Device for in-vitro simulation detection of implantable blood glucose sensor

Abstract

The utility model belongs to the technical field of testing, and discloses a device for in-vitro simulation detection of an implantable blood glucose sensor, which comprises a bionic skin layer and a bionic tissue layer, the bionic skin layer is positioned on the top layer of the device and comprises a strength adjustable layer and an external electric field electrode electrically connected with two sides of the strength adjustable layer, and the external electric field electrode is positioned on the bottom layer of the bionic skin layer. The regulation and control circuit is electrically connected with one end, far away from the intensity adjustable layer, of the external electric field electrode on one side; the bionic tissue layer is located below the bionic skin layer and comprises a hydrogel layer attached to the lower portion of the strength-adjustable layer, a circulating pipeline layer attached to the bottom of the hydrogel layer and a pumping system located on the outer side of the hydrogel layer, a circulating pipeline of a zigzag surrounding structure is arranged on the circulating pipeline layer, a constant pressure valve is arranged on the circulating pipeline, and the constant pressure valve is connected with the strength-adjustable layer. And the pumping system is communicated with the circulating pipeline. The implantable blood glucose sensor is helpful for medical instrument researchers to obtain more real and reliable data in the in-vitro test and calibration process of the implantable blood glucose sensor.

Description

Technical Field

[0001] This invention belongs to the field of testing technology, specifically relating to a device for in vitro simulated detection of implantable blood glucose sensors. Background Technology

[0002] Traditional blood glucose monitoring typically requires collecting blood samples from patients. This method has drawbacks such as the need for frequent blood sampling, invasiveness, and inconvenience for long-term monitoring. To address these issues, implantable blood glucose sensors have been developed. By implanting the sensor under the patient's skin, continuous monitoring of blood glucose levels can be achieved.

[0003] Due to batch-to-batch variability in the manufacturing process of implantable blood glucose sensors, each sensor requires in vitro testing and calibration before leaving the factory to improve accuracy during actual in vivo measurements. Therefore, extensive simulated in vivo testing is necessary during the manufacturing process of implantable blood glucose sensors. Simultaneously, the development of implantable sensors also requires simulated testing of the sensor electrode insertion into the skin and the semi-embedded process to determine biophysical indicators such as the strength of the electrode outer membrane and the wear resistance of the material. Currently, in vitro simulation testing of implantable blood glucose sensors is conducted in aqueous solutions, with the electrodes directly placed in a sugar-containing solution. This cannot effectively simulate the force process of penetrating the skin and the tissue compression caused by skin friction.

[0004] Furthermore, in the actual in vivo sensing environment, the sugar distribution in human tissue fluid is constantly changing. Currently, the testing environment for most implantable electrodes is typically a static state, which differs from the flowing tissue fluid environment in the human body. This discrepancy between the testing environment and the actual working environment leads to deviations in the calibration values ​​obtained from in vitro simulated testing. Utility Model Content

[0005] To address the technical problem of distortion in in vitro simulation of existing implantable blood glucose sensors, the purpose of this invention is to propose a device for in vitro simulation testing of implantable blood glucose sensors. This device uses biomimetic flexible materials to fully simulate the skin puncture process and the influence of subcutaneous tissue activity on the electrodes, accurately and reliably feeding back the response data of the sensor electrodes to different concentrations of glucose after skin puncture. This provides researchers with a more realistic and reliable means of evaluating the transdermal dynamic process and operational stability of implantable blood glucose sensors.

[0006] To achieve the above objectives, the present invention adopts the following technical solution:

[0007] This invention provides a device for in vitro simulated detection of blood glucose using an implantable blood glucose sensor, comprising at least:

[0008] A bionic skin layer, located on the top layer of the device, includes an intensity adjustable layer, external electric field electrodes electrically connected to both sides of the intensity adjustable layer, and a control circuit electrically connected to one end of the external electric field electrode away from the intensity adjustable layer.

[0009] The biomimetic tissue layer, located below the biomimetic skin layer, includes a hydrogel layer attached to the strength adjustable layer, a circulation channel layer attached to the bottom of the hydrogel layer, and a pumping system located outside the hydrogel layer. The circulation channel layer has a tortuous, looping circulation channel, and a constant pressure valve is installed on the circulation channel. The pumping system is connected to the circulation channel.

[0010] In a preferred embodiment, the material of the strength-adjustable layer includes electrorheological fluid material, electroactive polymer material, or liquid crystal elastomer material.

[0011] In a preferred embodiment, the strength adjustment range of the strength-adjustable layer is 10-50 N / cm.

[0012] In a preferred embodiment, the electrorheological fluid material comprises one of polydimethylsiloxane and graphite dopant, titanium dioxide particles and silicone oil dopant, and polystyrene particles and silicone oil dopant; the electroactive polymer material comprises one of polypyrrole-perfluorosulfonic acid ion exchange polymer mixture and polyaniline-acrylate elastomer; and the liquid crystal elastomer material comprises one of acrylic liquid crystal elastomer, siloxane liquid crystal elastomer, polyurethane-liquid crystal copolymer, and styrene liquid crystal elastomer.

[0013] In a preferred embodiment, the thickness of the intensity-adjustable layer in the bionic skin layer is between 0.5 mm and 5 mm.

[0014] In a preferred embodiment, the hydrogel layer is composed of a hydrous porous gel with a tensile strength of 10-30 MPa.

[0015] In a preferred embodiment, the hydrophilic porous gel is made of one of the following materials: polyvinyl alcohol, polyacrylamide, sodium alginate, chitosan, hydroxyethyl methacrylate, hyaluronic acid, carboxymethyl cellulose, and gelatin.

[0016] In a preferred embodiment, the pipe wall of the circulation pipe that contacts the bottom surface of the hydrogel layer is configured as a semi-permeable membrane structure, and the molecular weight cutoff of the pipe wall is 1 KD.

[0017] In a preferred embodiment, the pumping system includes a test stock solution storage tank, a diluent storage tank, a wastewater tank, and a peristaltic pump. The test stock solution storage tank and the diluent storage tank are connected to one end of the circulation pipeline, and the wastewater tank is connected to the other end of the circulation pipeline.

[0018] Compared with the prior art, the present invention has the following advantages:

[0019] This invention improves the simulation and accuracy of in vitro testing of implantable blood glucose sensors by constructing a biomimetic simulated skin layer and a simulated subcutaneous tissue layer. The intensity of the biomimetic skin layer can be adjusted by an electric field to simulate the skin conditions of different populations, broadening the detection range of the implantable electrode. The biomimetic tissue layer simulates the diffusion process of glucose in subcutaneous tissue, making the sensor testing environment and dynamic response more closely resemble actual human conditions. A test liquid channel is constructed using circulation pipes and a pumping system, ensuring that the test liquid remains in a flowing state throughout the implantable blood glucose sensor testing process. This prevents liquid evaporation and volume reduction during testing, ensuring stable testing depth of the electrode. Simultaneously, the simulated tissue fluid continuously diffuses outward into the hydrogel layer, with controllable and constantly updated glucose content, providing a linear diffusion process and improving the simulation of in vitro testing. This design allows researchers and production quality control personnel to obtain more realistic and reliable evaluation methods in in vitro calibration, implantation process optimization experiments, and kinetic testing of implantable blood glucose sensors. Attached Figure Description

[0020] Figure 1 This is a schematic diagram of the structure of a device for in vitro simulated detection of an implantable blood glucose sensor in Example 1;

[0021] Figure 2 for Figure 1 A partial structural exploded view of the device shown.

[0022] Figure 3 This is a graph showing the relationship between the applied electric field voltage and the tear strength of the electrorheological fluid material in Example 2.

[0023] Figure 4 This is a concentration-time curve of glucose permeation in the chitosan hydrogel layer in Example 2;

[0024] Figure 5 This is a graph showing the relationship between the applied electric field voltage and the tear strength of the electroactive polymer material in Example 3;

[0025] Figure 6 This is a concentration-time curve of glucose permeation in the polyacrylamide hydrogel layer in Example 3.

[0026] In the diagram: 1. Bionic skin layer; 11. Intensity adjustable layer; 12. External electric field electrode; 13. Control circuit; 2. Bionic tissue layer; 21. Hydrogel layer; 22. Circulation pipeline layer; 221. Circulation pipeline; 222. Constant pressure valve; 23. Pumping system; 51. Diluent storage tank; 52. Test stock solution storage tank; 53. Wastewater tank. Detailed Implementation

[0027] To make the objectives, technical solutions, and advantages of this utility model clearer, the present utility model will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the present utility model and are not intended to limit the present utility model.

[0028] In the description of this utility model, it should be understood that the terms "upper," "lower," "front," "rear," "inner," and "outer," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are only for the convenience of describing this utility model and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this utility model. Relational terms such as "first" and "second" are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations.

[0029] In the description of this utility model, it should be noted that, unless otherwise explicitly specified and limited, the terms "installation", "connection" and "linking" should be interpreted broadly. For example, they can refer to a fixed connection, an integral connection, or a detachable connection; they can refer to the internal connection of two components; they can refer to a direct connection or an indirect connection through an intermediate medium. For those skilled in the art, the specific meaning of the above terms in this utility model can be understood according to the specific circumstances.

[0030] Example 1

[0031] like Figure 1 and Figure 2 As shown, this embodiment discloses a device for in vitro simulation detection of an implantable blood glucose sensor, including a bionic skin layer 1 and a bionic tissue layer 2. The bionic skin layer 1 is located on the top layer of the device and is mainly used to simulate the force state and friction during the skin puncture process of the implantable blood glucose sensor electrode. The bionic tissue layer 2 is located below the bionic skin layer 1 and can simulate the glucose permeation and diffusion process in tissue fluid to achieve the purpose of regulating the glucose test concentration.

[0032] In this embodiment, the biomimetic skin layer 1 includes an adjustable intensity layer 11, an external electric field electrode 12, and a control circuit 13. The two sides of the adjustable intensity layer 11 are electrically connected to the external electric field electrode 12, and the control circuit 13 is electrically connected to the end of the external electric field electrode 12 furthest from the adjustable intensity layer 11. The adjustable intensity layer 11 is composed of electrorheological fluid material, electroactive polymer material, or liquid crystal elastomer material, and can rapidly change the viscosity and shear modulus of the fluid under the action of an electric field, with the change process being reversible. Thus, by adjusting the external electric field electrode 12 through the control circuit 13, the adjustable intensity layer 11 forms simulated skin of different intensities under the action of electric fields of different magnitudes. This allows the implanted blood glucose sensor electrode to effectively simulate the force state and friction during the puncture of real skin, ensuring the simulation accuracy and realism of the in vitro simulation detection. The skin tear strength simulated by the adjustable intensity layer 11 is adjustable within the range of 10-50 N / cm. Preferably, the electrorheological fluid material is selected from one or a combination of several of the following: polydimethylsiloxane and graphite dopant, titanium dioxide particles and silicone oil dopant, and polystyrene particles and silicone oil dopant; the electroactive polymer material is selected from one or a combination of several of the following: polypyrrole-perfluorosulfonic acid ion exchange polymer mixture and polyaniline-acrylate elastomer; and the liquid crystal elastomer material is selected from one or a combination of several of the following: acrylic liquid crystal elastomer, siloxane liquid crystal elastomer, polyurethane-liquid crystal copolymer, and styrene liquid crystal elastomer. It should be noted that the thickness of the intensity-adjustable layer 11 in the biomimetic skin layer 1 is set between 0.5 mm and 5 mm.

[0033] Furthermore, in this embodiment, the biomimetic tissue layer 2 includes a hydrogel layer 21, a circulation channel layer 22, and a pumping system 23. The hydrogel layer 21 is attached to the strength-adjustable layer 11 and the external electric field electrode 12, and one side is in partial contact with the control circuit 13. It is composed of a hydrogel with a porous structure and is used to realize the concentration gradient diffusion of glucose from the circulation channel 221 to the biomimetic skin layer 1. Preferably, the material of the hydrogel layer 21 is selected from one or a combination of several of polyvinyl alcohol, polyacrylamide, sodium alginate, chitosan, hydroxyethyl methacrylate, hyaluronic acid, carboxymethyl cellulose, and gelatin. The tensile strength of this layer can be 10-30 MPa, which is close to the tensile strength of real subcutaneous tissue. The tensile strength can be adjusted by controlling the degree of crosslinking during the gel preparation process.

[0034] Furthermore, the circulation channel layer 22 is attached to the bottom of the hydrogel layer 21, and a tortuous, looping circulation channel 221 is provided on it to increase the contact area between the circulation channel 221 and the hydrogel layer 21. It should be noted that the wall of the circulation channel 221 in contact with the hydrogel layer 21 is designed as a semi-permeable membrane structure, which can mimic the selective permeability of blood vessel walls to allow glucose and other small test molecules to pass through. When the glucose solution used for testing flows within the circulation channel 221, it can diffuse through the semi-permeable membrane structure wall into the hydrogel layer 21. Preferably, the molecular weight cut-off of the semi-permeable membrane structure wall is 1 kDa. In addition, several constant pressure valves 222 are also provided on the circulation channel 221. Since the test liquid in the circulation channel 221 has the ability to diffuse and exchange with the hydrogel layer 21, the constant pressure valves 222 ensure that the pressure throughout the circulation channel 221 is basically uniform, allowing the test liquid to diffuse evenly into the hydrogel layer 21 and ensuring the accuracy of the test results.

[0035] Furthermore, in this embodiment, the pumping system 23 is located outside the hydrogel layer 21 and the circulation pipe layer 22, below the control circuit 13, and is connected to the circulation pipe 221 in the circulation pipe layer 22. Specifically, the pumping system 23 includes a test stock solution storage tank 52, a diluent storage tank 51, a wastewater tank 53, and a peristaltic pump. The test stock solution storage tank 52 and the diluent storage tank 51 are connected to one end of the circulation pipe 221, and can be mixed into a glucose solution of the target concentration according to the test requirements. Under the action of the peristaltic pump, the glucose solution of the target concentration is pumped from one end of the circulation pipe 221 into the circulation pipe 221. The wastewater tank 53 is connected to the other end of the circulation pipe 221 and is used to collect the waste liquid generated during the test. Under the action of the pumping system 23, the glucose solution is always kept in a flowing state in the circulation pipe 221, which can avoid the reduction of liquid volume due to evaporation during the test and ensure the stability of the blood glucose sensor electrode test depth. When the concentration of the glucose solution used for testing needs to be updated, the injection ratio of glucose stock solution in test stock solution storage tank 52 and water in dilution solution storage tank 51 is adjusted by pumping system 23 to prepare a new concentration of glucose test solution. As the new concentration of glucose test solution is pumped into circulation pipeline 221, the old test solution is discharged from the other end of circulation pipeline 221 into wastewater tank 53, thereby completing the update of the concentration of glucose solution used for testing.

[0036] Furthermore, the device for in vitro simulation testing of the implantable blood glucose sensor in this embodiment also includes an analysis device. It should be understood that during in vitro testing, the implantable blood glucose sensor's electrodes penetrate the intensity-adjustable layer 11 of the biomimetic skin layer 1 via a needle assist and guide needle, ensuring full contact with the hydrogel layer 21 of the biomimetic tissue layer 2. The sensor detection and emission module is fixed to the intensity-adjustable layer 11 and communicates with the analysis device, transmitting the detection data collected by the sensor electrodes to the analysis device in real time for analysis by researchers or quality control personnel.

[0037] Example 2

[0038] The device for in vitro simulated detection of implantable blood glucose sensors in this embodiment has an adjustable strength layer 11 in its biomimetic skin layer 1, which is a electrorheological fluid material composed of titanium dioxide particles and silicone oil dopant, with a thickness of 2.5 mm. A voltage is applied to the external electric field electrode 12 on one side via the control circuit 13, with the applied voltage amplitude ranging from 0 V to 10 V. The correspondence between the voltage amplitude and the strength of the electrorheological fluid material is as follows: Figure 3 As shown. The material's tear strength adjustment range effectively simulates adult male skin, and the puncture process of an implantable blood glucose sensor on such skin was tested.

[0039] Furthermore, in this embodiment, the biomimetic tissue layer 2 is located below the biomimetic skin layer 1. Its hydrogel layer 21 is composed of chitosan, and its tensile strength after chemical cross-linking is 14 MPa, which can simulate subcutaneous tissue mainly composed of fat. The circulation pipe layer 22 is located below the hydrogel layer 21, and it has a tortuous, encircling circulation pipe 221. A pumping system 23 draws diluent water and glucose stock solution from the diluent storage tank 51 and the test stock solution storage tank 52, respectively. The two liquids are mixed in a predetermined ratio according to the preset glucose solution concentration and then injected into the circulation pipe 221. During the flow of the liquid in the circulation pipe 221, glucose diffuses into the hydrogel layer 21 through the semi-permeable membrane structure under the action of the concentration gradient. The glucose concentration permeation time curve in the hydrogel layer 21 is shown below. Figure 4 As shown, by Figure 4 It can be seen that the data obtained in the gel simulation test of this embodiment has a similar trend and response time to the data from the implanted test. However, the concentration response changes drastically in the traditional aqueous solution environment test, which does not match the actual situation in a biological body. It should be noted that during the in vitro testing of the implanted blood glucose sensor, the sensor electrode penetrates the intensity-adjustable layer 11 of the biomimetic skin layer 1 through the needle aid and guide needle, and makes full contact with the hydrogel layer 21 of the biomimetic tissue layer 2. The sensor detection and emission module is fixed on the intensity-adjustable layer 11, and collects data in real time for researchers or quality inspectors to analyze.

[0040] Example 3

[0041] The device for in vitro simulated detection of implantable blood glucose sensors in this embodiment has an adjustable strength layer 11 in its biomimetic skin layer 1, which is an electroactive polymer material, specifically a polypyrrole-perfluorosulfonic acid ion-exchange polymer mixture, with a thickness of 1.5 mm. A voltage is applied to the external electric field electrode 12 on one side via a control circuit 13, with the applied voltage amplitude ranging from 0 V to 8 V. The relationship between the voltage amplitude and the strength of the electroactive polymer material is as follows: Figure 5 As shown. The material's tear strength adjustment range effectively mimics children's skin, and the puncture process of an implantable blood glucose sensor on such skin was tested.

[0042] Furthermore, in this embodiment, the biomimetic tissue layer 2 is located below the biomimetic skin layer 1. Its hydrogel layer 21 is composed of polyacrylamide, and its tensile strength after chemical cross-linking is 21 MPa, which can simulate subcutaneous tissue with less fat. The circulation pipe layer 22 is located below the hydrogel layer 21, and it has a tortuous, encircling circulation pipe 221. A pumping system 23 draws diluent water and glucose stock solution from the diluent storage tank 51 and the test stock solution storage tank 52, respectively. The two liquids are mixed in a predetermined ratio according to the preset glucose solution concentration and injected into the circulation pipe 221. During the flow of the liquid in the circulation pipe 221, glucose diffuses into the hydrogel layer 21 through the semi-permeable membrane structure under the action of the concentration gradient. The glucose concentration permeation time curve in the hydrogel layer 21 is shown below. Figure 6 As shown, the blood glucose levels exhibit a gradual upward trend, consistent with actual conditions in living organisms. It should be noted that during in vitro testing, the implantable blood glucose sensor uses a needle applicator and guide needle to penetrate the intensity-adjustable layer 11 of the biomimetic skin layer 1, ensuring full contact with the hydrogel layer 21 of the biomimetic tissue layer 2. The sensor's detection and emission module is fixed to the intensity-adjustable layer 11, collecting data in real time for analysis by researchers or quality control personnel.

Claims

1. A device for in vitro simulated detection of blood glucose using an implantable blood glucose sensor, characterized in that, At least including: Bionic skin layer (1), the bionic skin layer (1) is located on the top layer of the device, and includes an intensity adjustable layer (11), external electric field electrodes (12) electrically connected to both sides of the intensity adjustable layer (11), and a control circuit (13) electrically connected to one end of the external electric field electrode (12) away from the intensity adjustable layer (11). The biomimetic tissue layer (2) is located below the biomimetic skin layer (1). It includes a hydrogel layer (21) attached to the strength adjustable layer (11), a circulation channel layer (22) attached to the bottom of the hydrogel layer (21), and a pumping system (23) located outside the hydrogel layer (21). The circulation channel layer (22) is provided with a tortuous and circular circulation channel (221), and a constant pressure valve (222) is provided on the circulation channel (221). The pumping system (23) is connected to the circulation channel (221).

2. The device for in vitro simulated detection of implantable blood glucose sensors according to claim 1, characterized in that, The strength-adjustable layer (11) is made of electrorheological fluid material, electroactive polymer material or liquid crystal elastomer material.

3. The device for in vitro simulated detection of implantable blood glucose sensors according to claim 1, characterized in that, The strength adjustment range of the strength-adjustable layer (11) is 10-50 N / cm.

4. The device for in vitro simulated detection of implantable blood glucose sensors according to claim 2, characterized in that, The electrorheological fluid material includes one of polydimethylsiloxane and graphite dopant, titanium dioxide particles and silicone oil dopant, and polystyrene particles and silicone oil dopant; the electroactive polymer material includes one of polypyrrole-perfluorosulfonic acid ion exchange polymer mixture and polyaniline-acrylate elastomer; the liquid crystal elastomer material includes one of acrylic liquid crystal elastomer, siloxane liquid crystal elastomer, polyurethane-liquid crystal copolymer, and styrene liquid crystal elastomer.

5. The device for in vitro simulated detection of an implantable blood glucose sensor according to claim 1, characterized in that, The thickness of the intensity-adjustable layer (11) in the bionic skin layer (1) is between 0.5 mm and 5 mm.

6. The device for in vitro simulated detection of an implantable blood glucose sensor according to claim 1, characterized in that, The hydrogel layer (21) is composed of a hydroporous porous gel with a tensile strength of 10-30 MPa.

7. The device for in vitro simulated detection of implantable blood glucose sensors according to claim 6, characterized in that, The hydrophilic porous gel is made of one of the following materials: polyvinyl alcohol, polyacrylamide, sodium alginate, chitosan, hydroxyethyl methacrylate, hyaluronic acid, carboxymethyl cellulose, and gelatin.

8. The device for in vitro simulated detection of implantable blood glucose sensors according to claim 1, characterized in that, The wall of the circulation pipe (221) that is in contact with the bottom surface of the hydrogel layer (21) is configured as a semi-permeable membrane structure, and the molecular weight cutoff of the pipe wall is 1 KD.

9. The device for in vitro simulated detection of implantable blood glucose sensors according to claim 1, characterized in that, The pumping system (23) includes a test stock solution storage tank (52), a diluent storage tank (51), a wastewater tank (53), and a peristaltic pump. The test stock solution storage tank (52) and the diluent storage tank (51) are connected to one end of the circulation pipeline (221), and the wastewater tank (53) is connected to the other end of the circulation pipeline (221).

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