Wearable wireless temperature monitoring device utilizing a micromachined MEMS thermocouple for laboratory animals and human ICU patients

Abstract

A wearable wireless temperature monitoring device includes a micromachined thermocouple probe fabricated on a Silicon-On-Insulator (SOI) substrate, including an electrically insulated housing and a microneedle probe. A doped silicon (Si)Zchrome (Cr)Zgold (Au) junction on the microneedle probe provides a Seebeck coefficient of approximately 447 μV / °C. The device further includes a wireless data communication transceiver positioned in the housing for continuous real-time temperature monitoring. The microneedle has a diameter of less than 100 microns and a submicron sharp tip for minimally invasive temperature measurements.

Description

[0001] WEARABLE WIRELESS TEMPERATURE MONITORING DEVICE UTILIZING A MICROMACHINED MEMS THERMOCOUPLE FOR LABORATORY ANIMALS AND HUMAN ICU PATIENTS

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application is based on and claims priority to U. S. Provisional Patent Application 63 / 716,370, filed November 5, 2024, the entire contents of which is incorporated by reference herein as if expressly set forth in its respective entirety herein.

[0004] STATEMENT OF GRANT

[0005] The invention was made with government support under 2226930 awarded by the National Science Foundation. The government has certain rights in the invention.

[0006] BACKGROUND

[0007] Accurate and continuous monitoring of body temperature is essential in various biomedical and clinical settings, particularly in laboratory' research involving animals and in the intensive care of human patients. Traditional temperature measurement methods, such as rectal thermometry in animals, are invasive and stressful, often requiring sedation or restraint. This can skew physiological data due to the impact of stress or anesthesia on vital signs, including body temperature. For ICU patients, frequent manual temperature measurements can be uncomfortable and disruptive, especially in critical care environments.

[0008] In both research and clinical settings, the need for a non-invasive, accurate, and continuous temperature monitoring system is evident. Current alternatives, such as implanted telemetry devices or infrared thermography, are either invasive, cumbersome, or inaccurate, making them unsuitable for continuous monitoring. Furthermore, in research, especially with laboratory animals, the ethical implications of invasive procedures add another layer of complexity, affecting both the welfare of the animals and the validity of the experimental data.

[0009] What is therefore needs is a system for non-invasive, accurate and continuous monitoring of body temperature. SUMMARY OF THE DISCLOSURE

[0010] In one embodiment, a wearable wireless temperature monitoring device is provided and includes a micromachined thermocouple probe fabricated on a Silicon-On-Insulator (SOI) substrate, including an electrically insulated housing and a microneedle probe. A doped silicon (Si) / chrome (Cr) / gold (Au) junction on the microneedle probe provides a Seebeck coefficient of approximately 447 pV / °C. The device further includes a wireless data communication transceiver positioned in the housing for continuous real-time temperature monitoring. The microneedle has a diameter of less than 100 microns and a submicron sharp tip for minimally invasive temperature measurements.

[0011] In another aspect, a method for continuous and non-invasive temperature monitoring in a human ICU patient, includes the steps of:

[0012] attaching a wearable wireless temperature monitoring device to skin of the patient; continuously measuring body temperature using a micromachined thermocouple probe having a microneedle with a diameter of less than 100 microns; and

[0013] wirelessly transmitting temperature data measured by the thermocouple for real-time monitoring.

[0014] BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1A is a side view of a microneedle thermocouple probe designed for temperature measurements in biological samples according to an embodiment of the present disclosure. FIG. IB is a perspective view of the microneedle thermocouple probe shown in FIG. 1A. FIG. 1C is a graph of the relationship between the probe voltage (V) and temperature (T) obtained using a microneedle probe according to the present disclosure.

[0015] FIG. 2A-2H illustrates steps of an exemplary process for fabricating a thermocouple according to an embodiment of the present disclosure

[0016] FIG. 3A is a schematic diagram of an experimental setup for determining the Seebeck coefficient of the thermocouple according to the present disclosure.

[0017] FIG. 3B is a graph showing results of testing the Seebeck coefficient of various thermocouples according to the present disclosure using the testing setup shown in FIG. 3A.

[0018] FIG. 4A is a graph of temperature versus time at an Au-Si junction interface of the probe thermocouple simulated using finite element analysis (FEA).

[0019] FIG. 4B is a three-dimensional representation of the thermocouple probe showing a simulation of structural integrity of the probe. FIG. 5 A is a schematic diagram of a setup for testing the biological tissue with a thermocouple probe according to the present disclosure.

[0020] FIG. 5B is a graph of temperature versus time which shows the temperature rise within the tissue tested using the setup of FIG. 5A.

[0021] FIG. 6A is a schematic diagram of the experimental setup for testing the thermocouple probe according the present disclosure on the oocyte medium.

[0022] FIG. 6B is a graph of temperature versus time which shows the temperature rise of the oocytes using the setup of FIG. 6A.

[0023] DETAILED DESCRIPTION

[0024] The present disclosure addresses the limitations noted above by introducing a wearable wireless temperature monitoring device that incorporates a micromachined MEMS thermocouple probe. The device is designed for minimally invasive, continuous monitoring of body temperature in both laboratory animals and human patients, reducing stress and improving the accuracy of physiological data. This innovation stands to revolutionize temperature monitoring by offering a more humane, efficient, and reliable alternative to existing methods.

[0025] The thermocouple consists of two different electrically conductive materials, in particular metals joined at a junction while their free ends are connected to a voltage measuring apparatus. Temperature changes at this junction generate an electromotive force proportional to the temperature difference between the junction and the free end (named the cold junction) for each metal, a phenomenon known as the Seebeck effect. A distinct advantage of a thermocouple lies in its sensitivity to temperature changes solely at the thermocouple junction, rendering it unaffected by temperature fluctuations in other parts of the device. The thermocouples is also characterized by ease of calibration, insensitivity to fluid viscosity and chemical processes, non-toxicity to cells and tissues, and rapid response times.

[0026] In contrast to standard metal junction thermocouples, which exhibit relatively modest Seebeck coefficients (<100 pV / K combined Seebecks), doped Si stands out for its capacity to reach significantly higher values. Notably, intrinsic Si, in its undoped state, can achieve Seebeck coefficients around 1000 pV / K. The process of doping Si, wherein impurities are introduced to alter its properties, has a marked impact on its Seebeck coefficient. Light doping can result in coefficients within the range of several hundred pV / K, enhancing electrical conductivity, which promotes effective thermoelectric performance. However, as the doping level increases, there is a notable reduction in the Seebeck coefficient. The balance between Seebeck coefficient and electrical conductivity ensures the functionality of the thermocouple.

[0027] This probe of the wearable device according to the present disclosure includes a thermocouple that utilizes doped Si-Cr / Au junctions on an silicon-on-insulation (SOI) wafer. The probe offers several key advantages and is particularly beneficial for biological applications. The miniaturized design of the probe which is enabled by micromachining methods and the use of doped silicon (Si) and chrome-gold (Cr / Au) junctions, allows for precise temperature measurements within the constrained and sensitive environments of tissues and large cells. The probe has a needle-like design that enables effective penetration into tissues with structural integrity. The probe can penetrate to measurements at depths of 1 mm and beyond non-invasively. The thermocouple has a high Seebeck coefficient, reaching up to 447 pV / K, which resulted from the combined effects of the doped silicon and the Cr / Au composite stack of the probe. The probe also has a rapid response time which facilitates realtime monitoring of dynamic biological processes. The efficacy of the probe has been demonstrated in ex-vivo tissue samples and live Xenopus laevis oocytes as described below.

[0028] FIG. 1A is a side view of a microneedle thermocouple probe designed for temperature measurements in biological samples according to an embodiment of the present disclosure. The thermocouple probe 100 includes a housing 110 for one or more semiconductor device (chip) and a microneedle 120 which extends from the housing 110. The housing 110 is preferably a compact structure (e.g., 6 x 5 x 5 mm) comprising a waterproof and shockproof covering enclosure, making it suitable for long-term attachment to animals or patients. In some embodiments, the microneedle 120 is approximately 1500 pm in length (where “approximately” should be taken to mean ± five percent from the nominal magnitude through this disclosure). However, in other embodiments the microneedle is approximately 500 pm or 1000 pm in length. The structure of the microneedle 120 is shown in greater detail in the perspective view of FIG. IB. The microneedle 120 is formed as a cantilever with a triangularshaped tip 130 suspended from the housing, hi certain implementations the cantilevered needle measures 40 approximately pm in width, 10 pm in thickness. In certain implementations, the housing has dimensions of approximately 1500 pm in width, 685 pm in thickness, and 3700 pm in length. However, other sizes can be used. At the triangular tip 130 of the microneedle there is a first thermocouple junction 135. The second (reference) junction is situated in the housing 110 (not shown). In at least one embodiment, both junctions are composed of chromium(Cr) / gold (Au) (e.g., 40 nm / 160 nm) and doped silicon. Detailed fabrication steps of the microneedle and junction are described in are illustrated and described in FIG. 2A-2H. To ensure continuous monitoring, the device is powered wirelessly using an inductive charging system (positioned in the housing 110), eliminating the need for battery replacements. The data collected by the thermocouple is transmitted wirelessly to a receiver, enabling realtime monitoring and analysis. The wireless power system ensures that the device remains functional over extended periods without the need for manual intervention.

[0029] Before describing the fabrication process reference is first made to FIG. 1C which is a graph of the relationship between the probe voltage (V) and temperature (T) obtained using a microneedle probe according to the present disclosure. Each voltage measurement represents an average of 10 readings (N=10), with the standard deviation being smaller than the size of the points on the graph and the average coefficient of variation (CV) being 2.1%. According to the graph of FIG. 1C, the Seebeck coefficient of thermocouple is 447 pV / °C.

[0030] Device Fabrication

[0031] Reference is now made to FIGS. 2A-2H which illustrates steps of an exemplary process for fabricating a thermocouple according to an embodiment of the present disclosure. Prior to the first step the fabrication process begins with a 4-inch silicon-on-insulator (SOI) 'afer 205 which, in one implementation, consists of a 10 pm-thick device layer (top) 210, a 0.5-pm buried oxide (BOX) layer 215 (middle), and a 675-pm thick handle layer 220. Those of skill in the art will appreciate that other size wafers and layer thicknesses can be used. As illustrated in FIG. 2A, the fabrication process begins with a 4-inch silicon-on-insulator (SOI) wafer 205 which, in one implementation, consists of a 10 pm-thick device layer (top) 210, a 0.5-,um buried oxide (BOX) layer 215 (middle), and a 675-pm thick handle layer 220. Those of skill in the art will appreciate that other size wafers and layer thicknesses can be used. The 'afer is preferably thoroughly cleaned using a stripper solution (e.g., NanoStrip, CMC Materials) at 60 °C for 10 minutes to eliminate organic and inorganic contaminants, the substrate is doped with boron fluoride (BFz) by ion implantation forming a doped layer 225. Post-implantation, the wafers can annealed at 850cC for 30 minutes in a furnace to activate the implanted ions and repair lattice damage. In testing, the four-point probe sheet resistances measured 9450 ± 250 ohms per square before annealing and 291 + 3 ohms per square after annealing.

[0032] In the following step shown in FIG.2B, a relatively thick oxide layer 230 (e.g., approximately 100 nm) is deposited on the front side of the substrate (over the implanted ion layer 225). The deposition can be performed using conventional techniques such as Plasma Enhanced Chemical Vapor Deposition (PECVD). The oxide layer 230 serves as electrical insulation between the doped silicon layer 225 and the subsequent metal layers. As shown in FIG. 2C, a photoresist layer 235 (e.g., approximately 3 pm) is then spun onto the substrate. The patterns for the doped silicon-metal junctions are transferred to the photoresist layer and PECVD oxide using UV photolithography. The exposed photoresist can be removed with a resist stripper. The wafer is thereafter cleaned with a stripper solution prior to the next fabrication step.

[0033] As shown in FIG. 2D, an additional layer of photoresist is applied by spin-coating, and metal patterns are transferred to the photoresist layers using UV photolithography. Prior to metal deposition, the wafers were dipped in a diluted buffer solution (e.g., hydrofluoric acid) to remove the native oxide on the silicon surface. In the following step shown in FIG. 2E, metal layers 240 consisting of 40 nm thick Cr and 160 nm thick Au are then deposited on the wafers using an evaporation system. The metal layers on the photoresist are then removed using a lift-off solution revealing the metal patterns.

[0034] After the lift-off process, another photoresist is spun onto the spin-coating. As shown in FIG. 2F, the desired shape of the thermocouple on the front side of the substrate is transferred to the layer of the photoresist using UV photolithography, to the 100 nm thick PECVD oxide using plasma oxide etcher and to the SOI layer using silicon deep reactive ion etching, respectively. The photoresist is again removed by a resist stripper and the substrate is again cleaned with a stripper solution. After patterning of the metal layer 240 an electrical insulation layer 245 (e.g. of 35 nm AI2O3) is deposited by atomic layer deposition (over the metal layer 240 as shown in FIG. 2G. To pattern of the insulation layer 245 a layer of photoresist is applied on top of the insulation layer 245. A pattern of pad openings for electrical connections is created by photolithography. The insulation layer 245 in the pad opening area are etched using a wet oxide etchant and the photoresist is removed.

[0035] After forming all the features on the front side of the substrate, a new layer of photoresist is applied to the backside of the wafer. The backside etch pattern is transferred to the photoresist layer using UV photolithography. The substrate is then mounted on a silicon carrier wafer 250 to protect the front side during subsequent etching steps. The mounted wafer can loaded into an etching system to etch a 675 pm thick silicon handle layer 260 and into a plasma oxide to etch the 0.5 pm thick buried oxide. The photoresist on the etched SOI wafer is then removed and the etched SOI wafer is then detached from the carrier wafer and cleaned in acetone and isopropanol. Device Testing and Characterization

[0036] Tests were performed to measure the Seebeck coefficient of the thermocouple of the probe according to the present disclosure. A pre-calibrated titanium wire was used in an initial test. FIG. 3A is a schematic diagram of an experimental setup for determining the Seebeck coefficient of the thermocouple. As shown, the thermocouple probe 305 is in contact with wire 310. The wire is heated by a power source 315, and at each power setting, the temperature was recorded by the probe 305. Upon calibration of the wire 310, a voltmeter 320 was employed to monitor voltage changes in the probe 305. The temperature of the wire 310 was gradually probe was increased and the corresponding voltage of the probe 305 was recorded. Multiple measurements were taken for each specific power level applied to the wire 310 Testing multiple probes using this method yielded Seebeck coefficients ranging from 141.4 ± 11.9 p VAC to 447.3 ± 16.6 pV / °C.

[0037] A graph showing the results is shown in FIG. 3B. The observed variations in the Seebeck coefficients, as shown for example in linear trajectories 340, 345, 350 are caused by differences in silicon doping, manufacturing inconsistencies, and surface effects. In comparison, commercial thermocouples, such as K-type and E-type, have lower coefficients of around 40 pVAC and 68 p VAC, respectively.

[0038] Finite element analysis (FEA) simulations were also performed to better characterize the thermocouple probe according to the present disclosure. Simulations were based on a solid tissue model having temperature that matched a surrounding environment at 293 K. The dimensions of the tissue sample were specified as 2 mm by 2 mm. A convective heat flux boundary' condition was applied at the interface between the tissue and the environment, assuming a heat transfer coefficient of 10 W7 (m2-K) for air. The probe was initially set to a temperature of 313 K. The analysis was conducted in two dimensions. FIG. 4A is a graph of temperature versus time at the simulated Au-Si junction interface. The thermal time constant was estimated to be approximately 57 ps, by identifying the point at which the temperature difference decreased to 1 / e of its initial value.

[0039] The structural integrity of the thermocouple probe was also simulated using a three-dimensional representation of the probe shown in FIG. 4B. This analysis enabled calculation of a critical budding load, which is the lowest pressure that induces budding in the probe. The analysis indicated that for a probe length of 1.5 mm, the critical buckling load is approximately 3.46 MPa. For a probe measuring 1 mm in length, the bucking load value increases to approximately 7.71 MPa, and for a length of 0.5 mm, the critical buckling load increases further to approximately 30.47 MPa. These findings are particularly significant when compared against the typical resistance of human skin, which is approximately 3.18 MPa. This comparison suggests that all the thermocouple probes according to the present disclosure possess the mechanical capability to penetrate the skin, a conclusion that is also supported by experimental data described below.

[0040] Measurements by the Probe in Tissues and Live Cells

[0041] The thermocouple probe has been validated in both ex vivo and live biological samples. In ex vivo tissue tests (chicken breast), the device was compared with commercial thermocouples, demonstrating equivalent accuracy and faster response times. The device was also tested in Xenopus laevis oocytes, These tests successfully detected intracellular thermogenesis in the oocytes by measuring temperature rises in response to increased extracellular potassium concentrations. This capability to monitor intracellular temperature changes in real time represents a significant advancement in the study of cellular processes and metabolic activity. In the first set of tests, the probe was tested for temperature measurements on chicken breast tissue.

[0042] FIG. 5A is a schematic diagram of a setup for testing the biological tissue with a thermocouple probe according to the present disclosure. In the setup, the probe 505 is shown inserted into the biological tissue 510. A temperature controller 515 is used control a heating element 520 which is positioned to apply controlled heat to the tissue 515. Changes in voltage the probe 505 are monitored using voltmeter 525. Measurements are recorded by logger 530. During testing, after inserting the thermal probe 505 into the tissue 510 the temperature of the heat was increase observe the internal temperature changes of the tissue. Reference thermocouples placed in contact with but not penetrating the tissue were also used for comparison. FIG. 5B is a graph of temperature versus time of the test which shows the temperature rise within the tissue. The graph shows a match with reference thermocouples (which are not designed to penetrate the tissue in the same manner).

[0043] In another set of testing, the thermocouple probe was tested for its capability in detecting small amounts of heat produced by individual cells in a culture (as opposed to tissue). For this purpose, Xenopus laevis oocytes were used for testing, which were sourced from Ecocyte Bioscience US LLC. The oocytes were kept at 4°C in Modified Barth's Solution (MBS) supplemented with Penicillin / Streptomycin, with the solution being refreshed every 2-3 days. A subset of oocytes was transferred to a dish and the follicle cell layer was removed using collagenase, while the fibrous vitelline envelope was carefully eliminated by incubating the oocytes in 0.05 mg / ml protease (Type VIII; Sigma) for 4-5 minutes. The oocytes were allowed to equilibrate to room temperature for 2 hours in 5 ml of media. Nylon mesh discs were glued approximately 2.5 mm above the bottom surface of the dish to hold the oocytes in place. The oocytes were then transferred to the dish containing the mesh.

[0044] FIG. 6A is a schematic diagram of the experimental setup for testing the thermocouple probe according the present disclosure on the oocyte medium. The probe 605 is mounted on a manipulator 610, while a reference thermocouple was positioned on a separate manipulator 612 to monitor the media temperature. A microscope 625 and display screen 627 provide observation of the oocytes 615 during the testing. The probe measurements are recorded by a logging device 630.

[0045] In the experiment, the probe is inserted into the oocytes and after a certain duration (e.g., 2 minutes) 1 ml of potassium chloride (KC1) is added after to achieve a final concentration of 20 pM, which induces a temperature increase. Upon KC1 addition, an average temperature increase of 0.49°C with a standard deviation of 0.39°C as shown in FIG. 6B. The heating duration averaged 0.9 minutes with a standard deviation of 0.2 minute. To assess whether this response was physiological in nature, a series of control experiments were performed: KC1 was added to the setup without oocytes, the temperature outside the oocytes was monitored both with and without KC1, and culture media was introduced into the dish containing oocytes with the thermocouple / probe in place. No temperature changes were observed in any of the control experiments. By increasing the extracellular potassium [K+] to depolarize the oocyte membrane, various endogenous voltage-gated channels are likely activated, requiring the cells to expend additional energy to maintain homeostasis. It is proposed that the increased metabolic demand is responsible for the observed rise in intracellular temperature.

[0046] Tire non-invasive thermocouple probe of the present disclosure is particularly suited for use in laboratory animals, and, by not disturbing the animals, enables continuous temperature monitoring. Thereby, the probe reduces the need for sedation and minimizes stress, which can otherwise affect experimental outcomes. The device is suitable for long-term studies in dynamic environments, where traditional temperature monitoring methods are unsuitable. The probe is also suited for use with human ICU patients in clinical settings as the probe can be used to monitor the temperature of ICU patients continuously, reducing the need for invasive probes or manual measurements. Use of the probe thereby improves patient comfort and provides more accurate data, critical for managing patients in critical care. Application to Hyperthermia Treatments

[0047] One promising application of the thermocouple probe of the present disclose is in connection with magnetic nanoparticle (MNP)-mediated hyperthermia. MNP-medialed Hyperthermia is an advanced technique used for targeted cancer therapy. In this method, magnetic nanoparticles are introduced into tumor tissues and activated by an alternating magnetic field, generating localized heat that destroys cancer cells while sparing surrounding healthy tissues.

[0048] Precise temperature monitoring during this process is critical to ensure the effectiveness of the treatment and to prevent damage to adjacent healthy tissues.

[0049] The thermocouple probe of the present disclosure plays a crucial role in enhancing the safety and efficacy of hyperthermia treatments by aiding in the accurate modeling of thermal maps. Precise intra-tumoral temperature measurements with the ultra-fine microneedle of the probe enables minimally invasive insertion directly into tumor tissues. Additionally, the high Seebeck coefficient of up to 447 pV / °C enables the detection of subtle temperature variations within the tumor with a resolution down to 0.00024°C. Further, The rapid thermal response time of approximately 57 microseconds allows for real-time monitoring of temperature changes during hyperthermia treatment.

[0050] Since the probe is electrically insulated using a thin layer of AI2O3 deposited via atomic layer deposition (ALD) safe operation with within biological tissues is ensured and electrical interference with the magnetic fields used in MNP activation is prevented.

[0051] All of these features aid in the thermal mapping which is essential for visualizing and modeling the temperature distribution within the tumor and surrounding tissues in hyperthermia treatments. Accurate thermal maps enable clinicians to understand heat distributions in tissues. Knowledge of the exact temperatures at various points within the tissue allows clinicians to assess how heat propagates through the tumor and adjacent areas. With this information, treatment protocols can be optimized as thermal maps inform the adjustment of magnetic field strength, frequency, and duration to achieve optimal therapeutic temperatures that effectively kill cancer cells while minimizing harm to healthy tissue. Moreover, accurate and continuous temperature measurements help prevent temperatures from exceeding safe thresholds, thereby reducing the risk of thermal injury to non-targeted tissues.

[0052] In sum, the thermocouple probe of the present disclosure enhances thermal mapping by providing several advantages features. The microneedle can provide high spatial resolution by being positioned precisely within the tumor, providing localized temperature readings that contribute to a detailed thermal map. The probe’s rapid response provides high temporal resolution as well, enabling the capture of dynamic temperature changes that are essential for understanding transient thermal behaviors during treatment. Additionally, it is possible to deploy multiple thermocouple probes simultaneously at different locations within a tumor to gather comprehensive temperature data across the treatment area. All of the features provide the benefits of minimal invasiveness and enhanced data quality.

[0053] It is to be understood that like numerals in the drawings represent like elements through the several figures, and that not all components and / or steps described and illustrated with reference to the figures are required for all embodiments or arrangements.

[0054] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms "comprises" and / or "comprising", when used in this specification, specify the presence of stated features, integers, steps, operations, elements, and / or components, but do not precludes the presence or addition of one or more other features, integers, steps, operations, elements, components, and / or groups thereof.

[0055] Also, the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. The use of "including," "comprising," or "having," "containing," "involving," and variations thereof herein, is meant to encompass the items listed thereafter and equivalents thereof as well as additional items.

[0056] The subject matter described above is provided by way of illustration only and should not be construed as limiting. Various modifications and changes can be made to the subject matter described herein without following the example embodiments and applications illustrated and described, and without departing from the true spirit and scope of the present invention, which is set forth in the following claims.

Claims

WHAT IS CLAIMED IS:

1. A wearable wireless temperature monitoring device comprising:a micromachined thermocouple probe fabricated on a Silicon-On-Insulator (SOI) substrate, including an electrically insulated housing and a microneedle probe;a doped silicon (Si) / chrome (Cr) / gold (Au) junction on the microneedle probe providing a Seebeck coefficient of approximately 447 μV / °C; anda wireless data communication transceiver positioned in the housing for continuous real-time temperature monitoring;wherein the microneedle has a diameter of less than 100 microns and a submicron sharp tip for minimally invasive temperature measurements.

2. The device of claim 1, wherein the microneedle thermocouple measures temperature variations within biological tissues, with a temperature resolution of approximately 0.00024°C and a thermal time constant of approximately 57 microseconds, enabling real-time dynamic physiological monitoring.

3. The device of claim 1, further comprising a wireless power system positioned in the housing that enables continuous operation over extended periods and long-term temperature monitoring applications in biological tissues.

4. The device of claim 1, wherein the microneedle extends from the housing in a cantilevered manner.3b5. A method for continuous and accurate temperature monitoring in biological tissue, comprising:placing a wearable wireless temperature monitoring device having a micromachined thermocouple with a doped Si / Cr / Au junction in contact with or inserted into the tissue; measuring temperature variations in the tissue using the micromachined thermocouple;transmitting temperature data of the tissue measured by the thermocouple wirelessly to a receiver for real-time analysis; andcontinuously monitoring temperature changes in the tissue with minimal invasiveness and disruption to tissue integrity.

6. The method of claim 5, further comprising measuring precise temperature gradients in the tissue by continuous monitoring, wherein the temperature gradients indicate physiological changes in the tissue.

7. A wearable wireless temperature monitoring device for use in a laboratory animal, comprising:a micromachined thermocouple probe with a microneedle tip for monitoring temperature in the laboratory animal;a wireless power transmitter for powering the thermocouple probe and a data transceiver coupled to the thermocouple probe for continuous temperature monitoring; and a biocompatible housing coupled to the thermocouple probe and configured for attachment to skin or tissue of the laboratory animal,wherein the device is adapted to provide continuous temperature readings with high accuracy without need to sedate or restrain the laboratory animal.

8. The device of claim 7, wherein the micromachined thermocouple includes a microneedle that is dimensioned to minimize discomfort in the laboratory animal.

9. A method for continuous and non-invasive temperature monitoring in a laboratory animal, comprising:attaching a wearable wireless temperature monitoring device to the animal, the monitoring device having a thermocouple probe having a microneedle with a diameter of less than 100 microns;continuously measuring a body temperature of the animal using the thermocouple probe; andwirelessly transmitting measurements of the animal body temperature to a remote receiver,wherein the body temperature of the animal is monitored without inducing stress or the need for sedation.

10. A wearable wireless temperature monitoring device for use in human patients, particularly in ICU settings, comprising:a micromachined thermocouple probe with a doped Si / Cr / Au junction, wireless power and data transmission;a housing that is biocompatible and suitable for prolonged skin attachment, capable of providing continuous, real-time body temperature measurements with high sensitivity and accuracy.

11. The device of claim 10, wherein the micromachined thermocouple probe includes a microneedle having a diameter of less than 100 microns and is configured to non-invasively monitor body temperature continuously in human patients in critical care environments.

12. The device of claim 10, wherein the thermocouple probe is doped using Boron Fluoride (BF2)13. A method for continuous and non-invasive temperature monitoring in a human ICU patient, comprising:attaching a wearable wireless temperature monitoring device to skin of the patient; continuously measuring body temperature using a micromachined thermocouple probe having a microneedle with a diameter of less than 100 microns; andwirelessly transmitting temperature data measured by the thermocouple for real-time monitoring.

14. The method of claim 13, wherein the microneedle includes a doped silicon (Si)Zchrome (Cr) / gold (Au) junction providing a Seebeck coefficient of approximately 447 μV / °C.

15. The method of claim 11, wherein the wearable wireless temperature monitoring device includes a housing from which the microneedle projects in a cantilevered manner.

16. A wearable wireless temperature monitoring device comprising:an electrically insulated, compact housing less than one cubic centimeter in volume; a microneedle probe coupled to and extending from the housing at a proximal end and having a thermocouple junction at a distal end, wherein the thermocouple junction is probe fabricated on a Silicon-On-Insulator (SOI) substrate, and wherein the thermocouple junction couples a doped silicon (Si) / chrome (Cr) / gold (Au) junction providing a Seebeck coefficient of approximately 447 μV / °C; anda wireless data communication transceiver positioned in the housing and coupled to the microneedle probe for continuous real-time monitoring of electrical signals obtained from the probe which are translatable to temperature data.

17. The wearable wireless temperature monitoring device of claim 16, wherein the microneedle is between 500 and 1500 microns in length and has a diameter of less than 100 micron18. The wearable wireless temperature monitoring device of claim 16, wherein the microneedle probe is adapted to take accurate readings from biological tissues and cell cultures.

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