Integrated chip structure and application thereof

Abstract

According to the integrated chip structure and the application thereof, the probe end, the handle end and the connecting part are connected together through the integrated chip structure, the sensitive chip is arranged at the probe end, and the extraction electrode is arranged at the handle end, so that integration of testing and signal transmission is achieved, the integrated chip structure is convenient to carry, in-situ testing of a sample is achieved, and the testing efficiency is improved. The test volume is reduced, efficient and convenient operation is realized in trace liquid, and the test cost is reduced; the probe end adopts a plurality of cross section designs, a plurality of sensitive chips are arranged for cooperative work, and signal interference is reduced and the accuracy and the high efficiency of various parameter detection data are improved through extraction electrode output and signal processing. Besides, by arranging probe structures of different dimensions, the device can be synchronously operated in various liquid environments, the requirements of diversified and efficient application scenes are met, and the detection targets of portability, miniaturization, high sensitivity and multiple functions are finally achieved.

Description

Technical Field

[0001] The present invention belongs to the technical field of biological detection, and relates to an integrated chip structure and its application. Background Art

[0002] With the rapid development of biotechnology and chemical analysis technology, the demand for efficient and reliable detection of physical, chemical, and biological parameters in liquids is increasing, especially in the fields of medical diagnosis, environmental monitoring, and food safety. Traditional detection technologies usually rely on large-scale instrument equipment, which is large in volume, high in cost, complex in operation, and time-consuming, and it is difficult to meet the requirements of real-time, portable, and efficient detection. Traditional chips usually adopt a planar structure or are fixedly encapsulated on a bracket or base for detection, cleaning, and elution operations, which requires more space to accommodate the chip. At the same time, in some detection processes, the entire chip needs to be immersed in the solution for detection, and more complex devices may be required to fix the chip. Its application is relatively complex, time-consuming, and laborious, and it cannot achieve in-situ detection of the solution, and its flexibility and portability are poor.

[0003] Therefore, it is necessary to realize a portable, miniaturized, highly sensitive, low-cost, and multi-functional detection device.

[0004] It should be noted that the above introduction to the technical background is only for the convenience of clearly and completely explaining the technical solutions of the present application and facilitating the understanding of those skilled in the art. It cannot be considered that the above technical solutions are well-known to those skilled in the art just because these solutions are described in the background art part of the present application. Summary of the Invention

[0005] In view of the above-mentioned disadvantages of the prior art, the purpose of the present invention is to provide an integrated chip structure and its application, which are used to solve the problem of how to realize a portable, miniaturized, highly sensitive, low-cost, and multi-functional detection device.

[0006] To achieve the above purpose and other related purposes, the present invention provides an integrated chip structure, including:

[0007] A probe structure, the probe structure includes a probe end, a handle end, and a connecting portion, and the connecting portion connects the probe end and the handle end;

[0008] A sensitive chip, the sensitive chip is located at the probe end and is used to contact and operate on the target substance;

[0009] A lead-out electrode, the lead-out electrode is located at the handle end and is used to connect to a signal processing circuit for transmitting detection signals;

[0010] A lead wire, the lead wire is located at the connecting portion and is used to connect the sensitive chip and the lead-out electrode.

[0011] Optionally, the probe structure includes a single probe structure, a two-dimensional arranged probe structure, or a three-dimensional arranged probe structure.

[0012] Optionally, the sensitive chip includes a silicon-based sensitive chip, a carbon-based sensitive chip, a silicon carbide-based sensitive chip, or a gallium nitride-based sensitive chip.

[0013] Optionally, the probe end includes at least two sensitive chips working together to achieve comparison or calibration between the sensitive chips.

[0014] Optionally, the cross-section of the probe end includes a triangle, a quadrilateral, a hexagon, and a circle.

[0015] Optionally, the structure of the handle end includes one or a combination of an electromagnetic shielding structure, a differential signal transmission structure, or a filter structure.

[0016] Optionally, the connection manner between the sensitive chip and the lead includes one or a combination of wire bonding, welding, and coating with a conductive material.

[0017] Optionally, the material of the probe structure includes a single material such as ceramic, plastic, glass, rubber, fiber, etc., or a composite material composed of these materials.

[0018] Optionally, the material of the lead-out electrode includes one or a combination of gold, silver, copper, graphite, and conductive silicone; the material of the lead includes one or a combination of gold, silver, copper, graphite, and conductive silicone.

[0019] The present invention also provides an application of the integrated chip structure. The operations performed by the integrated chip structure as described above include one or a combination of modification, detection, cleaning, and elution; wherein, the modification refers to immersing the sensitive chip in a modifier solution for functionalization; the detection refers to immersing the sensitive chip in a sample solution to be measured for parameter detection, the cleaning refers to immersing the sensitive chip in a cleaning solution to remove surface impurities; the elution refers to immersing the sensitive chip in an elution solution to desorb the conjugate.

[0020] As described above, the present invention provides an integrated chip structure and its application. The integrated chip structure connects the probe end, the handle end, and the connecting part together. By setting a sensitive chip at the probe end and lead-out electrodes at the handle end, the integration of testing and signal transmission is achieved. This design is not only convenient to carry, but also realizes in-situ testing of samples, reduces the testing volume, and enables efficient and convenient operation in trace liquids, reducing the testing cost. The probe end adopts a variety of cross-sectional designs and sets multiple sensitive chips to work together. The signals are output through the lead-out electrodes and processed, reducing signal interference and improving the accuracy and efficiency of the detection data of multiple parameters. In addition, by setting probe structures of different dimensions, the device can operate synchronously in a variety of liquid environments, meet the requirements of diversified and efficient application scenarios, and ultimately achieve the detection goals of portability, miniaturization, high sensitivity, and multi-functionality. Description of the Drawings

[0021] Figure 1 It shows a schematic diagram of the integrated chip structure in the present invention.

[0022] Figure 2 It shows a schematic diagram of the integrated chip structure in the present invention where the cross-section of the probe end of the probe structure is triangular.

[0023] Figure 3 It shows a schematic diagram of the integrated chip structure in the present invention where the cross-section of the probe end of the probe structure is rectangular.

[0024] Figure 4 It shows a schematic diagram of the integrated chip structure with a comb-shaped probe structure in the present invention.

[0025] Figure 5 It shows a schematic diagram of the temperature drift change when testing the current of the test solution in the first embodiment of the present invention.

[0026] Figure 6 It shows a schematic diagram of the structure during the modification process of the sensitive chip in the second embodiment of the present invention.

[0027] Figure 7 It shows a schematic diagram of the structure during the detection, cleaning, and elution processes of the sensitive chip in the third embodiment of the present invention.

[0028] Figure 8 It shows the detection result diagram of exosomes by the sensitive chip in the third embodiment of the present invention.

[0029] Description of the Reference Numerals

[0030] 100 Probe Structure

[0031] 110 Handle End

[0032] 120 Connecting Part

[0033] 130 Probe tip

[0034] 200 Sensitive chip

[0035] 300 Lead

[0036] 310 Resin

[0037] 400 Lead-out electrode

[0038] 600 Modifier solution

[0039] 610 3-Aminopropyltriethoxysilane solution

[0040] 620 Glutaraldehyde solution

[0041] 631 Cluster of differentiation 63 antibody solution

[0042] 632 Epidermal growth factor receptor antibody solution

[0043] 633 Prostate specific antigen antibody solution

[0044] 640 Ethanolamine solution

[0045] 701 Solution to be measured

[0046] 702 Exosome solution

[0047] 703 Cleaning solution

[0048] 704 Elution solution Detailed implementation mode

[0049] The following specific examples illustrate the implementation modes of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. The present invention can also be implemented or applied through other different specific implementation modes. Various details in this specification can also be modified or changed based on different viewpoints and applications without departing from the spirit of the present invention.

[0050] When detailing the embodiments of the present invention, for the convenience of description, the cross-sectional views showing the device structure will be enlarged locally out of the general proportion, and the schematic diagrams are only examples and should not limit the scope of protection of the present invention herein. In addition, in actual preparation, three-dimensional spatial dimensions including length, width and depth should be included.

[0051] For ease of description, spatially relative terms such as "below", "beneath", "lower", "under", "above", "upper", etc. may be used herein to describe the relationship of one element or feature shown in the drawings to another element or feature. It will be understood that these spatially relative terms are intended to encompass other orientations of the device in use or operation in addition to the orientation depicted in the drawings. Further, when a layer is referred to as being "between" two layers, it can be the only layer between the two layers, or there can be one or more intervening layers. As used herein, "between... and..." means including the endpoint values.

[0052] In the context of the present application, the structure in which the first feature is "above" the second feature as described may include embodiments in which the first and second features are formed in direct contact, and may also include embodiments in which additional features are formed between the first and second features, such that the first and second features may not be in direct contact.

[0053] It should be noted that the diagrams provided in this embodiment only schematically illustrate the basic concept of the present invention. Therefore, only the components related to the present invention are shown in the diagrams, rather than being drawn according to the number, shape, and size of the components in actual implementation. The types, quantities, and proportions of the components in actual implementation can be arbitrarily changed, and the component layout type may also be more complex.

[0054] Embodiment 1

[0055] Refer to Figures 1 to 5 , this embodiment proposes an integrated chip structure and its application in testing. The following will introduce the relevant integrated chip structure in conjunction with the accompanying drawings of the specification.

[0056] Refer to Figure 1 , the integrated chip structure includes a probe structure 100, a sensitive chip 200, an extraction electrode 400, and a lead 300.

[0057] The probe structure 100 includes a probe end 130, a handle end 110, and a connecting portion 120, and the connecting portion 120 connects the probe end 130 and the handle end 110.

[0058] The sensitive chip 200 is located at the probe end 130 and is used to contact and operate on the target substance.

[0059] Specifically, the sensitive chip 200 is used to detect physical, chemical, and biological parameters in a liquid. In order to achieve high sensitivity and low power consumption, the size of the sensitive chip 200 is less than 5 mm * 5 mm. In order to facilitate insertion into a test solution or other medium, the sensitive chips 200 are arranged and distributed at the probe end 130. The sensitive chip 200 is fabricated based on semiconductor processes and has a detection structure corresponding to the physical, chemical, and biological parameters detected in the liquid.

[0060] As an example, the sensitive chip 200 includes a silicon-based sensitive chip, a carbon-based sensitive chip, a silicon carbide-based sensitive chip, or a gallium nitride-based sensitive chip.

[0061] Specifically, the silicon-based sensitive chip has high sensitivity, high precision, and good mechanical properties, and is compatible with traditional semiconductor processes; the carbon-based sensitive chip has high sensitivity, high selectivity, and good biocompatibility, and is suitable for biomedical detection and chemical sensors; the silicon carbide-based sensitive chip has high sensitivity, high temperature, and harsh environment adaptability; the gallium nitride-based sensitive chip has high sensitivity, high anti-interference ability, and good chemical stability, and is suitable for ultraviolet light detection and high temperature and high pressure environment detection; of course, the sensitive chip 200 can also be classified according to the physical, chemical, and biological parameters to be tested. Specifically, it will not be elaborated here.

[0062] As an example, the cross-section of the probe end 130 includes a triangle, a quadrilateral, a hexagon, and a circle.

[0063] Specifically, referring to Figures 1 to 3 , in order to consider different application scenarios of the probe end 130, the cross-sectional area of the probe end 130 will have different settings and can be adjusted according to specific requirements. The cross-section in this embodiment is a quadrilateral and is a flat rectangle. In other embodiments, the aspect ratio of the quadrilateral can be between 1:1 and 10:1 to achieve the largest contact area for liquid testing and improve the detection accuracy; when the cross-section of the probe end 130 is circular, it can be used to reduce stress concentration, avoid structural damage, and at the same time reduce the contact impedance with the sample, and is suitable for various detection environments; the shape settings of the cross-section being a triangle, a quadrilateral, a hexagon, etc. can provide different facet settings for the probe end 130, improve the space utilization rate of the test, and are conducive to realizing a high-density detection array. Of course, the cross-section of the probe end 130 is not limited to a triangle, a quadrilateral, a hexagon, and a circle. The selection of these shapes and sizes is aimed at optimizing the performance of the probe end 130 and ensuring its efficient operation in different detection environments.

[0064] Furthermore, when the cross-section of the probe tip 130 is polygonal, one or more of the sensitive chips 200 can be arranged on its prism surface, and the sensitive chips 200 can be fixed on the prism surface by means of patchwork, and can be evenly distributed or arranged in an array according to the detection target. The probe tip 130 can integrate the same or different types of the sensitive chips 200, which are used for in-situ detection of multiple physicochemical and biological parameters such as biomolecule concentration, ion concentration, temperature, and pressure. By analyzing the test results of multiple parameters, the detection efficiency and data reliability can be improved, and test contingency can be avoided. Of course, multiple sensitive chips 200 of the same type are integrated on different prism surfaces of the same probe tip 130. In addition, the sensitive chips 200 can also be arranged on some prism surfaces of the probe tip 130 according to actual needs.

[0065] Furthermore, since the probe tip 130 has multiple prism surfaces; the sensitive chips 200 can be fixed on its prism surface by means of a high-precision patchwork process to ensure good contact and electrical connection; the patchwork process can use conductive adhesive or thermosetting adhesive, and the specific selection depends on the detection environment and performance requirements. In addition, the sensitive chips 200 can also be fixed on the prism surface of the probe tip 130 by other fixing methods such as welding fixation and chip bonding.

[0066] The lead electrode 400 is located at the handle end 110 and is used to connect to a signal processing circuit for transmitting detection signals;

[0067] Specifically, the lead electrode 400 is used to transmit the signals detected by the sensitive chips 200 to an external signal processing circuit or device; the lead electrode 400 is made of a metal material with good electrical conductivity to ensure the high efficiency, stability, and anti-interference ability of signal transmission. The handle end 110 provides mechanical support for the lead electrode 400 and ensures the convenience of operation by designing a suitable shape and size.

[0068] As an example, the handle end 110 includes one or a combination of an electromagnetic shielding structure, a differential signal transmission structure, or a filter structure.

[0069] Specifically, the handle end 110 can be connected to the signal processing unit through a flexible circuit board or a micro coaxial cable to ensure low-noise transmission and high-fidelity of signals. In this embodiment, the handle end 110 is connected with a differential signal transmission structure 111, and signals with opposite phases are transmitted through two wires of a group of the sensitive chips 200 with opposite responses, which can effectively cancel out external interference. Of course, in other embodiments, a filter structure or an electromagnetic shielding structure can also be provided. By designing the electromagnetic shielding function, the influence of external interference on signal transmission can be reduced; by designing and adopting a filter structure, high-frequency noise can be further filtered out to improve the high-fidelity of signals. In other embodiments, the handle end 110 can also be directly connected to output signals, without setting a signal processing structure, but connected to a signal processing mechanism through other connection methods.

[0070] As an example, the probe end 130 includes at least two of the sensitive chips 200 that work together to achieve comparison or calibration between the sensitive chips 200.

[0071] As an example, to improve the accuracy and reliability of detection, two of the sensitive chips 200 can be provided to output signals, which are led out through the lead electrodes 400 and connected to the differential signal transmission structure. The two sensitive chips have opposite responses, and the corresponding two wires transmit signals with opposite phases, which can effectively cancel out external interference, and complementary comparison can be more conveniently realized to avoid false positive phenomena in detection. This design is also combined with an electromagnetic shielding structure to achieve noise shielding and further improve the accuracy and reliability of detection. In other embodiments, more than 2 or multiple groups of the sensitive chips 200 that work together can be adopted, and methods such as direct comparison method, master-slave calibration method, and statistical fusion method can be used to achieve comparison and calibration, which will not be elaborated here. Of course, in other embodiments, according to actual test requirements, the probe end 130 can also be a single sensitive chip, which is mentioned in subsequent Embodiment 2 and will not be elaborated here.

[0072] In this embodiment, refer to Figure 1 and Figure 5, the sensitive chips 200 are respectively an n-type silicon nanowire sensitive chip and a p-type silicon nanowire sensitive chip. By setting an n-type silicon nanowire sensitive chip and a p-type silicon nanowire sensitive chip on two surfaces of the probe end 130 respectively for current testing, and then dipping the probe end 130 into a to-be-tested solution (not labeled), the to-be-tested solution is a phosphate buffered saline (PBS) solution at 40 °C. The temperature of the PBS solution slowly decreases, gradually reducing the thermal excitation of carriers in the silicon nanowires and decreasing the carrier concentration. During the conventional chip detection process, the currents of both the n-type silicon nanowire sensitive chip and the p-type silicon nanowire sensitive chip decrease, and at the same time, the temperature drift is significant. However, in the integrated chip structure based on the probe structure of the present invention, the currents detected by the n-type silicon nanowire sensitive chip and the p-type silicon nanowire sensitive chip are led out through the lead-out electrode 400 and then through a differential signal transmission mechanism, and current differential processing can be conveniently performed, and the temperature drift is significantly reduced. Therefore, the probe structure 100 based on the combination of the n-type silicon nanowire sensitive chip and the p-type silicon nanowire sensitive chip can more conveniently reduce temperature interference, as Figure 5 shown. When the temperature interference is reduced, the current data tends to be real, greatly improving the reliability of the test results. Compared with the operation in the prior art that requires setting multiple chip test structures to be respectively connected to corresponding differential signal transmission mechanisms simultaneously to reduce temperature interference, the lead-out electrodes 400 of multiple sensitive chips 200 of the probe structure 100 of the present application are synchronously led out and connected to the differential signal transmission. Its application is simple, time-saving and labor-saving. It has a small volume and low cost, and has strong operability and convenience.

[0073] The lead 300 is located at the connecting portion 120 and is used to connect the sensitive chip 200 and the lead-out electrode 400.

[0074] Specifically, in order to ensure the high efficiency and stability of signal transmission, the lead 300 is made of a metal material with good electrical conductivity.

[0075] As an example, the material of the lead 300 includes one or a combination of gold, silver, copper, graphite and conductive silicone.

[0076] In this embodiment, the lead 300 uses a copper electrode; however, the material selection can be adjusted according to actual application requirements and is not limited thereto. For example, the gold material can achieve good electromagnetic interference resistance, stable signal transmission, and is suitable for high-precision and high-sensitivity detection; the silver material has good electrical conductivity and good thermal conductivity and mechanical properties, and is suitable for applications in high-temperature environments; the graphite material has good chemical stability and high-temperature resistance, and is suitable for complex environments; the conductive silicone material has good flexibility and is suitable for test environments that require deformation.

[0077] Further, the lead-out electrode 400 and the lead 300 can be formed by electroplating and etching processes, usually prepared using the same process and the same metal to simplify the process and reduce manufacturing costs. As an example, the material of the lead-out electrode 400 includes one or a combination of gold, silver, copper, graphite, and conductive silicone.

[0078] The selection of the lead-out electrode 400 is similar to that of the lead 300 and can be designed as a planar electrode, a needle-shaped electrode, or a flexible electrode. The specific design depends on application requirements and environmental conditions. In this embodiment, the lead-out electrode 400 is a copper electrode, but in other embodiments, materials such as gold, silver, graphite, and conductive silicone can also be used. To prevent oxidation and corrosion, the surface of the lead-out electrode 400 will be gold-plated or subjected to other protective treatments.

[0079] As an example, the connection methods between the sensitive chip 200 and the lead 300 include wire bonding, soldering, and coating with a conductive material.

[0080] Specifically, wire bonding is to connect the electrode pads of the sensitive chip 200 and the lead-out electrode 400 through a metal wire (such as a gold wire, a copper wire, or an aluminum wire), and use heat, pressure, or ultrasonic energy to achieve a tight bond to ensure stable signal transmission. Soldering is to connect the electrode pads of the sensitive chip 200 and the lead-out electrode 400 by heating the solder (such as tin, silver, copper, etc.) to melt, so as to improve the mechanical strength of the connection. Coating with a conductive material is to coat a conductive adhesive or other conductive material between the electrode pads of the sensitive chip 200 and the lead-out electrode 400 to achieve electrical connection, which is suitable for flexible or low-temperature test environments. These connection methods can all ensure stable signal transmission, and the specific selection can be determined according to actual application requirements. In this embodiment, the connection method between the sensitive chip 200 and the lead 300 is not limited.

[0081] As an example, the materials of the probe structure 100 include single materials such as ceramics, plastics, glass, rubber, and fibers, or composite materials composed of these materials.

[0082] Specifically, these materials can provide mechanical support, stability, waterproof and dustproof performance according to actual needs to ensure reliability and stability in harsh environments. In this embodiment, the material of the probe structure 100 is a PCB board with a size of 2mm * 30mm * 0.4mm to achieve a balance of mechanical strength, electrical insulation, and conductive performance.

[0083] As an example, the probe structure 100 includes a single probe structure, a two-dimensional arranged probe structure, or a three-dimensional arranged probe structure.

[0084] Specifically, the single probe structure can be used to detect the presence of specific biomolecules. This structure is simple, easy to operate and control, but its function is relatively limited, usually only capable of detecting single points or local areas; refer to Figure 4 , in the two-dimensional arranged probe structure, the probe ends 130 are arranged in a certain pattern on a plane to form an array; this structure can simultaneously contact multiple test points or samples on a two-dimensional plane. By optimizing the spacing between the probe ends 130, high-density detection can be achieved, and multiple signals or samples can be processed simultaneously, thereby improving work efficiency and data acquisition capabilities; in the three-dimensional arranged probe structure, the probe ends 130 are arranged in a specific geometric shape in three-dimensional space, and the signals between different probe ends 130 are isolated by insulating materials. This structure can simultaneously contact multiple test points in three-dimensional space and is suitable for complex multi-dimensional detections. Its advantage lies in providing more comprehensive information, achieving high-throughput and high-sensitivity detections, and being suitable for scenarios requiring multi-dimensional analysis.

[0085] In this embodiment, the preparation of the probe structure 100 generally includes the following steps:

[0086] First, prepare materials. Select appropriate materials according to the design requirements and cut them into the required sizes. The probe structure 100 is not limited to the PCB board.

[0087] Second, perform pattern transfer. Transfer the circuit pattern onto the substrate through lithography technology and form the pattern using exposure and development processes.

[0088] Third, perform electroplating and etching. Electroplate a metal layer in the pattern area to form the leads 300 and the lead-out electrodes 400, and remove the excess metal layer through chemical etching. To simplify the process and reduce costs, the leads 300 and the lead-out electrodes 400 are prepared using the same process and the same metal material.

[0089] Then, perform surface treatment. Coat solder mask ink on the non-welding areas to prevent welding short circuits.

[0090] Then, install the sensitive chip 200. Fix the sensitive chip 200 on the PCB board and connect the solder joints on the sensitive chip 200 to the leads 300 by wire bonding. The wire bonding area is covered with insulating materials to avoid leakage. The fixing method and wire bonding method of the sensitive chip 200 are not limited to the above methods.

[0091] As described above, the integrated chip structure of this embodiment integrates the probe end 130, the handle end 110, and the connecting portion 120 into one body to form the probe structure 100 that is convenient to carry; compared with the prior art, this structure does not require the sampled liquid to be placed in a chip testing device with a planar structure, nor does it require the chip structure to be fixedly encapsulated on a bracket or a base. By integrating the testing component and the signal transmission component into one body and setting the handle end 110 for convenient operation, the present invention realizes in-situ testing in the sample, reduces the volume of the testing structure, simplifies the operation process, and reduces the testing cost.

[0092] In addition, by designing probe structures with various cross-sections and multiple sensitive chips 200 working together, the present invention can accurately detect various parameters such as biomolecules, ion concentration, temperature, and pressure. The lead-out electrodes in the probe structure are connected to the signal processing structure, which can quickly lead out and process the signals, avoiding false positive phenomena caused by environmental interference, and improving the reliability and accuracy of the test data.

[0093] Embodiment Two

[0094] The main difference between this embodiment and Embodiment One is that the probe structure adopts a comb-shaped two-dimensional probe structure, and a modification process of the sensitive chip is proposed for this needle structure. Taking Figure 6 the modification process of the sensitive chip shown as an example, the integrated chip structure of this embodiment includes the probe structure 100, the sensitive chip 200, the lead-out electrode 400, and the lead wire 300.

[0095] The probe structure 100 includes a probe end 130, a handle end 110, and a connecting portion 120, and the connecting portion 120 connects the probe end 130 and the handle end 110.

[0096] The sensitive chip 200 is located at the probe end 130 and is used to contact and operate on the target substance.

[0097] As an example, the probe structure 100 includes a single probe structure, a two-dimensional arranged probe structure, or a three-dimensional arranged probe structure.

[0098] Specifically, as the probe structure 100 mentioned in Embodiment One is a single probe structure, it can work independently and is suitable for high-precision single-point detection. In this embodiment, the probe structure 100 adopts a comb-shaped two-dimensional arranged probe structure 100, which is composed of multiple parallel arranged probe ends 130, similar to the teeth of a comb. This structure can contact multiple test targets or areas simultaneously to realize multi-signal processing, thereby improving the test efficiency. In addition, by optimizing the spacing of the probe ends 130, high-density detection can be achieved within a limited space.

[0099] In this embodiment, the comb teeth of the probe structure 100 are three and equally spaced, and the probe ends 130 are arranged in the same direction. The position of the lead-out electrode 400 is designed as a handle for convenient signal connection and hand operation.

[0100] To achieve the modification operations for different sensitive chips 200, the modification operations include dipping the sensitive chip 200 into the modifier solution 600 for functionalization. The modifier solution 600 includes, but is not limited to, coupling agent solution, probe solution, and blocking agent solution. In this embodiment, the modification process first uses the coupling agent solution for treatment, and then different probe solutions are used to separately modify different sensitive chips 200. The coupling agent solutions are 3-aminopropyltriethoxysilane (APTES solution) 610 and glutaraldehyde solution 620 respectively. The probe solutions are 0.5 mg / mL cluster of differentiation 63 (CD63) antibody solution 631, epidermal growth factor receptor (EGFR) antibody solution 632, and prostate-specific antigen (PSA) antibody solution 633 respectively. In addition, the spacing between the comb teeth of the probe end 130 is set according to the spacing set between the modifier solutions 600 to ensure the high efficiency during the modification process.

[0101] As an example, the sensitive chip 200 includes a silicon-based sensitive chip, a carbon-based sensitive chip, a silicon carbide-based sensitive chip, or a gallium nitride-based sensitive chip.

[0102] In this embodiment, the sensitive chip 200 uses a silicon nanowire sensitive chip. In some other embodiments, the modification of the sensitive chip 200 can also use other types of silicon-based sensitive chips, carbon-based sensitive chips, silicon carbide-based sensitive chips, and gallium nitride-based sensitive chips. The types of the sensitive chips are similar to those in Embodiment 1 and will not be elaborated here.

[0103] In this embodiment, each probe end 130 of the probe structure 100 is arranged with a single sensitive chip 200. The sensitive chip 200 is a silicon nanowire sensitive chip, and the silicon nanowire sensitive chip is a p-type field effect transistor.

[0104] In this embodiment, refer to Figure 6 , the process of modifying the sensitive chip 200 includes the following steps:

[0105] S21, Use an oxygen plasma device to modify the surface of the silicon nanowire sensitive chip 200 for 15 minutes to complete the modification of hydroxyl groups.

[0106] S22, Dip the three comb-shaped probe ends 130 into the APTES solution 610 respectively, soak in the dark for 12 hours to complete the modification of amino groups for improving hydrophilicity.

[0107] S23. Immerse the three comb-shaped probe tips 130 into the glutaraldehyde solution 620 respectively, soak for 2 h in the dark to complete the modification of aldehyde groups.

[0108] S24. Immerse the three comb-shaped probe tips 130 into the CD63 antibody solution 631 at 0.5 mg / mL, the EGFR antibody solution 632 and the PSA antibody solution 633 respectively, soak for 2 h in the dark to respectively modify with CD63 antibody, EGFR antibody and PSA antibody.

[0109] S25. Immerse the three comb-shaped probe tips 130 into the ethanolamine solution 640 respectively, soak for 1 h in the dark to complete the modification of the sensitive chip 200.

[0110] Through the above modification process, the comb-shaped probe tips 130 can achieve simultaneous modification of multiple different sensitive chips 200, and at the same time, they can be taken by the handle end 110, which is convenient for operation. Compared with the prior art where the sensitive chip 200 needs to be immersed in the target solution and requires special devices or a taking device for operation, the operation is complex and time-consuming. The structure of this application greatly improves the modification efficiency of the chip in the liquid.

[0111] This embodiment solves the problems of complex process, troublesome operation, poor stability and poor repeatability in the modification operation application of the sensitive chip 200 in the prior art, and improves the modification efficiency, process stability and electrical and chemical stability of the modification layer. The manufacturing method of the probe structure 100 is similar to that of the first embodiment, and the pattern of the sensitive chip 200, the lead 300 and the lead-out electrode 400 are adjusted according to the specific requirements in this embodiment.

[0112] In other embodiments, the combs of the probe structure 100 can be designed in various forms according to the actual test situation. For example, the probe structure 100 can be composed of multiple comb-shaped units, and different values can be set for the probe spacing to meet different test requirements. In other embodiments, the probe structure 100 can also be a dendritic structure, and by bifurcating the probe tip 130, a larger detection area can be covered. In some other embodiments, the probe structure 100 can also adopt a three-dimensional arranged probe structure, that is, the probe tip 130 is arranged in a specific geometric shape in three-dimensional space. This structure can arrange probes in three-dimensional space, can achieve high-throughput and high-sensitivity detection of samples, and is suitable for more complex detection situations.

[0113] The lead-out electrode 400 is located at the handle end 110 and is used to connect the signal processing circuit to transmit the detection signal.

[0114] Specifically, the lead-out electrode 400 is used to transmit the signal detected by the sensitive chip 200 to an external signal processing circuit or device.

[0115] The lead 300 is located at the connecting portion 120 and is used to connect the sensitive chip 200 and the lead-out electrode 400.

[0116] To ensure that the signal is not interfered with during transmission and to maintain high efficiency and stability, the lead-out electrode 400 and the lead 300 are made of materials with good electrical conductivity and stable mechanical properties. To prevent current leakage and short circuits and improve test accuracy, in this embodiment, a copper wire wrapped with resin 310 is used. Refer to Figure 4 , this encapsulation method not only provides good electrical insulation but also protects the electrodes from the external environment (such as oxidation, corrosion, etc.). Thus, the mechanical stability and environmental adaptability of the entire probe structure 100 are improved.

[0117] As an example, the material of the lead-out electrode 400 includes one or a combination of gold, silver, copper, graphite, and conductive silicone; the material of the lead 300 includes one or a combination of gold, silver, copper, graphite, and conductive silicone.

[0118] The material selection of the lead-out electrode 400 and the lead 300 is described in Example 1 and will not be elaborated here.

[0119] As an example, the material of the probe structure 100 includes single materials such as ceramics, plastics, glass, rubber, and fibers, or composite materials composed of these materials.

[0120] Specifically, the material of the probe structure 100 is described in Example 1 and will not be elaborated here. In this embodiment, the material of the probe structure 100 is a PCB board, and the size is 50*65*0.4 mm.

[0121] As an example, the cross-section of the probe tip 130 includes a triangle, a quadrilateral, a hexagon, and a circle.

[0122] The cross-section of the probe tip 130 is set to adapt to different application scenarios. The selection of these shapes and sizes aims to optimize the efficient operation of the probe tip 130 in different detection environments, and the specific applications are described in detail in Example 1.

[0123] In this embodiment, the probe end 130 has a quadrilateral and flat rectangular cross-section, and one of its two faces can place one of the sensitive chips 200 for modification and detection. When the cross-section is a polygon, one of the sensitive chips 200 can be arranged on each edge surface to improve the detection sensitivity and reliability. The sensitive chip 200 can be fixed on the edge surface by means such as patch, welding fixation, chip bonding, and conductive adhesive fixation. At the same time, the sensitive chips 200 can be evenly distributed or arranged in an array on the corresponding edge surface. The specific fixation method and chip distribution can be optimized according to the detection target and retrograde to ensure good contact and electrical connection between the chip and the edge surface. In this embodiment, the sensitive chip 200 is fixed on the edge surface by means of patching to achieve better contact.

[0124] As an example, the connection method between the sensitive chip 200 and the lead 300 includes one or a combination of wire bonding, welding connection, or coating with a conductive material.

[0125] Specifically, the connection method ensures a stable electrical connection between the chip and the external circuit and meets the requirements of a certain mechanical strength. The specific connection methods between the sensitive chip 200 and the lead 300 are all mentioned in the first embodiment and will not be elaborated here.

[0126] As can be seen from the above, the probe structure 100 of the present invention can synchronously modify multiple different sensitive chips 200 by setting probes with a comb-like structure or the probe structure 100 of a higher dimension, realize operations in a variety of liquid environments, meet the needs of diversified and efficient application scenarios, and overcome the problems that the existing test structure needs to place the liquid to be tested in a chip test device with a planar structure or fix and package the chip on a bracket or base, with complex operations, large test equipment, high costs, and long operation times. The probe structure 100 of the present invention integrates the test component and the signal transmission component, and at the same time sets the handle end 110 for convenient handling, which can not only realize in-situ testing in the sample, but also reduce the volume of the test structure, with convenient and simple operation processes, saving time and effort, thereby realizing a portable, miniaturized, highly sensitive, low-cost, and multi-functional detection device, greatly improving the modification efficiency of the chip in the liquid.

[0127] Embodiment Three

[0128] The difference between this embodiment and the first embodiment lies in the application of a single sensitive chip at the probe end of the probe structure during detection, cleaning, and elution processes, and the sensitive chip is a pre-modified sensitive chip.

[0129] Take Figure 7Taking the detection, cleaning, and elution processes of the shown sensitive chip as an example, this embodiment proposes a probe structure and a process for detecting, cleaning, and eluting the probe structure; hereinafter, the integrated chip structure includes a probe structure 100, a sensitive chip 200, an extraction electrode 400, and a lead 300;

[0130] The probe structure 100 includes a probe end 130, a handle end 110, and a connecting portion 120, and the connecting portion 120 connects the probe end 130 and the handle end 110;

[0131] The sensitive chip 200 is located at the probe end 130 and is used to contact and operate on the target substance;

[0132] The extraction electrode 400 is located at the handle end 110 and is used to connect to a signal processing circuit for transmitting detection signals;

[0133] The lead 300 is located at the connecting portion 120 and is used to connect the sensitive chip 200 and the extraction electrode 400.

[0134] In this embodiment, the sensitive chip 200 is a silicon nanowire sensitive chip, and the extraction electrode 400 and the lead 300 are made of copper material. At the same time, the copper wire is wrapped with the resin (not labeled). The silicon nanowire sensitive chip is a p-type field effect transistor and is attached to the probe end 130 by a patch method. The surface of the sensitive chip 200 is modified with CD63 antibody. The cross-section of the probe end 130 is a flat rectangle. The material used for the probe structure 100 is a PCB board with dimensions of 2mm * 30mm * 0.4mm. This embodiment provides the processes of detecting, cleaning, and eluting the probe structure 100 for the test solution 701, and a modification operation is also performed during the detection process. The detection operation refers to immersing the sensitive chip 200 into the test solution 701 sample to detect physical, chemical, and biological parameters. The cleaning operation refers to immersing the sensitive chip 200 into the cleaning solution 703 to remove surface impurities. The elution operation refers to immersing the sensitive chip 200 into the elution solution 704 to desorb the conjugate. The specific process is as follows:

[0135] S31, Immerse the probe end 130 into the test solution 701 to measure the baseline current, and the test solution 701 is a PBS solution.

[0136] S32, Immerse the probe end 130 into the exosome solution 702 and incubate for 10 min for modification. The CD63 probe on the sensitive chip 200 will specifically capture exosomes in the solution.

[0137] S33. Immerse the probe end 130 in the cleaning solution 703 for cleaning to wash away non-specific adsorption on the surface, and the cleaning solution is deionized water.

[0138] S34. Immerse the probe end 130 in the test solution 701 to measure the response current after specifically capturing exosomes, and the test solution 701 is a PBS solution.

[0139] S35. Immerse the probe end 130 in the elution solution 704 to elute the exosomes captured by CD63 on the sensitive chip 200.

[0140] In other embodiments, the cleaning solution 703 is not limited to deionized water and may also include other cleaning solutions such as buffer solutions, which will not be elaborated here; the elution solution 704 includes but is not limited to deionized water, buffer solutions, and anionic detergents; the test solution 701 includes but is not limited to buffer solutions, body fluid samples, and environmental samples.

[0141] In this embodiment, the baseline current and the response current after specifically capturing exosomes are as Figure 8 shown. In the p-type silicon nanowire sensitive chip, the majority carriers are holes. The binding of negatively charged exosomes to CD63 on the sensitive chip 200 will increase the hole concentration, thereby increasing the current. The above probe structure 100 can be conveniently immersed in the solution for detection, cleaning, and elution operations, improving efficiency. At the same time, the sensitive chip 200 can be restored to its original state, thus realizing the secondary use of the sensitive chip 200.

[0142] As an example, the structure of the handle end 110 includes an electromagnetic shielding structure, a differential signal transmission structure, or a filter structure.

[0143] In this embodiment, the data signal measured by the probe end 130 is transmitted to the lead-out electrode 400 through the lead 300 and connected to the signal processing mechanism through the lead-out electrode 400 for analysis, and finally the measured response current is output. The process is simple and fast. Of course, in some other embodiments, the sensitive chip 200 is respectively set as a p-type field effect transistor and an n-type field effect transistor. After testing the above solutions, the differential signal transmission structure can be connected through the lead-out electrode 400 for signal amplification, thereby increasing the current. In some other embodiments, the sensitive chip 200 is respectively set as an n-type field effect transistor, and the binding of negatively charged exosomes to CD63 on the sensitive chip 200 will reduce the hole concentration, thereby reducing the current. However, these do not affect the application of the inventive structure described in this embodiment in solution cleaning, detection, and elution.

[0144] Of course, in this embodiment, the cleaning, detection, and elution operations performed by the probe structure 100 are not necessarily continuous operations. They can also be performed individually or in combination, but this does not affect the convenience and efficiency of the probe structure 100 of the present invention in performing cleaning, detection, and elution. At the same time, the number of the sensitive chips 200 at the probe end 130 can also be two, which will not be elaborated here.

[0145] As an example, the probe structure 100 includes a single probe structure, a two-dimensional arranged probe structure, or a three-dimensional arranged probe structure.

[0146] As an example, the sensitive chip 200 includes a silicon-based sensitive chip, a carbon-based sensitive chip, a silicon carbide-based sensitive chip, or a gallium nitride-based sensitive chip.

[0147] As an example, the probe end 130 includes at least two sensitive chips 200 that work together to achieve comparison or calibration between the sensitive chips 200.

[0148] As an example, the cross-section of the probe end 130 includes a triangle, a quadrilateral, a hexagon, and a circle.

[0149] As an example, the structure of the handle end 110 includes one or a combination of an electromagnetic shielding structure, a differential signal transmission structure, or a filter structure.

[0150] As an example, the connection method between the sensitive chip 200 and the lead 300 includes one or a combination of wire bonding, soldering, or coating with a conductive material.

[0151] As an example, the material of the probe structure 100 includes a single material such as ceramic, plastic, glass, rubber, fiber, etc., or a composite material composed of these materials.

[0152] As an example, the material of the lead-out electrode 400 includes one or a combination of gold, silver, copper, graphite, and conductive silicone; the material of the lead 300 includes one or a combination of gold, silver, copper, graphite, and conductive silicone.

[0153] The probe structure 100, the corresponding process methods, and materials involved in this embodiment are similar to those in Embodiment 1, and will not be elaborated here. The manufacturing method of the probe structure 100 is mentioned in Embodiment 1 and can also be applied to this embodiment, which will not be repeated here.

[0154] Furthermore, by providing the probe end 130 with a comb-like structure or the probe structure 100 of a higher dimension, the present invention can simultaneously modify a plurality of different sensitive chips 200 and synchronously perform operations such as cleaning, detection, and elution. This design meets the requirements of diverse application scenarios and solves the problems of complex operation, poor stability, and poor repeatability existing in the traditional sensitive chips during the processes of detection, cleaning, and elution. Compared with the prior art, the probe structure 100 of this embodiment is easy to operate and significantly reduces the test cost. It greatly improves the cleaning, detection, and elution efficiency of the sensitive chip 200 in liquid, while enhancing the stability and reliability of the process, and achieving the detection goals of high sensitivity and multi-functionality.

[0155] In summary, the present invention provides an integrated chip structure and its application. The integrated chip structure connects the probe end, the handle end, and the connecting part together. By providing a sensitive chip at the probe end and a lead-out electrode at the handle end, the integration of testing and signal transmission is achieved. This design is not only convenient to carry, but also realizes in-situ testing of samples, reduces the test volume, and enables efficient and convenient operation in trace liquids, reducing the test cost. The probe end adopts a variety of cross-sectional designs and is provided with a plurality of sensitive chips working together. The signals are output through the lead-out electrodes and processed, reducing signal interference and enhancing the accuracy and efficiency of the detection data for multiple parameters. In addition, by providing probe structures of different dimensions, the device can perform synchronous operations in a variety of liquid environments, meeting the requirements of diverse and efficient application scenarios, and ultimately achieving the detection goals of portability, miniaturization, high sensitivity, and multi-functionality. Therefore, the present invention effectively overcomes various drawbacks in the prior art and has high industrial utilization value.

[0156] The above embodiments are only illustrative of the principles and effects of the present invention and are not intended to limit the present invention. Any person familiar with this technology can modify or change the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or changes completed by those with ordinary knowledge in the technical field without departing from the spirit and technical idea disclosed by the present invention should still be covered by the claims of the present invention.

Claims

1. An integrated chip structure, characterized in that: The integrated chip structure comprises: A probe structure, the probe structure comprising a probe end, a handle end and a connecting portion, the connecting portion connecting the probe end and the handle end; A sensitive chip, located at the probe end, for contacting and operating with a target substance; An extraction electrode, located at the end of the handle, for connecting to a signal processing circuit so as to transmit a detection signal; A lead wire is located at the connecting portion and is used to connect the sensitive chip and the lead-out electrode.

2. The integrated chip structure according to claim 1, characterized in that: The probe structure includes a single probe structure, a two-dimensionally arranged probe structure or a three-dimensionally arranged probe structure.

3. The integrated chip structure according to claim 1, characterized in that: The sensitive chip includes a silicon-based sensitive chip, a carbon-based sensitive chip, a silicon carbide-based sensitive chip or a gallium nitride-based sensitive chip.

4. The integrated chip structure according to claim 1, characterized in that: The probe end includes at least two sensitive chips working in coordination with each other to achieve comparison or calibration between the sensitive chips.

5. The integrated chip structure according to claim 1, characterized in that: The cross-section of the probe end includes a triangle, a quadrilateral, a hexagon and a circle.

6. The integrated chip structure according to claim 1, characterized in that: The handle end includes one or a combination of an electromagnetic shielding structure, a differential signal transmission structure or a filter structure.

7. The integrated chip structure according to claim 1, characterized in that: The connection method between the sensitive chip and the lead includes one or a combination of wire bonding, welding and conductive material coating.

8. The integrated chip structure according to claim 1, characterized in that: The material of the probe structure includes single materials such as ceramics, plastics, glass, rubber, fiber, etc., or composite materials composed of these materials.

9. The integrated chip structure according to claim 1, characterized in that: The material of the lead-out electrode includes one or a combination of gold, silver, copper, graphite and conductive silicone; the material of the lead wire includes one or a combination of gold, silver, copper, graphite and conductive silicone.

10. An application of an integrated chip structure, characterized in that: The operation performed on the integrated chip structure as described in any one of claims 1 to 9 includes one or a combination of modification, detection, cleaning, and elution; wherein the modification refers to immersing the sensitive chip in a modification solution for functionalization treatment; the detection refers to immersing the sensitive chip in a sample of a test solution for parameter detection; the cleaning refers to immersing the sensitive chip in a cleaning solution to remove surface impurities; and the elution refers to immersing the sensitive chip in an elution solution to desorb the conjugate.

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