A DNA Probe and Chip Connection Testing Device and Method

Abstract

The present invention discloses a connection testing device and method for a DNA probe and a chip. The connection testing device for the DNA probe and the chip includes: a main control module and a voltage application electrode; the main control module is connected to the electrical signal application electrode and a plurality of electrical signal sensors; the voltage application electrode is used to apply a test electrical signal to a conductive test solution on the DNA probe connection surface of the chip; the main control module is used to provide the test electrical signal for the voltage application electrode, and collect a first detection signal and a second detection signal of the plurality of electrical signal sensors before and after the DNA probe connection operation, and judge whether a DNA probe is connected to the chip according to the first detection signal and the second detection signal. The technical solution provided by the embodiments of the present invention can reduce the testing cost of the connection situation between the DNA probe and the chip and improve the testing accuracy.

Description

Technical Field

[0001] The embodiments of the present invention relate to the technical field of the connection between DNA probes and chips, and in particular, to a connection test device and method for DNA probes and chips. Background Art

[0002] A DNA microarray / chip formed by immobilizing a single-stranded DNA with a known sequence on the surface of a solid support (such as modified glass, polypropylene, polyacrylamide, etc.) is a powerful research tool in high-throughput molecular detection. The target DNA fragment hybridizes with the complementary sequence oligonucleotides immobilized on the surface of the DNA chip through the base pairing principle, and then the nucleotide sequence of the target DNA is detected and analyzed by optical or radiochemical methods. It can simultaneously analyze the expression profiles of thousands of genes, detect gene mutations (such as SNP detection), pathogen detection, and be used for high-throughput gene sequencing and enrichment of sequencing target genes.

[0003] There are a huge number of tiny target regions (spots / clusters / wells: regions where DNA probes are immobilized) on the DNA chip. The number of DNA probes (single-stranded) in the tiny target regions and the differences in the number of DNA probes between different target regions have an important impact on the detection signal. Therefore, before applying the DNA chip for high-throughput detection, it is necessary to measure the number of DNA probes on the surfaces of different target regions of the DNA chip and the differences in the number of DNA probes between different target regions. Currently, the commonly used measurement methods include optical methods and radiochemical methods. Exemplarily, Brown et al. detected the uniformity of DNA probe spots by laser scanning the scattered light generated by salts in the DNA probe spots immobilized on the glass surface. Although this method can immediately detect the DNA chip after DNA probe spotting, it cannot be used to measure the number of probes on the DNA chip after the salt washing process. Battaglia C. et al. stained the DNA probes immobilized on the glass surface with a fluorescent substance that can bind to DNA probes (such as a fluorescent substance that can efficiently bind to single-stranded DNA: SYBRGreen II), eluted the fluorescent substance that did not bind to the DNA probes, and then used laser scanning to measure the number of DNA probes in the target region. Although compared with the method of Brown et al., the fluorescence staining method can detect the number of probes on the DNA chip after the completion of the entire production process, during the process of staining with the fluorescent substance and eluting the fluorescent dye that did not bind to the DNA probes, the fluorescent substance may adsorb on the glass surface and thus affect the subsequent DNA hybridization detection.

[0004] How to reduce the high cost caused by expensive fluorescence excitation devices, high-resolution fluorescence detection devices, and reagent consumables in high-throughput molecular detection of DNA chips, and avoid the decrease in accuracy caused by mutual contamination of optical signals is a problem to be further solved in microarray chips. Summary of the Invention

[0005] The present invention provides a connection testing device and method for a DNA probe and a chip, so as to reduce the testing cost of the connection between the DNA probe and the chip and improve the testing accuracy.

[0006] In a first aspect, an embodiment of the present invention provides a connection testing device for a DNA probe and a chip. The chip includes one or more electrical signal sensors, and the DNA probe is connected to the surface of the electrical signal sensor. The electrical signal sensor is used to detect the electrical signal on its surface. The connection testing device for the DNA probe and the chip includes:

[0007] A main control module and a voltage application electrode;

[0008] The main control module is connected to the electrical signal application electrode and the plurality of electrical signal sensors;

[0009] The voltage application electrode is used to apply a test electrical signal to the conductive test solution on the DNA probe connection surface of the chip;

[0010] The main control module is used to provide the test electrical signal for the voltage application electrode, collect the first detection signal and the second detection signal of the plurality of electrical signal sensors before and after the DNA probe connection operation, and judge whether a DNA probe is connected to the chip according to the first detection signal and the second detection signal.

[0011] In a second aspect, an embodiment of the present invention further provides a connection testing method for a DNA probe and a chip, which is executed by using the connection testing device for a DNA probe and a chip described in the first aspect. The connection testing method for a DNA probe and a chip includes:

[0012] Before the connection operation of the DNA probe and the chip, place a conductive test solution on the DNA probe connection surface of the chip. The main control module applies a test electrical signal to the conductive test solution through the voltage application electrode and collects the first detection signal of the plurality of electrical signal sensors;

[0013] After the connection operation of the DNA probe and the chip, place a conductive test solution on the DNA probe connection surface of the chip. The main control module applies the test electrical signal to the conductive test solution through the voltage application electrode and collects the second detection signal of the plurality of electrical signal sensors;

[0014] The main control module judges whether a DNA probe is connected to the chip according to the first detection signal and the second detection signal.

[0015] The DNA probe and chip connection test device provided by the embodiment of the present invention includes a main control module and a voltage application electrode. The main control module is connected to the electrical signal application electrode and multiple electrical signal sensors. The voltage application electrode is used to apply a test electrical signal to the conductive test solution on the DNA probe connection surface of the chip. The main control module is used to provide a test electrical signal for the voltage application electrode, and collect the first detection signal and the second detection signal of multiple electrical signal sensors before and after the DNA probe connection operation. According to the first detection signal and the second detection signal, it is determined whether a DNA probe is connected to the chip, realizing the judgment of the connection situation between the DNA probe and the chip through electrical signals, without using fluorescent substances, avoiding the problem of optical signal pollution caused by fluorescent substances, improving the accuracy of the judgment result, and without expensive test equipment and reagent consumables, etc., reducing the test cost of the connection situation between the DNA probe and the chip. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] By reading the detailed description of the non-restrictive embodiments with reference to the following drawings, other features, objectives, and advantages of the present invention will become more obvious:

[0017] Figure 1 is a schematic connection structure diagram of a DNA probe and chip connection test device provided by an embodiment of the present invention;

[0018] Figure 2 is a schematic top view structure diagram of a chip provided by an embodiment of the present invention;

[0019] Figure 3 is along Figure 2 the cross-sectional structure diagram of the dashed line AA in

[0020] Figure 4 is another schematic top view structure diagram of a chip provided by an embodiment of the present invention;

[0021] Figure 5 is along Figure 4 the cross-sectional structure diagram of the dashed line BB in

[0022] Figure 6 is a schematic flow diagram of a DNA probe and chip connection test method provided by an embodiment of the present invention;

[0023] Figure 7 is a histogram of the chip output voltage and the number of micro-holes before DNA probe connection provided by an embodiment of the present invention;

[0024] Figure 8 is a histogram of the chip output voltage and the number of micro-holes after DNA probe connection provided by an embodiment of the present invention;

[0025] Figure 9It is a relationship curve graph of microhole current and voltage before DNA probe ligation provided by an embodiment of the present invention;

[0026] Figure 10 It is a relationship curve graph of microhole current and voltage after DNA probe ligation provided by an embodiment of the present invention. Specific Embodiments

[0027] To further elaborate on the technical means and effects adopted by the present invention to achieve the intended invention purpose, the following specifically describes in detail the specific embodiments, structures, features, and effects of a DNA probe and chip connection test device and method according to the present invention in conjunction with the accompanying drawings and preferred embodiments.

[0028] An embodiment of the present invention provides a DNA probe and chip connection test device. The chip includes one or more electrical signal sensors, the DNA probe is connected to the surface of the electrical signal sensor, the electrical signal sensor is used to detect the electrical signal on its surface, and the DNA probe and chip connection test device includes:

[0029] A main control module and a voltage application electrode;

[0030] The main control module is connected to the electrical signal application electrode and the multiple electrical signal sensors;

[0031] The voltage application electrode is used to apply a test electrical signal to the conductive test solution on the DNA probe connection surface of the chip;

[0032] The main control module is used to provide the test electrical signal for the voltage application electrode, collect the first detection signal and the second detection signal of the multiple electrical signal sensors before and after the DNA probe connection operation, and judge whether a DNA probe is connected to the chip according to the first detection signal and the second detection signal.

[0033] The DNA probe and chip connection test device provided by the embodiment of the present invention includes a main control module and a voltage application electrode. The main control module is connected to the electrical signal application electrode and multiple electrical signal sensors. The voltage application electrode is used to apply a test electrical signal to the conductive test solution on the DNA probe connection surface of the chip. The main control module is used to provide a test electrical signal for the voltage application electrode, collect the first detection signal and the second detection signal of the multiple electrical signal sensors before and after the DNA probe connection operation, and judge whether a DNA probe is connected to the chip according to the first detection signal and the second detection signal, realizing the judgment of the connection situation between the DNA probe and the chip through electrical signals, without the use of fluorescent substances, thereby avoiding the problem of optical signal pollution caused by fluorescent substances and improving the accuracy of the judgment result.

[0034] The above is the core idea of this application. Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative efforts belong to the scope of protection of the present invention.

[0035] In the following description, many specific details are set forth in order to provide a thorough understanding of the present invention. However, the present invention may be implemented in other ways different from those described herein. Those skilled in the art can make similar generalizations without departing from the spirit of the present invention. Therefore, the present invention is not limited by the specific embodiments disclosed below.

[0036] Secondly, the present invention will be described in detail in conjunction with schematic diagrams. When detailing the embodiments of the present invention, for the sake of illustration, the schematic diagrams showing the structures of device components are not enlarged locally according to a general scale, and the schematic diagrams are only examples and should not limit the scope of protection of the present invention herein. In addition, in actual production, three-dimensional spatial dimensions including length, width, and height should be included.

[0037] Figure 1 It is a schematic connection structure diagram of a connection test device for a DNA probe and a chip provided by an embodiment of the present invention. The connection test device for the DNA probe and the chip is used to test whether a DNA probe has been connected to the chip after the DNA probe connection operation. Figure 2 It is a schematic top view structure diagram of a chip provided by an embodiment of the present invention. Figure 3 It is along Figure 2 The cross-sectional structure diagram of the dashed line AA in. As Figure 2 and Figure 3 shown, the chip includes one or more electrical signal sensors 130, and the DNA probe 113 is connected to the surface of the electrical signal sensor 130, and the electrical signal sensor 130 is used to detect the electrical signal on its surface.

[0038] As Figure 1 shown, the connection test device 10 for the DNA probe and the chip includes a main control module 100 and a voltage application electrode 200. The main control module 100 is connected to the electrical signal application electrode 200 and a plurality of electrical signal sensors 20. The voltage application electrode 200 is used to apply a test electrical signal to the conductive test solution on the DNA probe connection surface of the chip. Specifically, the DNA probe connection surface of the chip is the side surface of the chip facing the DNA probe, such as Figure 3 the surface 131 in. Exemplarily, the voltage application electrode 200 can be set, for example, in the area of the chip where no electrical signal sensor is provided, such as Figure 2The main control module 100 is used to provide a test electrical signal to the voltage application electrode 200, and collect the first detection signal and the second detection signal of the multiple electrical signal sensors 20 before and after the DNA probe connection operation, and judge whether the DNA probe is connected to the chip according to the first detection signal and the second detection signal.

[0039] Optional, Figure 4 It is a schematic diagram of a top view structure of another chip provided by an embodiment of the present invention. Figure 5 is along Figure 4 The cross-sectional structure diagram of the dotted line BB is shown in FIG. Figure 4 and Figure 5 As shown, the chip includes a bottom plate 110 having a micropore array 111 formed thereon, the micropore array 111 includes a plurality of micropores 112, and the micropores 112 correspond one to one with the electrical signal sensors 130. Specifically, the voltage applying electrode 200 may be disposed in a region outside the micropore array 111 on the chip, such as Figure 4 shown.

[0040] Exemplarily, the chip may be a gold-plated chip having a microwell array of 512 rows and 512 columns, such as a KK3-SA chip, and the DNA probe may be a single-stranded DNA modified with 5'-thiol and having several T bases.

[0041] It should be noted that the "DNA probe connection surface" is the surface of the chip used to connect the DNA probe. The conductive test liquid is conductive and covers the entire DNA probe connection surface. When the chip has a micropore array, the conductive test liquid covers all the micropores of the chip. During the actual test process, the voltage applying electrode 200 contacts the conductive test liquid and applies a test electrical signal to the conductive test liquid, thereby making the electrical signal at each position in the DNA probe connection surface of the chip the same as the test electrical signal. When the chip has a micropore array, the electrical signals of all the micropores are the same as the test electrical signal.

[0042] It should also be noted that experiments have shown that DNA probes carry negative charges. Therefore, after the chip is connected to the DNA probe, the electrical signal on the electrical signal sensor will change, and then it can be determined whether the DNA probe is connected based on the change in the electrical signal on the electrical signal sensor. The electrical signal sensor on the chip can directly detect the electrical signal on its surface. By using the electrical signal sensor to detect the electrical signal on its surface before and after the DNA probe connection operation, it can be determined whether the DNA probe is connected to the surface of the electrical signal sensor after the DNA probe connection operation.

[0043] The DNA probe and chip connection test device provided by this embodiment includes a main control module and a voltage application electrode. The main control module is connected to the electrical signal application electrode and multiple electrical signal sensors. The voltage application electrode is used to apply a test electrical signal to the conductive test solution on the DNA probe connection surface of the chip. The main control module is used to provide a test electrical signal for the voltage application electrode, and collect the first detection signal and the second detection signal of multiple electrical signal sensors before and after the DNA probe connection operation. According to the first detection signal and the second detection signal, it is judged whether a DNA probe is connected to the chip, realizing the judgment of the connection situation between the DNA probe and the chip through electrical signals, without using fluorescent substances, thereby avoiding the problem of optical signal pollution caused by fluorescent substances and improving the accuracy of the judgment result.

[0044] Optionally, the electrical signal sensor may include an ion field effect transistor sensor, a nanowire field effect transistor sensor, a graphene field effect transistor sensor, a molybdenum disulfide field effect transistor sensor, and a carbon nanotube field effect transistor sensor.

[0045] Exemplarily, the voltage application electrode 200 may be an AgCl electrode.

[0046] It should be noted that the AgCl electrode has good stability and high withstand voltage, and is suitable for use as a voltage application electrode. It can be understood that only the AgCl electrode is used as an exemplary electrode here rather than a limitation. In other embodiments of this embodiment, the voltage application electrode 200 may also be an electrode formed of other materials.

[0047] Optionally, the voltage application electrode 200 multiplexes the built-in electrode of the chip, and the built-in electrode is electrically connected to the DNA probe connection surface of the chip.

[0048] It should be noted that the chip internally includes multiple functional film layer structures, and electrodes may be provided in the metal functional film layer, that is, the built-in electrodes of the chip. When the built-in electrode is electrically connected to the DNA probe connection surface of the chip, the electrical signal applied to the built-in electrode can be transmitted to the conductive test solution on the DNA probe connection surface, thereby playing the role of the voltage application electrode 200. Specifically, the built-in electrode may be provided in the fifth metal functional film layer inside the chip, that is, a layer spaced four metal functional film layers from the chip substrate.

[0049] It should also be noted that when the voltage application electrode 200 multiplexes the built-in electrode of the chip, there is no need to additionally set a voltage application electrode independent of the chip, which is beneficial to the structural simplification of the DNA probe and chip connection test device and the reduction of the preparation difficulty.

[0050] In this embodiment, the main control module 100 is further used to provide an initial electrical signal for the voltage application electrode 200, and the voltage application electrode 200 is further used to apply the initial electrical signal to the conductive test solution.

[0051] It should be noted that to test the electrical signal, the chip needs to be turned on. To accurately and quickly determine the test electrical signal, one or more initial electrical signals are used to test whether the chip is turned on before the test, and the initial electrical signal that can effectively turn on the chip is selected to determine the test electrical signal.

[0052] Figure 6 It is a schematic flowchart of a method for testing the connection between a DNA probe and a chip provided by an embodiment of the present invention. The method for testing the connection between the DNA probe and the chip is executed by using the device for testing the connection between the DNA probe and the chip provided by any embodiment of the present invention. Specifically, as Figure 6 shown, the method for testing the connection between the DNA probe and the chip specifically includes the following:

[0053] Step 11: Before the connection operation between the DNA probe and the chip, a conductive test solution is placed on the DNA probe connection surface of the chip. The main control module applies a test electrical signal to the conductive test solution through the voltage application electrode and collects the first detection signals of multiple electrical signal sensors.

[0054] Exemplarily, the conductive test solution can be Tris-HCl buffer solution. The pH value of the Tris-HCl buffer solution ranges from 6 to 10, and the concentration of the Tris-HCl buffer solution ranges from 1 to 100 mM.

[0055] Optionally, the test electrical signal can be a sawtooth wave electrical signal. Further, the voltage range of the sawtooth wave electrical signal can be 400 - 1300 mV, and the step voltage of the sawtooth wave electrical signal can be 0.8 - 20 mV.

[0056] Step 20: After the connection operation between the DNA probe and the chip, a conductive test solution is placed on the DNA probe connection surface of the chip. The main control module applies a test electrical signal to the conductive test solution through the voltage application electrode and collects the second detection signals of multiple electrical signal sensors.

[0057] Step 23: The main control module determines whether a DNA probe is connected to the chip according to the first detection signal and the second detection signal.

[0058] It should be noted that determining whether a DNA probe is connected to the chip includes at least one of the following two aspects: 1. Taking the chip as the object, determining whether a DNA probe is connected to the chip; 2. Taking the electrical signal sensors on the chip as the object, determining whether a DNA probe is connected to the surface of each electrical signal sensor. The specific determination method will be described in detail in the following content.

[0059] Exemplarily, the main control module can use the following software to analyze the first detection signal and the second detection signal: sdPCR Data Capture&Analysis software and QCTool software.

[0060] In the technical solution provided in this embodiment, before and after the connection operation between the DNA probe and the chip, a conductive test solution is placed on the DNA probe connection surface of the chip. The main control module applies a test electrical signal to the conductive test solution through a voltage application electrode, collects the first detection signal and the second detection signal of multiple electrical signal sensors respectively, and determines whether a DNA probe is connected to the chip according to the first detection signal and the second detection signal, realizing the judgment of the connection between the DNA probe and the chip through electrical signals, without using fluorescent substances, thereby avoiding the occurrence of optical signal pollution problems caused by fluorescent substances and improving the accuracy of the judgment result.

[0061] Optionally, before the main control module applies a test electrical signal to the conductive test solution through a voltage application electrode and collects the first detection signal of multiple electrical signal sensors, it may further include: the main control module applies an initial electrical signal to the conductive test solution through a voltage application electrode.

[0062] Exemplarily, the initial electrical signal is at least one fixed voltage applied in sequence, and the value range of the fixed voltage U can be: 400 ≤ U ≤ 600 mV. It can be understood that the initial electrical signal is used to probe the conduction voltage of the current chip. Therefore, a fixed voltage with a simple signal can be used as the initial electrical signal, and 400 - 600 mV including the conduction voltage of the conventional micro-well array chip can be set as the value range of the initial electrical signal.

[0063] In this embodiment, the main control module determines whether a DNA probe is connected to the chip according to the first detection signal and the second detection signal, which may specifically include: the main control module constructs a histogram of the chip output voltage and the number of electrical signal sensors before and after the connection of the DNA probe according to the first detection signal and the second detection signal, and determines whether a DNA probe is connected to the chip according to the histogram of the chip output voltage and the number of electrical signal sensors before and after the connection of the DNA probe. For example, if the center position of the histogram after connection shifts to the right compared to the center position of the histogram before connection, it indicates that a DNA probe is linked to the surface of the electrical signal sensor. If the shift in mV is large, it indicates a large number or density of DNA probe links. The full width at half maximum of the histogram or the standard deviation STD of the entire distribution map can also be used to analyze the uniformity of DNA probe links. A small full width at half maximum (e.g., <20 mV) indicates that the DNA probes connected to each electrical signal sensor on the chip are relatively uniform, and the surface chemistry quality of the chip is good. If the full width at half maximum is very large (>50 mV), it indicates that the DNA probes connected to each electrical signal sensor on the chip are not very uniform.

[0064] And / or, the main control module constructs a relationship curve graph of the current and voltage of the electrical signal sensor before and after the DNA probe connection according to the first detection signal and the second detection signal, and determines whether there is a DNA probe connection on each electrical signal sensor according to the relationship curve graph (IV curve) of the current and voltage of the electrical signal sensor before and after the DNA probe connection. For example, if the IV curve after the connection shifts to the right compared to the IV curve before the connection, it indicates that a DNA probe is linked to the surface of the electrical signal sensor. If the mV shift to the right is large, it indicates a large number or density of DNA probe links.

[0065] Exemplarily, Figure 7 is a histogram of the gate voltage and the number of electrical signal sensors before the DNA probe connection provided by an embodiment of the present invention. Figure 8 is a histogram of the gate voltage and the number of electrical signal sensors after the DNA probe connection provided by an embodiment of the present invention. As Figure 7 and Figure 8 shown, compared with Figure 7 , Figure 8 the overall histogram of the gate voltage and the number of electrical signal sensors shifts to the right, indicating that after the DNA probe connection operation, negatively charged DNA probes have been connected to the chip.

[0066] Figure 9 is a relationship curve graph of the current and voltage of the electrical signal sensor before the DNA probe connection provided by an embodiment of the present invention. Figure 10 is a relationship curve graph of the current and voltage of the electrical signal sensor after the DNA probe connection provided by an embodiment of the present invention. As Figure 9 and Figure 10 shown, compared with Figure 9 , Figure 10 the overall relationship curve graph of the current and voltage of the electrical signal sensor shifts to the right, indicating that after the DNA probe connection operation, negatively charged DNA probes have been connected to the electrical signal sensor of the chip.

[0067] Note that the above is only a preferred embodiment of the present invention and the technical principles applied. Those skilled in the art will understand that the present invention is not limited to the specific embodiments described here, and various obvious changes, re-adjustments, combinations with each other, and substitutions can be made by those skilled in the art without departing from the protection scope of the present invention. Therefore, although the present invention has been described in more detail through the above embodiments, the present invention is not limited to the above embodiments only. Without departing from the concept of the present invention, more other equivalent embodiments can be included, and the scope of the present invention is determined by the scope of the appended claims.

Claims

1. A connection test device for a DNA probe and a chip, the chip comprising one or more electrical signal sensors, the DNA probe being connected to the surface of the electrical signal sensor, the electrical signal sensor being used to detect the electrical signal on its surface, characterized in that, The DNA probe and chip connection test device includes: a main control module and a voltage application electrode; the main control module is connected to the voltage application electrode and the multiple electrical signal sensors; the voltage application electrode is used to apply a test electrical signal to the conductive test solution on the DNA probe connection surface of the chip; the main control module is used to provide the test electrical signal for the voltage application electrode, and collect the first detection signal and the second detection signal of the multiple electrical signal sensors before and after the DNA probe connection operation, and judge whether a DNA probe is connected to the chip according to the first detection signal and the second detection signal; the main control module judges whether a DNA probe is connected to the chip according to the first detection signal and the second detection signal, including: the main control module constructs a histogram of the chip output voltage and the number of electrical signal sensors before and after the DNA probe connection according to the first detection signal and the second detection signal, and judges whether a DNA probe is connected to the chip electrical signal sensor according to the histogram of the chip output voltage and the number of electrical signal sensors before and after the DNA probe connection, and qualitatively and quantitatively analyzes the DNA density, quantity, and uniformity on the electrical signal sensor; and / or, the main control module constructs a relationship curve graph of the electrical signal sensor current and voltage before and after the DNA probe connection according to the first detection signal and the second detection signal, and judges whether a DNA probe is connected to each electrical signal sensor according to the relationship curve graph of the electrical signal sensor current and voltage before and after the DNA probe connection, and qualitatively and quantitatively analyzes the DNA density, quantity, and uniformity on the electrical signal sensor.

2. The connection test device according to claim 1, characterized in that The chip includes multiple micropores, and the micropores correspond to the electrical signal sensors one by one.

3. The connection test device according to claim 1, characterized in that The electrical signal sensors include ion field effect transistor sensors, nanowire field effect transistor sensors, graphene field effect transistor sensors, molybdenum disulfide field effect transistor sensors, and carbon nanotube field effect transistor sensors.

4. The connection test device according to claim 1, characterized in that The voltage application electrode multiplexes the built-in electrode of the chip, and the built-in electrode is electrically connected to the DNA probe connection surface of the chip.

5. The connection test device according to claim 1, characterized in that, The main control module is also used to provide an initial electrical signal for the voltage application electrode; the voltage application electrode is also used to apply the initial electrical signal to the conductive test solution.

6. The connection test device according to claim 1, wherein, The voltage application electrode is an Ag / AgCl electrode.

7. A method for testing the connection between a DNA probe and a chip, which is performed using the DNA probe and chip connection testing device described in any one of claims 1-6, characterized in that, including: Before the DNA probe connection operation with the chip, place a conductive test solution on the DNA probe connection surface of the chip, the main control module applies a test electrical signal to the conductive test solution through the voltage application electrode, and collects the first detection signal of the multiple electrical signal sensors; After the DNA probe connection operation with the chip, place a conductive test solution on the DNA probe connection surface of the chip, the main control module applies the test electrical signal to the conductive test solution through the voltage application electrode, and collects the second detection signal of the multiple electrical signal sensors; the main control module judges whether a DNA probe is connected to the chip according to the first detection signal and the second detection signal.

8. The connection test method according to claim 7, characterized in that The conductive test solution is Tris-HCl buffer solution, the pH value of the Tris-HCl buffer solution ranges from 6 to 10, and the concentration of the Tris-HCl buffer solution ranges from 1 to 100 mM.

9. The connection test method according to claim 7, characterized in that The test electrical signal is a sawtooth wave electrical signal.

10. The connection test method according to claim 7, characterized in that, Before the main control module applies the test electrical signal to the conductive test solution through the voltage application electrode and collects the first detection signals of the plurality of electrical signal sensors, it further includes: The main control module applies an initial electrical signal to the conductive test solution through the voltage application electrode.

11. The connection test method according to claim 10, wherein The initial electrical signal is at least one fixed voltage applied in sequence, and the value range of the fixed voltage U is: 400 ≤ U ≤ 600 mV.

12. The connection test method according to claim 7, characterized in that The main control module determines whether a DNA probe is connected to the chip according to the first detection signal and the second detection signal, including: The main control module constructs a histogram of the chip output voltage and the number of electrical signal sensors before and after the DNA probe connection according to the first detection signal and the second detection signal, and determines whether a DNA probe is connected to the chip electrical signal sensor according to the histogram of the chip output voltage and the number of electrical signal sensors before and after the DNA probe connection, and qualitatively and quantitatively analyzes the DNA density, quantity, and uniformity on the electrical signal sensor; and / or, The main control module constructs a relationship curve graph of the electrical signal sensor current and voltage before and after the DNA probe connection according to the first detection signal and the second detection signal, and determines whether a DNA probe is connected to each electrical signal sensor according to the relationship curve graph of the electrical signal sensor current and voltage before and after the DNA probe connection, and qualitatively and quantitatively analyzes the DNA density, quantity, and uniformity on the electrical signal sensor.

Images