Patent Description:
Conventionally, Type <NUM> diabetes has been treated with daily insulin injections. However, this inevitably results in insulin levels that do not match the normal and rapid changes in blood glucose which occur in a patient throughout the day. On the one hand, insufficient insulin and high glucose levels lead to immediate symptoms and contribute to long-term complications. On the other hand, too much insulin may result in too little blood sugar leading to loss of consciousness and convulsions. As an alternative to injections, insulin pump therapy is intended to mimic the normal physiology of the healthy pancreas. Unlike multiple daily insulin injections, an insulin pump is able to provide a constant background infusion of insulin that can be adjusted according to individual need, compensating for daily activity and exercise routines. The pump may also be programmed to deliver bolus doses of insulin to address the big glucose swings in the blood that would otherwise result from eating and drinking. By mimicking the natural physiology of the pancreas, insulin pump therapy aims to maintain a constantly normal blood glucose level; avoiding the highs that are associated with meals or the lows that come from too much insulin.

It is important for the patient to know that the insulin pump is successfully delivering insulin to his or her body. It is therefore important for the patient to be made aware when a blockage is preventing this.

<CIT> discloses a therapeutic product delivery device, comprising a circuit layer, an actuator layer carrying an actuator, and a valve layer, through which a therapeutic product is conveyed to a patient by the action of the actuator as defined in the preamble of claim <NUM>. Further, there is an occlusion detection chamber in the fluid channel comprising a pressure switch or pressure sensor.

<CIT> discloses a cartridge-type detection apparatus which comprises a detection cartridge having a passage for passing a sample liquid containing a target substance, and a processing unit adapted to be loaded with the detection cartridge so as to produce information about the target substance contained in the sample liquid passed through the detection cartridge.

<CIT> discloses an infusion system comprising the infusion pump and the infusion set and furthermore to an infusion and monitoring system comprising the infusion system and a monitoring system for monitoring a parameter characteristic for the health condition of the person and relevant for the administration of the medicament.

<CIT> Sensor for dynamically detecting the residual fluid volume of a collapsible reservoir characterized by the fact that it is adapted to detect a threshold pressure which corresponds to a phase within said reservoir when only said residual fluid volume remains, said residual volume V corresponding to a safety volume sufficient to ensure a safety margin to alert the user before the reservoir is empty.

According to the present invention as defined in claim <NUM>, there is provided a therapeutic product delivery device, comprising:.

Preferably, there are conductive pins that provide at least two functions; firstly they align the layers of the cartridge (at assembly and during use), and a secondly they provide a conductive route between the circuit layer and the occlusion layer, permitting therapeutic product deposited at the occlusion layer to be able to complete an electric circuit with the circuit layer to enable occlusion detection. As an additional benefit, a leak within the device may electrically connect together the conductive pins thereby triggering an alarm as if a blockage had been detected. Advantageously, there is no need to provide for separate structures for mechanically connecting and aligning the layers of the device and electrically connected a circuit layer to an occlusion layer.

Preferably, the valve layer comprises an outlet valve via which the therapeutic product is required to pass to reach the patient, and a break-through valve through which the therapeutic product is only able to pass in the event that a blockage inhibits the therapeutic product from reaching the patient, the therapeutic product passing through the break-through valve being deposited at the detection region. The break-through valve is preferably disposed in series with, and at the exit of, the outlet valve. Preferably, a channel is provided for carrying the therapeutic product from the break-through valve to the detection region.

Control circuitry may be responsive to therapeutic product being detected in the detection region to trigger an alarm at the therapeutic product delivery device and/or at a control device. The control circuitry may be responsive to therapeutic product being detected in the detection region to discontinue the operation of the actuator. Preferably, the control circuitry is separate from the circuit layer (which itself merely provides the electrical connection required by the control circuitry).

Preferably, the occlusion detection layer and the valve layer are sealed from the circuit layer by a seal layer. In this case, it is even more advantageous to provide a double function for the conductive pins, since it is desirable to minimise the number of points of penetration through the seal layer to reduce the risk of a leak from within the sealed area to the actuator or circuit layer.

Preferably, the therapeutic product delivery device comprises a reservoir for storing the therapeutic product, and the valve layer comprises a pumping chamber from which the therapeutic product is pumped by action of the actuator. In this case, the pumping chamber is refilled from the reservoir via an inlet valve.

While it will be appreciated that the conductive pin arrangement will be beneficial for any layered structure comprising the elements mentioned above, preferably the circuit layer, the actuator layer, the occlusion detection layer and the valve layer are disposed in this order.

Preferably, the delivery device comprises the circuit layer, the actuator layer, the occlusion detection layer and the valve layer in a cartridge part. In this case, the delivery device comprises a device body part comprising a battery and control circuitry for applying an electric current to the actuator via the circuit layer. The cartridge part and the main body part are preferably releasably engageable with respect to each other.

Various other aspects and features of the present invention are described in the embodiments which follow.

The invention will now be described by way of example with reference to the following Figures in which:.

Referring to <FIG>, a drug delivery system <NUM> is schematically illustrated. The drug delivery system <NUM> in this case delivers insulin to a patient. However, it will be appreciated that embodiments of the present invention may be appropriate for delivering drugs other than insulin. The system <NUM> comprises a delivery device <NUM> which is worn on the patient's body, a handset <NUM> (which may appear similar to a smartphone) for controlling the delivery device <NUM>, and a server <NUM>. The delivery device <NUM> and the handset <NUM> are able to communicate via a first wireless connection <NUM>, for example a lower power ANT radio connection. The handset <NUM> and the server <NUM> are able to communicate via a second wireless connection <NUM>, for example a GPRS mobile data connection 6a and the Internet 6b. The server <NUM> comprises a patient database <NUM> for storing patient medical information and other information about the patient. Both the delivery device <NUM> and the handset <NUM> are powered by rechargeable batteries. Also shown in <FIG> is a charging cradle <NUM> into which the delivery device <NUM> is inserted in order to charge the delivery device <NUM>.

The delivery device comprises two parts, which are detachable from each other, as shown schematically in <FIG>. The first of the two parts is a body <NUM>, which contains a spring <NUM>, a biasing member <NUM> including a displacement sensor (for example as described in <CIT>), and a set of contact pins <NUM> for providing an electrical connection with the second part. The body <NUM> also comprises a battery, control circuitry and a transceiver for communicating with the handset, which are not separately shown in <FIG> in the interests of clarity, but are generally represented by element <NUM>. The second of the two parts is a disposable insulin cartridge <NUM>, which comprises a reservoir <NUM> of insulin, contact pads <NUM> for providing an electrical connection with the body <NUM> via the pins <NUM>, a pumping device (a wax actuator, for example as described in <CIT>) for pumping the insulin from the reservoir <NUM> into the patient's body, and a valve arrangement (for example as described in <CIT>). The pumping device and valve arrangement are not separately shown in <FIG> in the interests of clarity, but are generally represented by element <NUM>. It will be understood that the body <NUM> of the delivery device is reusable, while the disposable cartridge <NUM> is intended to be removed and disposed of when the reservoir <NUM> has been depleted, or when the cartridge has passed its use by date, or if it develops a fault. A new cartridge can then be engaged with the body <NUM>. While it is preferable that the cartridge is disposable, it will be appreciated that, in principle, the cartridge may be refilled and reused again rather than being disposed of. However, even in this case the cartridge should be removable from the body so that a new (full) cartridge can be used while the original cartridge is being refilled.

In use, the body <NUM> and the cartridge <NUM> of the delivery device <NUM> are physically and electrically connected. The electrical connection is via the pins <NUM> and pads <NUM>. The physical connection may be provided by clips or any other releasable engagement mechanism (not shown). The control circuitry in the body <NUM> is responsive to control signals received from the handset <NUM> via the wireless connection <NUM> to draw current from the battery and apply an electrical current via the pins <NUM> and the pads <NUM> to activate the pumping device within the cartridge <NUM> to draw fluid from the reservoir <NUM> through the valve arrangement and out of the delivery device <NUM> to a patient's body. The rate of delivery of the therapeutic product can be controlled by the control circuitry to achieve a particular basal delivery rate, or bolus dose, by controlling the amount and timing of electrical current to the pumping device. Although the basal rate is set by the handset, once set the delivery device <NUM> is able to maintain the set basal rate with no further communication from the handset <NUM>. As can be seen in <FIG>, when the body <NUM> and the cartridge <NUM> are in engagement, the reservoir <NUM> is received within the body <NUM>, displacing the biasing member (and displacement sensor) <NUM> and compressing the spring <NUM>. The compressed spring applies a biasing force to a base of the reservoir <NUM> via the biasing member <NUM>. The biasing force does not in isolation force insulin from the reservoir <NUM> through the valve arrangement and into the patient's body, but when combined with the pumping action of the pumping device, the biasing force pressurises the insulin in the reservoir <NUM> to refill a pumping chamber in advance of each pumping action. It is the pumping action which drives a controlled amount of insulin from the pumping chamber through an outlet valve and to the patient's body. The reservoir takes the form of a cylinder having a first end from which insulin is drawn under the action of the pump, and a second end opposite to the first end at which the (moveable) base is provided. The base of the reservoir moves inwardly of the reservoir (to effectively decrease the size of the reservoir) as the insulin is pumped from the reservoir, under the biasing force provided by the biasing member <NUM>. The position of the biasing member <NUM> is dependent on the current fill state of the reservoir - that is, how much insulin is remaining in the reservoir. The position of the biasing member <NUM>, and thus the base of the reservoir <NUM>, is determined by the displacement sensor. The displacement sensor is therefore able to generate a signal indicative of the remaining quantity of insulin in the reservoir. By monitoring the change in the remaining quantity of insulin with respect to time, an actual rate of insulin delivery can be determined. This can be used by the control circuitry to apply corrections to the actual delivery rate by adapting the amount and/or timing of electrical current to the pumping device. The quantity of insulin remaining in the reservoir is transmitted to the handset <NUM>, where it can be displayed to the patient and used as an indicator of when the patient should change the current cartridge for a new cartridge. The control circuitry in the body <NUM> may also transmit an indication of current battery level to the handset, so that the patient is made aware of when the battery requires recharging.

The delivery device also contains an activity monitor to track exercise (not shown). Exercise can have a significant effect on the amount of insulin needed for good control, so tracking exercise accurately is an important part of effective diabetes management. The activity monitor uses a sensor in the delivery device to detect movement of the delivery device, which can be used to infer when the user is engaged in physical activity. The detected activity is then wirelessly communicated to the handset via the wireless connection <NUM>, where the handset (and the server) is able to track and record the patient's activity. Through an online portal to the server, the patient and permitted medical professionals are able to compare activity peaks with blood glucose to identify how activity is influencing the patient's need for insulin. This can in turn be used to program the handset with appropriate dosages for the patient.

Due to the fact that the patient interfaces with the handset rather than the delivery device itself, the delivery device is able to be made small and discreet, and is provided without buttons or a physical connection to a control unit.

The handset <NUM> comprises two transceivers. The first transceiver is for communicating with the delivery device via the first wireless connection <NUM>, while the second transceiver is for communicating with the server <NUM> via the second wireless connection <NUM>. The handset also comprises a processor for running control software. The control software monitors the patient's condition and reports it to the central server <NUM>, and controls the delivery of insulin doses to the patient by transmitting control signals to the delivery device <NUM>. The handset <NUM> also comprises a touch screen display <NUM>, which displays information to the user and provides a user interface for the user to input data, modify the basal rate, and trigger extraordinary bolas doses.

As well as wirelessly controlling the pump, the handset <NUM> also has an integral blood glucose meter <NUM>. The blood glucose meter <NUM> detects the amount of glucose in the patient's blood. The blood may be analysed at the meter <NUM> by pricking the patient's finger and depositing a droplet of blood on a slide, which is inserted into the meter <NUM>. The detected blood glucose level can be brought to the attention of the patient on the handset <NUM>, and the patient can decide to trigger a bolas dose based on the blood glucose information. The result of every blood glucose test is automatically logged by the software and becomes immediately available for reference via the server <NUM> to the patient, medical professionals and even family members (such as parents). More generally, the handset <NUM> runs various software applications which help the user (and other authorised parties) to keep track of diet, insulin, blood glucose and exercise (which as explained above is recorded automatically from a sensor in the delivery device). By automating data collection, the handset <NUM> eliminates, or at least reduces, the need for a diabetes journal and ensures that comprehensive and accurate clinical information are constantly available to the patient and medical professionals via the server <NUM>.

When controlling the delivery device, the handset <NUM> sends wireless signals to the delivery device <NUM> to deliver regular periodic doses of insulin at a pre-determined basal rate, which is set on the handset <NUM> according to the recommendations of a medical professional. The basal rate may be adjustable by the user within certain constraints. However, the software is configured such that it is not allowed for the basal rate to be adjusted remotely by third parties such as doctors. The hand-held device <NUM> also allows the user to trigger extraordinary bolus doses, for example after eating carbohydrates or performing exercise. As with a basal dose, the bolus dose is delivered by the delivery device <NUM> in response to control signals sent wirelessly from the handset <NUM>. The user is able to input the volume of carbohydrates which have been consumed at a relevant time and is also able to input periods of exercise and the hand-held device is able to recommend adjustments to the basal rate or when a bolus is needed. As discussed above, the glucose monitor <NUM> may have an influence on the dosage. All of this information is transmitted to the server <NUM>. The hand-held device <NUM> also receives information from the delivery device <NUM>, for example to indicate whether it is faulty or when the insulin cartridge needs to be replaced. It also provides an indication of battery level.

It will be understood from the above that the handset <NUM> and the delivery device <NUM> monitor and record clinical information while delivering insulin according to the body's needs. By providing this information to the server <NUM>, it can be made almost immediately available to all those who need to see it. In particular, a mobile connection to a secure online management portal makes it possible for patients, clinicians and parents to be made constantly aware of, and able to react to, changing conditions. A diabetes clinic with patients using the system is able to see the current status of all its patients on a single screen, delivered to the clinic in real time. The portal can be accessed over the Internet in the clinic or through a smartphone. In addition to making it possible for a patient to access their latest clinical information online, it is possible for the patient to see simple visual analysis of their data, for example to identify trends and patterns in their blood sugar, and to immediately see their insulin dosing habits. This information can all be viewed using a simple online web portal that can be accessed from home, from work or from a smartphone. The server can also transmit SMS messages to a child's parents to let them know their child's information and state of health.

A patient using the system is provided with a personal login to the secure mobile diabetes management portal. Once logged in the patient can see all of their automatically collected data in the form of charts and graphs to help them understand where they might need to make adjustments. Exercise habits are mapped out in pie charts. An indication of exactly how and when the patient's insulin was delivered is provided. The patient's clinicians are able to see the same analysis and information, enabling them to call or text the patient whenever needed with guidance and advice.

From a single online dashboard screen, the clinic has access to the status of all the patients on the system; including current blood sugar, average blood sugar, insulin dosing, hypo frequency and blood testing habits. At a glance, anyone having difficulties can easily be identified for an immediate response. With a single click, all the data for a patient is analysed and charted to identify trends, patterns and problems. Using the portal, clinics can completely reorganise the way in which patients are managed. Text and email can be used to check on recent events. Clinic visits are focused completely on current and accurate information.

Referring to <FIG>, a schematic exploded view of the structure of a disposable cartridge <NUM> is provided. From top left, the cartridge <NUM> comprises a reservoir assembly <NUM>. The reservoir assembly <NUM> comprises a reservoir <NUM> and a plunger assembly <NUM>. The cartridge <NUM> also comprises a pump stack <NUM>. The pump stack comprises an actuator assembly <NUM>, a piston <NUM>, a gearing/seal membrane <NUM>, an occlusion layer <NUM>, a fluidic layer <NUM> and a fluidic membrane <NUM>. The cartridge <NUM> further comprises a housing assembly <NUM> and an infusion set <NUM>.

Referring to <FIG>, a schematic exploded view of the structure of the actuator assembly <NUM> is provided. From top left, the actuator assembly <NUM> comprises a base <NUM>, a PCB (circuit) layer <NUM> from one side of which protrudes three conductive pins <NUM>, an actuator insert <NUM>, a block of wax <NUM>, a diode assembly <NUM>, and an actuator body <NUM>.

In use, the reservoir <NUM> stores the insulin (or other therapeutic product) which is to be delivered to the patient's body, and the plunger assembly <NUM> is urged inwardly of the reservoir <NUM> by a biasing member on the main body of the delivery device, onto which the cartridge <NUM> is fitted. It will be understood that the reservoir <NUM> is generally cylindrical in shape, and the plunger <NUM> forms a moveable base end of the cylinder. The other end of the cylinder is formed by an internal structure of the housing assembly <NUM>. The pressure applied by the plunger <NUM> on the insulin in the reservoir <NUM> pressurises the therapeutic product in the reservoir <NUM>. When assembled, the reservoir <NUM> is received through an aperture in the base <NUM> of the actuator assembly <NUM> to engage with the housing assembly <NUM>, which provides a channel for carrying the therapeutic product from the reservoir <NUM> under the pressure exerted by the plunger <NUM> through the fluidic membrane <NUM> and into a pumping chamber within the fluidic layer <NUM>. From the pumping chamber, the insulin can be pumped in a controlled manner (under the influence of the piston <NUM>) out to the infusion set <NUM>, again via a channel in the housing assembly <NUM>. The housing assembly <NUM> also has a channel for carrying insulin to the occlusion layer <NUM> when there is a blockage preventing the insulin exiting via the infusion set <NUM>. The fluidic layer <NUM>, fluidic membrane <NUM> and part of the housing assembly <NUM> form a valve arrangement. This valve arrangement comprises the pumping chamber, an inlet valve through which insulin passes from the reservoir <NUM> to fill the pumping chamber, an outlet valve through which insulin passes when the pumping chamber is compressed by the piston <NUM> causing the insulin to be expelled from the pumping chamber and out through the outlet valve, and a breakthrough valve through which the insulin is forced in the event of a blockage between the outlet valve and the delivery site on the patient. The fluidic membrane <NUM> comprises silicone membranes which are stretched over mesa structures in the fluidic layer <NUM>, forming one-way valves by way of the mechanism described in <CIT> (for example). The gearing membrane <NUM> is disposed between the piston <NUM> and the pumping chamber in the fluidic layer <NUM>. The gearing membrane <NUM> both seals the pumping chamber and is displaced by the piston <NUM> on actuation to push liquid out of the pumping chamber and towards the outlet valve.

In <FIG>, the base <NUM> comprises an aperture through which the reservoir <NUM> is received to engage with the housing assembly <NUM>, and a smaller slot aperture which exposes contact pads (not shown) on the PCB assembly <NUM> to the outside of the cartridge <NUM>. Pins on the device body of the delivery device can therefore access the contact pads to provide an electrical connection between the two parts of the delivery device. The base <NUM> also comprises lugs (not shown) which are able to be inserted into the device body to engage with clips inside the device body to hold the two parts of the delivery device together. On the other side of the PCB assembly <NUM> are the conductive pins <NUM>. These extend away from the PCB assembly (circuit layer) <NUM> through the various layers of the cartridge <NUM> described above. The conductive pins in the present embodiment extend to engage with the housing assembly <NUM>, and therefore pass through all interior layers of the cartridge <NUM>. These conductive pins effectively serve three purposes. Firstly, they properly align the layers of the cartridge <NUM> at the point of assembly, and ensure that they do not come out of alignment when the cartridge is in use. Secondly, they provide a conductive route between the PCB assembly <NUM> and the occlusion layer <NUM>, these layers otherwise being sealed away from each other by the gearing membrane <NUM>. In the case of a blockage, as explained above the insulin exiting the outlet valve is routed to the occlusion layer <NUM> via a breakthrough valve. In particular, the insulin is routed to a detection region comprising two contact points, each contact point being electrically connected to one of the conductive pins <NUM> (the third conductive pin being for structural purposes only). The presence of insulin at the detection region bridges the gap between the two contact points, thereby completing a circuit via the conductive pins to the PCB assembly <NUM>, resulting in detection of the blockage at the PCB assembly <NUM> (or at control circuitry within the device body, which is electrically connected to the PCB assembly <NUM> via the contact pads), which may result in the sounding of an alarm on one or both of the delivery device and the handset. Thirdly, in the case of a leak permitting insulin to breach its designated channels through the various layers between the gearing membrane <NUM> and the housing assembly <NUM>, the leaked insulin may spread out to electrically connect together the conductive pins (directly, at any one or more layers), thereby triggering an alarm as if a blockage had been detected.

The actuator assembly <NUM> also comprises an actuator insert <NUM> which is mounted to the PCB assembly <NUM> and receives a block of wax <NUM>. A diode assembly <NUM> is provided, which includes a diode which will be embedded within the wax <NUM>, and a conductive element for connecting the diode to the PCB assembly <NUM>. The actuator insert <NUM>, the wax <NUM> and the diode assembly <NUM> are trapped on assembly by the actuator body <NUM>, which is received on the conductive pins <NUM>, and which is able to receive the piston <NUM> as shown in <FIG>.

<FIG> schematically illustrates a cross section through the cartridge <NUM>. In the cross section, a diode A is shown embedded within wax B. The wax B is sealed into the actuator insert by the actuator body, which sits above it. A piston C extends from proximate the wax B (the piston C being separated from the wax B by a first flexible membrane) to a second flexible membrane which separates the piston from a pumping chamber D. The pumping chamber D is fed insulin by a reservoir H via an inlet valve E. An outlet valve F is arranged to allow insulin from the pumping chamber to exit under the pumping action of the piston C. An occlusion (breakthrough) valve G is provided which, as discussed previously, allows insulin to pass through it when there is a blockage between the outlet valve F and the infusion site on the patient, for example within infusion set J. It will be appreciated that the valves E, F and G are formed by the sandwiching of the components <NUM>, <NUM> and <NUM> of <FIG>.

<FIG> schematically illustrate the operation of the cartridge of <FIG>. In <FIG>, a syringe and needle is used to pierce a septa in the base of the cartridge and fill the cartridge. Initially, the insulin fills the reservoir H. Referring to <FIG>, once the reservoir is full, the liquid progresses through the pumping chamber D. The liquid continues through the valves to prime the infusion set J. To start pumping the insulin, an electric current is applied, as shown in <FIG>. This causes the diode A to heat up, melting the wax B, which causes the wax B to expand. In <FIG>, it can be seen that the wax expansion pushes the piston C into the pumping chamber D, reducing the capacity of the pumping chamber D and causing the insulin in the pumping chamber D to be displaced towards the outlet valve F (it will be appreciated that the insulin cannot exit the pumping chamber D through the inlet valve E, since the valve only permits the passage of fluid in one direction - into the pumping chamber). The liquid is therefore forced through the one-way outlet valve F to the infusion site via the infusion set J. In <FIG>, the electric current has been discontinued, allowing the diode and the wax to cool and contract, consequently permitting the piston C to move back out of the pumping chamber D to its original position. It will be appreciated that one or more of the membrane between the wax and the piston, the membrane between the piston and the pumping chamber, and the pressure applied by the fluid in the reservoir through the inlet valve E and into the pumping chamber, may provide a bias to the piston C to keep it in its original position except for when the expansion of the wax B overcomes the bias. When the piston C returns to its original position, the pumping chamber D refills with liquid through the one-way inlet valve. This completes the pumping cycle. <FIG> demonstrates what happens if there is an occlusion during the pumping action. In <FIG>, as with <FIG>, an electric current is applied to the diode to heat the wax B and move the piston C into the pumping chamber D. The fluid from the pumping chamber D is forced through the outlet valve F, as with <FIG>, but in this case there is a blockage preventing the fluid from reaching the infusion site. This causes a build-up in pressure to the one way breakthrough (occlusion) valve G sufficient for the fluid to be redirected through the occlusion valve G to be conveyed to a detection region (on the occlusion layer <NUM> as discussed above).

Referring to <FIG>, the structure and operation of the one-way valves used for each of the inlet valve, the outlet valve and the occlusion valve are schematically illustrated. In <FIG>, liquid is under pressure at the inlet of the valve in a first direction (the direction of the arrow). The pressure of the liquid in <FIG> is insufficient to open the valve and allow the liquid to pass through. In <FIG>, the pressure is increased, and is now sufficient to deflect a membrane <NUM> away from the mouth of the inlet, allowing the liquid to enter into a chamber <NUM>. The membrane <NUM> comprises apertures <NUM> which then allow the liquid in the chamber <NUM> to exit the valve. It is this mechanism which allows liquid to pass through the valve in a first direction (following the direction of the arrows through the valve as shown in <FIG>), subject to pressure at the inlet being sufficient. In the case of the three valves in the cartridge <NUM>, the pressure required may be the same or different for each of these. Referring now to <FIG>, liquid is under pressure at the outlet to the valve (attempting to flow in the direction of the arrow). While this liquid can enter the chamber <NUM> through the apertures <NUM> in the membrane <NUM>, it is unable to pass through the portion of the membrane which is seated on the inlet, and therefore the liquid cannot pass through the valve in this direction. This valve mechanism is described in detail in <CIT>.

Referring now to <FIG>, the occlusion layer <NUM> is shown mounted to the PC layer <NUM> via two conductive pins 155a, and a pin (which need not be conductive) 155b. Each of the conductive pins 155a is electrically connected to a conductive track <NUM> on the PCB layer <NUM> which connects it to detection circuitry. On the occlusion layer, each of the conductive pins 155a is electrically connected to a conductive track <NUM>. The two conductive tracks terminate near each other at a detection region <NUM>. The presence of insulin in the detection region <NUM> bridges the (air) gap between the two termination points, completing the electrical connection with the detection circuitry. It will be appreciated that, in the interests of clarity, the remaining layers and other components of the cartridge are omitted from <FIG>.

Claim 1:
A therapeutic product delivery device, comprising:
a circuit layer (<NUM>);
an actuator layer (<NUM>) carrying an actuator for delivering a therapeutic product to a patient;
a valve layer (<NUM>), through which the therapeutic product is conveyed to the patient by the action of the actuator, the valve layer (<NUM>) comprising an outlet valve via which the therapeutic product is required to pass to reach the patient, characterised by
a break-through valve (G) through which the therapeutic product is only able to pass in the event that a blockage inhibits the therapeutic product from reaching the patient; and
an occlusion detection layer (<NUM>) comprising a plurality of contacts (<NUM>) in a detection region at which said therapeutic product is deposited after passing through the break-through valve in the event said blockage inhibits the therapeutic product from reaching the patient, the circuit layer (<NUM>) being arranged to detect said blockage when the therapeutic product deposited in the detection region provides an electrical connection between said contacts (<NUM>).