Integrated chip structure and applications thereof

Abstract

The application provides an integrated chip structure and application thereof, wherein the integrated chip structure connects a probe end, a handle end and a connecting part together, a sensitive chip is arranged on the probe end, and an outgoing electrode is arranged on the handle end, so that integration of testing and signal transmission is realized; the design is convenient to carry, realizes in-situ testing of a sample, reduces a testing volume, realizes efficient and convenient operation in trace liquid, and reduces testing cost; the probe end adopts multiple cross-section designs, and multiple sensitive chips are arranged to work cooperatively, signal output is performed through the outgoing electrode, and signal processing is performed, so that signal interference is reduced, and the accuracy and efficiency of detection data of multiple parameters are improved. In addition, by arranging probe structures with different dimensions, the device can be synchronously operated in multiple liquid environments, diversified and efficient application scene requirements are met, and finally, the detection goals of portability, miniaturization, high sensitivity and multifunction are realized.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of biological detection, and relates to an integrated chip structure and application thereof. BACKGROUND

[0002] With the rapid development of biological technology and chemical analysis technology, there is an increasing demand for efficient and reliable detection of physicochemical and biological parameters in liquids, especially in the fields of medical diagnosis, environmental monitoring and food safety. Traditional detection techniques usually rely on large-scale instruments and equipment, which are bulky, costly, complex to operate and time-consuming, and thus cannot meet the requirements of real-time, portable and efficient detection. Traditional chips usually adopt a planar structure or are fixedly packaged on a support or base for detection, cleaning and elution operations, which requires more space to accommodate the chips. Meanwhile, in some detection processes, the entire chip needs to be immersed in a solution for detection, which may require more complex devices to fix the chip, and the application thereof is relatively complex, time-consuming and laborious. Moreover, the chip cannot be used for in-situ detection of the solution, and the flexibility and portability are poor.

[0003] Therefore, it is necessary to realize a portable, miniaturized, high-sensitivity, low-cost and multifunctional detection device.

[0004] It should be noted that the above introduction to the technical background is only for the convenience of clearly and completely describing the technical solutions of the present application and facilitating the understanding of those skilled in the art. The above technical solutions cannot be considered as known to those skilled in the art merely because they are described in the background section of the present application. SUMMARY

[0005] In view of the above-mentioned shortcomings of the prior art, the present application aims to provide an integrated chip structure and application thereof, which can solve the problem of how to realize a portable, miniaturized, high-sensitivity, low-cost and multifunctional detection device.

[0006] To achieve the above object and other related objects, the present application provides an integrated chip structure, comprising:

[0007] 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;

[0008] a sensitive chip, the sensitive chip being located at the probe end and being used for contacting and operating with a target substance;

[0009] an extraction electrode, the extraction electrode being located at the handle end and being used for connecting a signal processing circuit to transmit a detection signal;

[0010] a lead wire, the lead wire being located at the connecting portion and being used for connecting the sensitive chip and the extraction electrode.

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

[0012] Optionally, the sensitive chip comprises 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 comprises at least two of the sensitive chips working in cooperation to achieve comparison or calibration between the sensitive chips.

[0014] Optionally, the cross section of the probe end comprises a triangle, a quadrilateral, a hexagon or a circle.

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

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

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

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

[0019] The application further provides an application of the integrated chip structure, and the operation performed by the integrated chip structure as described above comprises one or a combination of modification, detection, cleaning and elution; wherein the modification refers to functionalization treatment of the sensitive chip by immersing the sensitive chip in a modifier solution; the detection refers to parameter detection of the sensitive chip by immersing the sensitive chip in a sample to be detected; the cleaning refers to removal of surface impurities by immersing the sensitive chip in a cleaning solution; and the elution refers to desorption of a combined substance by immersing the sensitive chip in an elution solution.

[0020] As described above, the present application provides an integrated chip structure and its application, which connects the probe end, the handle end and the connecting part together, sets the sensitive chip at the probe end and the lead electrode at the handle end, so as to realize the integration of testing and signal transmission. This design not only is convenient to carry, but also realizes the in-situ testing of the sample, reduces the testing volume, and realizes the efficient and convenient operation in the trace liquid, reduces the testing cost; the probe end adopts a plurality of cross section designs, and a plurality of sensitive chips are arranged to work cooperatively, and the signal is output through the lead electrode and processed, so as to reduce the signal interference and improve the accuracy and efficiency of the detection data of a plurality of parameters. In addition, by setting the probe structure with different dimensions, the device can operate synchronously in a plurality of liquid environments, meets the diversified and efficient application scene demand, and finally realizes the detection goals of portability, miniaturization, high sensitivity and multifunction. BRIEF DESCRIPTION OF DRAWINGS

[0021] Figure 1 An integrated chip structure in the present application is shown.

[0022] Figure 2 An integrated chip structure in which the probe end cross section of the probe structure in the present application is triangular is shown.

[0023] Figure 3 An integrated chip structure in which the probe end cross section of the probe structure in the present application is rectangular is shown.

[0024] Figure 4 An integrated chip structure in which the comb-shaped probe structure in the present application is shown.

[0025] Figure 5 A temperature drift change diagram when a test solution current is tested in the first embodiment of the present application is shown.

[0026] Figure 6 A structure diagram in the modification process of the sensitive chip in the second embodiment of the present application is shown.

[0027] Figure 7 A structure diagram in the detection, cleaning and elution process of the sensitive chip in the third embodiment of the present application is shown.

[0028] Figure 8 A detection result diagram of the sensitive chip on the exosome in the third embodiment of the present application is shown.

[0029] REFERENCE SIGNS

[0030] 100 probe structure

[0031] 110 handle end

[0032] 120 connecting part

[0033] 130 probe end

[0034] 200 sensitive chip

[0035] 300 lead wire

[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 washing solution

[0048] 704 elution solution DETAILED DESCRIPTION

[0049] The present application is herein described, by way of example only, with the assistance of specific details to facilitate a comprehensive understanding of the application by those skilled in the art. The application can be practiced without recourse to these specific details. The description herein is intended to be illustrative only and is presented to assist in understanding the scope of the application. Various modifications to the details of the application can be made by those skilled in the art, without departing from the spirit of the application, which is defined by the appended claims.

[0050] In the detailed description of embodiments of the application, reference is made to the accompanying drawings that form a part hereof, and in which are shown by way of illustration various embodiments by which the application can be practiced. These embodiments are described in sufficient detail to enable those skilled in the art to practice the application, and it is to be understood that other embodiments can be utilized and that structural, logical, and electrical changes can be made without departing from the spirit and scope of the present application. The following detailed description is, therefore, not to be taken in a limiting sense, and the scope of the present application is defined only by the appended claims.

[0051] For ease of description, spatially relative terms, such as "beneath", "below", "lower", "under", "above", "upper", and the like, can be used herein for ease of description to describe one element or feature's relationship to another element(s) or feature(s) as illustrated in the figures. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientations depicted in the figures. For example, if a layer overlies another layer, it can be the case that the layer is the only layer between the other layer and the underlying layer, or that there are one or more intervening layers between the other layer and the underlying layer. The term "between" as used herein is intended to encompass both endpoints of the range.

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

[0053] It should be noted that the drawings provided in the embodiments only schematically illustrate the basic concept of the present application, and thus only the components related to the present application are shown in the drawings, rather than being drawn according to the number, shape and size of the components in actual implementation. The shape, number and proportion of each component in actual implementation can be arbitrarily changed, and the layout pattern of the components can be more complex.

[0054] Embodiment One

[0055] Referring to Figures 1-5 The present embodiment proposes an integrated chip structure and application in testing, which will be described below in conjunction with the accompanying drawings.

[0056] Referring to Figure 1 The integrated chip structure includes a probe structure 100, a sensitive chip 200, a lead electrode 400 and a lead wire 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 with a target substance.

[0059] Specifically, the sensitive chip 200 is used to detect physicochemical 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 5mm*5mm. In order to facilitate insertion into a test solution or other medium, the sensitive chip 200 is arranged to be distributed at the probe end 130. The sensitive chip 200 is prepared based on a semiconductor process, and has a detection structure corresponding to the physicochemical and biological parameters in the detection 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 physicochemical and biological parameters to be tested, and specific details will not be described 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 1-3 In order to consider different application scenarios of the probe end 130, the cross-sectional area of the probe end 130 will be different, and can be adjusted according to specific needs. The cross section in this embodiment is a flat rectangle, and in other embodiments, the aspect ratio of the quadrilateral can be between 1:1 and 10:1, in order to achieve the maximum contact area of liquid testing and improve detection accuracy; the cross section of the probe end 130 is a circle, which can be used to reduce stress concentration and avoid structural damage, while also reducing contact impedance between the probe end 130 and the sample, suitable for various detection environments; the cross section of the probe end 130 is a triangle, a quadrilateral, a hexagon, etc. The shape setting can provide different edge settings for the probe end 130, improve the space utilization rate of the test, and be 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] Further, when the cross section of the probe end 130 is polygonal, the edges thereof can be arranged with one or more sensitive chips 200, and the sensitive chips 200 can be fixed on the edges by means of patching, and can be uniformly distributed or arrayed according to the detection target. The probe end 130 can integrate the same or different sensitive chips 200 for in-situ detection of the concentration of biomolecules, ions, temperature, pressure and other physicochemical biological parameters. Analysis of the test results of multiple parameters can improve the detection efficiency and data reliability, and avoid accidental testing. Of course, multiple same sensitive chips 200 can be integrated on different edges of the same probe end 130. In addition, the sensitive chips 200 can also be arranged on part of the edges of the probe end 130 according to actual needs.

[0065] Further, since the probe end 130 has multiple edges, the sensitive chips 200 can be fixed on the edges by high-precision patching process to ensure good contact and electrical connection; the patching process can use conductive glue or thermosetting glue, and the specific selection is determined according to the detection environment and performance requirements. In addition, the sensitive chips 200 can also be fixed on the edges of the probe end 130 by welding, chip bonding and other fixing methods.

[0066] The lead electrode 400 is located at the handle end 110, and is used to connect the signal processing circuit to transmit the detection signal.

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

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

[0069] Specifically, the handle end 110 can be connected with the signal processing unit through a flexible circuit board or a micro coaxial cable, to ensure low-noise transmission and high fidelity of the signal. In the embodiment, the handle end 110 is connected with a differential signal transmission structure 111, which transmits signals with opposite phases through two wires of the sensitive chip 200 in response to opposite signals, to effectively offset external interference. Of course, in other embodiments, a filter structure or an electromagnetic shielding structure can be provided, to reduce the influence of external interference on signal transmission by designing electromagnetic shielding functions, and to further filter high-frequency noise by designing a filter structure to improve signal high fidelity. In other embodiments, the handle end 110 can also directly output signals without setting a signal processing structure, but connecting the signal processing mechanism through other connection modes.

[0070] As an example, the probe end 130 includes at least two cooperative sensitive chips 200 to realize comparison or calibration between the sensitive chips 200.

[0071] As an example, to improve the accuracy and reliability of detection, two sensitive chips 200 can be provided to output signals through the lead-out electrode 400 and be connected to the differential signal transmission structure. The two sensitive chips respond oppositely, and two wires transmit signals with opposite phases, which can effectively offset external interference, more conveniently realize complementary comparison, and avoid false positive phenomenon in detection. This design also combines with an electromagnetic shielding structure to realize noise shielding, further improve the accuracy and reliability of detection, and in other embodiments, more than two or multiple groups of cooperative sensitive chips 200 can be used to realize comparison and calibration by using direct comparison method, master-slave calibration method, statistical fusion method, etc., which will not be described here. Of course, in other embodiments, the probe end 130 can also be a single sensitive chip according to actual test requirements, which will be mentioned in subsequent embodiment two, and will not be described here.

[0072] In the embodiment, refer to Figure 1 and Figure 5The sensitive chip 200 is respectively an n-type silicon nanowire sensitive chip and a p-type silicon nanowire sensitive chip, current test is performed by respectively arranging the n-type silicon nanowire sensitive chip and the p-type silicon nanowire sensitive chip on two surfaces of the probe end 130, then the probe end 130 is immersed in a to-be-tested solution (not indicated), the to-be-tested solution is a phosphate buffered saline (PBS) solution at 40 DEG C, the PBS solution temperature is slowly cooled to gradually reduce thermal excitation of a carrier in the silicon nanowire and reduce a carrier concentration; in a conventional chip detection process, the currents of the n-type silicon nanowire sensitive chip and the p-type silicon nanowire sensitive chip are reduced, and temperature drift is significantly reduced. In the integrated chip structure based on the probe structure of the application, the detection currents of 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 processed by a differential signal transmission mechanism, 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 shown in FIG. 6, in the case of reduced temperature interference, current data tends to be true, greatly improving the reliability of test results. Compared with the operation of setting multiple chip test structures to simultaneously connect corresponding differential signal transmission mechanisms to reduce temperature interference in the prior art, the probe structure 100 of the application synchronously leads out the lead-out electrodes 400 of multiple sensitive chips 200 to connect differential signal transmission, which is simple to apply, saves time and effort, has small size and low cost, and has strong operability and convenience. Figure 5

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

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

[0075] For example, the material of the lead wire 300 includes one or a combination of gold, silver, copper, graphite and conductive silica gel.

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

[0077] ​Further, the lead-out electrode 400 and the lead wire 300 can be formed by electroplating and etching process, and are usually made of the same process and the same metal to simplify the process and reduce the manufacturing cost. 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 the lead wire 300, and can be designed as a planar electrode, a needle electrode or a flexible electrode, and the specific design depends on the application requirements and environmental conditions. In the embodiment, the lead-out electrode 400 adopts a copper electrode, but in other embodiments, materials such as gold, silver, graphite and conductive silicone can also be used. In order to prevent oxidation and corrosion, the surface of the lead-out electrode 400 can be gold plated or subjected to other protection treatment.

[0079] As an example, the connection mode of the sensitive chip 200 and the lead wire 300 includes wire bonding, soldering connection and coating conductive material.

[0080] Specifically, the wire bonding is to connect the electrode pad 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 to realize close combination by using heat, pressure or ultrasonic energy to ensure stable transmission of signals. The soldering connection is to connect the electrode pad of the sensitive chip 200 and the lead-out electrode 400 by melting solder (such as tin, silver, copper, etc.) through heating to improve the mechanical strength of the connection. The coating conductive material is to realize electrical connection by coating conductive glue or other conductive materials between the electrode pad of the sensitive chip 200 and the lead-out electrode 400, and is suitable for flexible or low-temperature test environment. These connection modes can ensure stable transmission of signals, and the specific selection can be determined according to actual application requirements. In the embodiment, the connection mode of the sensitive chip 200 and the lead wire 300 is not limited.

[0081] As an example, the material of the probe structure 100 includes a single material such as ceramic, plastic, glass, rubber and fiber, or a composite material composed of these materials.

[0082] Specifically, these materials can provide mechanical support, stability, waterproof and dustproof performance according to actual requirements to ensure reliability and stability in harsh environments. In the embodiment, the material of the probe structure 100 adopts a PCB board with a size of 2mm*30mm*0.4mm to realize the 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 arrangement probe structure or a three-dimensional arrangement probe structure.

[0084] Specifically, the single probe structure can be used to detect the presence of a specific biomolecule. This structure is simple, easy to operate and control, but its function is relatively limited, and it can usually only detect a single point or a local area. See Figure 4 In the two-dimensional arrangement 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 in 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 capability. In the three-dimensional arrangement 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 detection. Its advantages include providing more comprehensive information, achieving high-throughput and high-sensitivity detection, and being suitable for scenarios that require multi-dimensional analysis.

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

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

[0087] Second, perform pattern transfer. The circuit pattern is transferred to the substrate by photolithography technology, and the pattern is formed using exposure and development processes.

[0088] Third, perform electroplating and etching. The lead 300 and the lead electrode 400 are formed by electroplating a metal layer in the pattern area, and the excess metal layer is removed by chemical etching. In order to simplify the process and reduce costs, the lead 300 and the lead electrode 400 are prepared using the same process and the same metal material,

[0089] Next, perform surface treatment. Apply solder resist ink to the non-soldering area to prevent soldering short circuits.

[0090] Next, install the sensitive chip 200. The sensitive chip 200 is fixed on the PCB board, and the solder points on the sensitive chip 200 are connected to the lead 300 by wire bonding. The wire bonding area is covered with insulating material to prevent electrical leakage. The fixation method and wire bonding method of the sensitive chip 200 are not limited to the above methods.

[0091] Compared with the prior art, the integrated chip structure of the embodiment integrates the probe end 130, the handle end 110 and the connecting part 120 into one, forming the probe structure 100 convenient to carry. The structure does not need to place the sample liquid to be tested in the chip testing device of the planar structure, nor needs to fix and package the chip structure on the support or base. By integrating the testing part and the signal transmission part into one and setting the handle end 110 to facilitate operation, the application realizes in-situ testing of the sample, reduces the volume of the testing structure, simplifies the operation process and reduces the testing cost.

[0092] In addition, by designing the probe structure with multiple cross sections and multiple sensitive chips 200 working cooperatively, the application can accurately detect multiple parameters such as biological molecules, ion concentration, temperature and pressure. The lead-out electrode in the probe structure can quickly lead out and process the signal, avoiding false positive phenomenon caused by environmental interference and improving the reliability and accuracy of the test data.

[0093] Embodiment two

[0094] The main difference between the embodiment and embodiment one is that the probe structure adopts a two-dimensional comb-shaped probe structure, and a modification process of the sensitive chip is proposed for the probe structure. Figure 6 As shown in the modification process of the sensitive chip, the integrated chip structure of the 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 the probe end 130, the handle end 110 and the connecting part 120, and the connecting part 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 the target substance.

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

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

[0099] In the embodiment, the three comb teeth of the probe structure 100 are arranged in the same direction with equal spacing, and the position of the lead electrode 400 is designed as a handle to facilitate signal connection and handheld operation.

[0100] In order to realize the modification of different sensitive chips 200, the modification operation includes functionalization treatment by immersing the sensitive chip 200 in a modifier solution 600, which includes but is not limited to a coupling agent solution, a probe solution and a blocking agent solution; in the embodiment, the modification process is first treated by using a coupling agent solution, and then different probe solutions are used to modify different sensitive chips 200 respectively; the coupling agent solution uses 3-aminopropyltriethoxysilane (APTES solution) 610 and glutaraldehyde solution 620 respectively; the probe solution uses 0.5mg / mL of cluster of differentiation 63 (CD63) antibody solution 631, EGFR (epidermal growth factor receptor) antibody solution 632 and PSA (prostate specific antigen) antibody solution 633. In addition, the spacing between the comb teeth of the probe end 130 is set according to the spacing between the modifier solutions 600 to ensure the efficiency of 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 the embodiment, the sensitive chip 200 uses a silicon nanowire sensitive chip, and 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, which are similar to the sensitive chip in Embodiment One, and will not be repeated here.

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

[0104] In the embodiment, referring to Figure 6 , the modification process of the sensitive chip 200 includes the following steps:

[0105] S21, using 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, immerse the three comb tooth-shaped probe ends 130 in the APTES solution 610 respectively, and avoid light soaking for 12 hours to complete the modification of amino groups to improve hydrophilicity.

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

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

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

[0110] Through the above modification process, the comb-shaped probe ends 130 can realize the simultaneous modification of multiple different sensitive chips 200, and the handle end 110 is used for taking, which is convenient to operate. Compared with the prior art, the sensitive chip 200 needs to be immersed in the target solution, and needs special devices or uses a taking device for operation, which is complicated and time-consuming. The structure of the present application greatly improves the modification efficiency of the chip in the liquid.

[0111] The embodiment solves the problems of complex process, troublesome operation, poor stability and poor repeatability of the sensitive chip 200 in the modification operation application in the prior art, 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 electrode 400 are adjusted according to the specific requirements in the embodiment.

[0112] In other embodiments, the combs of the probe structure 100 can be designed in various forms according to actual testing conditions. For example, the probe structure 100 can be composed of multiple comb-shaped units, and the probe spacing can be set to different values to adapt to different testing requirements. In other embodiments, the probe structure 100 can also be a dendritic structure, which branches through the probe end 130, and can cover a larger detection area. In some other embodiments, the probe structure 100 can also adopt a three-dimensional arrangement of the probe structure, that is, the probe end 130 is arranged in a specific geometric shape in three-dimensional space. This structure can arrange the probe in three-dimensional space, and can realize high-throughput and high-sensitivity detection of samples, and is suitable for more complex detection conditions.

[0113] The lead electrode 400 is located at the handle end 110, and is used for connecting a signal processing circuit to transmit a detection signal.

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

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

[0116] In order to ensure that the signal is not disturbed during transmission, maintain high efficiency and stability, the lead-out electrode 400 and the lead wire 300 will choose materials with good electrical conductivity and stable mechanical properties. In order to prevent current leakage and short circuit, improve test accuracy, the copper wire wrapped with resin 310 is connected. Referring to Figure 4 This packaging method not only provides good electrical insulation, but also protects the electrode from the influence of 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 wire 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 wire 300 is described in embodiment one, which will not be repeated here.

[0119] 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.

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

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

[0122] The cross section of the probe end 130 is set to adapt to different application scenarios. The selection of these shapes and sizes is aimed at optimizing the efficient operation of the probe end 130 in different detection environments, which is described in detail in embodiment one.

[0123] In the embodiment, the probe end 130 adopts a quadrilateral and flat rectangular cross section, and two faces can each place one of the sensitive chips 200 for modification and detection. When the cross section is polygonal, each edge face can arrange one of the sensitive chips 200 to improve the detection sensitivity and reliability. The sensitive chip 200 can be fixed on the edge face by means of patching, soldering, chip bonding, conductive glue fixing, etc. At the same time, the sensitive chip 200 can be uniformly distributed or arrayed on the corresponding edge face, and the specific fixing mode and chip distribution can be optimized according to the detection target and reverse to ensure good contact and electrical connection between the chip and the edge face. In the embodiment, the sensitive chip 200 is fixed on the edge face by patching to achieve better contact.

[0124] As an example, the connection mode of the sensitive chip 200 and the lead 300 includes one or a combination of wire connection, soldering connection or coating of conductive material.

[0125] Specifically, the connection mode ensures stable electrical connection between the chip and the external circuit and meets the requirement of certain mechanical strength. The specific connection mode of the sensitive chip 200 and the lead 300 is mentioned in embodiment one, which will not be repeated here.

[0126] As can be seen from the above, the probe structure 100 of the present application can realize synchronous modification of multiple different sensitive chips 200 by setting the probe with a comb-shaped structure or the probe structure 100 with a higher dimension, realize operation in multiple liquid environments, meet the needs of diversified and efficient application scenarios, and overcome the problems of the existing test structure, i.e. the need to place the sample liquid to be tested on a chip test device with a planar structure or fix and package the chip on a support or base, complicated operation, large test equipment, high cost, long operation time, etc. The probe structure 100 of the present application sets the test component and the signal transmission component in one body, and sets the handle end 110 for easy taking, which can realize in-situ testing in the sample, reduce the volume of the test structure, and is convenient and simple in operation process, saving time and effort, thereby realizing a portable, small-sized, high-sensitivity, low-cost and multifunctional detection device, greatly improving the efficiency of chip modification in liquid.

[0127] Embodiment three

[0128] The difference between the present embodiment and embodiment one is that the probe end of the probe structure is used for the application of a single sensitive chip in the detection, cleaning and elution process, and the sensitive chip is a modified sensitive chip.

[0129] In the embodiment, the probe end 130 adopts a quadrilateral and flat rectangular cross section, and two faces can each place one of the sensitive chips 200 for modification and detection. When the cross section is polygonal, each edge face can arrange one of the sensitive chips 200 to improve the detection sensitivity and reliability. The sensitive chip 200 can be fixed on the edge face by means of patching, soldering, chip bonding, conductive glue fixing, etc. At the same time, the sensitive chip 200 can be uniformly distributed or arrayed on the corresponding edge face, and the specific fixing mode and chip distribution can be optimized according to the detection target and reverse to ensure good contact and electrical connection between the chip and the edge face. In the embodiment, the sensitive chip 200 is fixed on the edge face by patching to achieve better contact. Figure 7The detection, cleaning and elution process of the sensitive chip is taken as an example, and the embodiment provides a probe structure and a process of detecting, cleaning and eluting the probe structure. The integrated chip structure includes a probe structure 100, a sensitive chip 200, an electrode 400 and a lead 300.

[0130] The probe structure 100 includes a probe end 130, a handle end 110 and a connecting part 120, and the connecting part 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 with target substances.

[0132] The electrode 400 is located at the handle end 110 and is used to connect a signal processing circuit to transmit a detection signal.

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

[0134] In the embodiment, the sensitive chip 200 is a silicon nanowire sensitive chip, and the electrode 400 and the lead 300 are made of copper. Meanwhile, the copper wire is wrapped with the resin (not labeled), the silicon nanowire sensitive chip is a p-type field effect transistor, is attached to the probe end 130 in a patch manner, the surface of the sensitive chip 200 is modified with a CD63 antibody, the cross section of the probe end 130 is a flat rectangle, the material of the probe structure 100 is a PCB board, and the size is 2mm*30mm*0.4mm. The embodiment provides a process of detecting, cleaning and eluting the probe structure 100 in the to-be-tested solution 701, and also performs a modification operation in the detection process. The detection operation refers to immersing the sensitive chip 200 in a sample of the to-be-tested solution 701 to detect a physical and chemical parameter, the cleaning operation refers to immersing the sensitive chip 200 in a cleaning solution 703 to remove surface impurities, and the elution operation refers to immersing the sensitive chip 200 in an elution solution 704 to desorb a combined substance. The specific process is as follows.

[0135] S31, immerse the probe end 130 in the to-be-tested solution 701 to test a baseline current, and the to-be-tested solution 701 is a PBS solution.

[0136] S32, immerse the probe end 130 in an exosome solution 702, incubate for 10 minutes to modify. The CD63 probe on the sensitive chip 200 can specifically capture exosomes in the solution.

[0137] S33, the probe end 130 is immersed in the cleaning solution 703 to clean the surface of non-specific adsorption, and the cleaning solution is deionized water.

[0138] S34, the probe end 130 is immersed in the test solution 701 to test the response current after specific capture of exosomes, and the test solution 701 is a PBS solution.

[0139] S35, the probe end 130 is immersed 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, but can also include buffer solution and other cleaning solutions, which are not described in detail here; the elution solution 704 includes but is not limited to deionized water, buffer solution and anionic detergent; the test solution 701 includes but is not limited to buffer solution, body fluid sample and environmental sample.

[0141] In this embodiment, the baseline current and the response current after specific capture of exosomes are shown in FIG. 6. Figure 8 The majority carriers in the p-type silicon nanowire sensitive chip are holes, and the combination of the negatively charged exosomes and CD63 on the sensitive chip 200 increases the hole concentration, thereby increasing the current. The probe structure 100 described above can be conveniently immersed in the solution for detection, cleaning and elution operations, improving efficiency, and at the same time, the sensitive chip 200 can be restored to its original state, thereby realizing the reuse 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 tested by the probe end 130 is transmitted to the lead-out electrode 400 through the lead 300, connected to the signal processing mechanism through the lead-out electrode 400, analyzed, and finally output the response current of the test. The process is simple and fast. Of course, in some other embodiments, the sensitive chip 200 is respectively provided as a p-type field effect transistor and an n-type field effect transistor, and after testing the above-mentioned solution, the signal can be amplified through the lead-out electrode 400 connected to the differential signal transmission structure, thereby increasing the current. In some other embodiments, the sensitive chip 200 is respectively provided as an n-type field effect transistor, and the combination of the negatively charged exosomes and CD63 on the sensitive chip 200 reduces the hole concentration, thereby reducing the current. However, these do not affect the application of the application structure in solution cleaning, detection and elution.

[0144] Of course, in the present embodiment, the cleaning, detection and elution operations performed by the probe structure 100 are not necessarily continuous operations, but can be separate operations or a combination of both, without affecting the convenience and efficiency of the cleaning, detection and elution operations performed by the probe structure 100. Meanwhile, the number of sensitive chips 200 at the probe end 130 can also be two, which will not be described in detail here.

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

[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 of the sensitive chips 200 working cooperatively 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 electromagnetic shielding structure, differential signal transmission structure, or filter structure.

[0150] As an example, the connection between the sensitive chip 200 and the lead 300 includes one or a combination of wire bonding, soldering, or coating with 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 and the corresponding process methods and materials involved in the present embodiment are similar to those in Embodiment One, which will not be described in detail here. The manufacturing method of the probe structure 100 is mentioned in Embodiment One and can also be applied to the present embodiment, which will not be described here.

[0154] Further, by setting the probe end 130 of the comb-shaped structure or the probe structure 100 of higher dimension, the application can simultaneously modify multiple different sensitive chips 200 and simultaneously realize cleaning, detection, elution and other operations. This design meets the needs of diversified application scenarios and solves the problems of complex operation, poor stability and poor repeatability in the detection, cleaning and elution process of traditional sensitive chips. Compared with the prior art, the probe structure 100 of the 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 the liquid, improves the stability and reliability of the process, and realizes the detection goal of high sensitivity and multi-function.

[0155] In summary, the application provides an integrated chip structure and its application. The integrated chip structure connects the probe end, the handle end and the connecting part together. The sensitive chip is arranged on the probe end, and the lead electrode is arranged on the handle end, so as to realize the integration of testing and signal transmission. This design not only is convenient to carry, but also realizes in-situ testing of the sample, reduces the testing volume, realizes efficient and convenient operation in a small amount of liquid, and reduces the test cost. The probe end adopts a plurality of cross-sectional designs, and a plurality of sensitive chips are arranged to work cooperatively. The signal is output through the lead electrode and is processed, the signal interference is reduced, and the accuracy and efficiency of the detection data of a plurality of parameters are improved. In addition, by arranging the probe structure of different dimensions, the device can be operated synchronously in a variety of liquid environments, meet the needs of diversified and efficient application scenarios, and finally realize the detection goal of portability, miniaturization, high sensitivity and multi-function. Therefore, the application effectively overcomes the shortcomings of the prior art and has high industrial utilization value.

[0156] The above embodiments only exemplarily illustrate the principles and effects of the application, and are not used to limit the application. Any person skilled in the art can modify or change the above embodiments without departing from the spirit and scope of the application. Therefore, all equivalent modifications or changes completed by those skilled in the art without departing from the spirit and technical thought disclosed by the application should be covered by the claims of the application.

Claims

1. An integrated chip structure, characterized in that, The integrated chip structure includes: A probe structure, comprising a probe end, a handle end, and a connecting part, wherein the connecting part connects the probe end and the handle end; A sensitive chip, located at the probe end, is used to contact and operate with the target substance; The lead-out electrode is located at the end of the handle and is used to connect to the signal processing circuit so as to transmit the detection signal; A lead wire, located at the connection portion, 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-dimensional probe arrangement structure, or a three-dimensional probe arrangement 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 cooperating sensitive chips to enable 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 tip includes triangles, quadrilaterals, hexagons, and circles.

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, soldering, and coating with conductive material.

8. The integrated chip structure according to claim 1, characterized in that: The probe structure is made of ceramic, plastic, glass, rubber, fiber, or composite materials composed of these materials.

9. The integrated chip structure according to claim 1, characterized in that: The material of the lead 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, modification refers to immersing the sensitive chip in a modifying solution for functionalization; detection refers to immersing the sensitive chip in a test solution sample for parameter detection; cleaning refers to immersing the sensitive chip in a cleaning solution to remove surface impurities; and elution refers to immersing the sensitive chip in an elution solution to desorb the adsorbed compounds.

Images