Sensing device having decellularized extracellular matrix and method for manufacturing decellularized extracellular matrix

Abstract

A sensing device (10) having a decellularized extracellular matrix and a method for manufacturing the decellularized extracellular matrix. The sensing device (10) is configured to be applied to a first biological tissue (20) of a first biological organ of a first organism, and the sensing device (10) comprises a second biological tissue (101) composed of a decellularized extracellular matrix and a sensor assembly (102). The second biological tissue (101) is biologically matched with the first biological tissue (20). The sensor assembly (102) is disposed on the second biological tissue (101) and has a thin film substrate (1021) and at least one signal sensing element (1022). The thin film substrate (1021) is biocompatible with the second biological tissue (101). The signal sensing element (1022) is formed on the thin film substrate (1021) and has a stack structure comprising at least two layers, and is configured to sense a physiological signal of the first biological tissue (20) or an environmental signal around the first biological tissue (20).

Description

[0001] Sensing Device with Decellularized Extracellular Matrix and Method for Manufacturing the Decellularized Extracellular Matrix Technical Field This disclosure relates to a sensing device, and more particularly to a sensing device with a decellularized extracellular matrix. Background Art With the advancement of electronic technology, the size of various sensors is evolving from the micrometer scale to the nanometer scale. Simultaneously, the application scope of attaching or implanting various sensors into biological tissues to sense signals from those tissues is expanding. However, technically, how to attach or implant sensors into biological tissues, and how to reduce or even eliminate biocompatibility problems and immune rejection reactions between biological tissues and all electronic components in the sensors, has always been a challenge in this technical field. Furthermore, from a manufacturing perspective, how to integrate multiple sensors with different functions into a single fabrication is also a technical problem that needs to be solved. For example, the dermis of human skin has an uneven surface, posing a significant challenge to fabricating electronic components for sensors on it. In view of the above-mentioned problems, this disclosure proposes a sensing device with decellularized extracellular matrix (dECM) and a method for manufacturing the decellularized extracellular matrix. The first aspect of this disclosure proposes a sensing device with decellularized extracellular matrix, which fabricates multiple sensors with different functions on a biocompatible thin-film substrate. Various logic circuits are designed according to the functional combinations of the sensors to realize logical judgment and data processing of physiological signals from biological tissues or environmental signals surrounding biological tissues. Furthermore, the proposed sensing device with decellularized extracellular matrix is ​​formed by attaching a thin-film substrate carrying multiple sensors to a second biological tissue whose biological characteristics are closely similar to those of a first biological tissue of a first biological organ of a first organism to which the sensing device is to be applied, thereby reducing adverse reactions of the applied first biological tissue to the sensing device. In one embodiment, the proposed sensing device is used to be applied to a first biological tissue of a first biological organ of a first organism, and includes a second biological tissue and a sensor assembly. The second biological tissue is composed of a decellularized extracellular matrix with multiple pores, obtained by decellularizing a tissue from a second biological organ of a second organism. Furthermore, the second biological tissue and the first biological tissue are biocompatible, or the second biological organ and the first biological organ are homologous or analogous organs. A sensor assembly is disposed on the second biological tissue and has a thin-film substrate and at least one signal sensor.The thin film substrate has a first surface and a second surface facing away from each other, is disposed on a second biological tissue, and is biocompatible. A signal sensing element is formed on the first surface of the thin film substrate and has a stacked structure of at least two layers, used to sense physiological signals of the first biological tissue or environmental signals surrounding the first biological tissue. In one embodiment, the physiological signal is, for example, a blood glucose signal, a lactic acid concentration signal, a uric acid concentration signal, a histamine concentration signal, a glucose concentration signal in tissue fluid, a metabolic product concentration signal in tissue fluid, an electrolyte ion concentration signal in blood, a pH value signal, a temperature signal, a pressure signal, an abnormal brainwave discharge signal, a current signal, a signal indicating the growth status of perennial woody or herbaceous plants, a signal indicating whether crops are ripe, a signal indicating the sweetness of fruits, or a chemical molecule signal. The environmental signal may be, for example, temperature, external force, external stimulus, pressure, sound waves, visible light, ultraviolet light, taste molecules, odor molecules, or other external stimulus signals that trigger a response in a biological receptor, such as a warmth receptor or cold receptor. In one embodiment, the proposed sensing device further includes an adhesive layer disposed between the second biological tissue and the sensor assembly, bonding the second surface of the thin film substrate and the second biological tissue together. In one embodiment, the adhesive layer is made of a biocompatible adhesive, polylactic acid, modified polylactic acid, cellulose, hyaluronic acid, starch, collagen, gelatin, sodium alginate, chitosan, polyvinyl alcohol, and polymethyl methacrylate. In one embodiment, a plurality of spaced conductive pads are formed on the first surface of the thin film substrate of the proposed sensing device, and each signal sensing element has a signal sensing material layer formed on one of the conductive pads. In one embodiment, the signal sensing material layer of the proposed sensing device is formed on the conductive pad by deposition or droplet coating. In another embodiment, the signal sensing material layer of the proposed sensing device comprises polylactic acid doped with a substance selected from the group consisting of retinoic acid, lycopene, and astaxanthin. In one embodiment, the thickness of the thin film substrate of the proposed sensing device is from 1 nm to 400 nm; or, the thickness of the second biological tissue is from 0.01 mm to 5 mm.In one embodiment, the thickness of the second biological tissue is 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, or 5 mm. In one embodiment, the second biological tissue comprises a decellularized collagen scaffold structure. In one embodiment, the proposed sensing device is implanted on the first biological tissue of the first biological organ of the first organism, and the decellularized extracellular matrix comprises: an extracellular matrix network structure having the pores; and at least one functional molecule distributed in the extracellular matrix network structure to induce a stem cell or other cell related to the physiological function of the first biological organ to migrate into the extracellular matrix network structure, thereby gradually expanding the non-free-flowing tissue fluid in the first biological organ into the extracellular matrix network structure; thereby, the transmission efficiency of the physiological signal or the environmental signal from the first biological organ to the sensing device is improved, and the sensitivity of the sensing device in detecting the physiological signal or the environmental signal is increased. In one embodiment, the pores accommodate 1 to 10 of the stem cells or the other cells.In one embodiment, the average inner diameter of the aperture is from 10 nm to 1000 nm. In another embodiment, the average inner diameter of the aperture is 10 nm, 20 nm, 25 nm, 30 nm, 40 nm, 50 nm, 60 nm, 70 nm, 75 nm, 80 nm, 90 nm, 100 nm, 120 nm, 140 nm, 150 nm, 160 nm, 180 nm, 200 nm, 220 nm, 240 nm, 250 nm, 260 nm, 280 nm, 300 nm, 320 nm, 340 nm, 350 nm, 360 nm, 380 nm. 400 |J m, 420 |J m, 440 |J m, 450 |J m, 460 |J m, 480 |J m, 500 |J m, 520 |J m, 540 |J m, 550 |jm, 560 |J m, 580 |J m, 600 |J m, 620 |J m, 640 |J m, 650 |J m, 660 |J m, 680 |J m, 700 |J m, 720 |J m, 740 |J m, 750 |J m, 760 |J m, 780 |J m, 800 |J m, 820 |J m, 840 |im, 850 |J m, 860 |J m, 880 |J m, 900 |J The material is selected from one of m, 920 |J m, 940 |J m, 950 |J m, 960 |im, 980 |im, and 1000 |J m. In one embodiment, the film substrate is made of one of polylactic acid, modified polylactic acid, cellulose, hyaluronic acid, starch, collagen, gelatin, sodium alginate, chitosan, PVA, and PMMA, or any combination thereof. In one embodiment, the film substrate is made of polylactic acid doped with triethyl citrate, and the mass ratio of triethyl citrate to polylactic acid is 5% to 10%. In one embodiment, the mass ratio of triethyl citrate to polylactic acid is one of 5%, 6%, 7%, 8%, 9%, and 10%.In one embodiment, the signal sensing element is one of the following: a thin-film transistor signal sensing element, a temperature sensor signal sensing element, an ultraviolet light sensor signal sensing element, a strain sensor signal sensing element, and a synapse-like sensor signal sensing element. In one embodiment, the signal sensing element comprises at least one temperature sensor signal sensing element, one synapse-like sensor signal sensing element, and one thin-film transistor signal sensing element to form a logic circuit. In one embodiment, the logic circuit formed by the signal sensing elements is used to perform edge computing of the physiological signal or the environmental signal. In one embodiment, the sensor assembly outputs an action potential signal to the actuator of the first organism. In one embodiment, the actuator of the first organism is a motor nerve, a muscle, a gland, or other actuator of the first organism. In one embodiment, the number of signal sensing elements is two or more, and the physiological signal or the environmental signal sensed by all signal sensing elements is different. In one embodiment, the operating voltage of the sensor assembly is as low as 1mV. In one embodiment, the number of signal sensors per square centimeter of the thin film substrate is at least 1000. In another embodiment, the proposed sensing device is connected to an electronic device disposed outside the first biological organ and used to receive the physiological signal or the environmental signal output from the sensing device. In one embodiment, the electronic device has a threshold range for one of the physiological signal and the environmental signal; when the signal strength of one of the physiological signal and the environmental signal exceeds the threshold range, the electronic device outputs a strain signal and transmits the strain signal to the first biological organ through the sensing device. In one embodiment, the proposed sensing device with a decellularized extracellular matrix has functions similar to those of human skin sensory receptors, such as sensing touch, pain, temperature, pressure, sensory receptor potentials, pain nerve potentials, or potentials of other nerves. In one embodiment, the tissue of the second biological organ is one of animal skin, the dermis of animal skin, animal meninges, animal cornea, animal intestinal membrane, animal diaphragm, animal blood vessels, plant leaf veins, plant bark, plant microvascular bundles, and bamboo membrane. In one embodiment, the second biological organ is one of the heart, small intestine, lungs, spleen, kidneys, liver, stomach, pancreas, bladder, colon, rectum, and brain. In one embodiment, the first organism and the second organism are different species. In one embodiment, the first organism is a human and the second organism is a pig.A second aspect of this disclosure provides a method for manufacturing the decellularized extracellular matrix of a sensing device having a decellularized extracellular matrix, comprising: step (a) obtaining the tissue from a second biological organ of a second organism; and step (b) removing cells from the tissue of the second biological organ to form the decellularized extracellular matrix. In one embodiment, the proposed method for manufacturing the decellularized extracellular matrix further comprises: step (c) washing the tissue of the second biological organ after cell removal. In one embodiment, step (b) comprises: treating the tissue of the second biological organ with at least one supercritical fluid under at least one pressure condition and at least one temperature condition. In one embodiment, step (b) comprises: treating the tissue of the second biological organ under a first temperature condition and a static pressure condition with the supercritical fluid in the presence of a first co-solvent for a first time interval; then treating the tissue of the second biological organ treated with the supercritical fluid under the static pressure condition under a dynamic pressure condition with the supercritical fluid in the presence of a second co-solvent for a second time interval, the second time interval being longer than the first time interval, wherein the supercritical fluid is simultaneously depressurized and pressurized under the dynamic pressure condition. In one embodiment, the first temperature condition is 30 to 500°C, the static pressure condition is 200 to 500 bar, the dynamic pressure condition is 200 to 500 bar, the second time interval is 10 to 100 minutes, and the flow rate of the supercritical fluid during depressurization is 10 to 30 liters per minute. In one embodiment, the supercritical fluid is independently selected from the group consisting of supercritical carbon dioxide (ScCO2), supercritical nitrous oxide (ScN2O), supercritical alkane > supercritical alkene > supercritical alcohol > supercritical acetone, and combinations thereof. In one embodiment, the first co-solvent or the second co-solvent is 30% (vol%) to 100% (vol%) ethanol. Preferably, the first co-solvent or the second co-solvent is 75% (vol%) ethanol.In one embodiment, the first co-solvent may be a C1-4 alcohol, selected from the group consisting of ethanol, propanol, isopropanol, butanol, isobutanol, sec-butanol, t-butanol, and cyclobutanol. In one embodiment, step (b) includes: step (b1): treating the tissue of the second biological organ with ScCO2 at a static pressure of 350 to 500 bar for a first time interval of 10 to 80 minutes at a temperature of 40 to 50°C; step (b2): treating the product of step (b1) with ScCO2 at a dynamic pressure of 350 to 500 bar and a depressurization flow rate of 20 liters per minute for a second time interval of 10 to 80 minutes at a temperature of 40 to 50°C. In one embodiment, step (b1) includes: The tissue of the second biological organ is treated with ScCO2 at a static pressure of 200 to 500 bar for 10 to 100 minutes at a temperature of 30 to 500°C. In one embodiment, step (b2) includes treating the tissue of the second biological organ with ScCO2 at a dynamic pressure of 200 to 500 bar, wherein the supercritical fluid is depressurized and pressurized, wherein the pressurized supercritical fluid is pumped to the product of step (b1) at a flow rate of 0.1 to 100 liters per minute. In one embodiment, the proposed method for manufacturing decellularized extracellular matrix further includes, between steps (a) and (b): step (x) soaking the tissue of the second biological organ in a hypertonic solution for 10 to 60 minutes, the hypertonic solution being a salt solution containing 0.5 to 4.0 M NaCl; and step (y) soaking the tissue of the second biological organ treated with the hypertonic solution in a hypotonic solution for 10 to 60 minutes, the hypotonic solution being water. In one embodiment, step (c) comprises treating the tissue of the decellularized second biological organ with an alkaline solution of 0.01 to 1.0 N to neutralize the pH of the tissue of the decellularized second biological organ. In one embodiment, the alkaline solution is one of sodium hydroxide solution, calcium hydroxide solution, potassium hydroxide solution, sodium carbonate solution, and sodium bicarbonate solution. In one embodiment, the proposed method for manufacturing the decellularized extracellular matrix further comprises, before or after step (b), removing contaminating pathogens from the tissue of the second biological organ.In summary, the sensing device with decellularized extracellular matrix proposed in this disclosure fabricates multiple signal sensors with different sensing functions on a biocompatible thin film substrate. The fabricated sensor assembly is then bonded to another biological tissue that is biocompatible with the biological tissue to which the decellularized extracellular matrix sensing device is applied, allowing the other biological tissue to contact the applied biological tissue. This significantly reduces adverse reactions and immune rejection reactions of the applied biological tissue to the sensor assembly. Furthermore, since the thin film substrate itself is biocompatible and the signal sensors are also fabricated from biocompatible materials, the entire decellularized extracellular matrix sensing device and the applied biological tissue are also biocompatible. On the other hand, because the sensing functions of all signal sensors are different, various logic circuits can be combined from different signal sensors to perform logical judgments and edge computing of biological tissue signals as needed, significantly reducing the workload at the remote end and thus improving work efficiency. Furthermore, the proposed sensing device with decellularized extracellular matrix can also communicate bidirectionally with external electronic devices, enabling external control or adjustment of the operation of this sensing device. To make the above-mentioned features and advantages of the invention disclosed herein more apparent and understandable, the following will provide a detailed description with reference to embodiments and illustrations. Brief Description of the Drawings: Figure 1 is a schematic diagram of a sensing device with decellularized extracellular matrix according to an embodiment of the present disclosure applied to the skin of a human wrist. Figure 2 is a cross-sectional schematic diagram of a sensing device with decellularized extracellular matrix according to an embodiment of the present disclosure. Figure 3 is an assembly schematic diagram of a sensing device with decellularized extracellular matrix according to an embodiment of the present disclosure. Figure 4 is a process schematic diagram of a sensing device with decellularized extracellular matrix according to an embodiment of the present disclosure. Figure 5 is a perspective schematic diagram of the signal sensing element of the sensor assembly of the sensing device with decellularized extracellular matrix in Figure 4. Figure 6 is a flowchart of a manufacturing method for a sensing device with decellularized extracellular matrix according to an embodiment of the present disclosure. Figure 7 is a schematic diagram of a sensor device with decellularized extracellular matrix according to an embodiment of the present disclosure as a neural action potential conduction circuit. Figure 8 is a schematic diagram of a sensor device with decellularized extracellular matrix according to an embodiment of the present disclosure conducting action potentials to an actuator in human skin tissue. Figure 9 is a schematic diagram of a sensor device with decellularized extracellular matrix according to an embodiment of the present disclosure as an AND logic gate circuit. Figure 10 is a schematic diagram of a sensor device with decellularized extracellular matrix according to an embodiment of the present disclosure as an OR logic gate circuit. Figure 11 is a flowchart of a method for manufacturing decellularized extracellular matrix according to an embodiment of the present disclosure.Figure 12 shows a further sub-step included in method step (b) of Figure 11.

[0002] [Symbol Explanation]

[0003] 10: Sensing devices with decellularized extracellular matrix

[0004] 10a, 10b, 10c: Sensing device circuits with decellularized extracellular matrix

[0005] 101: Second biological tissue

[0006] 102: Sensor Components

[0007] 1021: Thin film substrate

[0008] 10211: First Surface

[0009] 10212: Second Surface

[0010] 1022: Signal sensing device

[0011] 10221: Conductive pad

[0012] 10222: Signal sensing material layer

[0013] 1022a, N: Signal sensing device as a synapse-like sensor

[0014] 1022b, S, SI, S2: Signal sensing element used as a temperature sensor

[0015] 1022c, T1, T2, T3, T4: used as signal sensing devices in thin-film transistors.

[0016] 103: Adhesive layer

[0017] 20: First biological tissue

[0018] 30: Glass substrate

[0019] 31: Photoresist layer

[0020] 311: Groove

[0021] 32: Conductive layers 501-508, (a)~(c), (bl)~(b2): Steps

[0022] 801: Human skin

[0023] 802: External Stimuli

[0024] 803: Central Nervous System

[0025] 804: Actuator

[0026] Vin1, Vin2, Vin3: Input voltage

[0027] Vg, Vgl, Vg2: Gate voltages

[0028] Vd: Drain voltage; lout: Output current

[0029] GND: Grounding Terminal Detailed Implementation Figure 1 is a schematic diagram of a sensing device with a decellularized extracellular matrix, according to an embodiment of the present disclosure, applied to the skin of a human wrist. Figure 2 is a cross-sectional schematic diagram of a sensing device with a decellularized extracellular matrix, according to an embodiment of the present disclosure. Figure 3 is an assembly schematic diagram of a sensing device with a decellularized extracellular matrix, according to an embodiment of the present disclosure. As shown in Figures 1, 2, and 3, the present disclosure proposes a sensing device with a decellularized extracellular matrix for application to a first biological tissue of a first biological organ of a first organism to sense signals on the first biological tissue. The first organism refers to all animals or plants, the first biological organ refers to an organ of an animal or plant, and the first biological tissue refers to the tissue of all animals or plants. The term "application" includes behaviors such as dressing and implantation, but is not limited thereto. As shown in Figure 1, in one embodiment, the first organism is a human body, the first biological organ is human skin, and the first biological tissue 20 is, for example, human wrist skin tissue, but is not limited thereto. The signals referred to include biochemical signals, such as blood glucose, lactic acid, uric acid, histamine, blood electrolyte ions (Na+, K+), and blood pH value, as well as physical signals, such as temperature, pressure, and bioelectric current. As shown in Figures 2 and 3, in one embodiment, the sensing device 10 proposed in this disclosure includes at least a second biological tissue 101, a sensor assembly 102, and an adhesive layer 103, wherein the adhesive layer 103 is disposed between the second biological tissue 101 and the sensor assembly 102. The second biological tissue 101 is composed of a decellularized extracellular matrix with multiple pores obtained by decellularizing a tissue taken from a second biological organ of a second organism. The so-called second organism can be an animal or a plant, and the tissue of the so-called second biological organ can include tissues of any animal or plant, such as animal skin, animal meninges, animal cornea, animal intestinal membrane, animal diaphragm, animal blood vessels, plant leaf veins, plant bark, plant microvascular bundles, or bamboo membrane, etc. In this disclosure, the second biological tissue 101 preferably includes a decellularized collagen scaffold structure, because decellularization can reduce the rejection response of the first biological tissue 20 to the second biological tissue 101. The decellularized extracellular matrix constituting the second biological tissue 101 has a scaffold structure and simultaneously forms multiple pores, providing the space and environment required for the cell growth of the first biological tissue 20.In one embodiment, the second biological tissue 101 can also be used as a wound dressing to improve wound healing efficiency through its cell-growth-promoting properties. In some embodiments of this disclosure, when the second biological tissue 101 is prepared by decellularization, it has a specific preparation method. This preparation method mainly involves first obtaining the second biological tissue 101, that is, obtaining the tissue of a second biological organ from a second organism. The second organ and the first organ are homologous organs or analogous organs. The second organism and the first organism can be the same organism, allogeneic, or different species. For example, the first organism is a human (Homo sapiens), and the second organism is a pig (Sus scrofa), cow, sheep, goat, rabbit, monkey, chicken, or human. As shown in Figure 11, in one embodiment, the method for preparing the decellularized extracellular matrix constituting the second biological tissue 101 includes at least two steps: step (a) obtaining tissue of a second biological organ from a second organism; step (b) removing cells from the tissue of the second biological organ to form a decellularized extracellular matrix. In another embodiment, the preparation method further includes step (c) washing the tissue of the second biological organ after cell removal. In yet another embodiment, the following step is included before or after step (b): removing contaminating pathogens from the tissue of the second biological organ. In some embodiments of this disclosure, the proposed sensing device with decellularized extracellular matrix is ​​implanted on a first biological tissue of a first biological organ of a first organism. In this case, the decellularized extracellular matrix comprises: an extracellular matrix network structure having the aforementioned pores; and at least one functional molecule derived from the extracellular matrix of a second biological organ, distributed within the extracellular matrix network structure, to induce a stem cell or other cell related to the physiological function of the first biological organ to migrate into the extracellular matrix network structure, thereby gradually expanding the non-free-flowing tissue fluid in the first biological organ into the extracellular matrix network structure. This improves the transmission efficiency of physiological or environmental signals from the first biological organ to the sensing device and increases the sensitivity of the sensing device in detecting physiological or environmental signals. The pores can accommodate 1 to 10 of the stem cells or other cells, or the average inner diameter of the pores is 10 μm to 1000 nm.In one embodiment, the cavity can accommodate one of 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10 of the aforementioned stem cells or other cells; or, the average inner diameter of the cavity is 10 μm, 20 μm, 25 μm, 30 μm, 40 μm, 50 μm, 60 μm, 70 μm, 75 μm, 80 μm, 90 μm, 100 μm, 120 μm, 140 μm, 150 μm, 160 μm, 180 μm, 200 μm, 220 μm, 240 μm, 250 μm, 260 μm, 280 μm, 300 μm, 320 μm, 340 μm, 350 μm, etc. 360 (im, 380 | m, 640 |J m, 650 |J m, 660 |J m, 680 |J m, 700 |jm, 720 |J m, 740 |J m, 750 |J m, 760 |J m, 780 |J m, 800 |J m, 820 |J m, 840 |J m, 850 |J m, 860 |J m, 880 |J m, One of 900 |J m, 920 |J m, 940 |J m, 950 960 m, 980 |J m, and 1000 |J m. In some embodiments of this disclosure, as shown in FIG12, step (b) further includes the following steps: Step (b1): Treating the tissue of the second biological organ with a supercritical fluid (SCF) in the presence of a first co-solvent at a static pressure of 200 to 500 bar and a temperature of 30 to 5 CTC for a first time period of about 10 to 100 minutes; Step (b2): Treating the tissue of the second biological organ treated with the supercritical fluid in step (b1) with the same supercritical fluid in the presence of a second co-solvent at a dynamic pressure of 200 to 500 bar and a temperature of 30 to 5 CTC for a second time period of 10 to 100 minutes.The second time interval is typically longer than the first time interval. Static pressure refers to the pressure value of a supercritical fluid remaining constant at a fixed value over a period of time, or in other words, the flow rate of the supercritical fluid is zero. Dynamic pressure refers to the pressure value of a supercritical fluid undergoing dynamic changes, including decreases and increases, due to simultaneous depressurization via, for example, a valve and pressurization via, for example, a pump, but still remaining around a certain value or within a certain range, or in other words, the flow rate of the supercritical fluid is not zero. In one embodiment, the depressurization flow rate of the supercritical fluid is preferably 10 to 30 liters per minute, and the pressurization flow rate is 0.1 to 100 liters per minute, meaning that the supercritical fluid is delivered to the tissue to be treated via, for example, a pump, at a flow rate of 0.1 to 100 liters per minute. In some embodiments of this disclosure, the supercritical fluid is independently selected from the group consisting of supercritical carbon dioxide (ScCO2), supercritical nitrous oxide (ScN2O), supercritical alkane > supercritical alkene, supercritical alcohol > supercritical acetone, and combinations thereof. In some operational embodiments, the supercritical fluid is ScCO2. According to certain embodiments of this disclosure, in step (b1), the tissue of a second biological organ is treated with ScCO2 at a static pressure of 350 to 500 bar for a first time interval of 10 to 80 minutes at a temperature of 40 to 50°C; and in step (b2), the product of step (b1) is treated with ScCO2 at a dynamic pressure of 350 to 500 bar and a depressurization flow rate of 20 liters per minute for a second time interval of 10 to 80 minutes at a temperature of 40 to 50°C. In one embodiment, the first time interval is 30 minutes and the second time interval is 60 minutes. In another embodiment, the first time interval is 10 minutes and the second time interval is 80 minutes. In yet another embodiment, the first time interval is 80 minutes and the second time interval is 10 minutes.In some embodiments of this disclosure, the first co-solvent may be a C1-4 alcohol, selected from the group consisting of: ethanol > propanol > isopropanol, butanol > isobutanol > sec-butanol > t-butanol and cyclobutanol. According to some embodiments, the first co-solvent is 30% (vol%) to 100% (vol%) ethanol, for example 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%.

[0030] 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%

[0031] 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%

[0032] 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%

[0033] 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%

[0034] 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%

[0035] 98%, 99%, or 100% (vol%) ethanol. Preferably, the first co-solvent is 50% (vol%) to...

[0036] 90% (vol%) ethanol. More preferably, the first co-solvent is 70% (vol%) to 80% (vol%) ethanol, such as 70% (vol%), 75% (vol%), or 80% (vol%) ethanol. In a particular embodiment, the first co-solvent is 75% (vol%) ethanol by volume. In some embodiments of this disclosure, the second co-solvent may be a C1-4 alcohol, selected from the group consisting of: ethanol > propanol > isopropanol, butanol > isobutanol > sec-butanol > t-butanol and cyclobutanol. According to some embodiments, the second co-solvent is 30% (vol%) to 100% (vol%) ethanol, for example, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, ...

[0037] 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56

[0038] 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72,

[0039] 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88

[0040] 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% (vol%) ethanol. Preferably, the second co-solvent is 50% (vol%) to 90% (vol%) ethanol. More preferably, the second co-solvent is 70% (vol%) to 80% (vol%) ethanol, for example, 70% (vol%), 75% (vol%), or 80% (vol%) ethanol. In a particular embodiment, the second co-solvent is 75% (vol%) ethanol by volume. In some embodiments of this disclosure, the first co-solvent and the second co-solvent may be selectively the same or different, so those skilled in the art can select appropriate reagents, such as C1-4 ethanol, and adjust their concentrations according to their own purposes. In some embodiments of this disclosure, step (b1) includes treating the tissue of the second biological organ under certain temperature conditions and at a certain static pressure using a supercritical fluid for a first time period. In one embodiment, the tissue of the second biological organ is treated for a first time period at a temperature of 30 to 500°C and a static pressure of 200 to 500 bar using a supercritical fluid. The static pressure can be 200, 210, 220, 230, 240, 250, 260, 270, 280, or 290 bar.

[0041] 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420

[0042] 430, 440, 450, 460, 470, 480, 490 or 500 bar, preferably 300 to 400 bar. The temperature can be 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 5°C, preferably 35 to 45°C. OThe first time interval can be 10 to 100 minutes, for example, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 minutes. In some embodiments of this disclosure, step (b2) includes processing the product of the second biological organ tissue after step (b1) in a second time interval under certain temperature conditions and with a certain dynamic pressure of supercritical fluid. During this process, the supercritical fluid undergoes both depressurization and pressurization. Depressurization can be achieved via a valve, and pressurization can be achieved via a pump. The depressurization flow rate of the supercritical fluid is 10 to 30 liters per minute, while the pressurization flow rate is 0.1 to 100 liters per minute, for example, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20.

[0043] 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52,

[0044] 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68

[0045] 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84

[0046] The flow rate is 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 liters. In some embodiments of this disclosure, the supercritical fluid pressurization flow rate is preferably 1 to 50 liters per minute, more preferably 10 to 30 liters per minute. In one operational embodiment of this disclosure, the supercritical fluid pressurization flow rate is 20 liters per minute. In some embodiments of this disclosure, the time intervals for the static pressure stage and the dynamic pressure stage treatment may vary depending on the type of supercritical fluid, the type of tissue of the second biological organ being treated, and the depressurization flow rate of the supercritical fluid in the dynamic pressure stage. In some embodiments of this disclosure, during the static pressure phase, the static pressure and temperature are maintained at 350 to 500 bar and 40 to 50°C, respectively, and the second biological organ is treated with ScCO2 for 30 minutes. Then, during the dynamic pressure phase, the dynamic pressure and temperature are maintained at 350 to 500 bar and 40 to 50°C, respectively, while ScCO2 is depressurized and pressurized simultaneously. The depressurization flow rate of ScCO2 is 20 liters per minute, and the second biological organ is treated with ScCO2 under this dynamic pressure change for 60 minutes. In some embodiments of this disclosure, during the static pressure phase, the static pressure and temperature are maintained at 350 to 500 bar and 40 to 5°C respectively, and the second biological organ is treated with ScCO2 for 10 minutes. Then, during the dynamic pressure phase, the dynamic pressure and temperature are maintained at 350 to 500 bar and 40 to 5°C respectively, while ScCO2 is depressurized and pressurized simultaneously. The depressurization flow rate of ScCO2 is 20 liters per minute, and the second biological organ is treated with ScCO2 under this dynamic pressure change for 80 minutes. In some embodiments of this disclosure, during the static pressure phase, the static pressure and temperature are maintained at 350 to 500 bar and 40 to 50°C, respectively, and the second biological organ is treated with ScCO2 for 80 minutes. Then, during the dynamic pressure phase, the dynamic pressure and temperature are maintained at 350 to 500 bar and 40 to 50°C, respectively, while ScCO2 is depressurized and pressurized simultaneously. The depressurization flow rate of ScCO2 is 20 liters per minute, and the second biological organ is treated with ScCO2 under this dynamic pressure change for 10 minutes.In some embodiments of this disclosure, step (a) and step (b) may optionally include: step (x) immersing the tissue of the second biological organ in a hypertonic solution for 10 to 60 minutes; and step (y) immersing the tissue of the second biological organ immersed in the hypertonic solution in a hypotonic solution for 10 to 60 minutes. In some embodiments of this disclosure, the hypertonic solution is a salt solution containing 0.5 to 4.0 M NaCl (e.g., 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.5, 2, 2.5, 3, 3.5, 4 M, etc.), and the hypotonic solution is water. According to some operational embodiments, the tissue of the second biological organ is immersed in a salt solution containing 2.0 M NaCl for 30 minutes, followed by immersion in water for 30 minutes. In some preferred embodiments of this disclosure, steps (x) and (y) are repeated at least twice. In some embodiments of this disclosure, step (c) may further include the following step: treating the tissue of the second biological organ treated with the second supercritical fluid with an alkaline solution to neutralize the pH value of the tissue of the second biological organ after cell removal. The alkaline solution is one of sodium hydroxide solution, calcium hydroxide solution, potassium hydroxide solution, sodium carbonate solution, and sodium bicarbonate solution. In some embodiments of this disclosure, the tissue of the second biological organ treated with the second supercritical fluid is treated with an alkaline solution containing 0.01 to 1.0 N NaOH (e.g., 0.01 > 0.02, 0.03 > 0.04 > 0.05 > 0.06, 0.07 > 0.08 > 0.09 > 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1N, etc.). Preferably, this disclosure involves soaking the product of step (b) in an alkaline solution containing 0.1NNaOH for a period of time until its pH value substantially reaches 7.0. Preferably, this disclosure involves washing the organ with copious amounts of water after each step and before proceeding to the next treatment to remove any soluble substances. In some embodiments of this disclosure, the source of the second organism is an animal, including but not limited to pigs, cattle, sheep, goats, rabbits, monkeys, chickens, and humans. Depending on the intended use, the second biological organ used as the source organ can be the heart, small intestine, lungs, spleen, kidneys, liver, stomach, pancreas, bladder, colon, rectum, or brain. In this disclosure, the second biological tissue 101 and the first biological tissue 20 are biocompatible.The sensor assembly 102 is disposed on the second biological tissue 101 and includes a thin film substrate 1021 and one or more signal sensors 1022. The thin film substrate 1021 has a first surface 10211 and a second surface 10212 facing away from each other. The thickness of the thin film substrate 1021 can be from 1 nm to 400 μm. oIn one embodiment, the number of signal sensing elements 1022 per square centimeter of the thin film substrate 1021 can reach 1000c. The thin film substrate 1021 is disposed on the second biological tissue 101 and is biocompatible. Preferably, the tensile elasticity of the thin film substrate 1021 is substantially equivalent to that of the second biological tissue 101. The aforementioned definition of "biocompatibility" is that the second biological tissue 101 and the first biological tissue 20 have similar biological characteristics and do not repel each other, while the definition of "biocompatibility" is that the thin film substrate 1021 does not cause adverse reactions in the biological tissue or material. Figure 4 is a process schematic diagram of a sensing device 10 with decellularized extracellular matrix according to an embodiment of the present disclosure. Figure 5 is a perspective schematic diagram of the signal sensing element 1022 of the sensor assembly of the sensing device 10 with decellularized extracellular matrix in Figure 4. As shown in Figures 2 and 4 or 5, the signal sensing element 1022 is formed on the first surface 10211-L of the thin film substrate 1021 and has a stacking layer structure of two or more layers, for sensing physiological signals of the first biological tissue 20 or environmental signals around the first biological tissue. The physiological or environmental signal can be a biochemical or physical signal, such as blood glucose signal, lactic acid concentration signal, uric acid concentration signal, histamine concentration signal, glucose concentration signal in tissue fluid, metabolic product concentration signal in tissue fluid, electrolyte ion concentration signal in blood, pH signal, temperature signal, pressure signal, abnormal brainwave discharge signal, current signal, glucose or metabolic product concentration signal in phloem sap, growth status signal of perennial woody or herbaceous plants, whether crops are ripe, sweetness signal of fruits, chemical molecular signal, signal that triggers receptor response in organisms, sensory receptor potential signal, nerve potential signal, and other physiological signals, or an external force signal, mechanical stimulation signal, visible light signal, ultraviolet light signal, taste molecule signal, odor molecule signal, sound wave signal, or other external stimulation signal. The adhesive layer 103 adheres the second surface 10212 of the thin film substrate 1021 and the second biological tissue 101 together. Since the tensile elasticity of the thin film substrate 1021 and the second biological tissue 101 is substantially equivalent, they are not easily separated after being bonded together.Experiments showed that the sensor device 10 prepared according to the method in Figure 4 did not cause tissue rejection or inflammation after being implanted subcutaneously into mice, and the mice still survived. Therefore, the sensor device 10 prepared according to this disclosure is expected to reduce rejection reactions. Figure 6 is a flowchart of a manufacturing method for a sensor device 10 with a decellularized extracellular matrix according to an embodiment of this disclosure. As shown in Figures 4, 5, and 6, in one embodiment, the manufacturing method of the sensor device 10 with a decellularized extracellular matrix proposed in this disclosure includes the following steps: Step 501: A photoresist layer 31 is formed on a glass substrate 30, and a desired pattern, such as a plurality of spaced grooves 311, is formed on the photoresist layer 31 using microlithography. Step 502: A conductive layer 32 is formed on the photoresist layer 31, and the conductive material of the conductive layer 32 fills the grooves 311 on the patterned photoresist layer 31. In this step, the method of forming the conductive layer 32 on the photoresist layer 31 includes, but is not limited to, sputtering or evaporation. oPreferably, the conductive material of the conductive layer 32 is biocompatible and has good conductivity, including but not limited to gold (Au) or graphite. Step 503: Remove the conductive material from the portion of the photoresist layer 31 and the patterned photoresist layer 31 other than the groove 311, exposing the conductive material in the groove 311 to serve as conductive pads 10221. Step 504: Form a film base 1021 on the glass substrate 30, covering all the conductive pads 10221. Then, completely peel the film base 1021 containing the conductive pads 10221 from the glass substrate 30 and flip it over so that the conductive pads 10221 separated from each other on the first surface 10211-E of the film base 1021 face upwards. In one embodiment, the material of the thin film substrate 1021 comprises one of the following: biocompatible polylactic acid (PLA), modified polylactic acid, cellulose, hyaluronic acid, starch, collagen, gelatin, sodium alginate, chitosan, polyvinyl alcohol (PVA), or polymethyl methacrylate (PMMA). The modified polylactic acid is polylactic acid doped with a substance to obtain the desired properties, which includes, but is not limited to, triethyl citrate. Experiments have shown that when the mass ratio of triethyl citrate to polylactic acid is 5% to 10%, the thin film substrate 1021 has a better elongation at break. Step 505: The second surface 10212 of the thin film substrate 1021, which is opposite to the first surface 10211, is attached to another glass substrate 30. Step 506: A signal sensing material layer 10222 is formed on the conductive pad 10221 on the thin film substrate 1021, thereby constituting the signal sensing element 1022o. In various embodiments, the material of the signal sensing material layer 10222 has biocompatibility and specific functionality, and its formation on the conductive pad 10221 includes, but is not limited to, deposition or bead coating. oFurthermore, the signal sensing material layers 10222 formed on different conductive pads 10221 can be the same or different as required, so that the different signal sensing elements 1022 provided on the thin film substrate 1021-E have the same or different functions. In specific embodiments, the signal sensing element 1022 of the thin film substrate 1021-E can be, but is not limited to, a signal sensing element as a thin film transistor, a signal sensing element as a temperature sensor, a signal sensing element as a visible light and / or ultraviolet light sensor, a signal sensing element as a strain sensor, or a signal sensing element as a synapse-like sensor. As shown in FIG5, the thin film substrate 1021-E may have a signal sensing element 1022a as a synapse-like sensor, a signal sensing element 1022b as a temperature sensor, and a signal sensing element 1022c as a thin film transistor. The sensing principles and common manufacturing methods of the thin film transistor, temperature sensor, visible light and / or ultraviolet light sensor, strain sensor, or synapse-like sensor are known technologies and will not be described in detail here. In one embodiment, the conductive pad 10221 is made of one or more of the following: polylactic acid (PLA), modified polylactic acid, cellulose, hyaluronic acid, starch, collagen, gelatin, sodium alginate, chitosan, polyvinyl alcohol (PVA), or polymethyl methacrylate (PMMA), or any combination thereof.In one embodiment, the signal sensing material layer 10222 may contain polylactic acid doped with 0.5-30% triethyl citrate to achieve biocompatibility. Thus, the signal sensing element 1022, composed of the signal sensing material layer 10222 and the conductive pad 10221, can have similar biological characteristics to the first biological tissue 20, such as elastic modulus > elongation > and / or tensile strength, thereby reducing the uncomfortable feeling caused by foreign object after implantation into the first biological tissue. In some embodiments, the signal sensing material layer 10222 may be doped with 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, or 30% triethyl citrate. In another embodiment, the signal sensing material layer 10222 may contain polylactic acid doped with vitamin A, thus possessing biocompatibility. This allows the signal sensing element 1022, composed of the signal sensing material layer 10222 and the conductive pad 10221, to be used to sense ultraviolet or visible light, or to function as a synapse-like sensor to sense changes in electrical signals. In yet another embodiment, the signal sensing material layer 10222 may contain polylactic acid doped with lycopene, thus possessing biocompatibility. This allows the signal sensing element 1022, composed of the signal sensing material layer 10222 and the conductive pad 10221, to be used to sense inductive changes, such as strain caused by contact or pressure. In some embodiments, the signal sensing material layer 10222 may comprise polylactic acid doped with 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, or 30% lycopene, or polylactic acid doped with 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, or 30% lycopene and a certain proportion of triethyl citrate.In another embodiment, the signal sensing material layer 10222 may be polylactic acid doped with astaxanthin to be biocompatible, allowing the signal sensing element 1022, composed of the signal sensing material layer 10222 and the conductive pad 10221, to be used to sense temperature. In several embodiments, since the signal sensing element 1022 is made of biocompatible material, its operating voltage can be as low as 1mV, resulting in extremely low power consumption compared to known electronic signal sensing elements. Step 507: The thin film substrate 1021 carrying the signal sensing element 1022 is peeled off from the glass substrate 30 to form a sensor assembly 102. Step 508: The sensor assembly 102 is attached to the second biological tissue 101 using an adhesive layer 103 to form a sensing device 10 with a decellularized extracellular matrix. At this point, the adhesive layer 103 is located between the second biological tissue 101 and the second surface 10212 of the film substrate 1021. In one embodiment, the material of the adhesive layer 103 includes or is one of the following: a biocompatible adhesive, polylactic acid (PLA), modified polylactic acid, cellulose, hyaluronic acid, starch, collagen, gelatin, sodium alginate, chitosan, polyvinyl alcohol (PVA), or polymethyl methacrylate (PMMA), or any combination thereof, but not limited thereto. Table 1 shows the difference between the adhesion effect between the film substrate and the second biological tissue and the material selected for the adhesive layer. It is evident that collagen is a good choice of adhesive layer material and also possesses biocompatibility. Table 1. Figure 7 is a circuit diagram of a sensor device 10 with decellularized extracellular matrix as a neural action potential conduction circuit according to an embodiment of the present disclosure. Figure 8 is a schematic diagram of the sensor device 10 with decellularized extracellular matrix conducting action potentials to human skin tissue actuators according to an embodiment of the present disclosure. In one embodiment, as shown in Figures 7 and 8, the signal sensing element 1022 disposed on the thin film substrate 1021-E of the sensor device circuit 10a with decellularized extracellular matrix may include a total of four elements, such as a signal sensing element 1022a as a neural synapse sensor, a signal sensing element 1022b as a temperature sensor, and a signal sensing element 1022c as a thin film transistor, and all signal sensing elements 1022 constitute a logic circuit. As shown in Figure 7, in one embodiment, the sensing device circuit 10a with decellularized extracellular matrix includes a signal sensor 1022a (denoted by N) serving as a synapse-like sensor, a signal sensor 1022b (denoted by S) serving as a temperature sensor, and two signal sensors 1022c (denoted by T1 and T2, respectively) serving as thin-film transistors. In Figure 7, Vin1 and Vin2 represent input voltages, Vg represents gate voltage, Vd represents drain voltage, lout represents output current, and GND represents ground. As shown in Figure 8, the logic circuit of this sensing device circuit 10a with decellularized extracellular matrix can serve as an equivalent circuit for human skin 801 transmitting physiological signals to the nerve center 803 after being stimulated by external factors 802, and then transmitting action potentials from the nerve center 803 to the actuator 804. Therefore, by applying this sensor circuit 10a with decellularized extracellular matrix to human skin 801, the action potential can be directly transmitted from the sensor circuit 10a with decellularized extracellular matrix to the actuator 804 without passing through the nerve center 803. This allows the human skin 801 to react immediately to external stimuli, avoiding damage to human skin 801 and other human tissues. Figure 9 is a schematic diagram of the sensor circuit 10b with decellularized extracellular matrix as an AND logic gate circuit according to an embodiment of this disclosure.As shown in Figure 9, in one embodiment, the thin film substrate 1021-E of the sensing device circuit 10b with decellularized extracellular matrix is ​​provided with seven signal sensing elements 1022, such as signal sensing element 1022a as a synapse-like sensor, signal sensing element 1022b as a temperature sensor, and signal sensing element 1022c as a thin film transistor, and all signal sensing elements constitute a logic circuit. The sensing device circuit 10b with decellularized extracellular matrix shown in Figure 9 includes one signal sensing element 1022a (denoted as N) as a synapse-like sensor, two signal sensing elements 1022b (denoted as S1 and S2) as temperature sensors, and four signal sensing elements 1022c (denoted as T1, T2, T3, and T4, respectively) as thin film transistors. In Figure 9, Vin1, Vin2, and Vin3 represent the input voltage, Vgl and Vg2 represent the gate voltage, Vd represents the drain voltage, lout represents the output current, and GND represents the ground terminal. The logic circuit of this sensing device circuit 10b with decellularized extracellular matrix is ​​an AND logic gate circuit used to process AND logic operations on signals. Figure 10 is a schematic diagram of the sensing device circuit 10c with decellularized extracellular matrix according to an embodiment of the present disclosure as an OR logic gate circuit. In one embodiment, as shown in Figure 10, seven signal sensing elements are disposed on the thin film substrate 1021-E of the sensing device circuit 10c with decellularized extracellular matrix, including, for example, a signal sensing element 1022a as a synapse-like sensor, a signal sensing element 1022b as a temperature sensor, and a signal sensing element 1022c as a thin film transistor, and all signal sensing elements 1022 constitute a logic circuit. The sensing device circuit 10c with decellularized extracellular matrix shown in Figure 10 includes a signal sensor 1022a (denoted as N) serving as a synapse-like sensor, two signal sensors 1022b (denoted as S1 and S2) serving as temperature sensors, and four signal sensors 1022c (denoted as T1, T2, T3, and T4) serving as thin-film transistors. In Figure 10, Vin1, Vin2, and Vin3 represent the input voltage, Vgl and Vg2 represent the gate voltage, Vd represents the drain voltage, lout represents the output current, and GND represents the ground terminal.The logic circuit of the sensing device circuit 10c with decellularized extracellular matrix is ​​an OR logic gate circuit used to process OR logic operations on signals. In one embodiment, the logic circuit of the sensing device 10 with decellularized extracellular matrix disclosed herein has the ability to perform edge computing on physiological or environmental signals. That is, signal data processing can be completed on the sensing device 10 with decellularized extracellular matrix disclosed herein, without having to be completed after transmission to a remote end, thereby reducing the workload of the remote end. In one embodiment, the sensing device with decellularized extracellular matrix proposed herein can communicate bidirectionally with an electronic device disposed outside the first biological organ or in the external environment, so as to achieve external control or regulation of the operation of the sensing device 10 with decellularized extracellular matrix. This electronic device is used to receive one of the physiological signals and environmental signals output by the sensing device. In addition, when the intensity of the physiological signal or environmental signal exceeds a threshold range, the electronic device outputs a strain signal and transmits the strain signal to the first biological organ through the sensing device. In summary, the sensing device with decellularized extracellular matrix proposed in this disclosure fabricates multiple signal sensors with different sensing functions on a biocompatible thin film substrate. The fabricated sensor assembly is then bonded to another biological tissue that is biocompatible with the biological tissue to which the decellularized extracellular matrix sensing device is applied, allowing the other biological tissue to contact the applied biological tissue. This significantly reduces adverse reactions and immune rejection reactions of the applied biological tissue to the sensor assembly. Furthermore, since the thin film substrate itself is biocompatible and the signal sensors are also fabricated from biocompatible materials, the entire decellularized extracellular matrix sensing device and the applied biological tissue are also biocompatible. On the other hand, because the sensing functions of all signal sensors are different, various logic circuits can be combined from different signal sensors to perform logical judgments and edge computing of biological tissue signals as needed, significantly reducing the workload at the remote end and thus improving work efficiency. Moreover, the proposed sensing device with decellularized extracellular matrix has the function of a human-like sensory receptor. Furthermore, the proposed sensing device with decellularized extracellular matrix can also communicate bidirectionally with external electronic devices, enabling external control of the sensing device. Various embodiments of this disclosure are presented above, but this disclosure is not limited thereto. Anyone skilled in the art can make modifications and refinements without departing from the spirit and scope of this invention. Therefore, the scope of protection of this disclosure should be determined by the appended claims.

Claims

The International Bureau received the amended claims on April 9, 2026 (09.04.2026).

1. A sensing device having a decellularized extracellular matrix, for application to a first biological tissue of a first biological organ of a first organism, the device comprising: a second biological tissue, consisting of a decellularized extracellular matrix having multiple pores obtained by decellularizing a tissue taken from a second biological organ of a second organism, wherein the second biological tissue and the first biological tissue are biocompatible, or the second biological organ and the first biological organ are either homologous organs or organ with the same function; a sensor assembly disposed on the second biological tissue, the sensor assembly comprising: a thin film substrate having a first surface and a second surface facing away from each other, the thin film substrate being disposed on the second biological tissue and being biocompatible; and at least one signal sensor formed on the first surface of the thin film substrate and having a stacked structure of at least two layers, for sensing physiological signals of the first biological tissue or sensing environmental signals surrounding the first biological tissue; and an adhesive layer disposed between the second biological tissue and the sensor assembly, the adhesive layer being formed of an adhesive layer material. The second surface of the thin film substrate and the second biological tissue are bonded together.

2. The sensing device as claimed in claim 1, wherein the physiological signal or the environmental signal is one of the following: a blood glucose signal, a lactic acid concentration signal, a uric acid concentration signal, a histamine concentration signal, a glucose concentration signal in tissue fluid, a metabolic product concentration signal in tissue fluid, an electrolyte ion concentration signal in blood, a pH signal, a temperature signal, a pressure signal, a discharge signal, a current signal, a chemical molecule signal, a signal that triggers a biological receptor response, a sensory receptor potential signal, a nerve potential signal, an external force signal, a mechanical stimulation signal, a visible light signal, an ultraviolet light signal, a taste molecule signal, an odor molecule signal, and a sound wave signal.

3. The sensing device of claim 1, wherein the adhesive layer is made of a biocompatible adhesive, polylactic acid, modified polylactic acid, cellulose, hyaluronic acid, starch, collagen, gelatin, sodium alginate, chitosan, or polyvinyl alcohol. 29 Amended page (Article 19 of the Treaty) And polymethyl methacrylate is one of them.

4. The sensing device of claim 1, wherein a plurality of conductive pads spaced apart from each other are formed on the first surface of the thin film substrate, and the signal sensing element includes a signal sensing material layer formed on one of the conductive pads.

5. The sensing device of claim 4, wherein the signal sensing material layer is formed on the conductive pad by one of the following methods: deposition or droplet coating.

6. The sensing device of claim 4, wherein the signal sensing material layer comprises polylactic acid doped with a substance selected from the group consisting of retinoic acid, lycopene and astaxanthin.

7. The sensing device of claim 1, wherein the thickness of the thin film substrate is 1 nm to 400 μm, or the thickness of the second biological tissue is 0.01 mm to 5 mm.

8. The sensing device of claim 1, wherein the second biological tissue comprises a collagen scaffold structure obtained by decellularization of the dermis layer of an animal skin of the second organism.

9. The sensing device of claim 1, wherein, The sensing device is implanted on the first biological tissue of the first biological organ of the first organism, and the decellularized extracellular matrix includes: an extracellular matrix network structure having the aforementioned pores; and at least one functional molecule distributed in the extracellular matrix network structure to induce a stem cell or other cell related to the physiological function of the first biological organ to migrate into the extracellular matrix network structure, thereby causing the non-free-flowing tissue fluid in the first biological organ to gradually expand into the extracellular matrix network structure; thereby, the transmission efficiency of the physiological signal or the environmental signal from the first biological organ to the sensing device is improved, and the sensitivity of the sensing device in detecting the physiological signal or the environmental signal is increased.

10. The sensing device of claim 9, wherein, These pores can accommodate 1 to 10 of the stem cell or other cells.

1. The sensing device as claimed in claim 1, wherein, The average of these holes 30 Amended page (Article 19 of the Treaty) 12. The sensing device as claimed in claim 1, wherein, The average inner diameters of these holes are 10 μm, 20 μm, 25 μm, 30 μm, 40 μm, 50 μm, and 60 μm. 70 |i m、 75 |i m、 80 |i m、 90 |i m、 100 |i m、 120 |i m、 140 |i m、 150 m、 160 m、 180 m、 200 m、 220 m、 240 m、 250 m、 260 m、 280 m、 300 m、 320 m、 340 m、 350 m、 360 m、 380 m、 400 m、 420 m、 440 m、 450 m、 460 m、 480 m、 500 m、 520 m、 540 m、 550 m、 560 m、 580 m、 600 m、 620 m、 640 m、 650 m、 660 m、 680 m、 700 m、 720 m、 740 m、 750 m、 760 m、 780 m、 800 m、 820 m、 840 m、 850 m、 860 m、 880 m、 900 m、 920 m、 940 m、 950 m、 960 One of 980 |jm and 1000 |J m.

13. The sensing device of claim 1, wherein the thin film substrate is made of polylactic acid, modified polylactic acid, cellulose, hyaluronic acid, starch, collagen, gelatin, sodium alginate, chitosan, polyvinyl alcohol, polymethyl methacrylate, or any combination thereof.

14. The sensing device of claim 1, wherein the thin film substrate is made of modified polylactic acid and the modified polylactic acid is polylactic acid doped with triethyl citrate, and the mass ratio of triethyl citrate to polylactic acid is 5% to 10%.

15. The sensing device of claim 1, wherein the signal sensing element is one of a thin-film transistor signal sensing element, a temperature sensor signal sensing element, an ultraviolet light sensor signal sensing element, a strain sensor signal sensing element, and a synapse-like sensor signal sensing element.

16. The sensing device of claim 1, wherein the signal sensing element comprises at least a signal sensing element as a temperature sensor, a signal sensing element as a synapse-like sensor, and a signal sensing element as a thin-film transistor, forming a logic circuit.

17. The sensing device of claim 16, wherein the logic circuit is configured to perform edge computing of the physiological signal or the environmental signal.

18. The sensing device of claim 1, wherein the sensor assembly outputs an action potential signal to the actuator of the first organism. 31 Amended page (Article 19 of the Treaty) 19. The sensing device of claim 1, wherein the number of signal sensors is two or more and all the signal sensors sense different physiological signals or environmental signals.

20. The sensing device of claim 1, wherein the operating voltage of the sensor assembly is as low as 1 mV. o 21. The sensing device of claim 1, wherein the number of signal sensors per square centimeter of the thin film substrate is at least 1000.

22. The sensing device of claim 1, wherein the sensing device is configured to be connected to an electronic device disposed outside the first organism and configured to receive one of the physiological signal and the environmental signal output from the sensing device.

23. The sensing device of claim 22, wherein the electronic device provides a threshold range for one of the physiological signal and the environmental signal, and when the signal strength of one of the physiological signal and the environmental signal exceeds the threshold range, the electronic device outputs a strain signal and transmits the strain signal to the first biological organ through the sensing device.

24. The sensing device of claim 1, wherein the sensing device has a function similar to that of a human skin sensory receptor.

25. The sensing device as claimed in claim 1, wherein the tissue of the second biological organ is one of animal skin, the dermis of animal skin, animal meninges, animal cornea, animal intestinal membrane, animal diaphragm, animal blood vessels, plant leaf veins, plant bark, plant microvascular bundles, and bamboo membrane.

26. The sensing device of claim 1, wherein the second biological organ is one of the heart, small intestine, lung, spleen, kidney, liver, stomach, pancreas, bladder, colon, rectum and brain.

27. The sensing device of claim 1, wherein the first organism and the second organism are different species.

28. The sensing device of claim 27, wherein the first organism is a human and the second organism is a pig.

29. A method for manufacturing a sensing device having a decellularized extracellular matrix as described in claim 1, comprising: 32 Amended page (Article 19 of the Treaty) Steps of obtaining the tissue from the second biological organ of the second organism (a) ; the step of removing cells from the tissue of the second biological organ to form the decellularized extracellular matrix (b), wherein the decellularized extracellular matrix constitutes the second biological tissue; and the step of attaching the sensor assembly to the second biological tissue using the adhesive layer material to form the sensing device having the decellularized extracellular matrix.

30. The method of claim 29, further comprising: Step (C) O of washing and removing cells from the tissue of this second biological organ 31. The method of claim 29, wherein step (b) comprises: treating the tissue of the second biological organ with a supercritical fluid under at least one pressure condition and at least one temperature condition.

32. The method of claim 31, wherein step (b) comprises: treating the tissue of the second biological organ under a first temperature condition and at a static pressure condition with the supercritical fluid in the presence of a first co-solvent for a first time interval; and then treating the tissue of the second biological organ treated with the supercritical fluid under the static pressure condition under a second time interval and at the first temperature condition and at a dynamic pressure condition with the supercritical fluid in the presence of a second co-solvent for a second time interval, the second time interval being longer than the first time interval, wherein... Under this dynamic pressure condition, the supercritical fluid simultaneously undergoes depressurization and pressurization.

33. The method of claim 32, wherein the first temperature condition is 30 to 50 °C, the static pressure condition is 200 to 500 bar, the dynamic pressure condition is 200 to 500 bar, the second time interval is 10 to 100 minutes, and the flow rate of the supercritical fluid during the depressurization is 10 liters per minute to 30 liters per minute.

34. The method of claim 32, wherein the supercritical fluid is independently selected from the group consisting of supercritical carbon dioxide (ScCO2), supercritical nitrous oxide (ScN2O), supercritical alkanes, supercritical alkenes, supercritical alcohols, supercritical acetone, and combinations thereof. 33 Amended page (Article 19 of the Treaty) 35. The method of claim 32, wherein one of the first co-solvent and the second co-solvent is 30% (vol%) to 100% (vol%) ethanol, or one of the first co-solvent and the second co-solvent is 75% (vol%) ethanol.

36. The method of claim 29, wherein the adhesive layer is made of one of the following: a biocompatible adhesive, polylactic acid, modified polylactic acid, cellulose, hyaluronic acid, starch, collagen, gelatin, sodium alginate, chitosan, polyvinyl alcohol, and polymethyl methacrylate.

37. The method of claim 32, wherein the first co-solvent may be an 0,4 alcohol and is selected from the group consisting of ethanol, propanol, isopropanol, butanol, isobutanol, sec-butano I, t-butano I, and cyclobutanol.

38. The method of claim 29, wherein step (b) comprises: Step (b1) involves treating the tissue of the second biological organ with ScCO2 at a static pressure of 350 to 500 bar for 10 to 80 minutes at a temperature of 40 to 50°C; and step (b2) involves treating the product of step (b1) with ScCO2 at a dynamic pressure of 350 to 500 bar and a depressurization flow rate of 20 liters per minute at a temperature of 40 to 50°C for a second time interval of 10 to 80 minutes.

39. The method of claim 29, wherein between step (a) and step (b) the method further comprises: Step (x) involves immersing the tissue of the second biological organ in a hypertonic solution for 10 to 60 minutes, the hypertonic solution being a salt solution containing 0.5 to 4.0 M NaCl; and step (y) involves immersing the tissue of the second biological organ, which has been immersed in the hypertonic solution, in a hypotonic solution, water, for 10 to 60 minutes.

40. The method of claim 30, wherein step (c) comprises: treating the tissue of the cell-removed second biological organ with an alkaline solution to neutralize the pH of the tissue of the cell-removed second biological organ.

41. The method of claim 40, wherein the alkaline solution is sodium hydroxide. 34 Amended page (Article 19 of the Treaty) One of the following: solution, calcium hydroxide solution, potassium hydroxide solution, sodium carbonate solution, and sodium bicarbonate solution.

42. The method of claim 29, further comprising, before or after step (b): removing contaminating pathogens from the tissue of the second biological organ. 35 Amended page (Article 19 of the Treaty)

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