Patent Publication Number: US-2021162409-A1

Title: Biological detection chip, biological detection device, and detection method thereof

Description:
TECHNICAL FIELD 
     The embodiments of the present disclosure relate to a biological detection chip, a biological detection device, and a detection method thereof. 
     BACKGROUND 
     Microfluidics technology is a technology that can manipulate or detect fluids at the micrometer scale. Microfluidic technology has the ability to miniaturize the basic functions of biological, chemical, and other laboratories onto a chip of a few square centimeters, so that basic operations such as sample preparation, reaction, separation, and detection during a biochemical analysis process can be completed automatically. Micro-electro-mechanical systems (MEMS) technology is a new discipline developed on the basis of microelectronics and micro-machining, and is playing an increasingly important role in a field of biological detection. 
     Nerve cells, also called neurons, are the basic structural and functional units that make up the mammalian nervous system. Structurally, neurons are divided into two parts: soma and neurites. The neurite is divided into a dendrite and an axon. The dendrite mostly shows dendritic branches and can receive stimuli and transmit impulses to the soma; the axon mostly shows slender shape and have fewer branches, and can achieve impulse conduction. Generally, each neuron includes one or more dendrites, but only one axon. The transmission of impulses between neurons mainly depends on synapses, and a large number of neurons contact each other through synapses to form the nervous system. 
     Generally, the synapse includes two membrane layers, and the two membrane layers are called presynaptic membrane and postsynaptic membrane (thickness ranging from 7 to 10 nanometers), there is a synaptic gap (20-30 nanometers) between the presynaptic membrane and the postsynaptic membrane. In a case where the impulse of the presynaptic neuron reaches the synaptosome, neurotransmitters in the synaptic vesicle are released from the presynaptic membrane, enters the synaptic gap, and acts on the postsynaptic membrane. In a case where the chemical effect exceeds a certain threshold, it can cause excitatory response or inhibition response in the postsynaptic neurons, thereby transmitting the impulses to the postsynaptic neurons. 
     SUMMARY 
     An embodiment of the present disclosure provides a biological detection chip, a biological detection device, and a detection method thereof. The biological detection chip comprises: a first base substrate; and a plurality of detection units arranged in an array along a row direction and a column direction on the first base substrate. Each of the plurality of detection units comprises a thin film transistor and an electrode, the thin film transistor is on the first base substrate and comprises a gate electrode, a source electrode, and a drain electrode, and the electrode is on a side of the thin film transistor away from the first base substrate and is connected to the drain electrode, and the electrode is configured to carry a biological material to be detected. Thus, the biological detection chip can reduce the complexity of the routing of the plurality of detection units, thereby increasing the density of the plurality of detection units, furthermore achieving flexible control of electrical stimulation and impulse detection at different positions of the biological material to be detected (such as nerve cells). On the other hand, the biological detection chip can also increase the effective area for culturing and detecting the biological material to be detected, and can avoid the electrical stimulation process of the biological material to be detected from interfering the gate lines and the data lines. 
     At least one embodiment of the present disclosure provides a biological detection chip, and the biological detection chip includes: a first base substrate; and a plurality of detection units arranged in an array along a row direction and a column direction on the first base substrate. Each of the plurality of detection units comprises a thin film transistor and an electrode, the thin film transistor is on the first base substrate and comprises a gate electrode, a source electrode, and a drain electrode, and the electrode is on a side of the thin film transistor away from the first base substrate and is connected to the drain electrode, and the electrode is configured to carry a biological material to be detected. 
     For example, the biological detection chip provided by an embodiment of the present disclosure further includes: a plurality of gate lines; and a plurality of data lines arranged to intersect the plurality of gate lines. Each of the plurality of gate lines and the gate electrodes of the detection units in a same row are connected and are on a same layer, and each of the plurality of data lines and the source electrodes of the detection units in a same column are connected and are on a same layer. 
     For example, in the biological detection chip provided by an embodiment of the present disclosure, the plurality of detection units comprise stimulation units and receiving units, the stimulation units are configured to apply stimulation voltages, and the receiving units are configured to receive electrophysiological signals. 
     For example, in the biological detection chip provided by an embodiment of the present disclosure, in the row direction, the stimulation units and the receiving units are alternately arranged, and one stimulation unit and one receiving unit, which are adjacent, are axisymmetric with respect to a separation line between the one stimulation unit and the one receiving unit, which are adjacent. 
     For example, in the biological detection chip provided by an embodiment of the present disclosure, in the column direction, the stimulation units and the receiving units are alternately arranged, and two stimulation units and two receiving units constitute a detection point, and in the detection point, orthographic projections of the two stimulation units on the first base substrate and orthographic projections of the two receiving units on the first base substrate form a 2*2 matrix. 
     For example, in the biological detection chip provided by an embodiment of the present disclosure, an orthographic projection of the detection point on the first base substrate is substantially a rectangle, and a side length of the rectangle ranges from 4 to 6 microns. 
     At least one embodiment of the present disclosure further provides a biological detection device, and the biological detection device comprises: the biological detection chip according to any one of the above embodiments; and an opposite substrate, cell-assembled with the biological detection chip to form a culture cavity between the biological detection chip and the opposite substrate. 
     For example, in the biological detection device provided by an embodiment of the present disclosure, the opposite substrate comprises: a second base substrate; a breathable film, on a side of the second base substrate away from the biological detection chip; and a cover plate, on a side of the breathable film away from the second base substrate. The cover plate and the breathable film are spaced apart to form a gas channel between the cover plate and the breathable film, and the second base substrate is provided with a vent hole, and an orthographic projection of the vent hole on the second base substrate is located within an orthographic projection of the gas channel on the second base substrate. 
     For example, the biological detection device provided by an embodiment of the present disclosure further includes: a plurality of support members, between the biological detection chip and the opposite substrate and surrounding the plurality of detection units. The plurality of support members are spaced apart to form a liquid flow channel that is between adjacent ones of the plurality of support members and in communication with the culture cavity. 
     For example, the biological detection device provided by an embodiment of the present disclosure further includes: a reagent module, which is in communication with the culture cavity through the liquid flow channel. The reagent module comprises at least two reagent reservoirs and a reagent mixing region, the at least two reagent reservoirs are configured to store different types of detection reagents, and the reagent mixing region is configured to mix different types of detection reagents. 
     For example, in the biological detection device provided by an embodiment of the present disclosure, the reagent mixing region further comprises a fish-bone mixing structure. 
     At least one embodiment of the present disclosure further provides a biological detection method of a biological detection device, wherein the biological detection device is the above-mentioned biological detection device, and the biological detection method comprises: cultivating the biological material to be detected on the electrode on the biological detection chip, the biological material to be detected covering at least part of the detection units; cell-assembling the biological detection chip and the opposite substrate; introducing a detection reagent into the culture cavity; and using the detection units covered by the biological material to be detected to detect an influence of the detection reagent on the biological material to be detected. 
     For example, in the biological detection method provided by an embodiment of the present disclosure, the opposite substrate comprises: a second base substrate; a breathable film, on a side of the second base substrate away from the biological detection chip; and a cover plate, on a side of the breathable film away from the second base substrate; the cover plate and the breathable film are spaced apart to form a gas channel between the cover plate and the breathable film, and the second base substrate is provided with a vent hole, and an orthographic projection of the vent hole on the second base substrate is located within an orthographic projection of the gas channel on the second base substrate; the biological detection method further comprises: introducing gas into the gas channel; and using the detection units covered by the biological material to be detected to detect an influence of the gas on the biological material to be detected. 
     For example, in the biological detection method provided by an embodiment of the present disclosure, the detection units covered by the biological material to be detected comprise a first detection point located at a stimulation position of the biological material to be detected and a second detection point located at a receiving position of the biological material to be detected, and using the detection units covered by the biological material to be detected to detect the influence of the detection reagent on the biological material to be detected comprises: applying electrical stimulation to the stimulation position of the biological material to be detected by the first detection point; and receiving an electrophysiological signal at the receiving position of the biological material to be detected by the second detection point. The first detection point comprises at least one of the detection units, and the second detection point comprises at least one of the detection units. 
     For example, in the biological detection method provided by an embodiment of the present disclosure, the detection units covered by the biological material to be detected comprises a first detection point located at a stimulation position of the biological material to be detected and a second detection point located at a receiving position of the biological material to be detected, and using the detection units covered by the biological material to be detected to detect the influence of the gas on the biological material to be detected comprises: applying electrical stimulation to the stimulation position of the biological material to be detected by the first detection point; and receiving an electrophysiological signal at the receiving position of the biological material to be detected by the second detection point. The first detection point comprises at least one of the detection units, and the second detection point comprises at least one of the detection units. 
     For example, in the biological detection method provided by an embodiment of the present disclosure, the biological material to be detected comprises at least one nerve cell, the stimulation position of the biological material to be detected comprises a dendrite of a nerve cell, and the receiving position of the biological material to be detected comprises an axon or a myelin sheath of a nerve cell at the stimulation position, or an axon or a myelin sheath of another nerve cell connected to the nerve cell at the stimulation position. 
     For example, the biological detection method provided by an embodiment of the present disclosure further includes: acquiring an image of the biological material to be detected on the biological detection chip; determining, according to the image, the detection units covered by the biological material to be detected and a positional relationship between the detection units and the biological material to be detected; and determining the first detection point and the second detection point according to the positional relationship between each of the detection units and the biological material to be detected 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       In order to clearly illustrate the technical solutions of the embodiments of the disclosure, the drawings of the embodiments will be briefly described in the following; it is obvious that the described drawings are only related to some embodiments of the disclosure and thus are not limitative to the disclosure. 
         FIG. 1  is a schematic plane diagram of a biological detection chip according to an embodiment of the present disclosure; 
         FIG. 2  is a schematic cross-sectional view of a biological detection chip along an AA direction in  FIG. 1  according to an embodiment of the present disclosure; 
         FIG. 3  is a schematic diagram of performing detection by a biological detection chip according to an embodiment of the present disclosure; 
         FIG. 4  is a schematic cross-sectional view of a biological detection device according to an embodiment of the present disclosure; 
         FIG. 5  is a schematic diagram of another biological detection device according to an embodiment of the present disclosure; and 
         FIG. 6  is a flowchart of a biological detection method of a biological detection device according to an embodiment of the present disclosure. 
     
    
    
     DETAILED DESCRIPTION 
     In order to make objects, technical details and advantages of the embodiments of the disclosure apparent, the technical solutions of the embodiments will be described in a clearly and fully understandable way in connection with the drawings related to the embodiments of the disclosure. Apparently, the described embodiments are just a part but not all of the embodiments of the disclosure. Based on the described embodiments herein, those skilled in the art can obtain other embodiment(s), without any inventive work, which should be within the scope of the disclosure. 
     Unless otherwise defined, all the technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art to which the present disclosure belongs. The terms “first,” “second,” etc., which are used in the present disclosure, are not intended to indicate any sequence, amount or importance, but distinguish various components. The terms “comprise,” “comprising,” “include,” “including,” etc., are intended to specify that the elements or the objects stated before these terms encompass the elements or the objects and equivalents thereof listed after these terms, but do not preclude the other elements or objects. The phrases “connect”, “connected”, etc., are not intended to define a physical connection or mechanical connection, but may include an electrical connection, directly or indirectly. 
     The impulse transmission of the nerve cell is mainly achieved through an electrochemical process. In a case where the nerve cell is not stimulated, a stable potential difference, which is called a transmembrane resting potential, is maintained on two sides of the cell membrane. In this case, a potential inside the cell membrane is low and a potential outside the cell membrane is high, and a range of the potential difference varies in tens of millivolts. In a case where the nerve cell is stimulated by the external electrophysiological signal, the ion permeability of the cell membrane changes sharply, so that the potential difference between the two sides of the cell membrane changes, and the potential difference formed with the adjacent cell membrane causes the potential to propagate sequentially, thereby achieving the transmission of impulses along the nerve cells. 
     Therefore, the effects of different types of detection reagents, different concentrations of detection reagents, different types of gases, and different concentrations of gases on nerve cells and nervous systems can be detected using a micro-electrode array (MEA) sensor. Generally, the micro-electrode array (MEA) sensor includes a base substrate and a micro-electrode array on the base substrate. In a case where the nerve cells or tissues are cultured on the surface of the micro-electrode array sensor, an externally applied electrical stimulation signal (such as, a pulse voltage) can be transmitted to the micro-electrodes, thereby stimulating the nerve cells and causing the nerve cells to generate impulses, and other micro-electrodes record the electrophysiological signals of different positions of the nerve cells or the electrophysiological signals of other nerve cells to achieve the research of the nerve cells or tissues. 
     However, due to the randomness of adherent growth of nerve cells, the synaptic connection manners and growth positions of different nerve cells are very different; and the connection manner between nerve cells in each cell culture is also random. The positions of the micro-electrodes on the micro-electrode array (MEA) sensor are relatively fixed, thereby making it impossible for researchers to perform electrical stimulation and impulse detection on the neurons in specific positions, which is not easy to evaluate the regularity of neural cell communication and the effectiveness of the nervous system constructed by nerve cells. On the other hand, each micro-electrode on a conventional micro-electrode array (MEA) sensor is connected and controlled by a separate wiring, which increases the complexity of the wiring, thus restricting the number of micro-electrode arrays and reducing the effective cultivation area. In addition, the conventional micro-electrode array (MEA) sensor can only use specific conditions to culture nerve cells or the nervous system constructed by the nerve cells. It cannot achieve flexible control of the culture environment, and it is not easy to study the influence of different detection reagents, different detection reagent concentrations, different gases, and different gas concentrations on the function of the nerve cells or the nervous system, thereby having large limitations. 
     An embodiment of the present disclosure provides a biological detection chip, a biological detection device, and a detection method thereof. The biological detection chip comprises: a first base substrate; and a plurality of detection units arranged in an array along a row direction and a column direction on the first base substrate. Each of the plurality of detection units comprises a thin film transistor and an electrode, the thin film transistor is on the first base substrate and comprises a gate electrode, a source electrode, and a drain electrode, and the electrode is on a side of the thin film transistor away from the first base substrate and is connected to the drain electrode, and the electrode is configured to carry a biological material to be detected. Because each detection unit includes a thin film transistor and an electrode, the plurality of detection units can be individually driven by the gate lines provided along the row direction and the data lines provided along the column direction; in addition, because the gate electrode, the source electrode and the drain electrode, and the electrode are located in different layers, the gate lines and the data lines for driving the plurality of detection units may be disposed at different layers from the electrode. Thus, the biological detection chip can reduce the complexity of the routing of the plurality of detection units, thereby increasing the density of the plurality of detection units, increasing the number of detection units per unit area, furthermore achieving flexible control of electrical stimulation and impulse detection at different positions of the biological material to be detected (such as nerve cells). On the other hand, the biological detection chip can also increase the effective area for culturing and detecting the biological material to be detected, and can avoid the electrical stimulation process of the biological material to be detected from interfering the gate lines and the data lines. 
     Hereinafter, the biological detection chip, the biological detection device, and the detection method thereof provided in the embodiments of the present disclosure will be described in detail with reference to the accompanying drawings. 
     An embodiment of the present disclosure provides a biological detection chip.  FIG. 1  is a schematic plane diagram of a biological detection chip according to an embodiment of the present disclosure;  FIG. 2  is a schematic cross-sectional view of a biological detection chip along an AA direction in  FIG. 1  according to an embodiment of the present disclosure. As illustrated by  FIG. 1 , the biological detection chip includes a first base substrate  110  and a plurality of detection units  120 . The plurality of detection units  120  are arranged in an array in a row direction and a column direction on the first base substrate  110 . As illustrated by  FIG. 2 , each detection unit  120  includes a thin film transistor  130  and an electrode  140 . The thin film transistor  130  is disposed on the first base substrate  110  and includes a gate electrode  131 , a source electrode  132 , and a drain electrode  133 . The electrode  140  is disposed on a side of the thin film transistor  130  away from the first base substrate  110  and is connected to the drain electrode  133 . The electrode  140  may carry a biological material to be detected, for example, the biological material to be detected may be cultured on the electrode  140 . 
     For example, as illustrated by  FIG. 2 , the thin film transistor  130  further includes a gate insulating layer  134  and an active layer  135 ; the gate electrode  131  is disposed on the first base substrate  110 , and the gate insulating layer  134  is disposed on a side of the gate electrode  131  away from the first base substrate  110 , the active layer  135  is disposed on a side of the gate insulating layer  134  away from the gate electrode  131  and is opposite to the gate electrode  131  (for example, the orthographic projection of the active layer  135  on the first base substrate  110  covers the orthographic projection of the gate electrode  131  on the first base substrate  110 ), the source electrode  132  and the drain electrode  133  are located on a side of the gate insulating layer  134  and the active layer  135  away from the gate electrode  131 . The biological detection chip further includes a passivation layer  190 , and the passivation layer  190  is located on a side of the thin film transistor  130  away from the first base substrate  110 . The electrode  140  can be electrically connected to the drain electrode  133  through a hole  195  in the passivation layer  190 . It can be seen that the gate electrode  131 , the source electrode  132 , and the drain electrode  133  of the thin film transistor  130 , and the electrode  140  are located in different layers. 
     In the biological detection chip provided by the embodiment of the present disclosure, because each detection unit includes a thin film transistor and an electrode, the plurality of detection units can be individually driven by the gate lines provided along the row direction and the data lines provided along the column direction, thereby reducing the number and complexity of the routing of the plurality of detection units. For example, in a case where a biological detection chip has 8*8 detection units, a general biological detection chip needs to be provided with 8*8 signal lines to drive the above 8*8 detection units, respectively; however, the biological detection chip provided in the embodiment of the present disclosure can drive 8*8 detection units by only providing (8+8) or (8+16) signal lines. Therefore, the biological detection chip can reduce the number and complexity of the routing of the plurality of detection units, thereby increasing the density of the plurality of detection units (the area for the routing in a unit area is reduced, and the density of the detection units can be increased), and furthermore achieving flexible control of electrical stimulation and impulse detection at different positions of the biological material to be detected. For example, in a case where the biological material to be detected is a nerve cell, if the density of the plurality of detection units increases, the number of detection units covered by the nerve cell will increase, so that the electrical stimulation and the impulse detection can be performed on more positions of the nerve cell, thereby improving the accuracy of detection. 
     On the other hand, because the gate electrode, the source electrode and the drain electrode, and the electrode are located in different layers, the gate lines and data lines used to drive the plurality of detection units can be disposed at different layers from the electrode, in this case, the orthographic projections of the gate lines and the data lines on the first base substrate is also close to or even overlapped with the orthographic projection of the electrode on the first base substrate. Therefore, the biological detection chip can further increase the density of the plurality of detection units (increasing the number of detection units per unit area), and further improve the degree of flexible control of electrical stimulation and impulse detection at different positions of the biological material to be detected (such as nerve cells). In addition, the biological detection chip can also increase the effective area for culturing and detecting the biological material to be detected, and can avoid the electrical stimulation process of the biological material to be detected from interfering the gate lines and the data lines. 
     For example, in some examples, as illustrated by  FIG. 1 , the biological detection chip further includes a plurality of gate lines  150  and a plurality of data lines  160 ; the plurality of gate lines  150  and the plurality of data lines  160  are intersected (intersected in different layers), each gate line  150  and the gate electrodes  131  of the detection units  120  belonging to the same row are connected and are arranged on the same layer, and each data line  160  and the source electrodes  132  of the detection units  120  belonging to the same row are connected and are arranged on the same layer. 
     For example, in some examples, the gate line  150  may be located on the same layer as the corresponding gate electrode  131 ; the gate line  150  and the gate electrode  131  may also be formed by the same conductive layer through a patterning process. In this case, the gate line  150  and the electrode  140  are disposed in different layers. 
     For example, in some examples, the data line  160  may be located on the same layer as the corresponding source electrode  132 ; for example, the data line  160 , the source electrode  132 , and the drain electrode  133  may be formed by the same conductive layer through a patterning process. In this case, the data lines  160  and the gate lines  150  are disposed in different layers, and the data lines  160  and the electrode  140  are disposed in different layers. 
     For example, in some examples, as illustrated by  FIGS. 1 and 2 , the plurality of detection units  120  include stimulation units  121  and receiving units  122 . The stimulation unit  121  is configured to apply a stimulation voltage, for example, to apply the stimulation voltage to the biological material to be detected through the electrode  140  of the stimulation unit  121 ; the receiving unit  122  is configured to receive an electrophysiological signal, for example, the electrode  140  of the receiving unit  122  receives the electrophysiological signal on the biological material to be detected. Therefore, the biological detection chip can achieve the electrical stimulation and impulse detection of the biological material to be detected through the stimulation unit and the receiving unit, respectively. It should be noted that one stimulation unit and one receiving unit may constitute a detection point, and the detection point corresponds to a position on the biological material to be detected, so that the electrical stimulation and the impulse detection may be performed simultaneously through the detection point on the position of the biological material to be detected; in addition, after the electrophysiological signal received by the receiving unit  122  can be transmitted to the data acquisition system through a corresponding data line, and is subjected to signal processing processes such as amplification, the processed electrophysiological signal can be recorded or analyzed. 
     For example, in some examples, as illustrated by  FIG. 1 , in the process of the electrical stimulation and impulse detection of the biological material to be detected, in order to avoid mutual interference between the applied stimulation voltage and the detected electrophysiological signal, the stimulation units  121  and the receiving units  122 , which belong to the same column, can be driven by different data lines. That is, for the detection units  120  belonging to the same column, the data lines  160  may include a first data line  161  and a second data line  162 , and the first data line  161  is connected to the source electrodes  132  of the receiving units  122  in the same column, and the second data line  162  is connected to the sources electrodes  132  of the stimulation units  121  in the same column. Of course, the embodiments of the present disclosure include, but are not limited thereto, the stimulation units  121  and the receiving units  122 , which belong to the same column, may be driven by the same data line in a time-sharing driving manner. 
     For example, in some examples, in a case where the stimulation units  121  and the receiving units  122 , which belong to the same column, can adopt different data lines, in order to avoid mutual interference of the signal on the first data line  161  and the signal on the second data line  162  and to facilitate the wiring of the first data line  161  and the second data line  162 , the first data line  161  and the second data line  162  may be respectively disposed on two sides of the detection units  120  in the same column, that is, the first data line  161  may be disposed on a left side of the detection units  120  in the same column, and the second data line  162  may be disposed on a right side of the detection units  120  in the same column. In this case, in the column direction, the stimulation units  121  and the receiving units  122  are alternately disposed, and the thin film transistor  130  of the stimulation unit  121  is disposed corresponding to the first data line  161 , and the thin film transistor  130  of the receiving unit  122  is disposed corresponding to the second data line  162 . 
     For example, in some examples, as illustrated by  FIG. 1 , in the row direction, the stimulating units  121  and the receiving units  122  are alternately arranged, and one stimulation unit  121  and one receiving unit  122 , which are adjacent, are axisymmetric with respect to a separation line between the one stimulation unit  121  and the one receiving unit  122 , which are adjacent, which can be conducive to ameliorating the wiring of the first data line  161  and the second data line  162  and reducing the manufacturing difficulty of the biometric detection chip. 
     For example, in some examples, as illustrated by  FIG. 1 , in the row direction, the stimulation units  121  and the receiving units  122  are alternately arranged, and in the column direction, the stimulation units  121  and the receiving units  122  are alternately arranged. Two stimulation units  121  and two receiving units  122  constitute a detection point  125 , in the detection point  125 , the orthographic projections of the two stimulation units  121  on the first base substrate  110  and the orthographic projections of the two receiving units  122  on the first base substrate  110  form a 2*2 matrix. Thus, two stimulation units  121  and two receiving units  122  are provided in each detection point  125 , and the two stimulation units  121  are distributed at two ends of a diagonal of the 2*2 matrix described above, so that in a case where the biological material to be detected does not completely cover the detection point  125 , the two stimulation units  121  can stimulate the biological material to be detected on the detection point  125 ; in addition, the two receiving units  122  are distributed at two ends of the diagonal of the 2*2 matrix described above, so that the electrophysiological signal of the biological material to be detected on the detection point  125  can be detected by the two receiving units  122  in a case where the biological material to be detected does not completely cover the detection point  125 . 
     Because the size of the area covered by the dendritic of a normal nerve cell is greater than 30 microns, and the width of the axon and myelin sheath is greater than 5 microns, in some examples, as illustrated by  FIG. 1 , the orthographic projection of the detection point  125  on the first base substrate  110  is substantially a rectangle, and a side length of the rectangle ranges from 4 to 6 microns. Therefore, the biological detection chip provided in this example can better match the size of the axon of the nerve cell, and thus can better achieve the flexible control of the electrical stimulation and impulsive signal capture position of the adherent nerve cells. 
     For example, in the detection point  125 , the orthographic projection of the electrode  140  in each detection unit  120  on the first base substrate  110  may also be a rectangle, and the side length of the rectangle ranges from 1.5 to 2.5 microns. For example, the side length of the rectangle is approximately 2 microns. The distance between adjacent detection units  120  is approximately 1 micron. 
     For example, in some examples, the first base substrate  110  is made of a transparent insulating material, such as an inorganic material such as glass or quartz or an organic material such as polyvinyl chloride or polycarbonate. Therefore, in a case where the biological detection chip performs detection, it is conducive to observing the biological material to be detected using a device such as a microscope. 
     For example, in some examples, the electrode  140  may be made of a transparent metal oxide material, such as Indium Tin Oxide. Of course, the embodiments of the present disclosure include, but are not limited thereto, the electrode  140  may also be made of other materials, such as metal materials such as gold and platinum. 
       FIG. 3  is a schematic diagram of performing detection by a biological detection chip according to an embodiment of the present disclosure. As illustrated by  FIG. 3 , the biological material to be detected is nerve cells  900 ; the nerve cells  900  include a first nerve cell  910  and a second nerve cell  920 . As illustrated by  FIG. 3 , the nerve cells  900  include a stimulation position  901  and a receiving position  902 ; the detection units  120  covered by the nerve cells  900  include a first detection point  1251  located at the stimulation position  901  of the nerve cells  900  and a second detection point  1252  located at the receiving position  902  of the nerve cells  900 . Therefore, the electrical stimulation can be applied to the stimulation position  901  of the nerve cells  900  through the first detection point  1251 ; and the electrophysiological signal at the receiving position  902  of the nerve cells  900  can be received by the second detection point  1252 , so that the electrical stimulation and impulse detection can be performed on the nerve cells. It should be noted that the above-mentioned receiving position is a position for detecting impulse, so the receiving position may include a plurality of positions at the same time. For example, as illustrated by  FIG. 3 , the receiving position  902  may include a first receiving position  9021 , a second receiving position  9022 , a third receiving position  9023 , a fourth receiving position  9024 , and a fifth receiving position  9025 . In addition, the above-mentioned first detection point  1251  may be a single detection unit, or a detection point composed of one stimulation unit and one receiving unit, or a detection point composed of two stimulation units and two receiving units, the embodiments of the present disclosure include but are not limited thereto. 
     For example, as illustrated by  FIG. 3 , the stimulation position  901  may be a dendrite of the first nerve cell  910 , and the receiving position  902  may be an axon or a myelin sheath (for example, the first receiving position  9021 , the second receiving position  9022 , and the third receiving position  9023 ) of the first nerve cell  910 , or the axon or myelin (e.g., fourth receiving position  9024  and fifth receiving position  9025 ) of the second nerve cell  920 . 
     An embodiment of the present disclosure also provides a biological detection device.  FIG. 4  is a schematic cross-sectional view of a biological detection device according to an embodiment of the present disclosure. As illustrated by  FIG. 4 , the biological detection device includes the biological detection chip provided by any one of the above embodiments. Therefore, the biological detection device can reduce the number and complexity of the routing of the plurality of detection units, thereby increasing the density of the plurality of detection units (the area for the routing in a unit area is reduced, and the density of the detection units can be increased), and furthermore achieving flexible control of electrical stimulation and impulse detection at different positions of the biological material to be detected and improving the accuracy of the detection. In addition, the biological detection device can also increase the effective area for culturing and detecting the biological material to be detected, and can avoid the electrical stimulation process of the biological material to be detected from interfering the gate lines and the data lines. For specific descriptions, reference may be made to the related descriptions of the biological detection chip. 
     For example, in some examples, as illustrated by  FIG. 4 , the biological detection device further includes an opposite substrate  200 , which is cell-assembled with the biological detection chip  100  to form a culture cavity  300  between the biological detection chip  100  and the opposite substrate  200 . The culture cavity  300  can be used for culturing the biological material to be detected, and provides certain life-sustaining conditions, thereby making the biological detection device more suitable for detecting and analyzing the biological materials. 
     For example, in a case where the biological material to be detected is a nerve cell, a phosphate buffer saline (PBS) can be added to the culture cavity. The PBS is the most widely used buffer solution in the biochemical research. 
     For example, the size of the culture cavity  300  in a direction perpendicular to the biological detection chip  100  is approximately 30 micrometers. 
     For example, in some examples, as illustrated by  FIG. 4 , the opposite substrate  200  includes a second base substrate  210 , a breathable film  220 , and a cover plate  230 ; the breathable film  220  is located on a side of the second base substrate  210  away from the biological detection chip  100 , the cover plate  230  is located on a side of the breathable film  220  away from the second base substrate  210 . The cover plate  230  and the breathable film  220  are spaced apart to form a gas channel  400  between the cover plate  230  and the breathable film  220 . A vent hole  212  is formed in the second base substrate  210 , and an orthographic projection of the vent hole  212  on the second base substrate  210  is located within an orthographic projection of the gas channel  400  on the second base substrate  210 . Therefore, the vent hole  212  can introduce the gas in the gas channel  400  into the culture cavity  300 . Thus, by adjusting the concentrations of different gases in the gas channel  400 , the type and concentration of the gas in the culture cavity  300  can be controlled to detect the influence on the biological material to be detected under the gas. For example, in a case where the biological material to be detected is a nerve cell, the damage of the conduction ability of the nerve cell in a hypoxic environment can be detected by adjusting the concentration of oxygen in the gas channel  400 . 
     For example, in some examples, the second base substrate  210  is made of a transparent insulating material, such as an inorganic material such as glass or quartz or an organic material such as polyvinyl chloride or polycarbonate. Therefore, in a case where the biological detection device performs detection, it is conducive to observing the biological material to be detected using a device such as a microscope. 
     For example, the vent hole  212  may be formed by an etching process. 
     For example, in some examples, the material of the breathable film  220  may include polydimethylsiloxane (PDMS), and the breathable film  220  is bonded to the second base substrate  210  through a plasma process. 
       FIG. 5  is a schematic diagram of another biological detection device according to an embodiment of the present disclosure. As illustrated by  FIG. 5 , the biological detection device includes a plurality of support members  500 , which are located between the biological detection chip  100  and the opposite substrate  200  and are disposed around the plurality of detection units  120 . The plurality of support members  500  are disposed at intervals to form a liquid flow channel  600  that is between the adjacent support members  500  and is in communication with the culture cavity  300 . Various liquid reagents, such as the aforementioned PBS, can be introduced into the culture cavity  300  through the liquid flow channel  600 . 
     For example, the orthographic projection of the support member  500  on the second base substrate  210  may be a square with a side length of about 1 mm. The distance between adjacent support members  500  may range from 150 to 250 microns, such as 200 microns. 
     For example, in some examples, as illustrated by  FIG. 5 , the biological detection device further includes a reagent module  700  that communicates with the culture cavity  300  through the liquid flow channel  600 . The reagent module  700  includes at least two reagent reservoirs  710  and a reagent mixing region  720 ; the at least two reagent reservoirs  710  are configured to store different types of detection reagents, and the reagent mixing region  720  is configured to mix different types of detection reagents. 
     For example, as illustrated by  FIG. 5 , the reagent module  700  includes five reagent reservoirs  710 , and the five reagent reservoirs  710  includes a first reagent reservoir  711 , a second reagent reservoir  712 , a third reagent reservoir  713 , a fourth reagent reservoir  714 , and a fifth reagent reservoir  715 . Any one of the five reagent reservoirs  710  can be used to add the PBS to the culture cavity  300 , and the other reagent reservoirs  710  can be used to add other detection reagents. 
     For example, in a case where the biological material to be detected is a nerve cell, the PBS can be added to the culture cavity  300  through the first reagent reservoir  711 , and then dopamine is added to the culture cavity  300  through the second reagent reservoir  712 , thereby detecting the influence of the dopamine on the conduction ability of the nerve cell. For example, the influences of different concentrations of dopamine on the conduction ability of nerve cell can be detected by controlling the ratio of dopamine and PBS. Of course, the detection reagents in the embodiments of the present disclosure include, but are not limited to dopamine, and the type and concentration of the specific detection reagent can be selected according to actual conditions. 
     For example, the reagent module may also be formed with two substrates facing each other, thereby forming the at least two reagent reservoirs and the reagent mixing region described above; in this case, the two substrates may be integrally formed with the biological detection chip and the opposite substrate, respectively. Of course, the embodiments of the present disclosure include, but are not limited thereto, the reagent module may also be a separate module, as long as the reagent module is in communication with the culture cavity through the liquid flow channel. 
     For example, in some examples, as illustrated by  FIG. 5 , the reagent mixing region  720  further includes a fish-bone mixing structure  725 . Of course, the embodiments of the present disclosure include, but are not limited thereto, the reagent mixing region may also adopt other kinds of mixing structures. 
     For example, in some examples, as illustrated by  FIG. 5 , the biological detection device further includes a liquid outlet  800  for discharging the liquid in the culture cavity  300 . 
     An embodiment of the present disclosure also provides a biological detection method of a biological detection device.  FIG. 6  is a flowchart of a biological detection method of a biological detection device according to an embodiment of the present disclosure. The biological detection device may also be any one of the biological detection devices described in the above embodiments. As illustrated by  FIG. 6 , the biological detection method includes the following steps S 301 -S 304 . 
     Step S 301 : cultivating the biological material to be detected on the electrode on the biological detection chip, the biological material to be detected covering at least part of the detection units. 
     For example, the biological material to be detected may be nerve cells; due to the randomness of adherent growth of nerve cells, the synaptic connection manners and growth positions of different nerve cells are very different; and the connection manner between nerve cells in each cell culture is also random. Therefore, the nerve cells cultured on the electrodes of the detection units arranged in an array will randomly cover at least part of the detection units. In this case, even if the adherent growth of nerve cells is random, the cultured nerve cells can be observed through a microscope or the like, and then the electrical stimulation and impulse detection are performed on the nerve cells through the detection units covered by the nerve cells. 
     Step S 302 : cell-assembling the biological detection chip and the opposite substrate. 
     For example, in a case where the biological material to be detected is a nerve cell, after the biological activity of the nerve cell is basically stable and communication between different nerve cells is established, the biological detection chip and the opposite substrate can be pair-boxed. 
     Step S 303 : introducing a detection reagent into the culture cavity. 
     For example, in a case where the biological material to be detected is a nerve cell, the PBS and other detection reagents, such as dopamine, can be added to the culture cavity to detect the influence of dopamine on the conduction ability of nerve cells. Of course, the detection reagents in the embodiments of the present disclosure include, but are not limited to dopamine, and the type and concentration of the specific detection reagent can be selected according to actual conditions. 
     Step S 304 : using the detection units covered by the biological material to be detected to detect an influence of the detection reagent on the biological material to be detected. 
     In the biological detection method provided by the embodiment of the present disclosure, a biological material to be detected may be cultured on an electrode on a biological detection chip, and then the detection units covered by the biological material to be detected is used to detect the influence of the detection reagent on the biological material to be detected. Because each detection unit includes a thin film transistor and an electrode, the plurality of detection units can be individually driven by the gate lines provided along the row direction and the data lines provided along the column direction, thereby reducing the number and complexity of routing of the plurality of detection units. Thus, the biological detection method can increase the density of the plurality of detection units (the area for routing in a unit area is reduced, and the density of the detection units can be increased), and furthermore achieve flexible control of electrical stimulation and impulse detection at different positions of the biological material to be detected. For example, in a case where the biological material to be detected is a nerve cell, if the density of the plurality of detection units increases, the number of detection units covered by the nerve cells increases, so that electrical stimulation and impulse detection can be performed on more positions of the nerve cells, thereby improving the accuracy of detection. 
     On the other hand, because the gate electrode, the source electrode and the drain electrode, and the electrode are located in different layers, the gate lines and the data lines for driving the plurality of detection units may be disposed at different layers from the electrode, and in this case, the orthographic projections of the gate lines and the data lines on the first base substrate is also close to or even overlapped with the orthographic projection of the electrode on the first base substrate. Thus, the biological detection method can further increase the density of the plurality of detection units (increasing the number of detection units per unit area), and further improve the degree of flexible control of electrical stimulation and impulse detection at different positions of the biological material to be detected (such as nerve cells). In addition, the biological detection method can also increase the effective area for culturing and detecting the biological material to be detected, and can avoid the electrical stimulation process of the biological material to be detected from interfering the gate lines and the data lines. 
     For example, detection reagents with different types and/or different concentrations can be introduced into the culture cavity, so that the detection units covered by the biological material to be detected can be used to detect the influence of the detection reagents with the different types and/or different concentrations on the biological material to be detected. 
     For example, in some examples, the detection units covered by the biological material to be detected include a first detection point located at a stimulation position of the biological material to be detected and a second detection point located at a receiving position of the biological material to be detected, using the detection units covered by the biological material to be detected to detect an influence of the detection reagent on the biological material to be detected comprises: applying electrical stimulation to the stimulation position of the biological material to be detected by the first detection point; and receiving an electrophysiological signal at the receiving position of the biological material to be detected by the second detection point. For a specific detection process, reference may be made to the related description of  FIG. 3 , and details are not described herein again. 
     For example, the first detection point may include at least one of the above-mentioned detection units, and the second detection point may include at least one of the above-mentioned detection units. That is, the above-mentioned first detection point may be a single detection unit, or a detection point formed by one stimulation unit and one receiving unit, or a detection point formed by two stimulation units and two receiving units. Embodiments of the present disclosure include but are not limited thereto. 
     For example, in some examples, the biological detection device may use a biological detection device as illustrated by  FIG. 4 . As illustrated by  FIG. 4 , in the biological detection device, the opposite substrate  200  includes: a second base substrate  210 , a breathable film  220  located on a side of the second base substrate  210  away from the biological detection chip  110 ; and a cover plate  230  located on a side of the breathable film  220  away from the second base substrate  210 . The cover plate  230  and the breathable film  220  are spaced apart to form a gas channel  400  between the cover plate  230  and the breathable film  220 , and the second base substrate  210  is provided with a vent hole  212 , and an orthographic projection of the vent hole  212  on the second base substrate  210  is located within an orthographic projection of the gas channel  400  on the second base substrate  210 . Therefore, the vent hole  212  can introduce the gas in the gas channel  400  into the culture cavity  300 . In this case, the biological detection method further includes: introducing gases (for example, gases of different types and/or different concentrations) into the gas channel; and detecting the influence of the gases on the biological material to be detected by using the detection units covered by the biological material to be detected. 
     For example, in a case where the biological material to be detected is a nerve cell, the damage of the conduction ability of the nerve cell in a hypoxic environment can be detected by adjusting the concentration of oxygen in the gas channel  400 . 
     For example, in some examples, the detection units covered by the biological material to be detected include a first detection point located at a stimulation position of the biological material to be detected and a second detection point located at a receiving position of the biological material to be detected, and using the detection units covered by the biological material to be detected to detect the influence of the gas on the biological material to be detected comprises: applying electrical stimulation to the stimulation position of the biological material to be detected by the first detection point; and receiving an electrophysiological signal at the receiving position of the biological material to be detected by the second detection point. For a specific detection process, reference may be made to the related description of  FIG. 3 , and details are not described herein again. 
     For example, the first detection point may include at least one of the above-mentioned detection units, and the second detection point may include at least one of the above-mentioned detection units. That is, the above-mentioned first detection point may be a single detection unit, or a detection point formed by one stimulation unit and one receiving unit, or a detection point formed by two stimulation units and two receiving units. Embodiments of the present disclosure include but are not limited thereto. For example, in some examples, the biological detection method further includes: acquiring an image of the biological material to be detected on the biological detection chip; determining, according to the image, the detection units covered by the biological material to be detected and a positional relationship between the detection units and the biological material to be detected; determining the first detection point and the second detection point according to the positional relationship between each of the detection units and the biological material to be detected. For example, the image of the biological material to be detected on the biological detection device may be acquired through a microscope or an image sensor. 
     For example, in some examples, the biological material to be detected comprises at least one nerve cell, the stimulation position of the biological material to be detected comprises a dendrite of a nerve cell, and the receiving position of the biological material to be detected comprises an axon or a myelin sheath of a nerve cell at the stimulation position, or an axon or a myelin sheath of another nerve cell connected to the nerve cell at the stimulation position. 
     For example, the biological material to be detected is nerve cells; the nerve cells include a first nerve cell and a second nerve cell that are in communicate with each other. The nerve cells include a stimulation position and a receiving position; the stimulation position may be a dendrite of the first nerve cell, and the receiving position may be an axon or myelin sheath of the first nerve cell, or an axon or myelin sheath of the second nerve cell 
     The following statements should be noted: 
     (1) The accompanying drawings involve only the structure(s) in connection with the embodiment(s) of the present disclosure, and other structure(s) can be referred to common design(s). 
     (2) In case of no conflict, features in one embodiment or in different embodiments can be combined. 
     What have been described above are only specific implementations of the present disclosure, the protection scope of the present disclosure is not limited thereto. Any modifications or substitutions easily occur to those skilled in the art within the technical scope of the present disclosure should be within the protection scope of the present disclosure. Therefore, the protection scope of the present disclosure should be based on the protection scope of the claims.