Miniature flexible temperature sensor for living organisms, method of manufacture and use thereof

Abstract

This invention relates to a miniature flexible temperature sensor for use in living organisms, its fabrication method, and its applications. The miniature flexible temperature sensor comprises a thermosensitive conductive layer polymerized in situ from acrylamide, glycerol, choline chloride, and lipoic acid, and a flexible encapsulation layer made of a flexible biocompatible material. The fabrication method includes mixing acrylamide, glycerol, and choline chloride to obtain a deep eutectic solvent; adding lipoic acid to the deep eutectic solvent to obtain a homogeneous solution; injecting the homogeneous solution into a mold made of the flexible biocompatible material to obtain a material to be cured; and subjecting the material to be cured to ultraviolet light curing to obtain the miniature flexible temperature sensor. Its advantages include good biocompatibility, reducing the potential bioaccumulation risk of traditional conductive polymers or nanomaterials; high sensitivity, good repeatability, linearity, and resolution; a thermosensitive layer thickness of 1–2 mm, suitable for non-invasive monitoring on the body surface and multi-point temperature detection in confined biological spaces; and a simple fabrication method with no leakage risk.

Description

Technical Field

[0001] This invention relates to the field of sensor technology, and in particular to a miniature flexible temperature sensor for biological organisms, its preparation method, and its application. Background Technology

[0002] Temperature monitoring is a fundamental technology in fields such as healthcare and smart wearables. Among these, contact temperature measurement has become the most widely used method due to its direct contact with the object being measured, accuracy, and controllable cost. Traditional contact temperature sensing elements mainly include metal resistors based on the resistance thermal effect, thermocouples based on the thermoelectric effect, and semiconductor thermistors and IC sensors. Their core common feature is that they all rely on the transport behavior of electrons or holes in rigid materials (metals or silicon-based materials) in response to temperature changes to achieve temperature measurement. This core characteristic determines that traditional contact temperature sensing elements have advantages such as robustness and reliability, mature technology, strong anti-interference ability, and wide temperature measurement range, and have been widely used in various scenarios for a long time.

[0003] However, with the rapid development of emerging fields such as wearable medical electronics and flexible electronic devices, the inherent limitations of traditional contact temperature sensing elements are becoming increasingly apparent: on the one hand, the characteristics of rigid materials make it difficult for them to overcome the shape limitations of rigid probes, making it impossible to conform to complex measurement interfaces such as the curved surfaces of the human body and the surfaces of flexible devices, resulting in poor skin comfort and failing to meet the needs of long-term non-invasive body temperature monitoring for wearable devices; on the other hand, these temperature sensing elements have a single function, usually only capable of temperature monitoring, making it difficult to achieve efficient integration with flexible electronic systems and unable to adapt to diversified application needs such as multimodal sensing and intelligent control.

[0004] In recent years, the rapid development of wearable medical electronics technology has greatly promoted the research and application of novel flexible temperature sensors. Compared with traditional rigid temperature sensing elements, flexible temperature sensors, with their excellent mechanical flexibility, skin comfort, stretchability, high precision, and long-term non-invasive monitoring capabilities, can closely conform to human skin or the surface of flexible devices to achieve accurate and real-time monitoring of target parameters such as body temperature and ambient temperature. They show broad application prospects in clinical temperature monitoring, health management, smart wearables, and flexible robotics. Currently, the working mechanisms of existing flexible temperature sensors can be mainly divided into three types: resistive, capacitive, and ion electronics. Each type of sensor has its own advantages and inherent limitations, as detailed below: I. Resistive Flexible Temperature Sensor These sensors primarily rely on composite materials such as carbon nanotubes, graphene, conductive polymers, or metal nanowires to construct conductive networks. Temperature measurement is achieved by detecting changes in the resistance of this conductive network caused by temperature variations. The temperature coefficient of resistance (TCR) is a core parameter for evaluating the sensor's temperature sensitivity; it is defined as the relative change in resistance when the temperature changes by 1°C. Existing resistive flexible temperature sensors typically have low TCRs, generally on the order of magnitude. Within the narrow physiological temperature range of the human body (32°C~42°C), the range of resistance changes is limited, resulting in insufficient temperature sensitivity. Furthermore, their conductive networks are susceptible to interference from external stress and deformation. When the sensor bends or stretches with human movement, the continuity of the conductive network is easily disrupted, leading to resistance signal drift and affecting measurement accuracy, making it difficult to meet the requirements of high-precision body temperature monitoring.

[0005] II. Capacitive Flexible Temperature Sensor These sensors utilize polymer composite temperature-sensitive layers combined with phase transition effects or the double-layer principle. Temperature changes alter parameters such as the dielectric constant and thickness of the temperature-sensitive layer, thereby controlling the capacitance value and ultimately measuring temperature by detecting these capacitance changes. They offer advantages such as low power consumption, good long-term stability, and strong resistance to electromagnetic interference. However, within the physiological temperature range of the human body, the dielectric constant of the temperature-sensitive layer changes relatively gradually, resulting in lower sensor sensitivity and difficulty in achieving high-resolution temperature monitoring. This makes them unsuitable for high-end applications such as precise clinical temperature measurement.

[0006] III. Ion Electronics Flexible Temperature Sensor These sensors use ions as charge carriers and employ soft ion-conductive materials as the sensitive layer. They combine good mechanical flexibility, biocompatibility, and high ion conductivity, making them better suited for skin-touch monitoring scenarios and possessing the potential for multimodal sensing. They have unique advantages in the field of wearable medical electronics. However, these sensors still have significant technical shortcomings: ions in the ion-conductive materials are prone to leakage, which can lead to sensor performance degradation and potentially pose biosafety risks. Furthermore, preventing ion leakage places extremely high demands on the packaging structure and materials, increasing the difficulty and cost of device fabrication and limiting their large-scale application.

[0007] In general, the performance bottleneck of flexible temperature sensors stems from the inherent contradiction and balance between the intrinsic physical properties of materials and the functional requirements of devices. On the one hand, the thermal expansion coefficient, thermal conductivity, and electron / ion conduction mechanism of the material directly determine the temperature response speed, temperature sensitivity, and linear range of the sensor. For example, a mismatch between the thermal expansion coefficient of the flexible substrate and the active layer can easily lead to interface delamination, affecting temperature conduction efficiency. On the other hand, mechanical flexibility requires the material to maintain a continuous conductive or ion transport network under deformation conditions such as bending, stretching, and twisting. This requirement inevitably introduces stress-response coupling effects, leading to signal drift and hysteresis in the sensor, reducing long-term operational stability. Furthermore, the structural non-uniformity of the substrate and active layer at the microscale, the mismatch of interfacial mechanical properties, and the limitations of packaging processes and system integration technologies further restrict the macroscopic measurement accuracy, linear range, and large-scale fabrication capability of flexible temperature sensors. Therefore, the core scientific problem of flexible temperature sensors lies in deeply understanding and precisely controlling the intrinsic thermo-electric coupling mechanism of materials to achieve synergistic optimization of flexible form and high-precision, high-stability temperature response.

[0008] To address the aforementioned technical challenges, researchers and related companies both domestically and internationally have conducted extensive research and development, proposing various improvement solutions. Related patents and academic literature have also disclosed a series of technical solutions for flexible temperature sensors, as detailed below: 1. Chinese invention patent CN115435912B discloses an embedded substrate flexible temperature sensor, in which the sensing electrode is almost completely embedded in the substrate membrane, which can effectively improve the bonding tightness between the sensing electrode and the substrate, thereby improving the mechanical performance and measurement stability of the flexible sensor. At the same time, the sensor has a simple structure and does not require complex fabrication processes, enabling low-cost and large-area fabrication. This solves to some extent the problems of poor mechanical stability and high fabrication cost of traditional flexible sensors. However, it does not optimize core performance such as temperature sensitivity and biocompatibility.

[0009] 2. Chinese invention patent application CN117232676A discloses a flexible temperature sensor with a buffer electrode layer. By setting the buffer electrode layer, a buffer space is provided for the sensing layer, ensuring that the encapsulation layer can achieve a greater degree of stretching or bending, meeting the deformation requirements of the sensor during human activity. This sensor reflects the change of temperature parameters by measuring the change of the resistance value of the thermistor, realizing accurate measurement of the flexible temperature sensor under deformation, and improving the practicality of the device. However, it still does not solve the inherent defects of resistive sensors that are susceptible to stress interference and have insufficient sensitivity.

[0010] 3. PCT international patent application WO2025222748A1 discloses a capacitive flexible temperature sensor for human body temperature monitoring. The sensor adopts a sandwich structure, with the core functional layer consisting of multiple layers of composite materials such as flexible electrodes, buffer layers, and temperature-sensitive layers. The outermost layer is encapsulated with a high thermal conductivity and waterproof material, which effectively improves the temperature measurement sensitivity and practicality of the sensor within the human body temperature range. However, due to the inherent limitations of the capacitive mechanism, its resolution is still difficult to meet the needs of high-end clinical temperature measurement, and the multi-layer structure increases the complexity of manufacturing and the difficulty of packaging.

[0011] 4. Chinese invention patent CN112345110B discloses a method for manufacturing a eutectic solvent-based temperature sensor. This method uses a deep eutectic solvent to prepare the temperature sensor, which has the advantages of simple preparation method, easy operation, stable device performance and high sensing efficiency. It provides a new idea for the large-scale preparation of flexible temperature sensors, but it does not solve the problems that may exist in the eutectic solvent system, such as ion leakage and insufficient biocompatibility.

[0012] 5. In the field of academic research, Adv. Mater. 2023, 35, 2300114. (DOI:10.1002 / adma.202300114) prepared supramolecular gels with high mechanical properties, self-healing ability, environmental stability and 3D printing characteristics by designing polymerizable deep eutectic solvents, and verified their application potential in wireless temperature monitoring and pressure sensing, providing a new direction for the material design of flexible temperature sensors; Sci. Adv. 9, eade0423 (2023). (DOI:10.1126 / sciadv.ade0423) introduced a flexible biomimetic thermal sensing polymer that mimics the ion transport dynamics of plant pectin. This material, through block copolymer structure design, has good flexibility and extensibility, can work stably in the temperature range of 15–55℃ and under repeated mechanical deformation, and realizes two-dimensional temperature mapping and infrared light detection, improving the environmental adaptability of flexible temperature sensors; Sci. Adv. 11, eady2547 (2025). (DOI:10.1126 / sciadv.ady2547) used a structure-programmed ion-electronic platform to construct a continuous potential well distribution by utilizing energy landscape engineering in a heteropolymer electrolyte, thereby achieving semiconductor-like thermally activated conduction of ion carriers and obtaining high temperature resolution. This provides a new technical path to solve the problem of insufficient sensitivity of ion-electronic sensors.

[0013] Although the technical solutions disclosed in the aforementioned patents and academic literature have made certain improvements in the mechanical stability, fabrication process, and sensitivity of flexible temperature sensors, thus promoting the technological development of flexible temperature sensors, existing flexible temperature sensors still have many shortcomings that urgently need to be addressed when considering the needs of practical applications such as wearable medical devices and high-end health monitoring. These shortcomings can be summarized into the following four aspects: 1. Deficiencies at the theoretical mechanism level Most existing flexible temperature sensors rely on non-intrinsic response mechanisms such as changes in the resistance of conductive networks and ion migration to measure temperature. The inherent drawback of this type of response mechanism is that the temperature signal is often strongly coupled with external stress, deformation and other factors. When the sensor undergoes bending, stretching and other deformations following human movement, it is prone to signal drift and hysteresis, resulting in a decrease in temperature measurement accuracy. At the same time, in the core application scenario of the narrow physiological temperature range of the human body (32℃~42℃), existing sensors cannot simultaneously achieve high sensitivity, high resolution and long-term stability. For example, some sensors can achieve high sensitivity, but their performance is prone to degradation after long-term operation, while some sensors have good stability but insufficient sensitivity. All of these limitations restrict the realization of accurate body temperature monitoring and cannot meet the high-end needs of clinical diagnosis, precision health management and other applications.

[0014] 2. Shortcomings in biocompatibility Wearable flexible temperature sensors require prolonged contact with human skin, making biocompatibility a core performance indicator. Some conductive fillers (such as PEOT:PSS, metal nanowires, and liquid metals), solvent systems (such as metal salts), or functional additives used in existing flexible temperature sensors may cause skin irritation, allergies, and other adverse reactions during long-term skin contact, posing potential biosafety risks. Furthermore, these materials are prone to oxidation, degradation, or swelling in complex physiological environments such as human sweat and sebum, leading to a decline in conductivity and temperature response performance. This, in turn, affects the long-term stable operation of wearable devices, making it difficult to meet the requirements for long-term non-invasive monitoring. In addition, while some materials possess a degree of biocompatibility, it is difficult to balance flexibility, sensitivity, and stability, resulting in a performance imbalance.

[0015] 3. Shortcomings at the miniaturization level As wearable devices become increasingly thinner and smaller, the requirements for the size of flexible temperature sensors are becoming more stringent. However, many existing flexible temperature sensor material systems rely on a certain thickness or solution-containing structure to maintain stable conductive or ion transport channels. When devices are made smaller and thinner (e.g., at the tens of micrometer level), problems such as signal attenuation, uneven thermal response, and decreased device consistency are easily encountered. For example, the conductive network is at risk of breakage due to size reduction, and the narrowing of the ion transport channel leads to a decrease in ion migration efficiency, thus affecting the accuracy and stability of temperature detection. At the same time, during miniaturization, interface defects between the substrate and the active layer are amplified, further exacerbating performance degradation and limiting the application of flexible temperature sensors in miniature wearable devices, implantable medical devices, and other scenarios.

[0016] 4. Leakage and packaging deficiencies Especially for flexible temperature sensors based on ion or liquid systems, the use of ion-conducting materials or liquid solvents in their sensitive layers poses a significant risk of ion or solvent leakage. This not only leads to rapid performance degradation but can also irritate human skin, thus placing extremely high demands on the packaging structure and materials. The packaging of flexible temperature sensors faces a core dilemma: on the one hand, the packaging structure must possess excellent airtightness and barrier properties to prevent ion and solvent leakage and the intrusion of external sweat and moisture; on the other hand, the packaging material must maintain good flexibility and stretchability to match the sensor's flexible shape, while also possessing good thermal conductivity to avoid affecting the temperature response speed. Existing packaging technologies struggle to simultaneously meet these requirements, either achieving good airtightness but insufficient flexibility, or meeting flexibility standards but poor barrier properties. This increases the complexity of device engineering and manufacturing costs, limiting their large-scale application.

[0017] In summary, existing flexible temperature sensors still have many technical shortcomings in terms of theoretical mechanism, biocompatibility, miniaturization, packaging, and leakage control, making it difficult to meet the demands of wearable medical devices, precision health monitoring, and other fields for high-precision, high-stability, high-biocompatibility, and miniaturized flexible temperature sensors. Therefore, developing a flexible temperature sensor that can overcome these technical deficiencies and achieve a flexible form factor, high precision, high stability, high biocompatibility, easy packaging, and miniaturization through synergistic optimization has become an urgent technical problem to be solved in this field. Summary of the Invention

[0018] The purpose of this application is to address the shortcomings of existing technologies by providing a miniature flexible temperature sensor for biological organisms, its fabrication method, and its application, thereby solving at least the problems of unstable performance, easy degradation, poor biocompatibility, easy accumulation of material toxicity, difficulty in miniaturization, and leakage risk in the fabrication method.

[0019] To achieve the above objectives, the technical solution adopted in this application is as follows: In a first aspect, a miniature flexible temperature sensor is provided, comprising: Thermosensitive conductive layer, wherein the thermosensitive conductive layer comprises acrylamide, glycerol, choline chloride, and lipoic acid; A flexible encapsulation layer, which is assembled with the temperature-sensitive conductive layer, wherein the flexible encapsulation layer comprises a flexible biocompatible material.

[0020] In some of these embodiments, the molar ratio of acrylamide, glycerol, choline chloride, and lipoic acid is 1:(0.4~0.6):1:(0.2~0.5).

[0021] In some of these embodiments, the flexible biomaterial includes polydimethylsiloxane.

[0022] In some of these embodiments, the thickness of the temperature-sensitive conductive layer is 1 to 2 mm.

[0023] In some of these embodiments, the flexible encapsulation layer is a hollow tubular or thin film.

[0024] In some embodiments, when the flexible encapsulation layer is a hollow tubular shape, the inner diameter of the flexible encapsulation layer is 0.1 to 10 mm.

[0025] In some embodiments, when the flexible encapsulation layer is in the form of a thin film, the size of the flexible encapsulation layer is no greater than 10 mm * 10 mm * 1 mm.

[0026] In some embodiments, the temperature measurement range of the miniature flexible temperature sensor is -30 to 120°C.

[0027] In a second aspect, a method for fabricating a miniature flexible temperature sensor is provided, for fabricating the flexible temperature sensor as described in the first aspect, comprising: S1. Acrylamide, glycerol, and choline chloride are mixed in a preset ratio at a preset temperature to obtain a deep eutectic solvent; S2. Add thioctic acid to the deep eutectic solvent according to a preset ratio and mix at a preset temperature to obtain a homogeneous solution; S3. Inject the homogeneous solution into the mold prepared by the flexible biocompatible material, add photoinitiator and crosslinking agent, and perform vacuum degassing to obtain the material to be cured. S4. The material to be cured is subjected to ultraviolet curing to obtain a miniature flexible temperature sensor.

[0028] In some of these embodiments, the molar ratio of acrylamide, glycerol, choline chloride, and lipoic acid is 1:(0.4~0.6):1:(0.2~0.5).

[0029] In some of these embodiments, the flexible biomaterial includes polydimethylsiloxane.

[0030] In some of these embodiments, the photoinitiator includes diphenyl (2,4,6-trimethylbenzoyl)phosphine oxide and benzoin dimethyl ether.

[0031] In some of these embodiments, the crosslinking agent includes methylenebisacrylamide.

[0032] In some of these embodiments, in step S1, the preset temperature is 45~75°C and the mixing time is 20~40 min.

[0033] In some of these embodiments, in step S2, the preset temperature is 45~75°C and the mixing time is 20~40 min.

[0034] In some of these embodiments, the curing time in step S4 is 20 to 40 minutes.

[0035] Thirdly, an application is provided for a miniature flexible temperature sensor as described in the first aspect or a miniature flexible temperature sensor prepared by the preparation method described in the second aspect, comprising at least one of the following: Non-invasive monitoring of the body surface; Temperature monitoring in confined biological spaces.

[0036] In some of these embodiments, non-invasive monitoring of the body surface includes temperature monitoring and respiratory rate monitoring.

[0037] In some of these embodiments, temperature monitoring in the confined biological space includes multi-point temperature monitoring of the organ to be transplanted, wherein the multi-point temperature monitoring includes temperature monitoring of the organ parenchyma, temperature monitoring of the organ blood vessels, and temperature monitoring of the organ surface.

[0038] Compared to related technologies, the miniature flexible temperature sensor for biological organisms, its fabrication method, and its application provided in this application have the following technical advantages: 1) It has good biocompatibility, reducing the potential bioaccumulation risk of traditional conductive polymers or carbon nanomaterials. Specifically, lipoic acid and choline chloride are usually used as nutrients or additives, glycerol is a safe ingredient recognized by the U.S. Food and Drug Administration (FDA), and polyacrylamide is hardly absorbed by the human body and is approved by the FDA for use at certain concentrations. The use of the above ingredients avoids the accumulation of toxicity in the human body of traditional PEDOT:PSS, carbon nanotubes (CNTs) / graphene, and metal nanomaterials. 2) Excellent performance: The miniature flexible temperature sensor of the present invention has a wide temperature measurement range and good repeatability, linearity and resolution; 3) Thermosensitive layer thickness is 1-2 mm, suitable for non-invasive monitoring on the body surface and multi-point temperature detection in narrow biological spaces: while maintaining high sensitivity and stability, the influence of the thickness of the thermosensitive conductive layer on the signal output is reduced, making it suitable for temperature monitoring on the body surface or in narrow spaces. 4) Simple preparation method with no leakage risk: The preparation method uses a one-step photocuring process with flexible biocompatible materials. Compared with the traditional method of preparing the sensing layer first and then encapsulating it, the preparation steps are greatly reduced, the preparation efficiency is improved, and the leakage risk is small. Attached Figure Description

[0039] The accompanying drawings, which are included to provide a further understanding of this application and form part of this application, illustrate exemplary embodiments and are used to explain this application, but do not constitute an undue limitation of this application. In the drawings: Figure 1 This is a schematic diagram of the sensing mechanism of the miniature flexible temperature sensor according to Embodiment 1 of the present invention; Figure 2 This is a schematic diagram of the structure of a miniature flexible temperature sensor according to Embodiment 2 of the present invention; Figure 3 This is a schematic diagram of the heating-cooling cycle performance test of the miniature flexible temperature sensor according to the test example of the present invention. Figure 4 This is a temperature-resistance change curve and a schematic diagram of TCR test of a miniature flexible temperature sensor according to the test example of the present invention. Figure 5 This is a schematic diagram of the resolution test of a miniature flexible temperature sensor according to a test example of the present invention; Figure 6 This is a schematic diagram of the resistance-temperature linearity test of a miniature flexible temperature sensor according to the test example of the present invention. Figure 7 This is a schematic diagram of respiratory frequency monitoring using the miniature flexible temperature sensor of Application Example 1 according to the present invention. Figure 8 This is a schematic diagram of multi-point monitoring of the organ to be transplanted according to Application Example 2 of the present invention. Detailed Implementation

[0040] To make the objectives, technical solutions, and advantages of this application clearer, the application is described and illustrated below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the scope of this application. All other embodiments obtained by those skilled in the art based on the embodiments provided in this application without inventive effort are within the scope of protection of this application.

[0041] Obviously, the accompanying drawings described below are merely some examples or embodiments of this application. Those skilled in the art can apply this application to other similar scenarios based on these drawings without any inventive effort. Furthermore, it is understood that although the efforts made in this development process may be complex and lengthy, for those skilled in the art related to the content disclosed in this application, any changes to design, manufacturing, or production based on the technical content disclosed in this application are merely conventional technical means and should not be construed as insufficient disclosure of the content of this application.

[0042] In this application, the reference to "embodiment" means that a specific feature, structure, or characteristic described in connection with an embodiment may be included in at least one embodiment of this application. The appearance of this phrase in various places in the specification does not necessarily refer to the same embodiment, nor is it a separate or alternative embodiment that is mutually exclusive with other embodiments. It will be explicitly and implicitly understood by those skilled in the art that the embodiments described in this application may be combined with other embodiments without conflict.

[0043] Unless otherwise defined, the technical or scientific terms used in this application shall have the ordinary meaning understood by one of ordinary skill in the art to which this application pertains. The terms “a,” “an,” “an,” “the,” and similar words used in this application do not indicate quantity limitation and may indicate singular or plural. The terms “comprising,” “including,” “having,” and any variations thereof used in this application are intended to cover non-exclusive inclusion; for example, a process, method, system, product, or device that includes a series of steps or modules (units) is not limited to the listed steps or units, but may also include steps or units not listed, or may include other steps or units inherent to these processes, methods, products, or devices. The terms “connected,” “linked,” “coupled,” and similar words used in this application are not limited to physical or mechanical connections, but may include electrical connections, whether direct or indirect. “Multiple” used in this application refers to two or more. “And / or” describes the relationship between related objects, indicating that three relationships may exist; for example, “A and / or B” can represent: A alone, A and B simultaneously, and B alone. The character " / " generally indicates that the preceding and following objects are in an "or" relationship. The terms "first," "second," and "third" used in this application are merely to distinguish similar objects and do not represent a specific ordering of the objects.

[0044] Example 1 This embodiment relates to a miniature flexible temperature sensor for biological organisms, its preparation method, and its application.

[0045] A miniature flexible temperature sensor is assembled from a temperature-sensitive conductive layer and a flexible encapsulation layer. The temperature-sensitive conductive layer comprises at least acrylamide, glycerol, choline chloride, and lipoic acid; the flexible encapsulation layer comprises a flexible biocompatible material, including but not limited to polydimethylsiloxane (PDMS).

[0046] In this invention, the temperature-sensitive conductive layer is used for temperature sensing and conductivity, which can present the changes in the migration energy of microscopic particles caused by changes in external temperature in a directly measurable electrical form.

[0047] In this invention, the flexible encapsulation layer is used to prevent leakage of the temperature-sensitive conductive layer, shield external interference, and maintain the stability of the internal conductive network.

[0048] It should be noted that the working principle of the miniature flexible temperature sensor of the present invention is as follows: like Figure 1 As shown, by introducing two different hydrogen bond acceptors, acrylamide and lipoic acid, into the polymer network, both their amide and carboxyl bonds can form hydrogen bonds of two different strengths with choline chloride, achieving differential structural regulation of hydrogen bond energy: as the temperature increases, weaker hydrogen bonds preferentially break or rearrange, while stronger hydrogen bonds remain stable. This multi-level reversible structural regulation alters local ion migration channels, thereby significantly amplifying the temperature response to conductivity. This synergistic mechanism enables the sensor to achieve highly sensitive temperature measurement while maintaining flexibility and biocompatibility. It is more suitable for flexible, wearable systems than traditional electronic conductors or thermistors, and its micro-design demonstrates the advanced nature of enhancing signals by differentially regulating ion migration through hydrogen bonds.

[0049] In this invention, lipoic acid is introduced as a functional regulating component into the temperature-sensitive conductive system. The carboxyl group in lipoic acid can form hydrogen bonds with the amide group of acrylamide and choline chloride, constructing bilayer hydrogen bond structures of varying strengths based on the existing deep eutectic system hydrogen bond network. On the one hand, this enhances the intermolecular interactions of the polymer network, improving the structural stability and mechanical properties of the material; on the other hand, the selective breaking or rearrangement of hydrogen bonds of different strengths with temperature changes can regulate local ion migration channels and amplify the effect of temperature on ion conductivity, thereby significantly improving the sensitivity and stability of the flexible temperature sensor.

[0050] It should be noted that the cross-sectional shape of the miniature flexible temperature sensor includes, but is not limited to, circles and rectangles.

[0051] Specifically, the miniature flexible temperature sensor can be either a cylindrical structure or a flat plate structure.

[0052] In other words, it is sufficient to expose at least a portion of the temperature-sensitive conductive layer to the outside environment.

[0053] In some of these embodiments, the molar ratio of acrylamide, glycerol, choline chloride, and lipoic acid is 1:(0.4~0.6):1:(0.2~0.5).

[0054] In some of these embodiments, the lipoic acid is at least one of R-lipoic acid, S-lipoic acid, and R / S-lipoic acid.

[0055] The cross-section of the temperature-sensitive conductive layer includes, but is not limited to, circles and rectangles.

[0056] When the cross-section of the temperature-sensitive conductive layer is circular, the diameter of the temperature-sensitive conductive layer is 0.1–10 mm.

[0057] When the cross-section of the temperature-sensitive conductive layer is rectangular, the length of the temperature-sensitive conductive layer shall not exceed 10 mm and the width shall not exceed 10 mm.

[0058] Furthermore, the thickness of the temperature-sensitive conductive layer is 1–2 mm. It should be noted that when the cross-section of the temperature-sensitive conductive layer is circular, the thickness refers to the axial extension dimension of the layer, such as its length when placed horizontally or its height when placed vertically. When the cross-section of the temperature-sensitive conductive layer is rectangular, the thickness refers to its height, which is less than its length and width.

[0059] The cross-section of the flexible encapsulation layer includes, but is not limited to, ring-shaped, rectangular, etc.

[0060] That is, when the cross-section of the flexible encapsulation layer is annular, the flexible encapsulation layer is a hollow tube. In this case, the inner diameter of the flexible encapsulation layer is 0.1–10 mm. At this time, the outer edge of the temperature-sensitive conductive layer is tightly attached to the inner edge of the flexible encapsulation layer, and the end of the temperature-sensitive conductive layer is approximately flush with the end of the flexible encapsulation layer.

[0061] That is, when the cross-section of the flexible encapsulation layer is rectangular, the flexible encapsulation layer is in the form of a thin film. In this case, the size of the flexible encapsulation layer is no greater than 10 mm * 10 mm * 1 mm (length * width * height). At this time, the edge of the temperature-sensitive conductive layer is approximately flush with the edge of the flexible encapsulation layer.

[0062] In some embodiments, the temperature measurement range of the miniature flexible temperature sensor is -30 to 120°C. Preferably, the temperature measurement range is -10 to 100°C.

[0063] The fabrication method for the miniature flexible temperature sensor described above is as follows: S1 (Preparation of deep eutectic solvent): Acrylamide, glycerol, and choline chloride are mixed in a preset ratio at a preset temperature to obtain a deep eutectic solvent. S2 (Preparation of homogeneous solution): Thioctic acid is added to a deep eutectic solvent in a preset ratio and mixed at a preset temperature to obtain a homogeneous solution; S3 (combination): The homogeneous solution is injected into a mold prepared from a flexible biocompatible material, and a photoinitiator and crosslinking agent are added. Vacuum degassing is then performed to obtain the material to be cured. S4 (UV curing) involves UV curing of the material to be cured to obtain a miniature flexible temperature sensor.

[0064] In step S1, the preset temperature is 45~75℃ and the mixing time is 20~40 min. Preferably, the preset temperature is 55~65℃ and the mixing time is 25~35 min. More preferably, the preset temperature is 60℃ and the mixing time is 30 min.

[0065] In step S2, the preset temperature is 45-75℃ and the mixing time is 20-40 min. Preferably, the preset temperature is 55-65℃ and the mixing time is 25-35 min. More preferably, the preset temperature is 60℃ and the mixing time is 30 min.

[0066] In step S3, the photoinitiator includes diphenyl (2,4,6-trimethylbenzoyl)phosphine oxide (TPO) and dimethyl benzoate (DMPA).

[0067] In step S3, the crosslinking agent includes methylenebisacrylamide.

[0068] In step S4, the curing time is 20–40 min. Preferably, the curing time is 30 min.

[0069] In step S4, curing is performed using 365 nm ultraviolet light.

[0070] In step S4, an ultraviolet lamp is used to cure the material. The power of the ultraviolet lamp is 5-20 W.

[0071] The miniature flexible temperature sensor of the present invention can be applied to at least non-invasive monitoring of the body surface and temperature monitoring in narrow biological spaces.

[0072] Non-invasive monitoring of the body surface includes temperature monitoring and respiratory rate monitoring.

[0073] Temperature monitoring in confined biological spaces includes at least multi-point temperature monitoring of the organ to be transplanted, which includes temperature monitoring of the organ parenchyma, temperature monitoring of the organ's blood vessels, and temperature monitoring of the organ's surface.

[0074] It should be noted that the application scenarios presented in this embodiment are not all applicable scenarios to which this miniature flexible temperature sensor is suitable. Any application scenario where the miniature flexible temperature sensor of this invention is used to achieve non-invasive detection without sensation on the body surface or temperature monitoring in confined biological spaces falls within the protection scope of this invention.

[0075] The technical effects of this invention are as follows: 1) Good biocompatibility: Alpha-lipoic acid and choline chloride are usually used as nutrients or additives. Glycerin is a safe ingredient recognized by the U.S. Food and Drug Administration (FDA). Polyacrylamide is hardly absorbed by the human body and is approved by the FDA for use at certain concentrations. The use of the above ingredients avoids the accumulation of toxicity in the human body of traditional PEDOT:PSS, carbon nanotubes (CNTs) / graphene, and metal nanomaterials. 2) Excellent performance: The miniature flexible temperature sensor of the present invention has a wide temperature measurement range and excellent repeatability, linearity and resolution; 3) Small size: While maintaining high sensitivity and stability, it reduces the impact of the thickness of the temperature-sensitive conductive layer on the signal output, making it suitable for temperature monitoring on the body surface or in narrow spaces; 4) Simple preparation method with no leakage risk: The preparation method uses a one-step photocuring process with flexible biocompatible materials. Compared with the traditional method of preparing the sensing layer first and then encapsulating it, the preparation steps are greatly reduced, the preparation efficiency is improved, and the leakage risk is small.

[0076] Example 2 This embodiment is a specific implementation of the present invention.

[0077] In this embodiment, the fabrication method of the miniature flexible temperature sensor is as follows: S1, Preparation of deep eutectic solvent Weigh out each component according to the molar ratio of acrylamide, glycerol, choline chloride, and R-lipoic acid 1:0.5:1:0.3 (masses of 3.55 g, 2.30 g, 6.98 g, and 3.21 g, respectively); Pre-dried acrylamide, glycerol, and choline chloride are weighed and added to the sample vial. The vial is heated and stirred at 60°C for 30 minutes. The solid powder will melt into a colorless, transparent, and homogeneous deep eutectic solvent.

[0078] S2. Preparation of homogeneous solution Add 3.21 g of solid R-lipoic acid to a deep eutectic solvent, heat and stir at 60°C for 30 min to obtain a yellow, transparent, homogeneous solution with a certain degree of fluidity.

[0079] S3, Combination Add 1 wt.% of photoinitiator TPO and crosslinking agent methylenebisacrylamide to the homogeneous solution obtained in step S2, mix well, and then inject 100 μl of the solution into a PDMS hollow tube with an inner diameter of 1 mm. Remove the air bubbles generated during the injection process under vacuum.

[0080] S4, UV curing The prepolymer obtained in step three above was photocured under a 5 W ultraviolet lamp with a wavelength of 365 nm for 30 min. This yielded the aforementioned miniature flexible temperature sensor with a core-sheath structure.

[0081] It should be noted that, as Figure 2 As shown, the core-sheath structure includes a core layer and a sheath layer. The core layer is a temperature-sensitive conductive layer (i.e.,...) Figure 2 The sensing layer in the middle), the sheath is a flexible encapsulation layer (i.e. Figure 2 (The encapsulation layer in the middle).

[0082] The miniature flexible temperature sensor in this embodiment is cylindrical with a diameter of 1.4 mm (inner diameter of 1 mm and wall thickness of 0.2 mm) and a length of approximately 1–2 mm. Its size is significantly smaller than currently commercially available NTC temperature probes, and it features flexibility and biocompatibility.

[0083] It should be noted that the sensor size provided in this embodiment is not the smallest sensor size that can be achieved by this method. Specifically, miniature flexible temperature sensors can be prepared by reducing the size of the flexible encapsulation layer to the limit of maintaining the conductivity of the conductive network of the temperature-sensitive conductive layer.

[0084] Example 3 This embodiment is a specific implementation of the present invention.

[0085] In this embodiment, the fabrication method of the miniature flexible temperature sensor is as follows: S1, Preparation of deep eutectic solvent Weigh out each component according to the molar ratio of acrylamide, glycerol, choline chloride, and R-lipoic acid 1:0.4:1:0.4 (masses of 3.55 g, 1.84 g, 6.98 g, and 4.12 g, respectively); Pre-dried acrylamide, glycerol, and choline chloride are weighed and added to the sample vial. The vial is heated and stirred at 60°C for 30 minutes. The solid powder will melt into a colorless, transparent, and homogeneous deep eutectic solvent.

[0086] S2. Preparation of homogeneous solution Add 4.12 g of solid R-lipoic acid to a deep eutectic solvent, heat and stir at 60°C for 30 min to obtain a yellow, transparent, homogeneous solution with a certain degree of fluidity.

[0087] S3, Combination Add 1 wt.% of photoinitiator TPO and crosslinking agent methylenebisacrylamide to the homogeneous solution obtained in step S2, mix well, and then inject 100 μl of the solution into a PDMS hollow tube with an inner diameter of 1 mm. Remove the air bubbles generated during the injection process under vacuum.

[0088] S4, UV curing The prepolymer obtained in step three above was photocured under a 5 W ultraviolet lamp with a wavelength of 365 nm for 30 min. This yielded the aforementioned miniature flexible temperature sensor with a core-sheath structure.

[0089] The miniature flexible temperature sensor in this embodiment is cylindrical with a diameter of 1.4 mm (inner diameter of 1 mm and wall thickness of 0.2 mm) and a length of approximately 1–2 mm. Its size is significantly smaller than currently commercially available NTC temperature probes, and it features flexibility and biocompatibility.

[0090] Test case This embodiment tests the miniature flexible temperature sensor prepared in Example 2.

[0091] Rapid heating-cooling tests were conducted on the miniature flexible temperature sensor within a temperature range of 30~40℃. For example... Figure 3 As shown, the resistance of the miniature flexible temperature sensor remains basically consistent with temperature changes, thus demonstrating that the miniature flexible temperature sensor provided in Example 2 has good repeatability.

[0092] In addition, such as Figure 4 As shown, the miniature flexible temperature sensor has a TCR value as high as -178 % / ℃ at low temperatures, which demonstrates that the miniature flexible temperature sensor has extremely high temperature detection sensitivity.

[0093] like Figure 5 As shown, when the temperature sensor is placed in a temperature difference of 0.1℃, the resistance signal output by the sensor can match the temperature change well and remains stable during the heating-cooling process, exhibiting high linearity R. 2 =0.9996, demonstrating excellent resolution and linearity.

[0094] like Figure 6 As shown, when the miniature flexible temperature sensor is placed in an environment of -10~100℃, the flexible temperature sensor provided in this embodiment realizes the change in resistance, proving that it has a temperature measurement range of at least 110℃.

[0095] The reason why the TCR value of the miniature flexible sensor in Example 2 is significantly higher than that of commercially available sensors and cutting-edge research papers is as follows: In ion-conducting temperature sensing systems, a high TCR often stems from the strong temperature dependence of ion migration. Unlike the conduction mechanism in metals or semiconductors, where electrons are the primary charge carriers, ion conduction typically follows a thermally activated process described by the Arrhenius equation, meaning ions must overcome a certain migration energy barrier to move within the system. As temperature increases, the system gains more thermal energy, making it easier for ions to cross the barrier, leading to an exponential increase in conductivity and thus a significant change in resistance.

[0096] In the miniature flexible temperature sensor of Example 2, ion migration in the thermosensitive conductive layer is often accompanied by the dynamic reconstruction of the bilayer hydrogen bond network. Temperature changes weaken or rearrange hydrogen bond interactions, altering the ion solvation state and local microstructure, further changing the ion diffusion path and mobility. This synergistic mechanism of thermally activated migration and bilayer hydrogen bond network regulation enables the ion-conductive system to exhibit a stronger response to temperature changes than conventional electronic conductors, thereby achieving higher TCR and higher temperature sensitivity.

[0097] Application Example 1 In this application example, the miniature flexible temperature sensor of Example 2 is used for non-invasive monitoring of the body surface.

[0098] In this application example, the length of the miniature flexible temperature sensor is 1 mm.

[0099] This application example also includes: Using conductive copper wire, a miniature flexible temperature sensor is connected to the circuit via a two-stage method. The resistance of this circuit is measured by a commercially available Bluetooth transmitter module (e.g., TRUEBOX 01RC, Shanghai Zhongbin Technology Co., Ltd.). Ultimately, it can receive measurement data in real time and accurately, and transmit the data to a mobile phone via Bluetooth, enabling real-time display, storage, and sharing of the data. It features fast response speed and high resolution.

[0100] like Figure 7 As shown, a miniature flexible temperature sensor with Bluetooth transmission capability is placed inside a mask, enabling non-invasive monitoring that is imperceptible to the skin. During monitoring, it can detect not only temperature during breathing but also real-time monitoring of respiratory rate.

[0101] The specific working principle is as follows: Respiratory frequency can be monitored by observing the periodic temperature changes during respiration. The key is that the temperature of the inhaled air is lower than the body temperature during inhalation and the temperature of the exhaled air is higher than the ambient temperature during exhalation, thus creating a periodic temperature fluctuation signal at the mouth and nose.

[0102] To achieve high-precision detection, a sensor with fast response and high sensitivity is required. The miniature flexible sensor fabricated in this invention can well meet this requirement. Although the signal amplitude may be affected by exhalation volume and external environmental factors, it can still stably acquire respiratory rate. Figure 7 As shown, in actual operation, it can distinguish between physiological phenomena such as normal breathing, bradybreathing, and tachybreathing. Therefore, this monitoring method is non-invasive, miniaturized, suitable for continuous monitoring, and can be extended to applications such as inspiratory / expiratory depth analysis or flexible patch-type long-term wearable monitoring.

[0103] Application Example 2 In this application example, the miniature flexible temperature sensor of Example 2 is used for multi-point temperature monitoring of the organ to be transplanted.

[0104] In this application example, the length of the miniature flexible temperature sensor is 1 mm.

[0105] This application example also includes: Using conductive copper wire, a miniature flexible temperature sensor is connected to the circuit via a two-stage method. The resistance of this circuit is measured by a commercially available Bluetooth transmitter module (e.g., TRUEBOX 01RC, Shanghai Zhongbin Technology Co., Ltd.). Ultimately, it can receive measurement data in real time and accurately, and transmit the data to a mobile phone via Bluetooth, enabling real-time display, storage, and sharing of the data. It features fast response speed and high resolution.

[0106] like Figure 8 As shown, multiple miniature flexible temperature sensors are placed in the organ parenchyma, organ blood vessels, and organ surface of the organ to be transplanted. The placement methods include attaching the miniature flexible temperature sensors to the organ surface and inserting them into the organ parenchyma or organ blood vessels via minimally invasive techniques.

[0107] By using multiple miniature flexible temperature sensors, multi-point real-time and continuous temperature monitoring can be achieved. Through specialized signal processing technology, external environmental interference can be effectively suppressed, thereby obtaining high-precision temperature data.

[0108] Multi-point temperature measurement can not only improve the accuracy of temperature measurement, but also assess the differences in metabolic activity in different parts of the organ to be transplanted, providing a reliable basis for organ preservation strategies, pre-transplant functional assessment and intraoperative regulation.

[0109] Traditional technologies relying on external organ temperature measurement boxes or surface probes are limited by the number of measurement points, reflecting only surface temperature and failing to accurately reflect the core temperature inside the organ. This leads to biases in the assessment of tissue metabolic status and activity, affecting organ preservation and transplantation decisions. Therefore, compared to traditional technologies, the miniature flexible temperature sensor of this invention can achieve multi-point temperature measurement and high-precision temperature measurement, reflecting the metabolic activity of different parts of the organ, facilitating subsequent operations by doctors.

[0110] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0111] The embodiments described above are merely illustrative of several implementation methods of this application, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the invention patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this application, and these all fall within the protection scope of this application. Therefore, the protection scope of this patent application should be determined by the appended claims.

Claims

1. A miniature flexible temperature sensor for use in living organisms, characterized in that, include: Thermosensitive conductive layer, wherein the thermosensitive conductive layer comprises acrylamide, glycerol, choline chloride, and lipoic acid; A flexible encapsulation layer, which is assembled with the temperature-sensitive conductive layer, wherein the flexible encapsulation layer comprises a flexible biocompatible material.

2. The miniature flexible temperature sensor according to claim 1, characterized in that, The molar ratio of acrylamide, glycerol, choline chloride, and lipoic acid is 1:(0.4~0.6):1:(0.2~0.5); and / or Flexible biomaterials include polydimethylsiloxane.

3. The miniature flexible temperature sensor according to claim 1 or 2, characterized in that, The thickness of the temperature-sensitive conductive layer is 1–2 mm; and / or The flexible encapsulation layer is in the form of a hollow tube or a thin film.

4. The miniature flexible temperature sensor according to claim 3, characterized in that, When the flexible encapsulation layer is a hollow tubular shape, the inner diameter of the flexible encapsulation layer is 0.1–10 mm; or When the flexible encapsulation layer is in the form of a thin film, the size of the flexible encapsulation layer is no greater than 10 mm * 10 mm * 1 mm.

5. The miniature flexible temperature sensor according to claim 1, characterized in that, The temperature measurement range of the miniature flexible temperature sensor is -30~120℃.

6. A method for fabricating a micro-flexible temperature sensor for biological organisms, used to fabricate the flexible temperature sensor as described in any one of claims 1 to 5, characterized in that, include: S1. Acrylamide, glycerol, and choline chloride are mixed in a preset ratio at a preset temperature to obtain a deep eutectic solvent; S2. Add thioctic acid to the deep eutectic solvent according to a preset ratio and mix at a preset temperature to obtain a homogeneous solution; S3. Inject the homogeneous solution into the mold prepared by the flexible biocompatible material, add photoinitiator and crosslinking agent, and perform vacuum degassing to obtain the material to be cured. S4. The material to be cured is subjected to ultraviolet curing to obtain a miniature flexible temperature sensor.

7. The preparation method according to claim 6, characterized in that, The molar ratio of acrylamide, glycerol, choline chloride, and lipoic acid is 1:(0.4~0.6):1:(0.2~0.5); and / or Flexible biomaterials include polydimethylsiloxane; Photoinitiators include diphenyl (2,4,6-trimethylbenzoyl)phosphine oxide, dimethyl benzoate; and / or Crosslinking agents include methylenebisacrylamide.

8. The preparation method according to claim 7, characterized in that, In step S1, the preset temperature is 45~75℃, and the mixing time is 20~40 min; and / or In step S2, the preset temperature is 45~75℃, and the mixing time is 20~40 min; and / or In step S4, the curing time is 20–40 min.

9. An application of a miniature flexible temperature sensor as described in any one of claims 1 to 5 or a miniature flexible temperature sensor prepared by the preparation method as described in any one of claims 6 to 8, characterized in that, Includes at least one of the following: Non-invasive monitoring of the body surface; Temperature monitoring in confined biological spaces.

10. The application according to claim 9, characterized in that, Non-invasive monitoring of the body surface includes temperature monitoring, respiratory rate monitoring; and / or Temperature monitoring in confined biological spaces includes multi-point temperature monitoring of the organ to be transplanted, which includes temperature monitoring of the organ parenchyma, temperature monitoring of the organ's blood vessels, and temperature monitoring of the organ's surface.

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