Bionic functional organic electronic device and preparation method and application thereof

Abstract

The invention relates to a bionic functional organic electronic device and a preparation method and application thereof.The preparation method comprises the steps that a flexible substrate is prepared, then photoetching and deposition of a connecting line, deposition of a poly-p-xylylene layer and a functional poly-p-xylylene layer serving as an initiator are conducted on the flexible substrate, and then a sacrificial layer is prepared; a window capable of integrating a sensing interface and a connecting line pin are exposed through an etching process, then the sensing interface is integrated, after a sacrificial layer is stripped, a functional poly-p-xylylene layer serving as an initiator is used for reacting to prepare a zwitterionic functional bionic packaging layer, and finally functional modification is carried out on the sensing interface. In the prepared device, the bionic encapsulation layer has a double-layer structure, the bottom layer is unmodified poly-p-xylene, and the upper layer is zwitterionic group modified poly-p-xylene; the device can be applied to capturing rare cells in a blood environment, recording physiological electric signals in a body fluid environment and recording skin electrophysiological signals. The method is simple; and the prepared device is excellent in performance and has a wide application prospect.

Description

Technical Field

[0001] The invention belongs to the technical field of organic bioelectronics and relates to a bionic functional organic electronic device and a preparation method thereof. Background Art

[0002] Faced with the combined challenges of high spatial resolution detection of tiny biological or electrophysiological activities and long-term stable integration into skin and tissues, organic bioelectronic devices are developing towards the combination of multiplexing, high sensitivity, conformal contact and biocompatibility.

[0003] However, bioelectronic devices usually work in complex physiological environments, where biomolecules or cells nonspecifically adhere to electrode interfaces, significantly increasing their impedance and / or even preventing their electrical communication with target cells and tissues. In addition, for those sensors used to detect proteins, cells and microorganisms in biofluids, nonspecifically bound proteins / cells can interfere with the signals due to their positive or negative charges. However, so far, little attention has been paid to the challenges of nonspecific protein / cell interactions on the surfaces of thin-film electronic devices.

[0004] In addition, conforming to the complex biological tissue surface is crucial for thin-film bioelectronic devices to achieve close integration and electrical coupling with biological tissues. Mechanical conformability of electronic arrays also helps to alleviate the stress between biological tissues and materials. There are two broad approaches to minimize the mismatch in mechanical properties and increase the mechanical conformability of thin-film devices, namely, fabricating ultrathin devices and using tissue-like carrier materials.

[0005] Reference 1 (Nature 499, 458-463 (2013)) provides plastics with a thickness of less than 10 μm with high bendability and a bending radius of up to sub-millimeter. However, reducing the film thickness will not only not reduce but increase the Young's modulus of the polymer film, which is several orders of magnitude higher than the tissue modulus (100 kPa) provided by reference 2 (Macromolecules 54, 8538-8547 (2021)). In addition, ultra-thin geometries will impair the mechanical properties and self-supporting properties of the film and increase the difficulty of operation.

[0006] Another approach is to use elastomers as sealing packaging materials, whose modulus can reach tissue-like levels. Reference 3 (Nat Biomed Eng 3, 58-68 (2019)) provides soft elastic hydrogel microelectronics for local low-voltage neuromodulation, however, compared with PI and polyparaxylene materials, their long-term sealing packaging and biocompatibility have not been verified, and their application in the real world also faces challenges. In addition, these organic elastomers are usually solution processed, are extremely susceptible to damage by organic solvents and ultraviolet radiation, are incompatible with standard photolithography processes, and are difficult to prepare organic bioelectronic devices. Summary of the invention

[0007] In order to solve the problems existing in the prior art, the present invention provides a bionic functional organic electronic device and a preparation method and application thereof;

[0008] To achieve the above object, the scheme adopted by the present invention is as follows:

[0009] A bionic functional organic electronic device, comprising a flexible substrate and a connecting circuit, and also comprising a bionic encapsulation layer and a bionic conductive polymer sensing interface;

[0010] The biomimetic encapsulation layer has a double-layer structure, the bottom layer is unmodified polyparaxylene, and the upper layer is polyparaxylene modified with zwitterionic groups;

[0011] Both the bionic encapsulation layer and the bionic conductive polymer sensing interface can repel the adhesion of nonspecific cells, viruses, fungi, bacteria and biomolecules.

[0012] As the preferred technical solution:

[0013] As described above, the bionic functional organic electronic device is in the form of a thin film, the thickness of the bionic functional organic electronic device is 1 to 30 μm, and the surface of the bionic encapsulation layer of the bionic functional organic electronic device has an adhesion force greater than 100 nN and a surface elastic modulus less than 1000 kPa in a wetted state.

[0014] A bionic functionalized organic electronic device as described in any of the above items, wherein the bionic conductive polymer sensing interface is a sensing interface modified by a bionic conductive polymer, and the bionic conductive polymer contains zwitterionic groups that can repel the adhesion of nonspecific cells, viruses, fungi, bacteria and biological molecules.

[0015] In a biomimetic functionalized organic electronic device as described in any of the above items, the biomimetic conductive polymer sensing interface may further contain a bio-coupleable group, which can be bio-coupled with a biological molecule (any one of a polypeptide sequence, an antibody, an aptamer and an avidin), so that the material can achieve specific effects with cells, viruses and biological molecules.

[0016] A biomimetic functional organic electronic device as described above, wherein the biomimetic functional organic electronic device is a biomimetic functional organic electrochemical transistor;

[0017] The bionic conductive polymer sensing interface is a channel modified by a bionic conductive polymer. The channel of the organic electrochemical transistor is modified by a bionic conductive polymer, thereby improving the response speed of the device. This is because zwitterions can increase ionic conductivity and cause the channel to swell slightly, which is beneficial for the entry and exit of ions.

[0018] A biomimetic functionalized organic electronic device as described above, wherein the biomimetic conductive polymer comprises a chemical structural unit as shown in formula (I);

[0019]

[0020] In formula (I):

[0021] is a thiophene derivative, a pyrrole derivative or an aniline derivative;

[0022] -L 1 -for-(CH 2 ) x1 -、-(CH 2 ) x1 -O-(CH 2 ) y1 -、-(CH2) x1 -O-CO-(CH 2 ) y1 -、-(CH 2 ) x1 -(CH 2 -CH 2 -O) y1 -、-(CH 2 ) x1 -O-(CH 2 -CH 2 -O) y1 -、-O-(CH 2 ) x1 -(CH 2 -CH 2 -O) y1 - and -O-(CH 2 ) x1 -O-(CH 2 -CH 2 -O) y1 -, wherein x1, 1y are integers, and 0≤x1≤20, 0≤y1≤20;

[0023] -L 2 -for-(CH 2 ) x2 -、-(CH 2 ) x2 -O-, -CO-O-(CH 2 ) x2 -、-O-CO-(CH 2 ) x2 -、-CO-NH-(CH 2 ) x2 -、-C(CH 3 ) 2-CO-O-(CH 2 ) x2 、-CH(CH 3 )-O-(CH 2 ) x2 、-S-CH 2 -CH 2 -O-(CH 2 ) x2 and-S-CH 2 -CH(CH 3 )-CO-O-(CH 2 ) x2 One or more of , wherein x2 is an integer and 0≤x2≤20;

[0024] -R 2 for

[0025] A biomimetic functionalized organic electronic device as described above, wherein the biomimetic conductive polymer further comprises a chemical structural unit as shown in formula (II);

[0026]

[0027] In formula (II):

[0028] is a thiophene derivative, a pyrrole derivative or an aniline derivative;

[0029] -L 3 -for-(CH 2 ) x3 -、-(CH 2 ) x3 -O-(CH 2 ) y3 -、-(CH2) x3 -O-CO-(CH 2 ) y3 -、-(CH 2 ) x3 -NH-CO-O-, -(CH 2 ) x3 -(CH 2 -CH 2 -O) y3 -、-(CH 2 ) x3 -O-(CH 2 -CH 2 -O) y3 -、-O-(CH 2 ) x33 -(CH 2 -CH 2 -O) y3- and -O-(CH 2 ) x3 -O-(CH 2 -CH 2 -O) y3 -, wherein x3 and y3 are integers, and 0≤x3≤20, 0≤y3≤20;

[0030] -L 4 -is -O-, -CO-O-, -O-CH 2 -CO-O-, -S-(CH 2 ) x4 -CO-O-(CH 2 ) y4 -、-CO-NH-(CH 2 ) x4 -、-NH-(CH 2 ) x4 -、-NH-CO-(CH 2 ) x4 -、-O-CO-(CH 2 ) x4 -、-CO-NH-(CH 2 ) x4 -、 One or more of, wherein x4 and y4 are integers, and 0≤x4≤20, 0≤y4≤20;

[0031] -R 3 is a bio-coupled group, which is -COOH, -NH 2 、-O-NH 2 、-N 3 ,

[0032] In the biomimetic functionalized organic electronic device as described above, the zwitterionic group-modified poly(p-xylene) has a chemical structure as shown in formula (III);

[0033]

[0034] In formula (III):

[0035] m, n, k are positive integers, and 10≤m≤5000, 10≤n≤5000, 20≤k≤5000;

[0036] -L 5 -for-(CH 2 ) x5 -、-(CH 2 ) x5 -O-(CH 2 )y5 -、-(CH 2 ) x5 -O-CO-(CH 2 ) y5 -、-(CH 2 ) x5 -(CH 2 -CH 2 -O) y5 -、-(CH 2 ) x5 -O-(CH 2 -CH 2 -O) y5 -、-O-(CH 2 ) x5 -(CH 2 -CH 2 -O) y5 -or-O-(CH 2 ) x5 -O-(CH 2 -CH 2 -O) y5 -, where x5, y5 are integers, and 0≤x5≤20, 0≤y5≤20;

[0037] -L 6 -for One or more of the following;

[0038] -L 7 -for-(CH 2 ) x6 -、-(CH 2 ) x6 -O-(CH 2 ) y6 -、-(CH 2 ) x6 -O-CO-(CH 2 ) y6 -、-(CH 2 ) x6 -(CH 2 -CH 2 -O) y6 -、-(CH 2 ) x6 -O-(CH 2 -CH 2 -O) y6 -、-O-(CH 2 ) x66 -(CH 2 -CH 2 -O) y6 -or-O-(CH 2 )x6 -O-(CH 2 -CH 2 -O) y6 -, where x6, y6 are integers and 0≤x6≤20, 0≤y6≤20;

[0039] -L 8 -for-(CH 2 ) x7 -、-O-(CH 2 ) x7 -、-C(O)-O-(CH 2 ) x7 -、-C(O)-NH-(CH 2 ) x7 -、-C(CH 3 ) 2 -C(O)-O-(CH 2 ) x7 -、-CH(CH 3 )-O-(CH 2 ) x77 -、-S-CH 2 -CH 2 -O-(CH 2 ) x7 -、-S-CH 2 -CH(CH 3 )-C(O)-O-(CH 2 ) x7 - and - (CH 2 ) x7 -CS-S-(CH 2 ) x7 -, wherein x7 is an integer and 0≤x7≤20;

[0040] -R 4 -H, (CH 2 ) x8 CH 3 Any one of , where x8 is a positive integer and 0≤x8≤8;

[0041] -R 5 for wherein M is K, Na, Li, Mg, Al or Fe, and X is F, Cl, Br or I;

[0042] -R 6 -Br, -Cl, -I,

[0043] A bionic functional organic electronic device as described above, wherein the flexible substrate material is any one of polyparaxylene, polydimethylsiloxane, polyurethane, styrene-butadiene-styrene block copolymer, polyvinyl alcohol, polyethylene terephthalate, polyimide, polyethylene naphthalate, paper and textile material, and the connecting line material is any one of gold, platinum, graphene, carbon nanotubes, metal nanowires and conductive polymers.

[0044] The present invention also provides a method for preparing a biomimetic functionalized organic electronic device as described in any one of the above items, comprising the following steps:

[0045] (1) First, a water-soluble soap layer (formed by drying a 2% (v / v) soap solution) is spin-coated on an electronic-grade glass plate to facilitate subsequent device peeling, and then a flexible substrate is deposited;

[0046] (2) photolithographic patterning is performed on the surface of the flexible substrate, and then connecting lines are deposited;

[0047] (3) depositing a polyparaxylene layer and a functionalized polyparaxylene layer on the flexible substrate on which the connection lines are deposited, and then preparing a sacrificial layer consisting of a water-soluble soap layer and a polyparaxylene layer on the functionalized polyparaxylene layer, wherein the sacrificial layer is used to protect the functionalized polyparaxylene layer from damage by subsequent photolithography, etching, solvent stripping and other preparation process steps; the chemical structure of the functionalized polyparaxylene layer is:

[0048] (4) exposing windows and connecting wire pins for integrating the sensing interface on the surface of the sacrificial layer by photolithography and plasma dry etching processes;

[0049] (5) Integrated sensor interface;

[0050] (6) soaking the product of step (5) in water, peeling it off from the electronic grade glass plate, and depositing a layer of functionalized polyparaxylene on the back side, or not depositing a layer of functionalized polyparaxylene;

[0051] (7) peeling off the sacrificial layer to expose the functionalized polyparaxylene layer, and modifying the zwitterionic functional groups on the surface to form a biomimetic encapsulation layer by using a controlled living free radical polymerization method in the presence of a ligand, a catalyst and a zwitterionic functionalized monomer, or in the presence of a free radical initiator and a zwitterionic functionalized monomer;

[0052] (8) depositing a biomimetic conductive polymer onto the exposed sensing interface;

[0053] Step (1) is specifically as follows: spin coating a water-soluble soap layer on an electronic-grade glass plate at a speed of 1500 rpm for 15 seconds, and drying on a 100°C hot plate for 90 seconds; using a chemical vapor deposition reactor to deposit polyparaxylene on the electronic-grade glass plate; placing polyparaxylene monomer in a sublimation zone of a vapor deposition reactor, evacuating the vacuum to below 5 Pa, and heating the pyrolysis zone to 450°C in 10 minutes, maintaining for 10 minutes, and then heating to 670°C in 20 minutes, maintaining for 3 hours, to form a flexible substrate;

[0054] Step (2) is specifically as follows: preparing a connection circuit on a flexible substrate using existing technology; spin-coating a photoresist on the flexible substrate at a speed of 3500 rpm, baking at 115° C. for 60 seconds, shielding with a mask and exposing with a photolithography machine for 2 seconds, and then developing with a developer; then, cleaning the flexible substrate with the photoresist with a low-temperature oxygen plasma processor at 400 watts for 10 minutes, and then depositing 10 nanometers of chromium and 100 nanometers of gold with an electron beam evaporation system; and rinsing off excess photoresist with N-methyl-2-pyrrolidone to form a patterned connection circuit;

[0055] Step (3) is specifically as follows: a layer of polyparaxylene is deposited on the flexible substrate with the patterned connection line in a chemical vapor deposition reactor, two polyparaxylene monomers are placed in the sublimation zone of the vapor deposition reactor, the vacuum degree is pumped to below 5 Pa, the temperature program of the pyrolysis zone is heated to 450° C. for 10 minutes, maintained for 10 minutes, and then heated to 670° C. for 20 minutes, maintained for 3 hours, to form an encapsulation layer; then, a functionalized polyparaxylene layer is deposited on the surface in the chemical vapor deposition reactor, the vacuum degree is pumped to below 5 Pa, the temperature program of the pyrolysis zone is heated to 30° C. for 10 minutes, and then, the functionalized polyparaxylene layer is deposited on the surface in the chemical vapor deposition reactor, the vacuum degree is pumped to below 5 Pa, and the temperature program of the pyrolysis zone is heated to 30° C. for 10 minutes. 0℃, hold for 5 minutes, then heat to 550℃ for 20 minutes and hold for 3 hours; then assemble a sacrificial layer consisting of a water-soluble soap layer and a polyparaxylene layer, spin-coat the water-soluble soap layer at a speed of 1500 rpm for 15 seconds, and dry on a 100℃ hot stage for 90 seconds; using a chemical vapor deposition reactor, put the polyparaxylene monomer into the sublimation zone of the vapor deposition reactor, and evacuate the vacuum to below 5Pa. The heating program of the pyrolysis zone is to heat to 450℃ for 10 minutes, hold for 10 minutes, and then heat to 670℃ for 20 minutes and hold for 3 hours;

[0056] Step (4) is specifically: spin coating the photoresist at 2000 rpm for 30 seconds, baking on a hot stage at 105° C. for 180 seconds, shielding with a mask and exposing with a photolithography machine for 30 seconds, and then developing with a developer for 7 minutes; etching with an oxygen plasma processor at 400 watts and 10 Pa for 45 minutes to expose the window and connecting wire pins for the integrated sensing interface;

[0057] Step (5) specifically includes: integrating the sensor interface into the window where the sensor interface can be integrated;

[0058] Step (6) soaking the product of step (5) in water for 5 minutes, peeling it from the electronic grade glass plate, and depositing a layer of functionalized polyparaxylene on the back; the vacuum degree is evacuated to below 5 Pa, and the temperature program of the pyrolysis zone is heated to 300° C. for 10 minutes, maintained for 5 minutes, and then heated to 550° C. for 20 minutes, and maintained for 3 hours; or only peeling it from the electronic grade glass plate without depositing the functionalized polyparaxylene layer;

[0059] Step (7) is specifically as follows: peeling off the sacrificial layer to expose the functionalized polyparaxylene layer, modifying the zwitterionic functional groups on the surface to form a bionic encapsulation layer by using an atom transfer radical polymerization method in the presence of a ligand, a catalyst and a zwitterionic functionalized monomer; or modifying the zwitterionic functional groups on the surface to form a bionic encapsulation layer by using a reverse addition-fragmentation chain transfer polymerization method in the presence of a free radical initiator and a zwitterionic functionalized monomer;

[0060] Step (8) is specifically as follows: using electrochemical polymerization, adding 3 mM of a conductive polymer monomer containing zwitterionic groups, 7 mM of a conductive polymer monomer containing bio-coupling groups, 100 mM of lithium perchlorate and 50 mL of acetonitrile into an electrolytic cell, taking the sensing interface as a counter electrode and Ag / Ag+ as a reference electrode, and performing polymerization by scanning cyclic voltammetry, with a scanning range of -0.6 to 1.26 V and a scanning speed of 100 mV / s. After scanning for 2 circles, a bionic conductive polymer is obtained, and the bionic conductive polymer is deposited onto the exposed sensing interface.

[0061] The present invention also provides an application of a biomimetic functionalized organic electronic device as described in any one of the above items, which is applied to capture rare cells such as human breast cancer tumor cells (MCF-7 cells) in body fluid and sweat environments.

[0062] The present invention also provides an application of a bionic functionalized organic electronic device as described in any one of the above items, which is used to record physiological electrical signals in a body fluid or sweat environment.

[0063] The present invention also provides an application of a bionic functionalized organic electronic device as described in any one of the above items, which is applied to record skin electrophysiological signals.

[0064] The principle of the present invention is:

[0065] The water droplets on the unmodified polyparaxylene encapsulated thin film device maintain their droplet morphology, while the surface of the polyparaxylene encapsulated thin film device modified by zwitterionic groups (i.e., the biomimetic functionalized organic electronic device of the present invention) has superhydrophilicity, and the water droplets can spread well on its surface. And unlike the unmodified polyparaxylene encapsulated thin film device, the zwitterionic group-modified polyparaxylene encapsulated thin film device will spontaneously bend and stick together after being lifted out of the water. The unmodified polyparaxylene encapsulated thin film device hardly follows the circular wavy surface. In contrast, the zwitterionic group-modified polyparaxylene encapsulated thin film device can conform to the circular wavy surface well without any interface gap. This wetting-driven adhesion should be caused by capillary adhesion between the hydrophilic device and the contact surface. The capillary force comes from the surface wetting of the liquid layer between the two interfaces, which is the sum of the pressure difference caused by surface tension and surface curvature. Under the condition of 65% humidity, we used the AFM method to directly test the capillary force on the surface of the thin film device, recorded the force-time curve, and defined the maximum attraction during the retraction process as the adhesion force between the thin film device and the AFM tip. The adhesion force between the thin film device encapsulated with zwitterion-functionalized polyparaxylene and the AFM tip is 30 times that of the thin film device encapsulated with unmodified polyparaxylene. In general, the magnitude of the capillary force depends on the radius of the wetted area and the surface tension of the liquid. Therefore, we believe that the difference in surface hydrophilicity is the main reason for the significant difference in their interfacial adhesion.

[0066] Although mechanical conformability can alleviate most of the macroscopic interface stress between thin film devices and tissues, the mismatch of elastic modulus between thin film devices and tissues will increase the mechanical tension of cells at the cellular level and activate immune cells, thereby causing an immune response. AFM studies have shown that the surface elastic modulus of unmodified polyparaxylene encapsulated thin film devices in water is much higher than the tissue modulus (less than 100 kPa). In contrast, the surface elastic modulus of the zwitterionic group-modified polyparaxylene encapsulated thin film devices in water of the present invention is more than three orders of magnitude smaller than that of the unmodified polyparaxylene encapsulated thin film devices. This should be attributed to the strong hydration effect of the molecular chains grafted on the surface of the device, which makes the mechanical properties of the zwitterionic group-modified polyparaxylene encapsulated thin film devices of the present invention very close to the surface elastic modulus of the soft biological surface, which is beneficial to the compatibility and biocompatibility with the soft biological surface.

[0067] For packaging systems, leakage current is an important indicator for evaluating the sealing performance of devices. Therefore, we monitored the leakage performance of gold electrode arrays of functionalized polyparaxylene encapsulation layers and unfunctionalized polyparaxylene encapsulation layers immersed in PBS buffer at 25℃, 37℃, 50℃ and 70℃ for 90 days. The results show that even if the temperature of the PBS buffer is increased to 50℃, the measured leakage current hardly changes within 90 days. It is also proved that the two-layer structure of zwitterionic functionalized polyparaxylene encapsulation layer (i.e., the lower layer is polyparaxylene encapsulation layer, and the upper layer is assembled with zwitterionic groups to modify polyparaxylene) maintains excellent packaging performance comparable to that of unfunctionalized polyparaxylene encapsulation layer.

[0068] The ideal sensing interface needs to have resistance to nonspecific protein / cell interactions and selective interactions with target cells. We verified the resistance of the biomimetic functionalized device of the present invention to BSA and leukocytes to evaluate its resistance to nonspecific interference. The results showed that compared with the unfunctionalized interface, the biomimetic functionalized device of the present invention can resist the adhesion of FITC-labeled BSA and leukocytes. This is because of the superhydrophilic properties of its surface, which can resist nonspecific adsorption or contamination from biomolecules and microorganisms, and prevent the occurrence of foreign body reactions. Therefore, the functionalized device can resist nonspecific adhesion well.

[0069] At the same time, we introduced recognition peptides at the sensing interface, so that the thin film electronic device has the ability to resist nonspecificity while also having the ability to recognize target cells. We verified the performance of the functionalized device in a complex environment. One of the main challenges in detecting rare cells is that blood samples mainly contain blood cells, which tend to interact with the sensing interface and seriously interfere with the interaction between the target cells and the device. Leukocytes compete with human breast cancer tumor cells (MCF-7 cells) on the unfunctionalized thin film device, resulting in a change in the generated signal. However, it is uncertain whether this response comes from the interference of leukocytes or target cells. In contrast, the functionalized device has no leukocytes bound to the sensing interface, so no corresponding device response is generated, because their nonspecific interactions are suppressed on the sensing interface surface. In addition, the thin film device further coupled with peptides can selectively interact with MCF-7 cells while resisting leukocyte attachment and generate a corresponding device response, which shows that functionalized devices can improve detection reliability and specificity. At the same time, the non-specificity of the encapsulation material may cause the target analyte to adhere to or settle on the surface of the encapsulation layer, thus hindering the perception of the target analyte by the electronic device sensing interface, especially for rare cells, resulting in the target cell not appearing on the sensing interface, but settling on the non-specific encapsulation layer occupying a large area with a high probability. However, the super-hydrophilicity of the surface of the functionalized encapsulation layer forms a dense hydration layer on the surface, which enables it to resist the binding and adhesion of biomolecules, so it is difficult for the target analyte to stay on its surface, and the target analyte is pushed to the sensing interface with specific recognition ability. Therefore, the simultaneous functionalization of the sensing interface and the encapsulation material has the effect of resisting non-specific adhesion, which can not only improve the accuracy of device sensing, but also push the target cell to the sensing interface with specific recognition through spatial limitation, thereby improving the sensitivity of detecting rare cells (if the sensing interface is not functionalized, it will not be able to selectively capture the target analyte and non-target analyte, and specific recognition cannot be achieved, while the functionalized sensing interface can specifically capture the target analyte on the premise of resisting non-target analytes due to the super-hydrophilic effect on its surface).

[0070] Recording physiological signals through bioelectronic devices also faces the challenge of nonspecific interactions between biomolecules and cells, because biomolecules and cells nonspecifically adhere to the sensing interface, which will lead to increased impedance and even hinder the electrical coupling between the electrode and the target cells / tissues. Experiments have found that leukocytes bind to unfunctionalized devices, hindering their electrical coupling with activated cardiomyocytes (HL-1). However, for thin-film devices that are functionalized and further coupled with peptides, only HL-1 cells can bind to the sensing surface. Therefore, the amplitude of the HL-1 action potential trajectory recorded by the functionalized device is much higher than that recorded by the unfunctionalized device; the signal-to-noise ratio of the signal recorded by the functionalized device is also much greater than that of the unfunctionalized device. In view of these results, we believe that this biomimetic design has great potential to prevent the device from being interfered by nonspecific interactions in complex environment tracking and selectively electrically couple with target cells, thereby giving it long-term stability in complex biological environments.

[0071] On the other hand, due to the mechanical mismatch between electronic and biological systems (e.g., modulus and conformal contact), many existing devices have poor contact (interface delamination), performance degradation, and sometimes even failure when operating in irregular living tissues. Therefore, this consistent contact and interaction between the device and the biological system is crucial for the stability and reliability of the device. When the unfunctionalized device records the ECG of a healthy male, more channels cannot record the signal. This is due to the poor contact between many channels and the skin. The surface of the unfunctionalized device is hydrophobic and cannot adhere well to the skin. However, the functionalized device array shows better conformal contact, and almost all channels can detect valid ECG signals. In addition, at the end of the first test of the unfunctionalized device, the sensing interface was contaminated by the oil on the skin surface, resulting in the loss of important signals or even no signal recorded during the second signal recording. The functionalized device can not only have good contact with the skin, but also resist the contamination of oil and fat. After a simple rinse with water, it can maintain the signal recording ability.

[0072] Beneficial Effects

[0073] (1) The present invention introduces functionalized conductive polymers containing zwitterionic groups and coupleable biological groups through organic electronic devices, thereby maintaining the conductivity of the material while achieving recognition with specific biological molecules under the background of maximum resistance to nonspecific adhesion;

[0074] (2) The present invention introduces polyparaxylene functionalized with zwitterionic groups into the encapsulation layer of the organic electronic device, thereby maintaining the sealing property of the material and increasing the mechanical conformability under the maximum degree of resistance to nonspecific adhesion and wet state;

[0075] (3) The biomimetic functionalized organic electronic device of the present invention can significantly inhibit nonspecific adhesion interference and adhesion of inflammatory factors under complex biological environmental conditions, and can further achieve specific effects with cells, viruses and biological molecules, thereby maximizing the selectivity, accuracy and long-term usability of the device sensing or recording;

[0076] (4) The method for preparing the bionic functional organic electronic device of the present invention has a simple process and is suitable for industrial production;

[0077] (5) The reliability and specificity of sensing detection are improved when the bionic functional organic electronic device of the present invention is used. BRIEF DESCRIPTION OF THE DRAWINGS

[0078] Figure 1 Comparison of the anti-fluorescence BSA adhesion of the unfunctionalized sensing interface (left) and the biomimetic conductive polymer sensing interface of Example 1 (right);

[0079] Figure 2 A comparison of the anti-leukocyte adhesion of the unfunctionalized sensing interface (left) and the biomimetic conductive polymer sensing interface of Example 1 (right);

[0080] Figure 3 Comparison of the spatial confinement of cells by an unfunctionalized sensing interface (left) and the biomimetic conductive polymer sensing interface of Example 1 (right);

[0081] Figure 4 A comparison diagram of the adhesion between an unfunctionalized organic electronic device (left) and a biomimetic functionalized organic electronic device of Example 1 (right);

[0082] Figure 5 A comparison of the adhesion forces of an unfunctionalized organic electronic device (left) and a biomimetic functionalized organic electronic device of Example 1 (right);

[0083] Figure 6 A comparison diagram of the surface elastic modulus of an unfunctionalized organic electronic device (left) and a biomimetic functionalized organic electronic device of Example 1 (right);

[0084] Figure 7 Comparison of an unfunctionalized organic electronic device (left) and a biomimetic functionalized organic electronic device of Example 1 (right) used to capture rare cells in a complex environment;

[0085] Figure 8 A comparison diagram of an unfunctionalized organic electronic device (upper figure) and a biomimetic functionalized organic electronic device of Example 2 (lower figure) used to record myocardial cell electrical signals in an in vitro simulated complex physiological environment;

[0086] Fig. 9A comparison diagram of an unfunctionalized organic electronic device (left) and a biomimetic functionalized organic electronic device of Example 3 (right) used for recording skin electrophysiological signals;

[0087] Fig.10 A comparison of the unfunctionalized organic electronic device (left) and the biomimetic functionalized organic electronic device of Example 4 (right) used to record skin electrophysiological signals against skin oil.

[0088] Fig.11 The time response of the organic electrochemical transistor with an unfunctionalized channel (left) and the organic electrochemical transistor with a biomimetic functionalized channel of Example 1 (right);

[0089] Fig.12 The quartz crystal microbalance is used to detect the film thickness change caused by the flow of deionized water and 0.1M sodium chloride solution. The black solid line is the film thickness change of the unfunctionalized organic electrochemical transistor channel, and the black dotted line is the film thickness change of the bionic functionalized channel in the embodiment. DETAILED DESCRIPTION

[0090] The present invention will be further described below in conjunction with specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and are not intended to limit the scope of the present invention. In addition, it should be understood that after reading the content taught by the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms fall within the scope limited by the appended claims of the application equally.

[0091] The testing method adopted by the present invention is as follows:

[0092] Adhesion force: The adhesion force was measured by atomic force microscopy (Bioscope Resolve system, Bruker) using a pre-calibrated AC160 probe (spring constant: 27 N·m -1 , Olympus), 100uL of water was dripped on the sample surface. Under the condition of 65% humidity, the needle tip slowly approached the sample surface at a speed of 2μm / s until the set repulsion force (10nN) was reached and the needle tip retracted from the sample surface. The capillary force on the device surface was tested using an atomic force microscope, the force-time curve was recorded, and the maximum force during the retraction process was defined as the adhesion force between the device and the probe. The final adhesion force value is the average of the three tested samples.

[0093] Surface elastic modulus: measured by atomic force microscopy (Bioscope Resolve system, Bruker) using a pre-calibrated PFQNM-LC-A-CAL probe (spring constant: 0.1 N·m -1, frequency: 45kHz), surface modulus tests were performed in water in PeakForce QNM mode. Force-distance curves were collected in water using force-volume mode (scan size 1×1μm 2 The area was calculated using AFM NanoScope analysis software v1.8 (Bruker) with an area of ​​1 × 1 μm 2 The Young’s modulus of the device is estimated by the root mean square of the modulus in the region (Rq).

[0094] The unfunctionalized organic electronic device in the embodiment means that compared with the embodiment, the encapsulation layer and the sensing layer are not functionalized; the wetted state means that water is added to the surface of the bionic functionalized organic electronic device.

[0095] Example 1

[0096] A method for preparing a biomimetic functional organic electrochemical transistor, the specific steps are as follows:

[0097] (1) Raw material preparation:

[0098] The flexible substrate material is polyparaxylene (Sai ​​En Chemical Technology Co., Ltd., type C);

[0099] The connecting line material is gold;

[0100] (2) firstly spin-coating a water-soluble soap layer formed by drying a 2% (v / v) soap aqueous solution on an electronic grade glass plate, and then depositing a flexible substrate;

[0101] (3) photolithographic patterning is performed on the surface of the flexible substrate, and then connecting lines are deposited;

[0102] (4) 5 g of di-p-xylene monomer and 1 g of The monomer forms a functionalized poly(p-xylene) layer, and then a sacrificial layer consisting of a water-soluble soap layer formed by drying a 2% (v / v) soap aqueous solution and a poly(p-xylene) layer is prepared on the functionalized poly(p-xylene) layer;

[0103] (5) exposing the source, drain and connecting wire pins by photolithography and plasma dry etching process;

[0104] (6) Spin coating the PEDOT:PSS solution between the source and drain electrodes at 1500 rpm for 45 s to prepare a PEDOT:PSS channel, followed by annealing at 120 °C for 1 h;

[0105] (7) The product of step (6) was immersed in water for 5 minutes, peeled off from the electronic grade glass plate, and 1 g of The monomer forms a functionalized parylene layer;

[0106] (8) Peeling off the sacrificial layer to expose the functionalized poly(p-xylene) layer, in a solution containing 2 mM cuprous bromide, 3 mM cupric bromide, 10 mM tris(2-pyridylmethyl)amine, and 400 mM In the reaction solution, a controlled active free radical polymerization reaction is carried out to form a bionic encapsulation layer;

[0107] (9) Using electrochemical polymerization, 3mM 7mM 100 mM lithium perchlorate and 50 mL acetonitrile were added to the electrolytic cell, and the channel was used as the counter electrode and Ag / Ag+ was used as the reference electrode. The polymerization was performed by scanning cyclic voltammetry, with a scanning range of -0.6 to 1.26 V and a scanning speed of 100 mV / s. After scanning for 2 circles, the bionic conductive polymer was obtained and deposited on the exposed channel.

[0108] The prepared bionic functional organic electrochemical transistor includes a flexible substrate, a connecting circuit, a bionic encapsulation layer and a channel modified by a bionic conductive polymer; the bionic functional organic electrochemical transistor is in the form of a thin film, the thickness of the bionic functional organic electrochemical transistor is 7μm, and the surface of the bionic encapsulation layer of the bionic functional organic electrochemical transistor has an adhesion force of 906nN and a surface elastic modulus of 35kPa in a wetted state.

[0109] like Figure 2 As shown, the prepared biomimetic functionalized organic electrochemical transistor is applied to capture rare cells in the blood environment, such as human breast cancer tumor cells (MCF-7 cells); leukocytes adhere to the unfunctionalized channel, and the channel modified with the biomimetic conductive polymer having zwitterionic groups in Example 1 can resist the adhesion of leukocytes. Therefore, due to the adhesion of leukocytes, the transfer curve of the unfunctionalized channel moves to a higher gate voltage, while the transfer curve of the organic electrochemical transistor having the channel modified with the biomimetic conductive polymer functionalized with zwitterionic groups does not change in the presence of leukocytes. Figure 3 As shown, for the unfunctionalized organic electrochemical transistor, the target cells (i.e., human breast cancer tumor cells) adhere to the channel and the encapsulation layer without selection, however, the biomimetic functionalized organic electrochemical transistor of Example 1 can confine the target cells to the channel through the anti-adhesion effect of the encapsulation layer. Figure 1 As shown in the figure, green fluorescein isothiocyanate labeled bovine serum albumin has a strong interaction with the unfunctionalized channel, while the biomimetic conductive polymer channel functionalized with zwitterionic groups does not adhere to green fluorescein isothiocyanate labeled bovine serum albumin at all. Therefore, due to the negative charge of bovine serum albumin, the transfer curve of the device with the unfunctionalized channel moves to a higher gate voltage, while the transfer curve of the organic electrochemical transistor with a channel modified by a biomimetic conductive polymer functionalized with zwitterionic groups does not change after being immersed in a buffer solution containing bovine serum albumin. Figure 4 As shown, the unfunctionalized organic electrochemical transistor cannot be attached to the circular groove and has a large gap. The biomimetic functionalized organic electrochemical transistor of Example 1 can conform well to the circular groove surface without any interface gap. Figure 5 As shown, the adhesion force between the unfunctionalized organic electrochemical transistor and the probe is 29nN, and the adhesion force between the biomimetic functionalized organic electrochemical transistor of Example 1 and the probe is 906nN. Figure 6 As shown, the surface elastic modulus of the unfunctionalized organic electrochemical transistor is as high as 450 MPa, which is much higher than the tissue modulus (less than 100 kPa); in contrast, the surface elastic modulus of the biomimetic functionalized organic electrochemical transistor of Example 1 is 35 kPa, which is three orders of magnitude smaller than that of the unfunctionalized organic electronic device. Figure 7 As shown, leukocytes compete with human breast cancer cells, bind to the unfunctionalized channel, and cause a voltage shift in the transfer curve. The bionic conductive polymer-modified channel of Example 1 is able to resist leukocyte adhesion and only bind to human breast cancer cells. This cell-selective interaction ensures that the voltage shift signal comes entirely from human breast cancer cells, thereby improving the reliability and specificity of the device detection.

[0110] Example 2

[0111] A method for preparing a bionic functional organic electronic device, the specific steps are as follows:

[0112] (1) Raw material preparation:

[0113] The flexible substrate material was polydimethylsiloxane (Sigma-Aldrich, DMPSV-500G);

[0114] The connecting line material is platinum;

[0115] Parylene (Sai ​​En Chemical Technology Co., Ltd., type D);

[0116] (2) firstly spin-coating a water-soluble soap layer formed by drying a 2% (v / v) soap aqueous solution on an electronic grade glass plate, and then depositing a flexible substrate;

[0117] (3) photolithographic patterning is performed on the surface of the flexible substrate, and then connecting lines are deposited;

[0118] (4) 5 g of di-p-xylene monomer and 1 g of The monomer forms a functionalized poly(p-xylene) layer, and then a sacrificial layer consisting of a water-soluble soap layer formed by drying a 3% (v / v) soap aqueous solution and a poly(p-xylene) layer is prepared on the functionalized poly(p-xylene) layer;

[0119] (5) exposing windows and connecting wire pins for integrating the sensing interface through photolithography and plasma dry etching processes;

[0120] (6) Integrated platinum sensing interface;

[0121] (7) The product of step (6) was immersed in water for 5 minutes, peeled off from the electronic grade glass plate, and 1 g of The monomer forms a functionalized parylene layer;

[0122] (8) Peeling off the sacrificial layer to expose the functionalized poly(p-xylene) layer, in a solution containing 2 mM cuprous bromide, 3 mM cupric bromide, 10 mM tris(2-pyridylmethyl)amine, and 400 mM In the reaction solution, a controlled active free radical polymerization reaction is carried out to form a bionic encapsulation layer;

[0123] (9) Using electrochemical polymerization, 7mM 3mM 100 mM lithium perchlorate and 50 mL acetonitrile were added to the electrolytic cell, and the sensing interface was used as the counter electrode and Ag / Ag+ was used as the reference electrode. The polymerization was performed by scanning cyclic voltammetry, with a scanning range of -0.6 to 1.26 V and a scanning speed of 100 mV / s. After scanning for 2 circles, the bionic conductive polymer was obtained and deposited on the exposed sensing interface.

[0124] The prepared bionic functional organic electronic device includes a flexible substrate, a connecting circuit, a bionic encapsulation layer and a bionic conductive polymer sensing interface; the bionic functional organic electronic device is in the form of a thin film, the thickness of the bionic functional organic electronic device is 8μm, and the bionic functional organic electronic device has an adhesion force of 600nN and a surface elastic modulus of 80kPa in a wetted state.

[0125] like Figure 8 As shown, the prepared bionic functionalized organic electronic device is used to record physiological electrical signals in a simulated body fluid environment; leukocytes bind to the unfunctionalized sensing interface and compete with mouse cardiomyocytes, hindering their electrical coupling with the device, while the bionic conductive polymer deposited on the sensing interface of Example 2 can resist leukocyte adhesion and only bind to mouse cardiomyocytes.

[0126] Example 3

[0127] A method for preparing a bionic functional organic electronic device, the specific steps are as follows:

[0128] (1) Raw material preparation:

[0129] The flexible substrate material is polyimide (DuPont, SP-1);

[0130] The material of the connecting line is graphene (Adamas, CN2459-250mg);

[0131] Parylene (Sai ​​En Chemical Technology Co., Ltd., type N);

[0132] (2) firstly spin-coating a water-soluble soap layer formed by drying a 2% (v / v) soap aqueous solution on an electronic grade glass plate, and then depositing a flexible substrate;

[0133] (3) photolithographic patterning is performed on the surface of the flexible substrate, and then connecting lines are deposited;

[0134] (4) 5 g of di-p-xylene monomer and 1 g of The monomer forms a functionalized poly(p-xylene) layer, and then a sacrificial layer consisting of a water-soluble soap layer formed by drying a 4% (v / v) soap aqueous solution and a poly(p-xylene) layer is prepared on the functionalized poly(p-xylene) layer;

[0135] (5) exposing windows and connecting wire pins for integrating the sensing interface through photolithography and plasma dry etching processes;

[0136] (6) Integrated graphene sensing interface;

[0137] (7) The product of step (6) was immersed in water for 5 minutes, peeled off from the electronic grade glass plate, and 1 g of The monomer forms a functionalized parylene layer;

[0138] (8) Peel off the sacrificial layer to expose the functionalized polyparaxylene layer, and then add 10 mM azobisisobutyronitrile and 400 mM In the reaction solution, a controlled active free radical polymerization reaction is carried out to form a bionic encapsulation layer;

[0139] (9) Using electrochemical polymerization, 7mM 3mM 100 mM lithium perchlorate and 50 mL acetonitrile were added to the electrolytic cell, and the sensing interface was used as the counter electrode and Ag / Ag+ was used as the reference electrode. The polymerization was performed by scanning cyclic voltammetry, with a scanning range of -0.6 to 1.26 V and a scanning speed of 100 mV / s. After scanning for 2 circles, the bionic conductive polymer was obtained and deposited on the exposed sensing interface.

[0140] The prepared bionic functional organic electronic device includes a flexible substrate, a connecting circuit, a bionic encapsulation layer and a bionic conductive polymer sensing interface; the bionic functional organic electronic device is in the form of a thin film, the thickness of the bionic functional organic electronic device is 9 μm, and the surface of the bionic encapsulation layer of the bionic functional organic electronic device has an adhesion force of 800 nN and a surface elastic modulus of 50 kPa in a wetted state.

[0141] like Fig. 9 As shown, the prepared bionic functionalized organic electronic device is used to record skin electrophysiological signals. Due to the poor contact with the skin surface, some channels of the unfunctionalized device cannot record ECG signals, as shown in the dotted box. In contrast, all channels of the bionic functionalized organic electronic device can monitor high-quality ECG signals because it fits well with the skin surface after wetting.

[0142] Example 4

[0143] A method for preparing a bionic functional organic electronic device, the specific steps are as follows:

[0144] (1) Raw material preparation:

[0145] The flexible substrate material is polyethylene terephthalate (Shanghai Fuzhong Industrial Co., Ltd., PET);

[0146] The connecting line material is carbon nanotube (Adamas, CN2368-5g);

[0147] Parylene (Sai ​​En Chemical Technology Co., Ltd., HT type);

[0148] (2) firstly spin-coating a water-soluble soap layer formed by drying a 2% (v / v) soap aqueous solution on an electronic grade glass plate, and then depositing a flexible substrate;

[0149] (3) photolithographic patterning is performed on the surface of the flexible substrate, and then connecting lines are deposited;

[0150] (4) 5 g of di-p-xylene monomer and 1 g of The monomer forms a functionalized poly(p-xylene) layer, and then a sacrificial layer consisting of a water-soluble soap layer formed by drying a 5% (v / v) soap aqueous solution and a poly(p-xylene) layer is prepared on the functionalized poly(p-xylene) layer;

[0151] (5) exposing windows and connecting wire pins for integrating the sensing interface through photolithography and plasma dry etching processes;

[0152] (6) Integrated carbon nanotube sensing interface;

[0153] (7) The product of step (6) was immersed in water for 5 minutes, peeled off from the electronic grade glass plate, and 1 g of The monomer forms a functionalized parylene layer;

[0154] (8) Peel off the sacrificial layer to expose the functionalized poly(p-xylene) layer, and add 20 mM azobismethoxyisoheptanenitrile and 400 mM In the reaction solution, a controlled active free radical polymerization reaction is carried out to form a bionic encapsulation layer;

[0155] (9) Using electrochemical polymerization, 7mM 3mM 100 mM lithium perchlorate and 50 mL acetonitrile were added to the electrolytic cell, and the sensing interface was used as the counter electrode and Ag / Ag+ was used as the reference electrode. The polymerization was performed by scanning cyclic voltammetry, with a scanning range of -0.6 to 1.26 V and a scanning speed of 100 mV / s. After scanning for 2 circles, the bionic conductive polymer was obtained and deposited on the exposed sensing interface.

[0156] The prepared bionic functional organic electronic device includes a flexible substrate, a connecting circuit, a bionic encapsulation layer and a bionic conductive polymer sensing interface; the bionic functional organic electronic device is in the form of a thin film, the thickness of the bionic functional organic electronic device is 9μm, and the surface of the bionic encapsulation layer of the bionic functional organic electronic device has an adhesion force of 650nN and a surface elastic modulus of 90kPa in a wetted state.

[0157] like Fig.10 As shown, the prepared bionic functionalized organic electronic device is used to record skin electrophysiological signals against skin oil. After the non-functionalized device is tested for electrocardiogram, the surface is contaminated by epidermal lipids, resulting in a significant decrease in recording performance during the second test, and the signal-to-noise ratio drops from 20dB to 14dB (the horizontal axis in the figure is time, the vertical axis is current amplitude, and the signal-to-noise ratio is calculated from the amplitude ratio of the signal and noise); the bionic functionalized organic electronic device can be restored to its cleanliness by simple water washing and can maintain the signal recording performance in the second test.

[0158] Example 5

[0159] A method for preparing a bionic functional organic electronic device, the specific steps are as follows:

[0160] (1) Raw material preparation:

[0161] The flexible substrate material is polyurethane (Wuhan Huawei Medical Instrument Co., Ltd., PU original film);

[0162] The connecting line material is metal nanowire (Xianfeng Nano Co., Ltd., XFJ42-1);

[0163] Parylene (Sai ​​En Chemical Technology Co., Ltd., type AF4);

[0164] (2) firstly spin-coating a water-soluble soap layer formed by drying a 2% (v / v) soap aqueous solution on an electronic grade glass plate, and then depositing a flexible substrate;

[0165] (3) performing photolithographic patterning on the surface of the flexible substrate and then depositing to form a sensing interface and connecting circuits;

[0166] (4) 5 g of di-p-xylene monomer and 1 g of The monomer forms a functionalized poly(p-xylene) layer, and then a sacrificial layer consisting of a water-soluble soap layer formed by drying a 6% (v / v) soap aqueous solution and a poly(p-xylene) layer is prepared on the functionalized poly(p-xylene) layer;

[0167] (5) exposing windows and connecting wire pins for depositing the sensing interface through photolithography and plasma dry etching processes;

[0168] (6) Integrated metal nanowire sensing interface;

[0169] (7) The product of step (6) was immersed in water for 5 minutes, peeled off from the electronic grade glass plate, and 1 g of The monomer forms a functionalized parylene layer;

[0170] (8) Peel off the sacrificial layer to expose the functionalized polyparaxylene layer, and add 10 mM 4,4'-azobis(4-cyanovaleric acid) and 400 mM In the reaction solution, a controlled active free radical polymerization reaction is carried out to form a bionic encapsulation layer;

[0171] (9) Using electrochemical polymerization, 7mM 3mM 100 mM lithium perchlorate and 50 mL acetonitrile were added to the electrolytic cell, and the sensing interface was used as the counter electrode and Ag / Ag+ was used as the reference electrode. The polymerization was performed by scanning cyclic voltammetry, with a scanning range of -0.6 to 1.26 V and a scanning speed of 100 mV / s. After scanning for 2 circles, the bionic conductive polymer was obtained and deposited on the exposed sensing interface.

[0172] The prepared bionic functional organic electronic device includes a flexible substrate, a connecting circuit, a bionic encapsulation layer and a bionic conductive polymer sensing interface; the bionic functional organic electronic device is in the form of a thin film, the thickness of the bionic functional organic electronic device is 10 μm, and the surface of the bionic encapsulation layer of the bionic functional organic electronic device has an adhesion force of 700 nN and a surface elastic modulus of 85 kPa in a wetted state.

[0173] The prepared biomimetic functionalized organic electronic devices are used to capture rare cells in the blood environment.

[0174] Example 6

[0175] A method for preparing a biomimetic functional organic electrochemical transistor, the specific steps are as follows:

[0176] (1) Raw material preparation:

[0177] The flexible substrate material is polyparaxylene (Sai ​​En Chemical Technology Co., Ltd., type C);

[0178] The connecting line material is gold;

[0179] (2) firstly spin-coating a water-soluble soap layer formed by drying a 2% (v / v) soap aqueous solution on an electronic grade glass plate, and then depositing a flexible substrate;

[0180] (3) photolithographic patterning is performed on the surface of the flexible substrate, and then connecting lines are deposited;

[0181] (4) 5 g of di-p-xylene monomer and 1 g of The monomer forms a functionalized poly(p-xylene) layer, and then a sacrificial layer consisting of a water-soluble soap layer formed by drying a 2% (v / v) soap aqueous solution and a poly(p-xylene) layer is prepared on the functionalized poly(p-xylene) layer;

[0182] (5) exposing the source, drain and connecting wire pins by photolithography and plasma dry etching process;

[0183] (6) Spin coating the PEDOT:PSS solution between the source and drain electrodes at 1500 rpm for 45 s to prepare a PEDOT:PSS channel, followed by annealing at 120 °C for 1 h;

[0184] (7) The product of step (6) was immersed in water for 5 minutes, peeled off from the electronic grade glass plate, and 1 g of The monomer forms a functionalized parylene layer;

[0185] (8) Peel off the sacrificial layer to expose the functionalized polyparaxylene layer, and then add 20 mM azobisisobutyronitrile and 400 mM In the reaction solution, a controlled active free radical polymerization reaction is carried out to form a bionic encapsulation layer;

[0186] (9) Using electrochemical polymerization, 10 mM 100 mM lithium perchlorate and 50 mL acetonitrile were added to the electrolytic cell, and the channel was used as the counter electrode and Ag / Ag+ was used as the reference electrode. The polymerization was performed by scanning cyclic voltammetry, with a scanning range of -0.6 to 1.26 V and a scanning speed of 100 mV / s. After scanning for 2 circles, the bionic conductive polymer was obtained and deposited on the exposed channel.

[0187] The prepared bionic functional organic electrochemical transistor includes a flexible substrate, a connecting circuit, a bionic encapsulation layer and a channel modified by a bionic conductive polymer; the bionic functional organic electrochemical transistor is in the form of a thin film, the thickness of the bionic functional organic electrochemical transistor is 7μm, and the bionic functional organic electrochemical transistor has an adhesion force of 906nN and a surface elastic modulus of 35kPa in a wetted state.

[0188] Example 7

[0189] A method for preparing a biomimetic functional organic electrochemical transistor, the specific steps are as follows:

[0190] (1) Raw material preparation:

[0191] The flexible substrate material is polyparaxylene (Sai ​​En Chemical Technology Co., Ltd., type C);

[0192] The connecting line material is gold;

[0193] (2) firstly spin-coating a water-soluble soap layer formed by drying a 2% (v / v) soap aqueous solution on an electronic grade glass plate, and then depositing a flexible substrate;

[0194] (3) photolithographic patterning is performed on the surface of the flexible substrate, and then connecting lines are deposited;

[0195] (4) 5 g of di-p-xylene monomer and 1 g of The monomer forms a functionalized poly(p-xylene) layer, and then a sacrificial layer consisting of a water-soluble soap layer formed by drying a 2% (v / v) soap aqueous solution and a poly(p-xylene) layer is prepared on the functionalized poly(p-xylene) layer;

[0196] (5) exposing the source, drain and connecting wire pins by photolithography and plasma dry etching process;

[0197] (6) Spin coating the PEDOT:PSS solution between the source and drain electrodes at 1500 rpm for 45 s to prepare a PEDOT:PSS channel, followed by annealing at 120 °C for 1 h;

[0198] (7) The product of step (6) was immersed in water for 5 minutes, peeled off from the electronic grade glass plate, and 1 g of The monomer forms a functionalized parylene layer;

[0199] (8) Peel off the sacrificial layer to expose the functionalized polyparaxylene layer, and then add 10 mM azobiscyanovaleric acid and 400 mM In the reaction solution, a controlled active free radical polymerization reaction is carried out to form a bionic encapsulation layer;

[0200] (9) Using electrochemical polymerization, 10 mM 100 mM lithium perchlorate and 50 mL acetonitrile were added to the electrolytic cell, and the channel was used as the counter electrode and Ag / Ag+ was used as the reference electrode. The polymerization was performed by scanning cyclic voltammetry, with a scanning range of -0.6 to 1.26 V and a scanning speed of 100 mV / s. After scanning for 2 circles, the bionic conductive polymer was obtained and deposited on the exposed channel.

[0201] The prepared bionic functional organic electrochemical transistor includes a flexible substrate, a connecting circuit, a bionic encapsulation layer and a channel modified by a bionic conductive polymer; the bionic functional organic electrochemical transistor is in the form of a thin film, the thickness of the bionic functional organic electrochemical transistor is 7μm, and the surface of the bionic encapsulation layer of the bionic functional organic electrochemical transistor has an adhesion force of 906nN and a surface elastic modulus of 35kPa in a wetted state.

[0202] Example 8

[0203] A method for preparing a biomimetic functional organic electrochemical transistor, the specific steps are as follows:

[0204] (1) Raw material preparation:

[0205] The flexible substrate material is polyparaxylene (Sai ​​En Chemical Technology Co., Ltd., type C);

[0206] The connecting line material is gold;

[0207] (2) firstly spin-coating a water-soluble soap layer formed by drying a 2% (v / v) soap aqueous solution on an electronic grade glass plate, and then depositing a flexible substrate;

[0208] (3) photolithographic patterning is performed on the surface of the flexible substrate, and then connecting lines are deposited;

[0209] (4) 5 g of di-p-xylene monomer and 1 g of The monomer forms a functionalized poly(p-xylene) layer, and then a sacrificial layer consisting of a water-soluble soap layer formed by drying a 2% (v / v) soap aqueous solution and a poly(p-xylene) layer is prepared on the functionalized poly(p-xylene) layer;

[0210] (5) exposing the source, drain and connecting wire pins by photolithography and plasma dry etching process;

[0211] (6) Spin coating the PEDOT:PSS solution between the source and drain electrodes at 1500 rpm for 45 s to prepare a PEDOT:PSS channel, followed by annealing at 120 °C for 1 h;

[0212] (7) soaking the product of step (6) in water for 5 minutes and peeling it off from the electronic grade glass plate without depositing the functionalized polyparaxylene layer;

[0213] (8) Peel off the sacrificial layer to expose the functionalized poly(p-xylene) layer, and add 20 mM azobismethoxyisoheptanenitrile and 400 mM In the reaction solution, a controlled active free radical polymerization reaction is carried out to form a bionic encapsulation layer;

[0214] (9) Using electrochemical polymerization, 10 mM 100 mM lithium perchlorate and 50 mL acetonitrile were added to the electrolytic cell, and the channel was used as the counter electrode and Ag / Ag+ was used as the reference electrode. The polymerization was performed by scanning cyclic voltammetry, with a scanning range of -0.6 to 1.26 V and a scanning speed of 100 mV / s. After scanning for 2 circles, the bionic conductive polymer was obtained and deposited on the exposed channel.

[0215] The prepared bionic functional organic electrochemical transistor includes a flexible substrate, a connecting circuit, a bionic encapsulation layer and a channel modified by a bionic conductive polymer; the bionic functional organic electrochemical transistor is in the form of a thin film, the thickness of the bionic functional organic electrochemical transistor is 7μm, and the surface of the bionic encapsulation layer of the bionic functional organic electrochemical transistor has an adhesion force of 906nN and a surface elastic modulus of 35kPa in a wetted state.

[0216] Example 9

[0217] A method for preparing a bionic functional organic electronic device, the specific steps are as follows:

[0218] (1) Raw material preparation:

[0219] The flexible substrate material is polyparaxylene (Sai ​​En Chemical Technology Co., Ltd., type C);

[0220] The connecting line material is gold;

[0221] (2) firstly spin-coating a water-soluble soap layer formed by drying a 2% (v / v) soap aqueous solution on an electronic grade glass plate, and then depositing a flexible substrate;

[0222] (3) photolithographic patterning is performed on the surface of the flexible substrate, and then connecting lines are deposited;

[0223] (4) 5 g of di-p-xylene monomer and 1 g of The monomer forms a functionalized poly(p-xylene) layer, and then a sacrificial layer consisting of a water-soluble soap layer formed by drying a 2% (v / v) soap aqueous solution and a poly(p-xylene) layer is prepared on the functionalized poly(p-xylene) layer;

[0224] (5) exposing windows and connecting wire pins for integrating the sensing interface through photolithography and plasma dry etching processes;

[0225] (6) Integrated gold sensing interface;

[0226] (7) soaking the product of step (6) in water for 5 minutes and peeling it off from the electronic grade glass plate without depositing the functionalized polyparaxylene layer;

[0227] (8) Peeling off the sacrificial layer to expose the functionalized poly(p-xylene) layer, in a solution containing 2 mM cuprous bromide, 3 mM cupric bromide, 10 mM tris(2-pyridylmethyl)amine, and 400 mM In the reaction solution, a controlled active free radical polymerization reaction is carried out to form a bionic encapsulation layer;

[0228] (9) Using electrochemical polymerization, 10 mM 100 mM lithium perchlorate and 50 mL acetonitrile were added to the electrolytic cell, and the sensing interface was used as the counter electrode and Ag / Ag+ was used as the reference electrode. The polymerization was performed by scanning cyclic voltammetry, with a scanning range of -0.6 to 1.26 V and a scanning speed of 100 mV / s. After scanning for 2 circles, the bionic conductive polymer was obtained and deposited on the exposed sensing interface.

[0229] The prepared bionic functional organic electronic device includes a flexible substrate, a connecting circuit, a bionic encapsulation layer and a bionic conductive polymer sensing interface; the bionic functional organic electronic device is in the form of a thin film, the thickness of the bionic functional organic electronic device is 7 μm, and the surface of the bionic encapsulation layer of the bionic functional organic electronic device has an adhesion force of 906 nN and a surface elastic modulus of 35 kPa in a wetted state.

Claims

1. A bionic functional organic electronic device, comprising a flexible substrate and a connecting circuit, characterized in that: It also includes a bionic encapsulation layer and a bionic conductive polymer sensing interface; The bionic encapsulation layer has a double-layer structure, wherein the bottom layer is unmodified polyparaxylene and the upper layer is polyparaxylene modified with zwitterionic groups.

2. A biomimetic functional organic electronic device according to claim 1, characterized in that: The surface of the bionic encapsulation layer of the bionic functionalized organic electronic device has an adhesion force greater than 100 nN and a surface elastic modulus less than 1000 kPa in a wet state.

3. A biomimetic functional organic electronic device according to claim 2, characterized in that: The bionic conductive polymer sensing interface is a sensing interface modified by a bionic conductive polymer, and the bionic conductive polymer contains zwitterionic groups.

4. A biomimetic functional organic electronic device according to claim 3, characterized in that: Bionic conductive polymers also contain bio-coupleable groups.

5. The biomimetic functional organic electronic device according to claim 4, characterized in that: The biomimetic functionalized organic electronic device is a biomimetic functionalized organic electrochemical transistor; The bionic conductive polymer sensing interface is a channel modified by bionic conductive polymer.

6. The biomimetic functional organic electronic device according to claim 3, characterized in that: The biomimetic conductive polymer comprises a chemical structural unit as shown in formula (I); In formula (I): is a thiophene derivative, a pyrrole derivative or an aniline derivative; -L 1 - is -(CH2) x1 - and -(CH2) x1 -O-(CH2) y1 - and -(CH2) x1 -O-CO-(CH2) y1 - and -(CH2) x1 -(CH2-CH2-O) y1 -、-(CH2) x1 -O-(CH2-CH2-O) y1 -、-O-(CH2) x1 -(CH2-CH2-O) y1 - and -O-(CH2) x1 -O-(CH2-CH2-O) y1 -, wherein x1, 1y are integers, and 0≤x1≤20, 0≤y1≤20; -L 2 - is -(CH2) x2 - or -(CH2) x2 -O-, -CO-O-(CH2) x2 - or -O-CO-(CH2) x2 - or -CO-NH-(CH2) x2 - or -C(CH3)2-CO-O-(CH2) x2 、-CH(CH3)-O-(CH2) x2 、-S-CH2-CH2-O-(CH2) x2 and -S-CH2-CH(CH3)-CO-O-(CH2) x2 One or more of , wherein x2 is an integer and 0≤x2≤20; -R 2 for 7. The biomimetic functional organic electronic device according to claim 4, characterized in that: The biomimetic conductive polymer also includes a chemical structural unit as shown in formula (II); In formula (II): is a thiophene derivative, a pyrrole derivative or an aniline derivative; -L 3 - is -(CH2) x3 - and -(CH2) x3 -O-(CH2) y3 - and -(CH2) x3 -O-CO-(CH2) y3 - and -(CH2) x3 -NH-CO-O-、 -(CH2) x3 -(CH2-CH2-O) y3 -,-(CH2) x3 -O-(CH2-CH2-O) y3 -,-O-(CH2) x33 -(CH2-CH2-O) y3 - and -O-(CH2) x3 -O-(CH2-CH2-O) y3 -, wherein x3 and y3 are integers, and 0≤x3≤20, 0≤y3≤20; -L 4 -O-、-CO-O-、-O-CH2-CO-O-、-S-(CH2) x4 -CO-O-(CH2) y4 -、-CO-NH-(CH2) x4 - -NH-(CH2) x4 -、-NH-CO-(CH2) x4 -、-O-CO-(CH2) x4 -、-CO-NH-(CH2) x4 -、 One or more of, wherein x4 and y4 are integers, and 0≤x4≤20, 0≤y4≤20; -R 3 -COOH, -NH2, -O-NH2, -N3, 8. The biomimetic functional organic electronic device according to claim 1, characterized in that: The zwitterionic group-modified poly(p-xylene) has a chemical structure as shown in formula (III); In formula (III): m, n, k are positive integers, and 10≤m≤5000, 10≤n≤5000, 20≤k≤5000; -L 5 - is -(CH2) x5 - or -(CH2) x5 -O-(CH2) y5 - or -(CH2) x5 -O-CO-(CH2) y5 - or -(CH2) x5 -(CH2-CH2-O) y5 -,-(CH2) x5 -O-(CH2-CH2-O) y5 -,-O-(CH2) x5 -(CH2-CH2-O) y5 - or -O-(CH2) x5 -O-(CH2-CH2-O) y5 -, where x5, y5 are integers, and 0≤x5≤20, 0≤y5≤20; -L 6 -for One or more of the following; -L 7 - is -(CH2) x6 - or -(CH2) x6 -O-(CH2) y6 - or -(CH2) x6 -O-CO-(CH2) y6 - or -(CH2) x6 -(CH2-CH2-O) y6 -、-(CH2) x6 -O-(CH2-CH2-O) y6 -、-O-(CH2) x66 -(CH2-CH2-O) y6 - or -O-(CH2) x6 -O-(CH2-CH2-O) y6 -, where x6, y6 are integers and 0≤x6≤20, 0≤y6≤20; -L 8 - is -(CH2) x7 -、-O-(CH2) x7 -、-C(O)-O-(CH2) x7 -、-C(O)-NH-(CH2) x7 -、 -C(CH3)2-C(O)-O-(CH2) x7 -、-CH(CH3)-O-(CH2) x77 -、-S-CH2-CH2-O-(CH2) x7 - -S-CH2-CH(CH3)-C(O)-O-(CH2) x7 - and -(CH2) x7 -CS-S-(CH2) x7 -, wherein x7 is an integer and 0≤x7≤20; -R 4 -H, (CH2) x8 Any one of CH3, wherein x8 is a positive integer and 0≤x8≤8; -R 5 for wherein M is K, Na, Li, Mg, Al or Fe, and X is F, Cl, Br or I; -R 6 -Br, -Cl, -I, 9. The biomimetic functional organic electronic device according to claim 1, characterized in that: The flexible substrate material is any one of polyparaxylene, polydimethylsiloxane, polyurethane, styrene-butadiene-styrene block copolymer, polyvinyl alcohol, polyethylene terephthalate, polyimide, polyethylene naphthalate, paper and textile materials, and the connection line material is any one of gold, platinum, graphene, carbon nanotubes, metal nanowires and conductive polymers.

10. A method for preparing a biomimetic functionalized organic electronic device according to any one of claims 1 to 9, characterized in that The steps include: (1) First, a water-soluble soap layer is spin-coated on an electronic-grade glass plate, and then a flexible substrate is deposited; (2) photolithographic patterning is performed on the surface of the flexible substrate, and then connecting lines are deposited; (3) depositing a polyparaxylene layer and a functionalized polyparaxylene layer on the flexible substrate on which the connection lines are deposited, and then preparing a sacrificial layer consisting of a water-soluble soap layer and a polyparaxylene layer on the functionalized polyparaxylene layer; the chemical structure of the functionalized polyparaxylene layer is (4) exposing windows and connecting wire pins for integrating the sensing interface on the surface of the sacrificial layer by photolithography and plasma dry etching processes; (5) Integrated sensor interface; (6) soaking the product of step (5) in water, peeling it off from the electronic grade glass plate, and depositing a layer of functionalized polyparaxylene on the back side, or not depositing a layer of functionalized polyparaxylene; (7) peeling off the sacrificial layer to expose the functionalized polyparaxylene layer, and modifying the zwitterionic functional groups on the surface to form a biomimetic encapsulation layer by using a controlled living free radical polymerization method in the presence of a ligand, a catalyst and a zwitterionic functionalized monomer, or in the presence of a free radical initiator and a zwitterionic functionalized monomer; (8) Depositing the biomimetic conductive polymer onto the sensing interface.

11. The use of a biomimetic functionalized organic electronic device according to any one of claims 3 to 9, characterized in that: Used to capture and sense rare cells, viruses, and proteins in body fluids and sweat environments.

12. The use of a biomimetic functionalized organic electronic device according to any one of claims 3 to 9, characterized in that: Used to record physiological electrical signals in body fluid and sweat environments.

13. The use of a biomimetic functional organic electronic device according to any one of claims 3 to 9, characterized in that: Used to record skin electrophysiological signals.

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