Technical Field

This invention relates to an artificial pancreas system with a piezoelectric pump that automatically detects the insulin requirement of Type 1 Diabetes patients and automatically injects insulin.

Prior Art

Diabetes is a disease caused by the glucose amount in the blood being outside of its normal level. There are two different types of diabetes depending on whether it is seen in children or adults, which are Type 1 and Type 2 diabetes, respectively.

In people with type 1 diabetes, pancreas cannot produce adequate level of insulin to lower the amount of glucose in the blood, or produces no insulin. Due to the lack of insulin, glucose in the bloodstream cannot enter the cell and therefore cannot be converted into energy. This causes the amount of glucose in the blood to rise and glucose being filtered through the kidneys and excreted in the urine. The passing of glucose into the urine causes fluid loss in the urine, and if this fluid loss is not met, this problem leads to thirst in the body.

In order to reduce the glucose level in the blood of diabetic patients, insulin needs to be injected into the body several times a day. For this, diabetic patients inject insulin to themselves manually, usually by means of an insulin pen or using an insulin pump. However, in these applications, hypoglycemia or hyperglycemia situations occur due to reasons such as diabetes patients injecting less or more insulin than the amount of insulin they need. Therefore, there have been some studies recently on automating these insulin pumps in order to eliminate the human factor that causes health problems during the determination of insulin amount.

As with manual (hand-controlled) insulin pumps used by diabetic patients, automatic insulin pumps also have syringes. A linear shaft is attached to the end of the syringe in the said automatic insulin pumps, and a motor is connected to this shaft. As the motor is rotated, the shaft in question compresses the syringe and moves the syringe, thus allowing the insulin in the syringe to be injected into the body. However, here, the friction force resistance when the syringe is first pressed, and the friction force resistance after it is started to be pressed, are different from each other. When pressing the syringe for the first time, negative situations arise such as pumping more insulin than the insulin normally intended to be pumped. Therefore, the controllability of syringe type insulin pumps is very difficult. The clinical use of syringe pumps in such applications poses several risks, including lack of control of the infusion rate, bleeding from the reflux, and overdose or underdose due to air entry. Since drug overdose can lead to serious complications such as hypersecretion, respiratory depression and hypoxia, this overdose problem is the most important problem among the above-mentioned problems.

Most of the artificial pancreas systems on the market typically used for insulin delivery in all research and clinical trial artificial pancreas studies (e.g. Minimed 670G of Medtronic, iLet of Beta Bionics, and t:thin x2 of Tandem...) contain a syringe pump.

The MiniMed 670G product encountered in the known status of the art is an automatic insulin pump. The insulin pump in question measures glucose in the blood from an invasively placed glucose sensor every 5 minutes. In the system in which a syringe type pump is used, the user enters a reference range and sets the range in which the glucose amount in his blood remains. Before injecting insulin, the semi-automatic pump waits for two hours for the glucose level in the patient's blood to automatically return to the healthy range, and if there is a possibility that it does not come to the mentioned range, the injection is made only with the consent of the patient.

DiAs according to the known status of the art is a modular artificial pancreas platform based on an Android smartphone. The smartphone application contains the computer program that controls the glucose level in the blood. The program also performs the function of predicting when glucose levels will rise or fall. It wirelessly receives data from the Dexcom G4 CGM (Continuous Glucose Monitoring) and commands an insulin pump (for example, Tandem t:slim or Accu- Check from Roche) via Bluetooth. This platform also includes a dedicated Bluetooth box that connects to local data servers and the Cloud. Also the controller is compatible with any CGM or insulin pump. The system is being tested in longterm (1-3 months) clinical trials at home.

Inreda artificial pancreas, which belongs to the Inreda company, according to known status of the art, has a waterproof feature and is a dual hormone (both insulin and glucagon) system with Wi-Fi connection. The device provides a completely autonomous regulation of glucose levels. In this system, there are a total of 2 pumps, one for each insulin and glucagon, 2 CGMs, Wi-Fi, sensors, alarm sets and 2 batteries. The system uses an intelligent reactive control algorithm that decides when and how much insulin or glucagon should be administered. Insulin delivery; current and target glucose levels are determined by the rate of glucose change, the user's insulin sensitivity, and the difference between the 2 glucose thresholds that trigger the delivery of a corrective insulin bolus. The controller is powered by an AA type battery and transfers data to the database every 24 hours. In addition, users are warned when they need to check something or take action thanks to audible alarms. iLet of Beta Bionics company, according to known status of the art, includes a fully integrated and automatic dual hormone closed-loop system. The system has a built- in wireless CGM that works with the Dexcom sensor and transmitter, and a special handheld controller with which dosing algorithms work. Control algorithms learn and adapt to the user's insulin needs, thus providing personalized management. The system also includes 2 independent pumps that are automatically commanded every 5 minutes by the insulin and glucagon dosing algorithms.

Therefore, there is a need for systems that pump insulin more reliably. The most unique feature of the present application is that it is the first insulin pump made using a Piezoelectric driven pump developed to eliminate the problems mentioned here.

Objects of the Invention

The object of the present invention is to increase the reliability of insulin pumps by using a valveless piezoelectric driven pump instead of a syringe pump. Since the amount of insulin to be injected into the body can be controlled more precisely thanks to the piezoelectric driven pump used in the artificial pancreas system of the invention, its controllability is higher than the prior art systems. Thus, since the overdose problem caused by the syringes used in the state of the art is eliminated, it has a more reliable system feature compared to the prior art systems.

Another object of the present invention is to realize an artificial pancreas system with reduced dimensions. Thanks to the small size of the present invention, it is also suitable for pumping different hormones (glucagon, etc.).

Another object of the present invention is to realize an artificial pancreas system that provides lower energy consumption than existing systems. Since the present invention provides much lower energy consumption than the insulin pumps on the market, it is an energy efficient insulin pump.

Another object of the present invention is to realize a lower cost artificial pancreas system than the prior art systems. In the present invention, since a cheaper piezoelectric pump is used instead of a syringe, products can be designed for single use (disposable), daily use or weekly use.

Brief Description of the Invention

The artificial pancreas system described in the present invention is a system that performs closed-loop glucose control, allowing the amount of glucose in the blood to be measured regularly and the amount of insulin to be pumped to be determined automatically.

An artificial pancreas system, as defined in the first claim and the other claims, realized in order to achieve the object of the present invention, comprises, in its most basic form, a glucose measurement unit and a piezoelectric driven pump. Said glucose measuring unit includes at least one glucose sensor for taking glucose level measurement; it comprises a first wireless data communication module, preferably a Bluetooth module, for wireless transmission of the measured data, and a first battery that meets the required energy needs. The said piezoelectric driven pump, in its most basic form, comprises at least one control unit adapted to determine, on the basis of data measured by the glucose meter, the amount of insulin to be pumped and to generate control signals accordingly; a second wireless data communication module, preferably a Bluetooth module, for wireless data exchange with the glucose meter or a smart device; a second battery meeting the required energy demand; at least one amplifier for amplifying control signals emanating from the control unit; at least one reservoir for containing insulin; at least one first piezoelectric disc having a nozzle (inlet) for connecting the reservoir and a diffuser (outlet) for connecting a catheter, and allowing the insulin in the reservoir attached to the nozzle to be sucked and pumped through the diffuser by making a vibratory motion that includes successive contraction and relaxation movements, in line with the control signals generated by the control unit. In one embodiment of the invention, the control unit comprises a PID controller, a State Feedback Controller or a controller performing Model Predictive Control, wherein said controller is adapted to generate control signals for bolus or basal insulin release according to the glucose level measured.

In an embodiment of the invention, batteries can be charged by wearable energy harvesting equipment that provides electricity from motion energy.

In an embodiment of the invention, a smart device, preferably a smartphone or tablet computer, is used, containing a processor adapted to determine the amount of insulin to be injected according to the data transmitted from the glucose measurement unit, and a mobile application run by this processor, in order to provide energy efficiency. Here, since the operations performed by the smart device reduce the load of the control unit, it ensures a longer life of the second battery feeding the control unit.

In one embodiment of the invention, there is a glucagon tank that stores glucagon in order to increase the low glucose level in the blood. Said glucagon tank is connected to the nozzle of a second piezoelectric disc. Thus, in case of low glucose level in the blood, it is possible to raise the glucose level again above a predetermined level.

In an embodiment of the invention, there is at least one safety valve that controls the passage of insulin through a line connected to the diffuser of the first piezoelectric disc and/or the second piezoelectric disc.

The working method of the artificial pancreas system, which is the subject of the invention, includes the following steps; measuring glucose by a glucose sensor, transmitting the measurement made to a control unit via a first wireless data communication module, production of a control signal by determining the amount of insulin to be secreted by the control unit, according to the glucose level information received, amplification of the control signals produced by the control unit by an amplifier, application of the generated control signal to opposite surfaces of a first piezoelectric disc, creating a potential difference between these surfaces, the first piezoelectric disc making a vibratory motion including contraction and relaxation movements, wherein insulin is sucked from the reservoir attached to the nozzle during expansion, pumping the sucked insulin through the diffuser during contraction.

In an application of the invention that includes a glucagon tank, the working method of the artificial pancreas system includes the following steps; measuring glucose by a glucose sensor, transmitting the measurement made to a control unit via a first wireless data communication module, production of a control signal by determining the amount of glucagon to be secreted by the control unit, according to the glucose level information received, amplification of the control signals produced by the control unit in an amplifier, transmitting the said control signal to a second piezoelectric disc having a glucagon tank connected to its nozzle, application of the generated control signal to opposite surfaces of a second piezoelectric disc, creating a potential difference between these surfaces, the second piezoelectric disc making a vibratory motion including contraction and relaxation movements, wherein glucagon is sucked from the glucagon tank attached to the nozzle during expansion, pumping the sucked glucagon through the diffuser during contraction.

Detailed Description of the Invention

An artificial pancreas system realized to achieve the aim of the present invention is illustrated in the attached figures, which are; Figure 1. is a schematic view of the artificial pancreas system.

Figure 2. is a front view of the piezoelectric disc.

Figure 3. is the view of the suction mode of the piezoelectric disc in Figure 2.

Figure 4. is the view of the pumping mode of the piezoelectric disc in Figure

2.

Figure 5. is a schematic view of the artificial pancreas system comprising a glucagon tank.

Figure 6. is a schematic representation of closed loop glucose control.

The components given in the figures are enumerated individually, and the meanings of these numbers are given below.

10. Artificial pancreas system

20. Glucose measurement unit

21. Glucose sensor

22. First wireless data communication module

23. First battery

30. Piezoelectric driven pump

31. Control unit

32. Second wireless data communication module

33. Second battery

34. Amplifier

35. Reservoir

36. First piezoelectric disc

37. Nozzle

38. Diffuser

39. Glucagon tank

40. Second piezoelectric disc

50. Smart device

60. Safety valve H. Patient

An artificial pancreas system (10), which automatically determines the amount of insulin needed and provides basal or bolus insulin release accordingly, in its most basic form comprising: at least one glucose sensor (21) for taking a glucose level measurement; a first wireless data communication module (22) for exchanging wireless data; and a glucose measurement unit (20) comprising a first battery (23) meeting the required energy demand, at least one control unit (31) adapted to determine, on the basis of data measured by the glucose meter (20), the amount of insulin to be pumped and to generate control signals accordingly; a second wireless data communication module (32) for exchanging wireless data; a second battery (33) that supplies the required energy demand; at least one amplifier (34) for amplifying control signals output from the control unit (31); at least one reservoir (35) for containing insulin; a piezoelectric driven pump (30) comprising a nozzle (37) (inlet) and a diffuser (38) (outlet), and comprising at least one first piezoelectric disc (36) that allows the insulin in the reservoir (35) attached to the nozzle (37) to be sucked and pumped through the diffuser (38) in line with said control signals.

A schematic view of the artificial pancreas system (10) which is the subject of the invention is given in Figure 1. Said artificial pancreas system (10) is basically; a more reliable and energy efficient system, which includes a piezoelectric driven pump (30) that provides basal or bolus insulin delivery to the body and determines the amount of insulin needed according to the glucose level in the blood measured by the glucose measurement unit (20).

The glucose sensor (21) located in the glucose measurement unit (20) is an invasive sensor in one embodiment of the invention and contains a needle and is inserted into the skin of the patient (H) and left in this way. Thus, the glucose level in the patient's (H) blood is measured at regular intervals by the glucose sensor (21). The needle of the glucose sensor (21) can be changed at regular intervals and the said sensor can be used again. In another embodiment of the invention, non-invasive glucose sensors (21) (for example, ring-shaped sensors, sensors measuring glucose from sweat on fingertips or different types of sensors) can also be used. In order for the glucose values to be measured by the glucose measurement unit (20) not to be affected by the insulin secreted from the piezoelectric driven pump (30), the said glucose measurement unit (20) and the piezoelectric driven pump (30) are positioned at different positions. Thus, the artificial pancreas system (10) is allowed to work in a healthier way.

The electrical energy required by the glucose measurement unit (20) for glucose measurement and data transmission is supplied by a first battery (22). The glucose level values measured by the glucose sensor (21) can be transmitted via a first wireless data communication module (22) to the control unit (31) containing a second wireless data communication module (32) and/or a smart device (50). Said first wireless data communication module (22), second wireless data communication module (32) or smart device (50) preferably each includes a Bluetooth module, but the invention is not limited to this, and different wireless data communication modules (e.g. GPRS (General Packet Radio Service), GSM (Global System for Mobile Communications), 3G, 4G, 5G, Infrared, Wi-Fi (Wireless Fidelity), NFC (Near Field Connection) etc. communication modules can also be used.

The control unit (31), in one embodiment of the invention, is an electronic board comprising a controller such as a microprocessor adapted to run a control algorithm, a microcontroller, FPGA (Field-Programmable Gate Array), DSP (Digital Signal Processor) etc. The controller in the control unit (31) is preferably a PID (Proportional Integral Derivative) controller, but the invention is not limited to this, and may as well be other controllers such as State Feedback Controller or Model Predictive Control (MPC) etc. The control algorithm operated by the control unit (31) receives the glucose data transmitted by the glucose measurement unit (20) and puts it into a function, and thanks to this function, it calculates the amount of insulin to be injected into the body and generates control signals that will control the first piezoelectric disc (36) accordingly. In other words, the control unit (31) determines the amount of insulin needed using subcutaneous insulin concentration, plasma insulin concentration and insulin values-integrated insulin/glucose models, and controls the delivery of the determined additional insulin amount to the patient's (H) body.

In an application of the invention, when the glucose level in the blood increases, bolus insulin is secreted accordingly, and if the blood glucose level falls within a certain range, insulin continues to be secreted at the basal insulin level. Therefore, in the present invention, both basal and bolus insulin release can be made with the control signals produced by the control algorithm operated by the control unit (31).

The control signals generated by the control unit (31) are transmitted to an amplifier (34) located at the output of the control unit (31). The control signals mentioned here are amplified, in other words they are adjusted to voltage and current levels at which the first piezoelectric disc (36) can be moved in the form of contractions and expansions. After the control signals generated by the control unit (31) are amplified by the amplifier (34), they are transmitted to the first piezoelectric disc (36) connected to the output of the amplifier (34).

The electrical energy needed for the operation of the control unit (31), the second wireless data communication module (32), the amplifier (34) and the first piezoelectric disc (36), which are the electronic components in the piezoelectric driven pump (3), is provided by a second battery (33).

In an embodiment of the invention, the said first battery (23) and/or the second battery (33) is a rechargeable battery and is charged with electrical energy obtained from the human body by means of at least one energy harvesting equipment connected to the human body. In an embodiment of the invention, piezoelectric shoes, piezoelectric slippers or other systems that generate electricity from energy harvesting equipment can be used. The electrical energy obtained with the energy harvesting equipment is transferred to an energy management card and, after being regulated here, this regulated electrical energy is transmitted to the first battery (23) and/or the second battery (33) in a wired or wireless fashion, thus, the first battery (23) and the second battery (33) are charged.

In another embodiment of the invention, the first battery (23) and/or the second battery (33), can be charged by at least one wireless charging circuit adapted to be charged via a wireless charging unit and located in the glucose meter (20) and/or the piezoelectric driven pump (30).

In an embodiment of the present invention, the processor in the control unit (31) is operated in a way that consumes the lowest possible power. For this, some or all of the operations to be performed by the control unit (31) (for example, determining the amount of insulin to be injected), are carried out by a mobile application operated by the processor of a smart device (50), which is a smartphone or a tablet computer, connected via the second wireless data communication module (32) (for example, Bluetooth), and then transmitted to the control unit (31). Therefore, since the control unit (31) is operated for a shorter time period, the second battery (33) feeding this control unit (31) can last longer.

The insulin reservoir (35) in the piezoelectric driven pump (30) is a reservoir containing insulin and is connected to the nozzle (37) of the first piezoelectric disc (36). In one embodiment of the invention, the insulin reservoir (35) is a flexible (patch type) reservoir, but the invention is not limited to this, and the insulin reservoir (35) can also be a rigid reservoir.

The piezoelectric driven pump (30) is designed to be used for a long time and as a disposable pump. In the said piezoelectric driven pump (30), there is a first piezoelectric disc (36) with a nozzle (37) (inlet part) and a diffuser (38) (output part) (Figure 2). The first piezoelectric disc (36) is a material that generates electrical energy when subjected to a mechanical pressure, and creates mechanical displacement (expansion or contraction) when its opposite surfaces (floor and ceiling surfaces) are exposed to an electrical voltage (potential difference). The first piezoelectric disc (36) used in the piezoelectric driven pump (30) is very cheap, and this provides cost advantage and enables the production of disposable insulin pumps. Thus, thanks to the piezoelectric driven pump (30) used in the artificial pancreas system (10), diabetic patient (H) can use the artificial pancreas system (10) according to the invention without encountering problems such as calibration, manual adjustment, catheter occlusion, etc. by using a disposable daily or weekly insulin pump.

The nozzle (37) of the first piezoelectric disk (36) shown in Figures 2-4 is in the form of a cone or truncated cone that narrows as it extends outward from the first piezoelectric disk (36). The diffuser (38) of the first piezoelectric disc (36) is in a conical or truncated conical form that expands as it extends outward from the first piezoelectric disc (36). However, the geometric form of the nozzle (37) and the diffuser (38) of the first piezoelectric disc (36) is not limited to this, and it may also have triangular pyramid, truncated triangular pyramid or equivalent geometries instead of a conical form.

A catheter is connected to the diffuser (38) of the first piezoelectric disc (36) and the said catheter enters the body of the patient (H) subcutaneously. The nozzle (37) of the first piezoelectric disc (36) opens to the insulin reservoir (35).

The operating principle of the valveless piezoelectric driven pump (3) described above is as follows: Glucose measurement is made by the glucose sensor (31) located in the glucose measurement unit (3). As a result of this measurement, the amount of insulin to be secreted is determined by the control unit (31) according to the glucose level information transmitted over the first wireless data communication module (22), and control signals are generated accordingly. After these control signals are amplified in the amplifier (34), they are applied to the opposite surfaces of the first piezoelectric disc (36), creating a potential difference between these surfaces. When the voltage transmitted to the first piezoelectric disc (36) is negative, a downward displacement occurs in the first piezoelectric disc (36), in other words it expands (Figure 3). Meanwhile, insulin is sucked from both the reservoir (35) attached to the nozzle (37) and the catheter attached to the diffuser (38), and this insulin accumulates inside the first piezoelectric disc (36). However, here, due to the geometrical difference between the nozzle (37) and the diffuser (38) of the first piezoelectric disc (36), more absorption, compared to the diffuser (38), occurs from the reservoir (35) connected to the nozzle (37). When the voltage transmitted to the first piezoelectric disc (36) is positive, the base of the first piezoelectric disc (36) makes an upward displacement, in other words, it narrows down (Figure 4). Meanwhile, the insulin contained in the first piezoelectric disc (36) is pumped from both the nozzle (37) and the diffuser (38) of the first piezoelectric disc (36). However, due to the geometrical difference between the nozzle (37) and the diffuser (38) of the first piezoelectric disc (36), more insulin is pumped from the diffuser (38) compared to the nozzle (37) this time. As a result of a high frequency control signal (e.g. a sinus signal) applied to the first piezoelectric disk (36) by the control unit (31), an electric current is applied in sequentially opposite directions, and said first piezoelectric disc (36) carries out minimal vibrations (e.g. 100-150 times of expansion and contraction per second). During this high frequency minimal vibration movement, suction and pumping processes are carried out serially from the nozzle (37) and the diffuser (38) of the first piezoelectric disc (36). Thus, in line with the control signals transmitted from the control unit (31), the amount of insulin needed by the patient (H) is transmitted to the patient (H) via a catheter by the piezoelectric driven pump (30).

In one embodiment of the invention, the piezoelectric driven pump (30) also comprises a glucagon tank (39) for glucagon storage therein and a second piezoelectric disc (40) having a glucagon tank (39) connected to its nozzle (37) (Figure 5). The structure and working principle of the said second piezoelectric disk (40) is similar to the working principle of the first piezoelectric disk (36). In this embodiment of the invention, if a low glucose level is detected by the glucose measurement unit (20), the amount of glucagon to be secreted by the control unit (21) is determined and control signals are generated accordingly. After these control signals are amplified in an amplifier (34), they are transmitted to the second piezoelectric disc (40), causing it to make a vibrational movement including contraction and relaxation movements. During this vibration, the glucagon in the glucagon tank (39) connected to the nozzle (37) of the second piezoelectric disc (40) is sucked and injected into the body through a catheter connected to the diffuser (38) of the second piezoelectric disc (40). Thus, the low glucose level in the patient's (H) blood can be increased and kept within the desired range.

In an embodiment of the invention, the first piezoelectric disc (36) connected to the insulin reservoir (35) and/or the second piezoelectric disc (40) connected to the glucagon tank (39), comprises at least one safety valve (60) controlling the passage of insulin from a line connected to the diffuser (38) and/or nozzle (37) (Figure 1, Figure 5). When the piezoelectric driven pump (30) is not operating, the line connected to the diffuser (38) and/or nozzle (37) to be pumped with insulin is closed by this safety valve (60) according to the control signals coming from the control unit (31). When the piezoelectric driven pump (30) works, the line connected to the said nozzle (37) and/or diffuser (38) is opened by the safety valve (60), and insulin passage is allowed through that line. Thus, the insulin flow can be prevented by activating the safety valve, when the piezoelectric driven pump (30) does not work and/or in case of possible malfunctions.

While diabetic patients (H) follow the cycle they have to control (measurement- quantification-injection) on their own, it is shown in Figure 6 that this cycle is automated with the closed-loop glucose control in the artificial pancreas system (10) of the invention.