one of these devices may be a sensor, while the other may be a communication hub for communicating with the outside world. Aspects of the invention may take many forms. There may be many sensors, many transmitters and one receiver. They may be transceivers so that both can transmit and receive in sequence according to known communication protocols. In certain aspects, the means of communication between two or more separate devices is a monopolar system, such as described above. In these aspects, each of these transmitters may be configured to sequentially transmit high frequency signals into the body using a monopole that pulls charge into and out of the body, which is a large capacitor and conductor. The receiver (monopole receiver) detects the charge in and out of the body at this frequency and decodes the encrypted signal, such as an amplitude modulated signal or a frequency modulated signal. This aspect of the invention has a wide range of uses. For example, multiple sensors may be placed and implanted at various parts of the body, which measure position or acceleration. Rather than connecting wires to a central hub, they may transmit this information over a communications medium.

In the methods of the invention in which the in vivo emitter is a composition that supports pharmaceutical informatics, an effective amount of the composition of the invention is administered to a subject in need of an active agent present in the composition, where "effective amount" means a dose sufficient to produce a desired result, e.g., an improvement in a disease condition or symptoms associated therewith, achievement of a desired physiological change, etc. The amount administered may also be considered a therapeutically effective amount. By "therapeutically effective amount" is meant an amount sufficient to effect treatment of a disease when administered to a subject to treat the disease.

The composition can be administered to the subject using any convenient means capable of producing the desired result, where the route of administration depends at least in part on the particular form of the composition, e.g., as described above. As noted above, the compositions may be formatted into various formulations for therapeutic administration, including, but not limited to, solids, semisolids, or liquids, such as tablets, capsules, powders, granules, ointments, solutions, suppositories, and injections. As such, administration of the composition may be accomplished in a variety of ways, including but not limited to: oral, buccal, rectal, parenteral, intraperitoneal, intradermal, transdermal, intratracheal (intratracheal), and the like. In the form of a pharmaceutical dose, a given composition may be administered alone or in combination with other pharmaceutically active compounds, for example it may also be a composition having a signal generating element stably associated therewith.

The present methods find use in the treatment of a variety of different conditions, including disease conditions. The particular disease state treatable with the present compositions varies with the type of active agent that may be present in the composition. Thus, disease conditions include, but are not limited to, cardiovascular disease, cell proliferative disease such as neoplastic disease, autoimmune disease, hormonal abnormality disease, infectious disease, pain management (pain management), and the like.

Treatment means at least ameliorating the symptoms associated with the disease condition afflicting the subject, where amelioration is used in a broad sense to mean at least reducing the magnitude of the parameters (e.g., symptoms) associated with the disease condition being treated. As such, treatment also includes situations where: wherein the pathological condition, or at least the symptoms associated therewith, are completely inhibited, e.g. prevented from occurring or stopped, e.g. terminated, so that the subject no longer experiences the pathological condition or at least no longer experiences the symptoms that characterize the pathological condition. Thus, "treating" or "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), providing alleviation of the symptoms or side effects of the disease (including palliative treatment), and relieving the disease (resulting in regression of the disease). For purposes of the present invention, "disease" includes pain.

Various subjects can be treated according to the method. Typically, such subjects are "mammals" or "mammalian", where these terms are used broadly to describe organisms in 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 a representative aspect, the subject will be a human.

In certain aspects, the methods described above are, for example, methods of managing a disease condition over an extended period of time, such as 1 week or more, 1 month or more, 6 months or more, 1 year or more, 2 years or more, 5 years or more, and the like. The present methods may be used in conjunction with one or more additional disease management protocols, such as: electrical stimulation-based schemes in cardiovascular disease management, such as pacing schemes, cardiac resynchronization schemes, and the like; lifestyle, such as recipes and/or exercise regimens for various different disease conditions, etc.

In certain aspects, the method comprises adjusting the treatment regimen based on data obtained from the composition. For example, data may be obtained that includes information regarding patient compliance with a prescribed treatment regimen. This data, with or without further physiological data, e.g. obtained using one or more sensors such as the sensor devices described above, may be employed, e.g. as required, together with appropriate decision tools to make a decision whether a given treatment regime should be maintained or modified in some way, e.g. by modifying a medication regime and/or an implantation activity regime. As such, the methods of the invention include methods in which the treatment regimen is modified based on the signal obtained from the composition(s).

In certain aspects, methods of determining the history of an inventive composition comprising an active agent, a marker element, and a pharmaceutically acceptable carrier are also provided. In certain aspects in which the marker transmits a signal in response to interrogation, the marker is interrogated, for example by a wand or other suitable interrogation device, to obtain the signal. The obtained signals are then used to determine historical information about the composition, such as source, chain of custody, and the like.

In other aspects in which the marker is a marker that survives digestion, the method generally includes obtaining a signal generating element of the composition, for example, by acquiring the signal generating element from a subject ingesting the composition, and then determining a history of the composition from the obtained signal generating element. For example, where the signal-generating element comprises a textured identifier (e.g., a bar code or other type of identifier), the textured identifier can be obtained from the subject ingesting the composition and then read to identify at least some aspect of the history of the composition, such as the last known purchaser, additional purchasers in the chain of custody of the composition, the manufacturer, the processing history, and so forth. In certain aspects, this determining step may include accessing a database or similar compilation of stored histories of the compositions.

Utility of

The medical aspect of the present invention provides clinicians with an important new tool in their therapeutic suite: automatic detection and identification of the pharmaceutical agent actually delivered into the body. The application of this new information device and system is multi-fold. Applications include, but are not limited to: (1) monitoring patient compliance with the prescribed treatment regimen; (2) adjusting the treatment regimen based on patient compliance; (3) monitoring patient compliance in a clinical trial; (4) monitoring the use of the controlled substance; and so on. Each of these different illustrative applications is described in more detail below in co-pending PCT application Serial No. PCT/US2006/016370, the disclosure of which is incorporated herein by reference. Additional applications for using the present receiver include, but are not limited to, the following U.S. provisional application serial No.: 60/887780 entitled "Receivers For pharmacy-information Systems" filed on 2/1 of 2007; 60/956694 entitled "Personal Health Receivers" filed on 8, 18.2007; and 60/949223 entitled "Ingestable Event Marker" filed on 11.7.2007, the disclosures of which are incorporated herein by reference.

External member (kits)

Kits for carrying out the methods are also provided. The kit may comprise one or more receptacles of the invention as described above. In addition, the kit may include one or more dosage compositions, such as dosage compositions that support pharmaceutical informatics. The dose of one or more agents provided in the kit may be sufficient for a single administration or multiple administrations. Thus, in certain aspects of the present kit there is a single dose of medicament, while in certain other aspects there may be multiple doses of medicament in the kit. In those aspects having multiple doses of medicament, the medicaments may be packaged in a single container, such as a single tube, bottle, vial, or the like, or one or more doses may be packaged separately so that certain kits may have more than one medicament container.

Suitable means for delivering one or more agents to a subject may also be provided in the present kit. As mentioned above, the particular delivery device provided in the kit is dictated by the particular medicament employed, for example: specific forms of the agent, such as whether the agent is formulated as a solid, semi-solid, liquid, or gaseous form, such as tablets, capsules, powders, granules, ointments, solutions, suppositories, injections, inhalants, aerosols, and the like; and the particular mode of administration, e.g., oral, buccal, rectal, parenteral, intraperitoneal, intradermal, transdermal, intratracheal, and the like. Accordingly, certain systems may include suppository applicators, syringes, i.v. bags and tubes (tubing), electrodes, and the like.

In certain aspects, the kit may also include an external monitoring device, such as described above, which may provide communication with a remote location, such as a doctor's office, central facility, or the like, that obtains and processes data obtained regarding the use of the composition.

In certain aspects, the kit may include an intelligent parenteral delivery system that provides specific identification and detection of a beneficial agent that enters the body either parenterally (beneficiary agent) or by other methods, such as by use of a syringe, inhaler, or other device that administers a drug, such as the device described in co-pending application serial No. 60/819750, the disclosure of which is incorporated herein by reference.

The kit may also include instructions for instructing how to use the components of the kit to carry out the method. The 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, among others. As such, the instructions may be present in the kit as package instructions in the form of a label or the like for the container of the kit or for a component thereof (i.e., associated with the package or sub-package). In other aspects, the instructions are present as an electronically stored data file on a suitable computer readable storage medium, such as a CD-ROM, diskette, and the like. In other aspects, the actual instructions are not present in the kit, but rather provide a means for obtaining the instructions from a remote source, e.g., via the internet. An example of this aspect is a kit that includes a network address from which instructions can be viewed and/or from which instructions can be downloaded. This means for obtaining the instructions is recorded on a suitable substrate just like the instructions.

Some or all of the components of the kit may be packaged in a suitable package to maintain sterility. In many aspects of the present kits, the components of the kit are packaged in kit containment elements, such as cassettes or similar structures, which may or may not be airtight containers, for example, to further maintain the sterility of some or all of the components of the kit, to produce a single, easily handled unit.

It is to be understood that the invention is not limited to the specific aspects described, as these may vary. 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 each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges and are also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the 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, representative illustrative methods and materials are now described.

All publications and patents cited in this specification are herein incorporated by reference as if each individual publication or patent 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. The citation of any publication is for its disclosure prior to the filing date and should not be construed as an admission that the present 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 is 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 drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as "solely," "only," etc., or use of the recitation of claim elements, or use of a "negative" limitation.

As will be apparent to those of skill in the art upon reading this disclosure, each of the individual aspects described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several aspects without departing from the scope or spirit of the present invention. Any described methods may be performed in the order of events described, 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 expressly to aid the reader in understanding the principles of the invention and the concepts contributed by the inventors 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 embodiments of the invention, as well as specific examples thereof, are intended to encompass both structural and functional equivalents thereof. Additionally, 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. Accordingly, 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 (20)

1. A system, comprising:

an in-vivo transmitter to transmit the encoded signal;

a transbody function module to facilitate communication of the encoded signal; and

the receiver is used for receiving the coded signal.

2. The system of claim 1, wherein the transbody function module is selected from the group consisting essentially of a beacon function module, a frequency hopping function module, and a collision avoidance function module.

3. The system of claim 2, wherein the beacon function module comprises at least one element selected from the group consisting essentially of:

the beacon wake-up module is used for providing a beacon wake-up function;

a beacon signal module for providing a beacon signal function;

a wave/frequency module to provide a continuous wave and a single frequency tone;

a multi-frequency module for providing a plurality of frequencies; and

and the modulation signal module is used for providing at least one modulation coding signal.

4. The system of claim 3, wherein a frequency ratio of the beacon and data channels is invariant to frequency errors in the ingestible event marker system to provide additional assurance of detection of the encoded signal.

5. The system of claim 3, wherein the frequency hopping function comprises a random module for providing random frequency hopping on the narrowband transmitted signal.

6. The system of claim 3, wherein the collision avoidance function comprises at least one element selected from the group consisting essentially of:

a transmitter module to provide a first in-body transmitter transmitting at a first frequency and a second in-body transmitter transmitting at a second frequency;

the duty ratio modulation module is used for providing a duty ratio modulation function;

a retransmission randomization module for providing random retransmission; and

and the spread spectrum module is used for providing a spread spectrum function.

7. The system of claim 6, wherein the duty cycle modulation module comprises a dithering module for dithering the duty cycle and a frequency spreading module for spreading the transmission among a plurality of frequencies.

8. The system of claim 6, wherein the transmitter module comprises a multi-bandpass filter module for providing multi-bandpass filtering by different devices, wherein the respective encoded signals are filtered by respective bandpass filters.

9. A method, comprising:

transmitting the encoded signal via an in-vivo transmitter;

facilitating communication of signals via the transbody function module; and

the encoded signal is received via a receiver.

10. The method of claim 9, further comprising:

providing a characteristic of the encoded signal, wherein the characteristic optimizes power consumption to facilitate a receiver in at least one of: spending maximum time in the inactive mode, waking up quickly, and waking up during periods when there is a high probability of a transmitter being present.

11. The method of claim 9, wherein facilitating communication of the signal via the transbody function module comprises at least one of:

facilitating communication of the encoded signals via the beacon function;

facilitating communication of the encoded signal via a frequency hopping function; and

communication of the encoded signals is facilitated via a collision avoidance function.

12. The method of claim 11, wherein facilitating communication of signals via the beacon function comprises at least one of:

providing a beacon wake-up function;

providing beacon signal functionality;

generating a continuous wave, single frequency tone;

providing a first frequency different from the data signal at the second frequency; and

the encoded signal is modulated.

13. The method of claim 11, wherein facilitating communication of the encoded signal via the frequency hopping functionality comprises generating random frequency hopping on the narrowband transmitted signal.

14. The method of claim 11, wherein facilitating communication of the encoded signal via the collision avoidance function comprises at least one of:

transmitting at a first frequency via a first in-body transmitter and at a second frequency via a second in-body transmitter;

modulating the duty cycle;

randomly retransmitting; and

spread over the spectrum.

15. The method of claim 14, wherein modulating the duty cycle comprises dithering the duty cycle and spreading among the frequencies.

16. The method of claim 14, wherein transmitting at different frequencies comprises providing multi-bandpass filtering by different devices, wherein respective encoded signals are filtered by respective bandpass filters.

17. The method of claim 9 in the form of a machine-readable medium containing a set of instructions which, when executed by a machine, cause the machine to perform the method of claim 8.

18. An article, comprising:

a storage medium having instructions that, when executed by a computing platform, cause performance of a method of providing transbody communication employing a communication channel in a living body, the method comprising:

transmitting the encoded signal via an in-vivo transmitter;

facilitating communication of signals via the transbody function module; and

the encoded signal is received via a receiver.

19. The article of claim 18, further comprising:

providing a characteristic of the encoded signal, wherein the characteristic optimizes power consumption to facilitate a receiver in at least one of: spending maximum time in the inactive mode, waking up quickly, and waking up during periods when there is a high probability of a transmitter being present.

20. The article of claim 18, wherein facilitating communication of the signal via the transbody function module comprises at least one of:

facilitating communication of the encoded signals via the beacon function;

facilitating communication of the encoded signal via a frequency hopping function; and

communication of the encoded signals is facilitated via a collision avoidance function.