HK1178469B - Sensor for use in liquid medicament delivery systems - Google Patents

Description

Sensor for use in a liquid medicament delivery system

Technical Field

The present invention relates to a sensor device for use in a liquid medicament delivery system having a microfluidic chamber and an optical detection system, to an infusion pump device and a liquid medicament delivery system having such a sensor device, and to the use of such a sensor device for measuring pressure and/or the presence of air bubbles in a fluidic system.

Background

Devices for automatically releasing liquid medicaments are generally used for patients who have a continuous need for a drug that can be administered by subcutaneous infusion and have a varying need during the course of the day. Specific applications are, for example, specific pain treatments and the treatment of diabetes. In these cases, a computer controlled infusion pump device is used, which can be carried around by the patient and contains a specific amount of liquid medicament in a drug depot. Drug depots typically include enough drugs for one or several days. The liquid medicament is supplied from the drug depot to the body of the patient through a fluid line or an injection needle.

Especially in self-administration of a medicament (e.g. insulin), patients using the medicament in question and self-administering the medicament by means of an infusion pump device tend to emphasize convenience and caution. Therefore, acceptable sizes of such infusion pump devices are limited so as not to be noticeable through dressing and to be as comfortable as possible to carry. In a preferred type of infusion pump device, the liquid medicament is obtained from a flexible container by a downflow pump. The flexible container has the advantage of a smaller volume surplus of the container compared to its capacity, which reduces the manufacturing costs and enables the design of an infusion pump device of smaller overall size.

In the context of liquid medicament administration via an infusion pump device, the sensor device may be used for controlling the dosage, monitoring the correct operation of the system, and for quickly detecting malfunctions and risks, such as a blocked infusion line or tube, an empty container, or a malfunctioning pump system. Typically, the pressure sensor device is disposed in the fluid path downstream of the pump device and upstream of the infusion tube.

Typically, such pressure sensor devices comprise a microfluidic chamber filled with a liquid and fluidly connected to a fluidic system. The chamber is covered by a flexible, elastic membrane, so that the pressure difference between the fluid pressure inside the sensor chamber and the external (e.g. atmospheric) pressure will temporarily deform the membrane. The resulting deflection (deflection) of the membrane can then be measured by suitable means to determine the internal pressure of the fluid system.

A suitable solution for measuring the deformation of the film is optical detection of the reflected light beam of the film. Such pressure sensor devices are disclosed, for example, in "A microfluidic experimental plants with internal pressure measurements," M.J. Kohl et al, Sensors and Actuators A118 (2005), pp. 212-. Fig. 1 schematically shows such a pressure sensor device 6 according to the prior art. The microfluidic chamber 1 connected to the fluidic system comprises a rigid base substrate 11 and a flexible, resilient top cover 12 (e.g. a membrane). The optical detection system 5 is arranged to measure the deformation of the cover film 12 by determining the interaction of the light beam 53a with the cover film 12. For this purpose, a light-emitting device 51 (e.g. a laser diode) directs a light beam 53a at a certain angle onto the surface of the cover film 12, where a light beam 53b is reflected. The pressure difference Δ p between the inner volume 14 of the microfluidic chamber and the external environment acts on the cover membrane 12 and, depending on the pressure difference, deforms the cover membrane 12 to a certain extent 12'. Thus, the angle of the reflected beam changes and the beam is laterally offset. By observing the position of the reflected light beams 53b, 53 b', the deformation of the cover film can be measured, and based on the obtained result, the pressure difference value can be determined.

In order to be able to observe the reflected light beam, the detector in the optical detection system 5 must be designed to be movable, or a plurality of detectors at different positions and different angles must be included in the device according to the prior art. Both of these aspects make such sensor devices expensive and difficult to manufacture.

The flexible, resilient top cover film 12 is quite fragile and therefore susceptible to breakage. A damaged or even destroyed cover membrane would lead to erroneous pressure measurements and/or leakage of the fluid system, both of which are not acceptable. Thus, the top cover film 12 should be protected from mechanical damage and other deleterious environmental effects. At the same time, the flexible cover 12 must remain accessible to the optical detection system 5.

The optical detection system 5 may be arranged within a suitable protective cover of the membrane 12. However, since the fluid system of the liquid infusion pump system including any pressure sensor device is typically designed as a disposable component, this solution is very expensive for hygienic reasons, since any light emitting and receiving device of the detector system 5 will have to be discarded together with the microfluidic chamber.

It is important that the microfluidic chamber of the pressure sensor device is free of bubbles to avoid systematic or random measurement errors. Bubbles in the microfluidic sensor chamber (and more generally anywhere within the fluidic system) reduce the stiffness of the fluidic system and thus delay the response of the sensor to pressure changes that may occur if the fluidic system becomes clogged. The resulting irreproducible measurement error may reduce the dosage accuracy of the infusion pump device and increase the response time to occlusion events.

The presence of air bubbles in the fluid system of the infusion pump device (in particular in the pump system) but also in other components (e.g. the container) poses further problems. If the bubbles remain in the fluid system, they may be administered instead of the liquid medicament, resulting in potentially dangerous dosage errors. Furthermore, for medical reasons, administration of air into a patient's body should generally be avoided.

Another problem with fluid systems, particularly in infusion pump devices, is dead volume in the fluid system. The dead volume cannot be used, which means that it cannot be completely emptied or emptied. Thus, dead volume significantly increases the effective cost per dose, and thus the overall treatment cost, since a certain percentage of the liquid medicament inevitably remains in the fluid system and must be disposed of. This negative cost effect is particularly important for expensive pharmaceutical agents. Furthermore, the relative fraction of a particular dead volume for a given overall library size increases as the absolute library size decreases. Therefore, minimizing dead volume becomes increasingly important as the reservoir size decreases.

In order to avoid air bubbles in the microfluidic chamber when the fluidic system is first filled (so-called priming of the system), the chamber must be filled in a controlled manner. However, this target may be hindered by an uncontrolled orientation of the microfluidic chamber in space during this first filling process, due to the gravitational field resulting in a buoyancy force acting on the gas bubbles. Depending on the orientation and design of the microfluidic chamber, bubbles can be trapped in specific regions of the chamber.

Due to the many problems that may be caused by bubbles in a fluid system as explained above, there is an urgent need for a reliable and inexpensive sensor capable of detecting bubbles in a fluid system.

For the purposes of this specification, the term "air" shall not be taken to include only air per se, but also any gas or gaseous composition that may be present in the fluid system, in particular pure nitrogen or other protective gas.

Object of the Invention

It is an object of the present invention to provide an advantageous sensor device for use in a fluid system, in particular in an infusion pump device for liquid medicaments, which overcomes one or more of the above-mentioned and other problems.

It is a further object of the present invention to provide an advantageous sensor device for use in a fluid system, which can be used as a pressure sensor and/or a bubble sensor.

It is a further object of the invention to provide a sensor device with a less complex optical detection system. Advantageously, in such a sensor device, the optical detection system can be easily aligned with other components.

Another object of the invention is to provide a sensor device that is insensitive to small variations in the assembly of its components.

In the sensor device according to the invention, any sensitive components should be capable of protecting against mechanical damage. Advantageously, any component of the sensor that is in contact with the liquid is arranged in a separate subunit that can be releasably attached to the reusable subunit.

Such a sensor device should provide a small dead volume and it should be fillable without air remaining in the chamber, essentially independent of its orientation in space. It should be producible inexpensively in large-scale manufacturing.

Furthermore, it is an object of the present invention to provide an infusion pump device or a component of an infusion pump device, and a liquid medicament delivery system with a sensor device according to the present invention.

These and other objects are achieved by a sensor device, an infusion pump device and a liquid medicament delivery system according to the independent claims. Advantageous embodiments are given in the dependent claims.

Disclosure of Invention

The sensor device according to the present invention for use in a liquid medicament delivery system has: a microfluidic chamber comprising a rigid base substrate and a lid; and an optical detection system arranged to emit one or more light beams towards the cover and to observe one or more light beams reflected from the cover. The optical detection system is arranged on a side of the base substrate opposite the lid.

Advantageously, one or more light beams impinging on the cover and/or one or more reflected light beams pass through the bottom structure of the microfluidic chamber. Reusable components including the optical detection system may be coupled to disposable components including the microfluidic chamber.

In an advantageous embodiment of such a sensor device, the cover is a flexible, elastic cover membrane and the optical detection system is arranged to determine a deformation of the cover membrane. Such an advantageous sensor device may be used as a pressure sensor device.

The top cover membrane remains flat when there is no pressure difference between the external pressure and the internal pressure of the fluid system. In the case of a positive pressure difference, the membrane will bulge outward. The resulting displacement of the outer surface of the flexible membrane is then used to determine the current pressure differential.

In such a pressure sensor device according to the invention, the optical detection system measures the deformation of the cover membrane by means of the bottom structure of the chamber and the liquid filled inner volume. Thus, the outside of the sensitive membrane can be protected from mechanical damage and environmental influences by covering the membrane with an inexpensive protective cover.

In a further advantageous embodiment of the sensor device, the wavelength of the emitted light beam is chosen such that the liquid in the microfluidic chamber shows a high absorption coefficient at this wavelength. Such an embodiment is particularly advantageous as a bubble sensor device.

In a further advantageous embodiment of the sensor device according to the invention, the optical detection system comprises two or more photosensors or photosensor arrays.

Advantageously, the sensor device according to the invention is adapted such that one or more light beams are reflected on the fluid contact surface of the cover.

The liquid in the fluid system is typically water or an aqueous solution. For water, an advantageous wavelength is, for example, 630 nm or 1400 nm. The absorption maximum for a typical insulin dosage form is given at 270 nm. Thus, such wavelengths are particularly advantageous for use with insulin pump systems.

When a bubble passes through the light beam, the absorption along the optical path is significantly reduced and more light is detected. Thus, such a sensor device may be used to identify the presence of air in the path of the light beam, and thus be able to detect the passage of air bubbles.

If the device according to the invention comprises two or more photosensors, or even an array of photosensors, the signals measured on the different detectors are evaluated compared to the signals on the other detectors in order to measure the deflection of the cover membrane and thereby determine the pressure in the fluid system. On the other hand, to detect the presence of air in the light path and thus to detect air bubbles, the absolute intensity of the detected light is evaluated. The two channels of information are essentially independent of each other. In case there is only one photosensor used in the sensor device according to the invention, it is also possible to detect bubbles. The bubble will cause an increase in the detected light signal, while deflection of the cover film will deflect the light beam away from the light sensor, thereby reducing the detected light signal. The sensor device according to the invention thus has the following particular advantages: the sensor device may be implemented in such a way that it can be used as both a pressure sensor and a bubble sensor.

In an advantageous embodiment of such a sensor device according to the invention, the bottom structure comprises a prism-like structure for coupling a light beam from a bottom structure material into a liquid in the inner volume of the microfluidic chamber and/or coupling a light beam from the liquid into the bottom structure material.

One of the main advantages of using such a prism structure is that: the path of the returned reflected light beam is defined by the prism structure. The optical sensor may be arranged below the prism structure. Thus, the optical detection system may be implemented as a static system without moving parts. Only a defined small number of detectors is required which can be easily aligned with respect to the prism structure.

The correct functioning of the optical detection system in the sensor device according to the invention is not sensitive to small variations in the position and orientation of the detector. Thus, the necessary accuracy in the manufacturing and assembly process is reduced, which reduces the overall cost of the sensor device.

In an advantageous embodiment, the top cover membrane of the sensor device is gas permeable, which has the following advantages: any air bubbles remaining in the sensor device can be vented through the cover membrane.

In a particularly advantageous embodiment of the sensor device according to the invention, one or more walls or fillings are located in the chamber, which walls or fillings define a fluid channel therebetween, such that the fluid channel extends from an inlet of the chamber to an outlet of the chamber. Each of the walls or fillers has a height that is less than a height of the chamber defined by a distance between the base structure and the cover film so as to define a fluid gap between a top surface of each wall or filler and the cover film. The dimensions of the wall or filling and the chamber are chosen such that when a liquid is introduced into the fluid chamber, the fluid gap is filled with the liquid via the fluid channel by capillary forces. In other words, the fluid gap adjacent to the part of the fluid channel filled by the liquid will be filled by capillary forces with the liquid introduced into the fluid chamber.

Such a sensor device according to the invention has a significantly reduced dead volume compared to the prior art. Furthermore, in the event of a negative pressure differential (in which case the cover membrane will be displaced inwardly towards the chamber), in particular embodiments the wall may support the cover membrane, thereby avoiding blocking of the microfluidic chamber by the membrane itself.

In an even more advantageous variant of such a sensor device according to the invention, prism-like structures are provided in the wall or filling for coupling light beams from the bottom structure material of the wall into the liquid in the inner volume of the microfluidic chamber and/or coupling light beams from the liquid into the bottom structure material.

Advantageously, at least a portion of a surface of the bottom structure, and/or the wall, and/or a top cover membrane facing the internal volume of the chamber is hydrophilic. This increases the capillary force in the gap, especially for aqueous solutions.

The height of the gap is advantageously between about 0.02 mm and about 0.2 mm, and more advantageously between 0.05 mm and 0.15 mm. The fluid channel may have a curved or serpentine-like shape, or may be straight. Some embodiments of the sensor device according to the invention have two or more fluid channels.

By fluidly connecting the inlet and outlet conduits of the microfluidic chamber of the sensor device according to the invention, an additional conduit bypassing the chamber may be provided, which has the advantage of increasing the flow rate of the microfluidic chamber and thus of the sensor device. Advantageously, the width of the inlet of the bypass duct is smaller than the width of the inlet duct to prevent bubbles from entering said bypass duct.

In a further advantageous variant of the sensor device according to the invention, one or more additional outlet conduits branch off from the fluid channel.

Since the microfluidic chambers of the sensor device according to the invention can be manufactured in large numbers and on a continuous production line, the effective cost per piece is sufficiently low that these microfluidic chambers can be realized as a single-use product.

The infusion pump device according to the invention and the liquid medicament delivery system according to the invention comprise a sensor device according to the invention as discussed above.

Another advantageous aspect of the invention is the use of a sensor device according to the invention as discussed above for measuring pressure in a fluid system and/or for measuring the presence of gas bubbles in a fluid system.

Drawings

In order to facilitate a more complete understanding of the present invention, reference is now made to the accompanying drawings. These references should not be construed as limiting the present invention, but are intended to be exemplary only.

Fig. 1 schematically shows in cross-sectional view a sensor device known in the art having a microfluidic chamber and an optical detection system.

Fig. 2 schematically shows an embodiment of the sensor device according to the invention in a cross-sectional view.

Fig. 3 shows schematically in a cross-sectional view a further embodiment of a sensor device according to the invention.

Fig. 4 (a) shows schematically in a top view and fig. 4 (b) shows in a cross-section along plane a-a an exemplary embodiment of a microfluidic chamber for use in a sensor device according to the present invention. Fig. 4 (c) shows a detailed view of fig. 4 (b).

Fig. 5 shows the distribution of liquid during filling of a microfluidic chamber used in a sensor device according to the invention in a real experiment in two subsequent stages in an embodiment of the chamber.

Fig. 6 (a) shows in top view and fig. 6 (b) shows schematically in cross-section along the line a-a an advantageous embodiment of a sensor device according to the invention having a prism-like structure in combination with a meandering fluid path.

Fig. 7 shows a different alternative variant of a prism structure for use in a sensor device according to the invention as shown in fig. 6.

Fig. 8 depicts four other possible exemplary embodiments of microfluidic chambers for use in a sensor device according to the present invention.

Fig. 9 schematically shows the sensor device according to fig. 6 with the presence of a bubble in the fluid channel.

Fig. 10 shows (a) an embodiment of a microfluidic chamber for use in a sensor device according to the present invention, having additional outlets along the fluidic channel in the chamber, thereby providing the ability to trap bubbles; and (b) an embodiment of a microfluidic chamber for use in a sensor device according to the invention, having a bypass additional conduit.

Detailed Description

A first embodiment of a sensor device 6 according to the invention is depicted in fig. 2 in a cross section through a microfluidic chamber 1 of a sensor device 6 according to the invention. The microfluidic chamber 1 comprises a bottom structure 11 and a top cover film 12, which define an inner volume 14 of the chamber 1. The chamber is fluidly connected to a fluid system (not shown). The cover film 12 is flexible and elastic.

During operation of the sensor device according to the invention as a pressure sensor, the inner volume 14 of the microfluidic chamber 1 is filled with a liquid. The pressure difference Δ p between the liquid of the inner volume 14 and the pressure of the external environment (e.g. atmospheric pressure) acts on the cover membrane 12 and protrudes the membrane 12' outwards. When the pressure difference drops, the deformed and thus biased membrane returns towards the unloaded flat state. The amount of deformation of the cover membrane 12 depends on the pressure difference ap. Thus, the deformation of the membrane 12 can be used to measure the pressure difference.

Using an elastic polymer as the material of the cover membrane, a circular membrane having a diameter in the range of, for example, 2mm to 7 mm can be used to measure the pressure difference between 0mbar and 200 mbar. For larger pressure differences, smaller diameters are used, since the deformation of the membrane should not exceed certain mechanical limits defined by the materials used.

In the shown embodiment of the sensor device according to the invention, a light emitting device 51 (e.g. a laser diode or a light emitting diode) emits a collimated light beam 53a towards the top cover film 12. The path of the light beam 53a passes through the transparent bottom structure 11 of the chamber and the liquid medium 4 in the inner volume. Advantageously, the base structure is made of a transparent polymeric material (for example, PMMA or polystyrene).

When light is transferred from the base structure material 112 to the liquid medium 4, the light beam is refracted according to the ratio of the refractive indices of the two materials. The light beam 53a is then reflected by the inner and/or outer surface of the cover film 12. The cover film may be a metal vapor coated to increase reflection. The reflected beam 53b passes through the liquid 4 and the underlying structural material 112 again and is ultimately received by a photosensor 52, 52' (e.g., a photodiode or phototransistor).

Both the light emitting device 51 and the photosensors 52, 52' are located on the opposite side of the microfluidic chamber to the membrane 12. The pressure sensor device 6 according to the invention as shown in fig. 2 thus has the following specific advantages compared to the prior art: the optical detection system 5 need not be attached to the outer surface of the membrane 12. Thus, by coupling light through the bottom structure 11 of the chamber, a protective cover or housing (not shown) may be provided to the membrane 12, thereby masking the membrane 12 from mechanical damage and environmental influences. The positioning or optical properties of the protective cover do not require high accuracy, which reduces manufacturing costs.

Furthermore, the protective cover may be used to limit the deformation of the membrane to a certain maximum level, thereby preventing the membrane from irreversible damage due to overpressure in the fluid system. Such advantageous additional use of the cover would not be possible if the membrane would have to be optically accessible from the outside.

The optical detection system may be part of a reusable subunit of the sensor device according to the invention, which reusable subunit may be releasably attached to the lower side of the microfluidic chamber opposite the cover film, which cover film is preferably permanently and non-accessibly protected by the cover. The chamber may be part of a disposable subunit of the sensor, including all components that come into contact with the liquid medicament and must not be reused. In a particularly advantageous embodiment, the optical detection system is part of a reusable unit of the infusion pump device, which is releasably coupled to a disposable unit of the pump device, which comprises a fluidic system with microfluidic chambers.

When the cover film is deformed 12 ', the path of the reflected light beam is shifted and deflected 53 b' according to the degree of deformation. The photosensor 52 can receive only the light beam 53b as long as it is within a certain spatial range. Thus, in the set-up of a sensor device with one single photosensor, it is only possible to determine whether the deformation of the cover membrane 12 or the corresponding pressure difference is within a predetermined target range, which corresponds to the spatial detection range of the photosensor. Thus, in such an embodiment, the optical detection system 5 delivers a binary on/off signal that is associated with a specific pressure threshold that may be used by the control unit of the infusion pump system. Such a relatively simple system is quite sufficient to detect a blockage in the fluid line.

In the embodiment shown in fig. 2, two photosensors 52, 52' are provided. The first sensor 52 receives a reflected beam 53b within a first range of membrane deformation, including a state for the undeformed membrane 12, equivalent to a zero pressure differential. The second photosensor 52 ' receives the reflected beam 53b ' in the adjacent deformation range, including the maximum allowable deformation state of the film 12 '.

Instead of one or two photosensors, a plurality of sensors may be used. In a particularly advantageous embodiment, the use of a CCD sensor array 52 to detect the reflected light beam will allow the membrane deformation to be determined with high lateral resolution and will thus allow the pressure difference to be measured with increased accuracy. Such an embodiment delivers more detailed information about the pressure and is therefore advantageous in case the control unit uses the pressure value to calculate and/or monitor the current flow of the liquid and the administered dose of the liquid medicament.

The use of a CCD sensor array has the following additional advantages: deviations of the array within a certain range with respect to the angular orientation of the microfluidic chamber may be taken into account by the calibration measurements. This improves the accuracy of the measurement and allows correction of variations in the alignment of the reusable optical detection system when it is coupled to a new sensor chamber.

The reflection point 531 of the light beam 53a can be selected at any position of the cover film 12. The closer the location 531 is to the center of the film, the greater the deflection of the film 12 in the vertical direction (perpendicular to the undeflected film), which corresponds to a greater lateral shift of the reflection point 531 'and thus of the reflected beam 53 b'. The closer the position 531 is to the boundary of the chamber, the greater the change in the inclination of the film surface 12 and, thus, the greater the change in the reflection angle at the time of deformation, which also corresponds to a greater shift in the reflected light beam 53 b. In order to obtain the highest resolution, the optimum value must be selected from the positions and orientations of the light emitting device 51 and the photosensors 52, 52'. For example, a good location is a reflection point at 50% of the radius of the microfluidic chamber.

In fig. 3, a further advantageous embodiment of the sensor device according to the invention is shown. In this particular embodiment, the bottom structure 11 is provided with prismatic structures 16, 16a, 16b protruding from the bottom structure 11. The first prism-like structure 16 serves to couple the collimated light beam 53a emitted by the light emitting device 51 from the bottom structured medium 112 into the liquid medium 4 in the chamber, allowing a steeper angle of incidence of the light beam 53a on the cover film 12.

Two other prism-like structures 16a, 16b are used to couple the reflected beams 53b, 53 b' back into the bottom-structure material 112. Instead of two prism-like structures and two photosensors 52, 52' (as shown in fig. 3), a plurality of such prisms and/or a plurality of photosensors comprising a CCD sensor array may be applied to improve the resolution.

Important advantages of such an embodiment of the sensor device according to the invention are: the optical detection system 5 is not sensitive to small deviations of its orientation with respect to the microfluidic chamber. This minor change may occur when the reusable and disposable components are coupled, even when a guiding structure is provided.

Since the reflected light beams 53b, 53b 'are guided by the prism structures 16a, 16b to the corresponding optical sensors 52, 52' located below the prism structures, a small lateral displacement of the sensors will not affect the accuracy of the optical detection system. Even larger displacements affecting the alignment of the prism and the sensor and thus the amount of light detected by the sensor can be corrected, since all sensors will suffer the same amount of misalignment.

Since all detectors are oriented in the same direction, assembly of the device can be performed by standard automated placement machines, which significantly reduces manufacturing costs.

A particularly advantageous embodiment of a microfluidic chamber suitable for use in a sensor device according to the invention is shown in fig. 4. The circular fluid chamber 1 comprises a bottom substrate 11 and a top cover 12. The top cover 12 is spaced apart from the bottom substrate 11 by a certain height H1, thereby defining an interior volume 14 of the chamber 1. Eight walls 13 are arranged in the fluid chamber 1 and define a serpentine-like fluid channel 12 extending from an inlet 21 to an outlet 22 located on the opposite side of the chamber 1. Thus, the inlet conduit 211 and the outlet conduit 221 are fluidly connected by the fluid channel 12.

The height H2 of the wall 13 is less than the overall height H1 of the chamber 1. Thus, there is a fluid gap 3 between the top cover 12 and the upper surface 131 of the wall 13, having a height H3 = H1-H2. The dimensions of the chambers and walls (in particular H1, H2, H3) are chosen such that there is a non-negligible capillary force acting on the fluid 4 present in the microfluidic chamber 1. The fluid 4 in the fluid channel 2 will be drawn into the fluid gap 3 by said capillary forces.

The specific dimensions depend on the one hand on the liquid used and on the other hand on the properties of the surface of the top cover 12 and the top 131 of the wall 13, since this will ultimately define the interfacial tension between the liquid, the surface and the gas/air in the chamber, which will then define the effective capillary force for the specific geometrical arrangement of the microfluidic chamber. Since the liquid medicament is in most cases an aqueous solution, preferably at least the majority of the relevant surfaces (i.e. the surface of the top surface 131 of the wall 13 and the surface of the cap 12 facing the surface 131) are hydrophilic, with a contact angle < 90 °, in order to increase the overall capillary effect. For aqueous solutions, the preferred range of height H3 of gap 3 is between 20 μm and 200 μm, and preferably between 50 μm and 150 μm.

The dimensions of the chamber 1 and the fluid channel 2 are less critical. A typical diameter of the microfluidic chamber 1 may be, for example, between about 2mm and 10 mm. The fluid channel may have a width of, for example, 0.1mm to 1mm, while the height H2 of the wall 13 is in the range between 0.25mm to 5mm, and preferably between 0.5 mm and 1 mm. The aspect ratio between the width of the fluid channel 2 and the height H2 may be between 0.25 and 5 and is preferably about 1.

When filling the microfluidic chamber 1 with liquid 4 through the inlet 21, the liquid will essentially flow along the fluid channel 2. Capillary forces will pull the liquid 4 in the fluid channel 2 into the adjacent part of the gap 3, effectively expelling air present in the gap. In the case of more energetically favorable conditions, the air forms spherical bubbles, the smallest surface of which faces the hydrophilic surroundings and, thus, no bubbles remain in the gap 3.

A first filling of such a microfluidic chamber 1 suitable for use with a sensor device according to the present invention is demonstrated experimentally in fig. 5. In fig. 5 (a), the aqueous solution 4 has flowed downstream through the inlet conduit 211 and inlet 21 into the fluid channel 2, and is now at position B. Due to capillary forces in the gap 3, the liquid 4 flows into the portions 3.1, 3.2, 3.3, 3.4 of the gap 3 adjacent to the filled fluid channel 2. In the gap, the surrounding part of the downstream fluid channel 2 at position B, which is still filled with air or gas 7, restricts the further flow of liquid. The gap 3 is thus filled part by part. Fig. 5 (b) shows a later stage, in which the liquid 4 has travelled in the fluid channel 2 to position C. All parts of the gap 3 except the part 3.10 are filled with liquid 4, the part 3.10 not yet being in contact with the liquid and still being filled with air 7. As is clearly visible in fig. 5, no air 7 remains in the part of the chamber that has been filled with liquid 4. When the liquid will eventually have reached the outlet 22 and the outlet conduit 221, the microfluidic chamber 1 will be completely filled. No air 7 remains in the microfluidic chamber.

The bubbles in the gap are less energetically favorable than the bubbles in the fluid channel 2. Therefore, bubbles will not be formed in the gap 3 at a later stage, and if bubbles are formed in the gap 3, they will migrate into the fluid passage 2. On the other hand, for energy reasons, gas bubbles in the fluid channel 2 will not enter the gap 3, but will be transported away by the liquid flow.

The illustrated capability of the microfluidic chamber 1 is independent of its orientation in space. Since the capillary forces and interfacial tensions responsible for the smooth filling of the gap are much stronger than the gravitational forces acting on the liquid and the buoyancy forces acting on the bubbles in the liquid, the microfluidic chamber will eventually be completely filled with liquid 4 regardless of its orientation. The filling behavior of such a microfluidic chamber is thus predictable and reproducible, which is very advantageous for use in the sensor device according to the invention.

Since the operational internal volume of the microfluidic chamber is smaller than that of a hollow microfluidic chamber of similar dimensions, the dead volume (the part of the fluid volume in the fluidic system that can never be evacuated and will eventually be lost when discarding the sensor device) is significantly reduced.

Another advantage of the disclosed microfluidic chamber lies in the fact that: bubbles entering the chamber through the inlet will be directed through the fluid channel to the outlet. Since the effective cross-sectional area of the fluid channel is essentially constant over its length, the liquid flow is also constant over its length and does not descend at a specific location. Therefore, bubbles cannot be trapped in the fluid chamber.

A particularly advantageous sensor device 6 is disclosed in fig. 6 and illustrates a particularly useful embodiment of the sensor device, wherein the advantageous optical detection scheme of the sensor device according to the present invention is combined with the advantages of a microfluidic chamber with a meandering fluid channel 2. The microfluidic chamber 1 of such a sensor device essentially corresponds to the embodiment shown in fig. 4, while detection is effected similarly to fig. 3.

In the rectangular detection area 55, the walls 13 of the chamber 1 are reduced to prismatic structures 16, 16a, 16b in order to couple the incident light beam 53a propagating in the walls into the liquid 4 and to couple the reflected light beams 53b, 53 b' back into the walls and the bottom structure 11. The prism structures only form narrow gaps in the walls 13. This prevents the fluidic resistance along the detection zone from falling below the flow resistance along the fluidic channel 2.

The light emitting device 51 is arranged directly below the first prism-like structure 16 and emits a collimated light beam 53a propagating in the wall until the collimated light beam 53a reaches the tilted prism surface where it is refracted towards the reflection point 531. After reflection on the cover film 12, the reflected light beam 53b is irradiated onto the prism surface of the second prism-like structure 16a, where it is refracted toward the photosensor 52 arranged directly below the prism 16 a.

When the pressure difference increases, the membrane deforms and the reflection point 531' moves to the right. The reflected beam 53b now impinges on the prismatic surface of the third prism-like structure 16b and reaches the second photosensor 52'. With a further increase in the pressure difference, the reflected beam reaches the next prism 16c, etc.

The inclination and overall size of the prism structures depend on the size and properties of the microfluidic chamber, the wavelength used for the light beam, the refractive indices of the base structure material and the liquid medium, and other factors, and must be employed for a particular sensor geometry.

Other examples of possible prism structures are depicted in fig. 7 (a) to (d). In the variation shown in fig. 7 (a) and (b), the prism structure is narrow, with a larger prism surface for collecting the illuminated light. This design is advantageous from an optical detection point of view. However, the narrow prism structure results in a reduced flow resistance along the detection region 55, which is less advantageous for the properties of the microfluidic chamber 1.

In the embodiment in fig. 7 (c) and (d), the prism-like structures are as wide as the other walls 13. This increases the flow resistance along the detection zone. On the other hand, the surface of the prism available for receiving light is reduced.

The microfluidic chamber may have a circular shape, as in the embodiment of the sensor device shown in fig. 6, or any other suitable shape. The same applies for the specific design of the fluid channels in the microfluidic chamber. Some embodiments of the microfluidic chamber may be preferred over others in accordance with the specific design of the sensor device according to the present invention. Fig. 8 shows a number of possible variations of microfluidic chambers suitable for use with a sensor device according to the present invention. In fig. 8 (a), the serpentine of the fluid channel 2 is arranged in an oval chamber 1, whereas in the embodiment of fig. 8 (b), the chamber 1 has a rectangular shape. In fig. 8 (c), a circular chamber 1 with an alternative route of the meandering fluid channel 12 is shown.

Instead of having only one fluidic channel 2, the walls 13 of the microfluidic chamber may define two or more fluidic channels within the chamber, extending from a common inlet to a common outlet. Fig. 8 (d) shows such an embodiment of the microfluidic chamber 1. The inlet conduit 211 opens to the chamber 1 through the common inlet 21. The fluid channel is then split into two separate fluid channels 2, 2 ', which two separate fluid channels 2, 2' are joined again at a common outlet 22. In such an embodiment, preferably, constructive means (e.g. a flow barrier) are provided, which ensure that during the filling process the chamber 1 is completely filled before the liquid flow travels further through the outlet 22.

The curved or serpentine design of the fluid channel is advantageous for fluid chambers with larger substrate areas, since the longest possible distance between the fluid channel and the outer edge of the gap is shorter. Furthermore, the serpentine fluid passage may be used as an efficient means for limiting the maximum flow through the fluid system.

In the embodiment of the sensor device according to the invention discussed so far, the microfluidic chamber 1 comprises a bottom structure 11 and a top cover membrane 12, the bottom structure 11 and the top cover membrane 12 being sealed together in a sealing area 15 along the outer edge of the chamber 1. Suitable materials for the base substrate 11 and the top cover 12 are, for example, polymeric materials. Suitable methods for joining the two substrates 11, 12 are thermal bonding, laser bonding, gluing, etc.

The wall 13 may be implemented as an integral part of the base substrate 11. In this case, as an example, the fluid channels 2 and even the inlet and outlet ducts may be created by embossing the necessary pore structure into a flat bottom structure 12. To obtain the necessary gap 3, a thin spacer layer of height H3 may be arranged between the substructure and the top layer 12 around the chamber, or gaps as well as fluid channels and walls may be created in the embossing step. Another suitable technique for fabricating microfluidic chambers is injection molding.

In a possible alternative, the walls 13 are realized as separate filling structures, which are mounted onto the flat bottom layer 11. In this solution, the filling body can be attached to the bottom layer and can then be arranged in a sandwich-like manner between said bottom layer and the adjacent top layer.

In a particularly advantageous embodiment of the sensor device according to the invention, the wavelength used for detection is chosen such that it has a high absorption coefficient in the liquid, which will in most cases be an aqueous solution. Useful wavelengths include those in which water has a high absorption coefficient (e.g., 630 nm or 1400 nm). The absorption maximum of a typical insulin dosage form is given at 270 nm. Thus, such wavelengths are particularly advantageous for use with insulin pump systems. Although a portion of the irradiated light is absorbed in the liquid medium 4, the photosensor receives a signal sufficient to deliver a reliable result.

However, if a bubble is pulled along the fluid channel 2 and reaches the detection region 55, the absorption strongly decreases and the signal received by one or more of the photosensors increases significantly. This sudden increase in signal strength may subsequently be used to generate the following warning message to the user and/or control system of the infusion pump device: the presence of bubbles in the fluid system; and the reliability of the sensor may suffer. Thus, the sensor device according to the invention may also be used to detect air bubbles in a fluid system and determine whether its pressure measurement may be erroneous due to the presence of air bubbles in the sensor.

Fig. 9 shows a sensor device according to the invention as shown in fig. 6 for use as a bubble sensor. The bubbles 71 in the liquid flow have entered the microfluidic chamber 1. For energy reasons it cannot enter the fluid gap and is dragged along the fluid channel 2. When the bubble 71 reaches the detection region 55, the incident light beam 53a and the reflected light beam 53b pass through the bubble as shown in fig. 9 (b). The intensity of the light detected by the detector 52 increases and the sensor device will interpret this as a detection of a bubble.

Such a sensor device according to the invention is even able to determine the volume of the passing bubble, taking into account the known geometry of the microfluidic chamber 1, the speed of current transfer of the liquid and the time period between the increase in light intensity (corresponding to the front of the bubble) and the decrease in light intensity back to the normal value (marking the end of the bubble). The control unit can then use this information to evaluate the situation and take the necessary steps.

In an embodiment of the sensor device according to the invention, which is particularly directed to use as a bubble sensor device, the membrane 12 may be realized as a semi-rigid membrane, or even as a rigid cover.

Two further advantageous variants of a microfluidic chamber 1 for use with a sensor device 6 according to the invention are disclosed in fig. 10. In fig. 10 (a), two additional outlet openings 23 are located at different positions along the serpentine fluid channel 2, with an additional outlet conduit 231 branching off from the serpentine fluid channel 2. Downstream of the primary outlet 22, the outlet ducts 221, 231 again converge to a common outlet duct. The additional outlet opening 23 is smaller than the main outlet opening 22. The width of the narrow outlet 23 should be 50% or less of the width of the fluid channel 2. For bubbles having a certain size, entering the narrow outlet 23 will not be energetically as advantageous as staying in the relatively wide fluid channel 2 due to interfacial tension. Thus, the gas bubbles will stay inside the fluid channel, where they will eventually be detected by the optical detection system 5. Since three outlets 23, 22 are available, the throughput of liquid through the sensor device 6 is increased.

Fig. 10 (b) depicts another preferred variant of the sensor device according to the invention, wherein the additional conduit 241 bypasses the microfluidic chamber 1. The bypass conduit 241 connects the inlet conduit 221 directly to the outlet conduit 221. The width of the inlet 24 of the bypass duct 241 is much smaller than the width of the inlet duct 211, being 50% or less of the width of the inlet duct 211. Thus, it is not advantageous for bubbles to enter the inlet 24 and the bypass conduit 241, and the bubbles will enter the sensor device, where they can be detected. To ensure that both the bypass conduit 241 and the microfluidic chamber 1 are completely filled during the first filling process, a flow barrier or similar device may be used, as already discussed.

The scope of the invention should not be limited by the specific embodiments described herein. Indeed, various modifications of the invention in addition to those described herein will become apparent to those skilled in the art from the foregoing description and accompanying drawings. Accordingly, such modifications are intended to fall within the scope of the appended claims. In addition, the disclosures of any references cited throughout this specification are hereby incorporated by reference in their entirety.

List of reference marks

1 microfluidic chamber

11 base substrate

112 base substrate material

12 Flexible elastic top cover film

12 ', 12 ' ' deformed cover film

13 walls, fillers

131 top surface of wall

14 internal volume

15 sealing area

16. 16a, 16b, 16c, 16d prism structure

2. 2' fluid channel

21 inlet

211 inlet duct

22 outlet port

221 outlet conduit

23 additional outlets

231 additional outlet conduit

24 inlet of bypass duct

241 bypass conduit

3 fluid gap

3.1, 3.2, … …, 3.10 gap parts

4 liquid

5 optical detection system

51 light emitting device

52. 52 ', 52 ' ' photoelectric sensor

53a incident light beam

53b reflected light beam

531. 531 ', 531 ' ' reflection points

55 detection area

6 sensor device

7 air, gas

71 bubble

Height of H1 fluid Chamber

Height of H2 wall

Height of H3 gap

Delta p pressure difference

Claims (17)

1. A sensor device (6) for use in a liquid medicament delivery system, the sensor device (6) having: a microfluidic chamber (1) comprising a rigid base substrate (11) and a lid (12); and an optical detection system (5) arranged to emit one or more light beams (53 a) towards the lid (12) and to observe the one or more light beams (53 b) reflected from the lid (12), characterized in that the optical detection system (5) is arranged on a side of a base substrate (11) opposite to the lid (12), wherein the base substrate (11) and the lid (12) define an inner volume (14) of the microfluidic chamber (1), and the microfluidic chamber (1) is fluidly connected to a fluidic system, the lid is a flexible, elastic lid film (12), and the optical detection system (5) is arranged to determine a deformation of the lid film (12).

2. Sensor device according to claim 1, characterized in that one or more light beams (53 a) impinging on the cover (12) and/or one or more reflected light beams (53 b) pass the bottom structure (11).

3. The sensor device according to any of claims 1 to 2, characterized in that the wavelength of the emitted light beam (53 a) is chosen such that the liquid (4) in the microfluidic chamber (1) shows a high absorption coefficient at this wavelength.

4. The sensor device according to any one of claims 1 to 2, characterized in that the optical detection system (5) comprises two or more photosensors (52, 52', 52 ") or an array of photosensors.

5. A sensor device according to any one of claims 1-2, characterized in that the sensor device is adapted such that one or more light beams (53 a) are reflected on the fluid contact surface of the cover (12).

6. Sensor device according to any one of claims 1 to 2, characterized in that the sensor device is a pressure sensor and/or a bubble sensor.

7. A sensor device according to any one of claims 1 to 2, characterized in that the base substrate (11) comprises a prism-like structure (16, 16a, 16b, 16 c) for coupling a light beam (53 a, 53 b) from a bottom structure material (112) into the liquid (4) in the inner volume (14) of the microfluidic chamber (1) and/or coupling a light beam (53 a, 53 b) from the liquid (4) into the bottom structure material (112).

8. The sensor device according to any one of claims 1 to 2, characterized in that one or more walls or fillings (13) are located in the chamber (1), the walls or fillings (13) defining a fluid channel (2) therebetween, such that the fluid channel (2) extends from an inlet (21) of the chamber to an outlet (22) of the chamber; wherein each of the walls or fillings (13) has a height (H2) which is smaller than the height (H1) of the chamber (1) defined by the distance between the base substrate (11) and the cover film (12) so as to define a fluid gap (3) between the top surface (131) of each wall or filling (13) and the cover film (12), and wherein the dimensions (H1, H2) of the walls or fillings (13) and the chamber (1) are selected such that the fluid gap (3) is filled with liquid (4) by capillary force via the fluid channel (2) when liquid (4) is introduced into the fluid chamber (1).

9. Sensor device according to claim 8, characterized in that prism-like structures (16, 16a, 16b, 16 c) are provided in the wall or filling (13) for coupling light beams (53 a, 53 b) from the bottom structure material (112) of the wall (13) into the liquid (4) in the inner volume (14) of the microfluidic chamber (1) and/or coupling light beams (53 a, 53 b) from the liquid (4) into the bottom structure material (112).

10. Sensor device according to claim 8, characterized in that the fluid channel (2) has a meander-like shape.

11. A sensor device according to claim 9, characterized in that the fluid channel (2) has a meander-like shape.

12. Sensor device according to claim 8, characterized in that an additional conduit (241) bypasses the chamber (1) and fluidly connects the inlet conduit (211) and the outlet conduit (221) of the chamber (1).

13. Sensor device according to claim 9, characterized in that an additional conduit (241) bypasses the chamber (1) and fluidly connects the inlet conduit (211) and the outlet conduit (221) of the chamber (1).

14. Sensor device according to claim 10, characterized in that an additional conduit (241) bypasses the chamber (1) and fluidly connects the inlet conduit (211) and the outlet conduit (221) of the chamber (1).

15. An infusion pump device for use in a liquid medicament delivery system, characterized in that the infusion pump device comprises a sensor device according to any of claims 1-14.

16. A liquid medicament delivery system, characterized in that it comprises a sensor device according to any one of claims 1 to 14.

17. Use of a sensor device according to any of claims 1 to 14 for measuring pressure in a fluid system and/or for measuring the presence of gas bubbles in a fluid system.