CN111521546A - Cell sensor array and cell detection chip - Google Patents
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Abstract
The invention provides a cell sensor array and a cell detection chip, and belongs to the technical field of biochips. The invention provides a cell sensor array which comprises a substrate, a plurality of cell sensors, a plurality of scanning lines and a plurality of reading lines. The cell sensors are distributed on the substrate in an array mode, the scanning lines are arranged on the substrate and extend along a first direction, each scanning line is connected with one row of cell sensors, the reading lines are arranged on the substrate and extend along a second direction, and each scanning line is connected with one column of cell sensors. Because each cell sensor is connected through many scanning lines and the mode of many reading lines, consequently can read the current signal on the cell sensor in real time to can reduce the lead wire that cell sensor array connects the external circuit board, and then be favorable to realizing integrating of cell sensor array.
Description
Technical Field
The invention belongs to the field of biochips, and particularly relates to a cell sensor array and a cell detection chip.
Background
The cell sensor is a kind of biosensor, because the ion concentration of the cell is different under different states (such as growth, transfer, death, etc.), the cell sensor can detect different current signals, can detect the state of the cell through the change of the current signals, can be used for studying the phenomena of cell growth, transfer, death, etc., or is used for testing the signal transmission between cells.
However, in the related art, the cell sensor needs to be connected to a peripheral circuit board (e.g., a driving circuit board) through a large number of leads for detection, and thus occupies a large space and is difficult to integrate.
Disclosure of Invention
The present invention is directed to at least one of the technical problems of the prior art, and provides a cell sensor array, which can read a current signal of a cell sensor in real time, and reduce the number of leads connecting the cell sensor array to an external circuit board, thereby facilitating the integration of the cell sensor array.
The technical scheme adopted for solving the technical problem of the invention is a cell sensor array, which comprises:
a substrate;
a plurality of cell sensors distributed in an array on the substrate;
the scanning lines are arranged on the substrate, extend along a first direction and are connected with one row of the cell sensors;
and a plurality of readout lines disposed on the substrate, the plurality of readout lines extending along a second direction, each readout line being connected to one of the columns of the cell sensors.
When the cell sensor array provided by the invention is used for detecting a cell sample, the cell sample can cause the current change of at least part of cell sensors in the cell sensor array, each row of scanning lines are sequentially scanned, each scanning line is conducted with one row of cell sensors corresponding to the scanning line, each reading line reads out the current signal of each cell sensor in one row of currently conducted cell sensors, the state of a cell can be detected through the current signal, and the cell sensor array is connected with each cell sensor in a mode of a plurality of scanning lines and a plurality of reading lines, so that the detection signal (namely the current signal) is quickly read, the cell sample can be detected in real time, the number of leads of the cell sensor array connected with an external circuit board can be reduced, and the integration of the cell sensor array is facilitated.
Preferably, each of the cell sensors includes a detection unit and a thin film transistor; wherein the content of the first and second substances,
the detection unit is connected with the source electrode of the thin film transistor; the scanning line is connected with the drain electrode of the thin film transistor; the reading line is connected with the source electrode of the thin film transistor.
Preferably, the method further comprises the following steps: a plurality of alternating voltage lines; the detection unit comprises a first electrode and a second electrode; wherein the content of the first and second substances,
the plurality of alternating voltage lines are connected with the second electrodes in the detection units and apply alternating voltages to the second electrodes;
the first electrode is connected with the source electrode of the thin film transistor.
Preferably, the first electrode and the second electrode are comb-shaped; wherein the content of the first and second substances,
the first electrode has a plurality of first conductive fingers, the second electrode has a plurality of second conductive fingers, and the plurality of first conductive fingers and the plurality of second conductive fingers are alternately arranged.
Preferably, in each of the detection units, a first insulating structure is provided between the first electrode and the second electrode.
Preferably, any adjacent cell sensors have a second insulating structure therebetween.
Correspondingly, the invention also provides a cell detection chip comprising the cell sensor array.
Preferably, the method further comprises the following steps:
a scanning line driving unit connected to the plurality of scanning lines, for inputting a scanning signal to the scanning lines;
the time sequence control unit is connected with the scanning line driving unit and is used for inputting time sequence signals to the scanning line driving unit;
and a storage unit connected to the plurality of readout lines and configured to store the detection signal of the cell sensor read by each readout line.
Preferably, the plurality of scanning lines are connected with the scanning line driving unit through a chip on film; the reading lines are connected with the storage unit through a chip on film.
Preferably, the method further comprises the following steps: and the calculation unit is connected with the storage unit and is used for calculating the impedance value of the cell detected by the cell sensor according to the detection signal in the storage unit.
Drawings
FIG. 1 is a schematic structural diagram of an embodiment of a cell sensor array provided in this embodiment;
fig. 2 is a schematic structural diagram (specific structure) of an embodiment of the cell sensor array provided in this embodiment;
fig. 3 is a schematic structural diagram of a single cell sensor in the cell sensor array provided in this embodiment;
fig. 4 is a schematic structural diagram of a first electrode and a second electrode in the cell sensor array provided in this embodiment;
FIG. 5 is a cross-sectional view (along the direction of FIGS. 3A-B) of a cell sensor in the cell sensor array provided in the present embodiment;
FIG. 6 is a graph showing the relationship between the current signal on the first electrode of the cell sensor array according to this embodiment and the voltage variation;
fig. 7 is an electric field distribution diagram of an electric field between the first conductive finger and the second conductive finger in the cell sensor array provided in the present embodiment;
FIG. 8 is a schematic diagram illustrating detection of a control group disposed in the cell sensor array provided in this embodiment;
FIG. 9 is a schematic structural diagram of an embodiment of a cell detection chip provided in this embodiment;
FIG. 10 is a graph showing complex impedance values of cells in a cell sample in the cell assay chip according to this embodiment at different times during growth.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention clearer, the present invention will be described in further detail with reference to the accompanying drawings, and it is obvious that the described embodiments are only some embodiments of the present invention, not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The shapes and sizes of the various elements in the drawings are not to scale and are merely intended to facilitate an understanding of the contents of the embodiments of the invention.
Unless otherwise defined, technical or scientific terms used herein shall have the ordinary meaning as understood by one of ordinary skill in the art to which this disclosure belongs. The use of "first," "second," and similar terms in this disclosure is not intended to indicate any order, quantity, or importance, but rather is used to distinguish one element from another. Also, the use of the terms "a," "an," or "the" and similar referents do not denote a limitation of quantity, but rather denote the presence of at least one. The word "comprising" or "comprises", and the like, means that the element or item listed before the word covers the element or item listed after the word and its equivalents, but does not exclude other elements or items. The terms "connected" or "coupled" and the like are not restricted to physical or mechanical connections, but may include electrical connections, whether direct or indirect. "upper", "lower", "left", "right", and the like are used merely to indicate relative positional relationships, and when the absolute position of the object being described is changed, the relative positional relationships may also be changed accordingly.
The transistors used in the embodiments of the present invention may be thin film transistors or field effect transistors or other devices with the same characteristics, and since the source and the drain of the transistors used are symmetrical, there is no difference between the source and the drain. In the embodiment of the present invention, to distinguish the source and the drain of the transistor, one of the poles is referred to as a first pole, the other pole is referred to as a second pole, and the gate is referred to as a control pole. In addition, the transistors can be divided into an N type and a P type according to the characteristics of the transistors, and in the following embodiment, a P type transistor is used for description, when the P type transistor is adopted, a first electrode is a source electrode of the P type transistor, a second electrode is a drain electrode of the P type transistor, and when a low level is input to a grid electrode, the source electrode and the drain electrode are conducted; when an N-type transistor is adopted, the first electrode is the source electrode of the N-type transistor, the second electrode is the drain electrode of the N-type transistor, and when the grid electrode inputs a high level, the source electrode and the drain electrode are conducted. It is contemplated that an implementation using N-type transistors will be readily apparent to one skilled in the art without inventive effort and, thus, is within the scope of the embodiments of the present invention.
It should be noted that, in the embodiment of the present invention, for example, all the transistors are P-type transistors, the working level refers to an effective level for turning on the P-type transistors, that is, a low level, and the non-working level refers to a high level. The initial control signal in the embodiment of the present invention is a fixed working level, that is, a fixed low level signal.
As shown in fig. 1, the present embodiment provides a cell sensor array including a substrate 1, a plurality of cell sensors 2, a plurality of scan lines 3, and a plurality of read lines 4.
Specifically, referring to fig. 1, a plurality of cell sensors 2 are distributed in an array on a substrate 1. A plurality of scan lines 3 are disposed on the substrate 1, the plurality of scan lines 3 extend in a first direction, and each scan line 3 is connected to a row of the cell sensors 2. A plurality of readout lines 4 are disposed on the substrate 1, the plurality of readout lines 4 extend along the second direction, and each readout line 4 is connected to one column of the cell sensors 2. The first direction may be, for example, a row direction parallel to the arrangement direction of the cell sensors 2 in each row in the cell sensors 2 arranged in an array, and the second direction may be, for example, a column direction parallel to the arrangement direction of the cell sensors 2 in each column in the cell sensors 2 arranged in an array. When the first direction is a row direction and the second direction is a column direction, the first direction and the second direction are approximately perpendicular or perpendicular to each other, and the first direction is the row direction and the second direction is the column direction in the embodiment of the present disclosure.
In the cell sensor array provided in this embodiment, when detecting a cell sample, the cell sample causes a current change of at least some of the cell sensors 2 in the cell sensor array, sequentially scans the scanning lines 3, each scanning line 3 turns on the corresponding cell sensor 2 in one row, and causes each reading line 4 to read out a current signal of each cell sensor 2 in the currently turned on row, and the state of the cell in the cell sample can be detected by the current signal, for example, the impedance of the cell can be calculated by the current signal caused by the cell sample, and the cell behavior (e.g., metastasis, growth, death, etc.) can be observed by the impedance of the cell, since each cell sensor 2 is connected by the plurality of scanning lines 3 and the plurality of reading lines 4, the detection signal (i.e., the current signal/voltage signal) on the cell sensor 2 can be rapidly read by high-frequency scanning, using the detection signal as the current signal below) to detect the cell sample in real time, and comparing the way that each cell sensor needs to independently set up many leads to link to each other with the external circuit board, because adopt scanning line 3 to connect a line of cell sensor 2, the way that line 4 of reading connects a column of cell sensor 2, therefore can significantly reduce the number of leads (e.g. scanning line 3 and reading line 4) that the cell sensor array needs to connect the external circuit board, thereby be favorable to realizing the integration of cell sensor array.
Alternatively, as shown in fig. 2, 3 and 5, fig. 5 is a sectional view taken along a direction a-B in fig. 3. Each cell sensor 2 may include a detection cell 21 and a Thin Film Transistor (TFT) 22, the detection cell 21 being disposed on a side of the TFT 22 facing away from the substrate. The thin film transistor 22 may include a gate (gate)221 disposed on the substrate 1, and an Active (Active) layer 222 disposed on a side of the gate away from the substrate, wherein a Gate Insulating (GI) layer 01 is disposed between the gate 221 and the Active layer 222, a Drain (Drain)223 and a Source (Source)224 are disposed on a side of the Active layer 222 away from the substrate 1, the Drain 223 and the Source 224 are disposed on the same layer, and a Buffer protection (Buffer) layer is disposed on a side of the Drain 223 and the Source 224 away from the substrate 1 to protect the layers of the thin film transistor 22. A flat insulating layer 02 is disposed between the thin film transistor 22 and the detection unit 21, and the flat insulating layer 02 is used for insulating electrical signals between the thin film transistor 22 and the detection unit 21 and planarizing a film layer on the thin film transistor 22. The sensing unit 21 is connected to the thin film transistor 22, and specifically, the sensing unit 21 is connected to the source 224 of the thin film transistor 22 through a Via hole (Via) provided in the flat insulating layer 02, the scanning line 3 is connected to the drain 223 of the thin film transistor 22, the reading line 4 is connected to the source 224 of the thin film transistor 22, the thin film transistor 22 serves as a switching device of the sensing unit 21, when the cell sample is required to be detected, each scanning line 3 is scanned in turn, the scanning line 3 applies a voltage to the drain 223 of the thin film transistor 22 connected thereto, thereby turning on the thin film transistor 22, the readout line 4 connected to the source 224 of the thin film transistor 22 reads out the current signal (i.e., the detection signal of the cell sample) in the detection unit 21 connected to the source 224 of the thin film transistor 22, when the scanning of each scanning line 3 is completed, the current signals in all the cell sensors 2 in the cell sensor array can be read out.
It should be noted that, in the cell sensor array provided in this embodiment, after the thin film transistor 22 is turned on by the scanning line 3, the current signal on the detection unit 21 is read out in real time by the reading line 4, and then a storage capacitor is not required to store the current signal, so that the space occupied by the cell sensor 2 can be reduced.
It should be noted that the structure of the thin film transistor 22 is merely an example, and in the cell sensor array provided in this embodiment, the thin film transistor 22 may be a transistor of various types, for example, an amorphous silicon (a-Si) type thin film transistor, an Indium Gallium Zinc Oxide (IGZO) type thin film transistor, or a low temperature polysilicon type thin film transistor, as long as the thin film transistor can function as a switching device of the detection unit 21, which is not limited herein.
Alternatively, as shown in fig. 2 to 5, the detection unit 21 of the cell sensor 2 may include a first electrode 211 and a second electrode 212, and an electric field is provided between the first electrode 211 and the second electrode 212, and referring to fig. 5, when a cell 001 in the cell sample is positioned in the electric field between the first electrode 211 and the second electrode 212, the electric field is affected, so that a change of a current signal is caused, and the state of the sample cell can be detected by detecting the current signal. Specifically, the cell in the cell sample may attach to the first electrode 211 or the second electrode 212, because the electrical property of the cell is close to the insulator due to the characteristics of the cell membrane, the impedance of the cell may increase with the increase of the coverage area of the cell on the electrode, so that the current on the first electrode 211 and/or the second electrode 212 attached by the cell may change, when the state of the cell changes, such as cell migration or cell death, the current path may change, and thus reading the current signal on the first electrode 211 may calculate the impedance of the cell, and the state of the cell may be detected through the impedance of the cell.
Further, referring to fig. 2, 3 and 6, the cell sensor array provided in this embodiment further includes a plurality of alternating voltage lines 5. The first electrode 211 is connected to the source 224 of the thin film transistor 22, the reading line 4 reads a current signal through the first electrode 211, the plurality of alternating voltage lines 5 are connected to the second electrodes 212 of the respective detecting units 21, and the alternating voltage lines 5 apply an alternating voltage to the second electrodes 212 to detect the cell sample by cyclic voltammetry. Specifically, the alternating voltage line 5 applies a cyclically varying voltage to the second electrode 212, which may vary from a first voltage to a second voltage and then from the second voltage to the first voltage in one cycle, and the first voltage is 0V and the second voltage is 5V, for example, the alternating voltage applied by the alternating voltage line 5 to the second motor 212 is changed to O-5-0V, the cells in the cell sample are attached to the first electrode 211 or the second electrode 212, different ion reactions occur under the action of the alternating voltage, for example, when the alternating voltage is changed from 5V to 0V, the cells generate a reduction reaction to generate a reduction wave, the current signal on the first electrode 211 corresponds to the reduction process, when the alternating voltage is changed from 0V to 5V, the product of the cell reduction reaction may generate an oxidation reaction again on the first electrode 211 and/or the second electrode 212, the oxidation wave is generated, the current signal on the first electrode 211 corresponds to the oxidation process, one reduction and oxidation process is completed by the change of primary voltage (0-5-0V), the change process of alternating voltage line 5 is circulated, the current signal of the cell reduction or oxidation process is read from the first electrode 211 by the reading line 4 at preset time intervals, and the state of the cell can be detected by the cyclic voltammetry.
Alternatively, if the cell measurement is performed by cyclic voltammetry, the material of the first electrode 211 and the second electrode 212 may include at least one of Indium Tin Oxide (ITO), platinum, glassy carbon, graphite, and the like, and is not particularly limited as long as the sensitivity of the first electrode 211 and the second electrode 212 to the cyclic voltammetry is high. Referring to fig. 6, fig. 6 is a graph of a current signal on the first electrode 211 as a function of voltage, and the dotted line in fig. 6 is an upper limit of an alternating voltage in cyclic voltammetry (5V in the 0-5-0V change as described above).
It should be noted that the frequency of scanning the scanning lines 3 may be X times of the voltage change frequency on the alternating voltage lines 5, where X is greater than or equal to the number of the scanning lines 3, that is, when the voltage changes once, it is ensured that one scanning can be completed, and therefore, the current signals on the cell sensors 2 in the cell sensor array can be read out. For example, if the frequency of the voltage change is 10Hz and the cell sensor array has 100 scanning lines 3, the frequency of the scanning may be 1000Hz or more.
Further, the number and arrangement of the alternating voltage lines 5 may be set arbitrarily, and are not limited thereto, as long as the alternating voltage lines 5 are connected to the second electrodes 212 in all the detection units 21, and the same voltage may be applied to all the second electrodes 212 in the cell sensors 2 at the same time, and the alternating voltage lines 4 need to apply the same voltage to all the second electrodes 212 at the same time, so that the voltages on the cell sensors 2 are changed identically. For example, the alternating voltage lines 5 may be arranged in parallel with the readout lines 4, and one alternating voltage line 5 is connected to the second electrodes 212 in one column of the cell sensors 2.
Alternatively, the first electrode 211 and the second electrode 212 may adopt the same structure, and the first electrode 211 and the second electrode 212 may be electrodes of various shapes, such as an interdigital electrode, or a ring electrode, which is not limited herein. The following description will take the first electrode 211 and the second electrode 212 as interdigital electrodes, that is, the first electrode 211 and the second electrode 212 are comb-shaped structures as an example.
Specifically, referring to fig. 3 to fig. 5, the first electrode 211 and the second electrode 212 in the detecting unit 21 are in a comb-like structure, wherein the first electrode 211 has a plurality of first conductive fingers 2111, the second electrode 212 has a plurality of second conductive fingers 2121, the plurality of first conductive fingers 2111 and the plurality of second conductive fingers 2121 are alternately arranged, and the distance between adjacent first conductive fingers 2111 and second conductive fingers 2121 can be as close as possible to reduce the influence of external factors on the detection result. For example, the first electrode 211 has 14 first conductive fingers 2111, the second electrode 212 has 14 second conductive fingers 2121, the first conductive finger 2111 has a length of 500um, a width of 20um and a height of 1um, the structure of the second conductive finger 2121 is approximately the same as that of the first conductive finger 2111, the distance between the adjacent first conductive finger 2111 and second conductive finger 2121 is 30um, and the area of the detection unit 21 is 0.7x1 mm. Referring to fig. 7, fig. 7 is an electric field distribution diagram of an electric field between the first conductive finger 2111 of the first electrode 211 and the second conductive finger 2121 of the second electrode 212, wherein the left ordinate and the abscissa respectively represent the distance between the two conductive fingers, and it can be seen from the figure that the electric field is mainly distributed in a range within 20um between the two conductive fingers, which is highly similar to the attachment range of the cell in the cell sample between the first electrode 211 and/or the second electrode 212, so that measuring the current signal on the first electrode 211 can effectively measure the impedance of the cell.
Alternatively, as shown in fig. 5, in the detection unit 21 of each cell sensor 2 in the cell sensor array, the first electrode 211 and the second electrode 212 have the first insulating structure 6 therebetween, and the first insulating structure 6 is disposed on the side of the flat insulating layer 02 facing away from the substrate 1, specifically, the first insulating structure 6 is disposed between the adjacent first conductive finger 2111 and the second conductive finger 2121 to prevent the two from being shorted, and noise of the detection signal can be reduced.
Further, as shown in fig. 5, between any adjacent cell sensors 2 in the cell sensor array, there is a second insulating structure 7 to prevent signal crosstalk between the adjacent cell sensors 2. The second insulating structure 7 is arranged on one side, away from the substrate 1, of the flat insulating layer 02, the thickness of the second insulating structure 7 is larger than that of the first insulating layer 6, the second insulating structure 7 is arranged around the periphery of the detection unit 21, and the second insulating structure 7 defines a detection area to contain a cell sample to be detected, so that the cell sample is detected by the detection unit 21 in the detection area.
Further, the material of the first insulating structure 6 and/or the second insulating structure 7 may include polyimide or the like.
Alternatively, referring to fig. 8, the cell sample at least includes a cell culture solution, and cells in the cell culture solution, and in order to eliminate errors caused by the cell culture solution when performing cell detection, a control group of the cell culture solution needs to be provided for the cell sample to be detected. Taking the example of detecting the cell type P and the cell type K as an example, when the cell sample of the cell type P is P1 and the cell sample P1 is detected by one cell sensor 2 in the cell sensor array, the cell culture solution P2 containing no impurities may be provided in the cell sensor 2 adjacent to the cell sensor 2, and the cell culture solution P2 may be the cell culture solution in the cell sample P1. Similarly, the cell sample of the cell type K is K1, the cell culture solution K2 is provided in the cell sensor 2 adjacent to the cell sensor 2 for detecting the cell sample K1, and the cell culture solution K2 is the cell culture solution in the cell sample K1. By comparing the current signals of the cell sensors 2 corresponding to P1 and P2 with the current signals of the cell sensors 2 corresponding to K1 and K2, the detection error caused by the cell culture solution can be eliminated, and the cell detection result is more accurate.
Alternatively, the substrate 1 may be various types of substrates, such as a glass substrate, a polyimide substrate, a Polydimethylsiloxane (PDMS) substrate, and the like, which are not limited herein.
Correspondingly, the embodiment also provides a cell detection chip, which comprises the cell sensor array.
Alternatively, as shown in fig. 9, the cell detecting new slope provided by the present embodiment further includes a scanning line driving unit (G-IC), a timing control unit (T-CON), and a storage unit C1. T-CON is connected to G-IC, G-IC is connected to multiple scanning lines 3, and memory cell C1 is connected to multiple reading lines 4. The T-CON inputs a timing signal to the G-IC, so that the G-IC sequentially inputs scanning signals to the scanning lines 3 according to a control timing of the timing signal, the scanning lines 3 receiving the scanning signals apply a voltage to the thin film transistors 22 in the cell sensors 2 connected thereto to turn on the detection cells 21, current signals in the detection cells 21 are read out by the reading lines 4 connected to the detection cells 21, and the reading lines 4 store the read current signals (i.e., detection signals of the cell sample) in the storage cells 2 to calculate the impedance of the cells.
Alternatively, a scanning line driving array (GOA) may be used as the driving of the scanning lines 3, and if the GOA is used, the GOA may be disposed on the substrate 1.
Alternatively, as shown in fig. 9, the plurality of scan lines 3 may be connected to the G-IC by a Chip On Flex (COF) method, and the plurality of read lines 4 may also be connected to the memory cell C1 by a COF method.
Accordingly, as shown in FIG. 9, the cell detecting chip may further include an alternating voltage driving (HV) connected to the plurality of alternating voltage lines 5 for inputting the alternating voltage to the alternating voltage lines 5. The alternate voltage line 5 may extend in the extending direction of the reading line 5 (i.e., the second direction) and be connected to the HV through a lead line, the extending direction of which is parallel to the scanning line 3 (i.e., the first direction). The alternating voltage lines 5 can be connected to the HV in the manner of COF.
It should be noted that the scan line 3 may also be connected to the G-IC in other manners, the read line 4 may also be connected to the storage unit C1 in other manners, and the alternating voltage line 5 may be connected to the HV in other manners, for example, may be connected in a plug-in manner, which is not limited specifically.
Optionally, the cell detecting ramp provided by this embodiment may further include a calculating unit (not shown in the figure), and the calculating unit may be connected to the storage unit C1 for detecting the current signal (i.e. the detection signal of the cell sample) from the storage unit C1. After the alternating voltage line 5 applies a cyclic voltage change (for example, a change of 0-5-0V) to the second electrode 212 once, a two-dimensional current signal value of each cell sensor 2 is obtained in the storage unit C1, where two dimensions are the position of the intersection of the corresponding scan line 3 and read line 4, that is, the position of the cell sensor 2 in the cell sensor array, and the complex impedance Z of the cell can be calculated by the following formula:
where ω is the angular frequency of the alternating voltage on the alternating voltage line, θ is the phase delay of the voltage, V is the voltage of the alternating voltage, and I is the current signal read out by the read line. Substituting each current signal value in a group of two-dimensional current signal values obtained after the cyclic voltage change for the calculation to obtain the complex impedance of the cells in the cell sample, and further detecting the states (transfer, growth, death and the like) of the cells.
Referring to fig. 10, fig. 10 is a graph of complex impedance values of cells in a cell sample at different times in a growth state, which are detected by the cell detection chip provided in this embodiment and calculated by the calculation unit, wherein the abscissa is the real part of the complex impedance and the ordinate is the imaginary part of the complex impedance, and the size of the data curve in the graph represents the charge transfer resistance, that is, the size of the impedance value of the cell membrane of the cell through which the surface charge of the first electrode passes, and the longer the time, the smaller the resistance of the cell membrane, and the smallest resistance when the cell is lysed due to cell death. The intercept of the intersection of the data curve with the horizontal axis represents the ease of charge transfer, i.e., the resistance of the cell sample, which gradually decreases over time and becomes the greatest when the cell dies.
It will be understood that the above embodiments are merely exemplary embodiments taken to illustrate the principles of the present invention, which is not limited thereto. It will be apparent to those skilled in the art that various modifications and improvements can be made without departing from the spirit and substance of the invention, and these modifications and improvements are also considered to be within the scope of the invention.
Claims (10)
1. A cell sensor array, comprising:
a substrate;
a plurality of cell sensors distributed in an array on the substrate;
the scanning lines are arranged on the substrate, extend along a first direction and are connected with one row of the cell sensors;
and a plurality of readout lines disposed on the substrate, the plurality of readout lines extending along a second direction, each readout line being connected to one of the columns of the cell sensors.
2. The cell sensor array according to claim 1, wherein each of the cell sensors includes a detection unit and a thin film transistor; wherein the content of the first and second substances,
the detection unit is connected with the source electrode of the thin film transistor; the scanning line is connected with the drain electrode of the thin film transistor; the reading line is connected with the source electrode of the thin film transistor.
3. The cell sensor array of claim 2, further comprising: a plurality of alternating voltage lines; the detection unit comprises a first electrode and a second electrode; wherein the content of the first and second substances,
the plurality of alternating voltage lines are connected with the second electrodes in the detection units and apply alternating voltages to the second electrodes;
the first electrode is connected with the source electrode of the thin film transistor.
4. The cell sensor array of claim 3, wherein the first and second electrodes are comb-like structures; wherein the content of the first and second substances,
the first electrode has a plurality of first conductive fingers, the second electrode has a plurality of second conductive fingers, and the plurality of first conductive fingers and the plurality of second conductive fingers are alternately arranged.
5. The cell sensor array according to claim 2, wherein each of the detection units has a first insulating structure between the first electrode and the second electrode.
6. The cell sensor array of claim 1, wherein a second insulating structure is provided between any adjacent cell sensors.
7. A cell detection chip comprising the cell sensor array according to any one of claims 1 to 6.
8. The cell detection chip according to claim 7, further comprising:
a scanning line driving unit connected to the plurality of scanning lines, for inputting a scanning signal to the scanning lines;
the time sequence control unit is connected with the scanning line driving unit and is used for inputting time sequence signals to the scanning line driving unit;
and a storage unit connected to the plurality of readout lines and configured to store the detection signal of the cell sensor read by each readout line.
9. The cell detection chip according to claim 8, wherein the plurality of scan lines are connected to the scan line driving unit through a chip on film; the reading lines are connected with the storage unit through a chip on film.
10. The cell detection chip according to claim 8, further comprising: and the calculation unit is connected with the storage unit and is used for calculating the impedance value of the cell detected by the cell sensor according to the detection signal in the storage unit.
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Citations (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040110277A1 (en) * | 2002-04-12 | 2004-06-10 | Seiko Epson Corporation | Sensor cell, bio-sensor, capacitance element manufacturing method, biological reaction detection method and genetic analytical method |
| TW200702777A (en) * | 2005-07-07 | 2007-01-16 | Chunghwa Picture Tubes Ltd | Liquid crystal display panel, thin film transistor array substrate and examining method thereof |
| US20070030408A1 (en) * | 2005-08-08 | 2007-02-08 | Kuang-Hsiang Lin | Liquid crystal display panel, thin film transistor array substrate and detection methods therefor |
| CN1981192A (en) * | 2004-05-14 | 2007-06-13 | 拜尔健康护理有限责任公司 | Voltammetric systems for assaying biological analytes |
| US20100270174A1 (en) * | 2006-01-20 | 2010-10-28 | Agency For Science, Technology And Research | Biosensor cell and biosensor array |
| JP2012078180A (en) * | 2010-09-30 | 2012-04-19 | Dainippon Printing Co Ltd | Biosensor |
| CN103412676A (en) * | 2013-07-29 | 2013-11-27 | 合肥京东方光电科技有限公司 | Touch screen and display device. |
| CN105301858A (en) * | 2015-11-06 | 2016-02-03 | 深圳市华星光电技术有限公司 | Display panel, preparation method of display panel and array substrate |
| US20160034745A1 (en) * | 2014-08-01 | 2016-02-04 | General Electric Company | High sensitivity flat panel microbiology detection and enumeration system |
| CN105425486A (en) * | 2015-12-11 | 2016-03-23 | 厦门天马微电子有限公司 | Array substrate and display panel |
| CN105527738A (en) * | 2016-02-17 | 2016-04-27 | 京东方科技集团股份有限公司 | Array substrate, data drive circuit, data drive method and display device |
| CN106047678A (en) * | 2016-05-20 | 2016-10-26 | 江苏大学 | Cell activity detection method and device based on impedance spectroscopy |
| CN106200183A (en) * | 2016-09-27 | 2016-12-07 | 昆山龙腾光电有限公司 | Thin-film transistor array base-plate and manufacture method and display panels |
| CN106405963A (en) * | 2016-10-31 | 2017-02-15 | 厦门天马微电子有限公司 | Array substrate and display panel comprising same |
| CN106462753A (en) * | 2016-08-09 | 2017-02-22 | 深圳信炜科技有限公司 | Biological information sensing device and electronic device |
| CN106970127A (en) * | 2017-03-28 | 2017-07-21 | 扬州大学 | One kind is used for bacterial community signaling molecule detection cell sensor and its preparation method and application |
| CN206400570U (en) * | 2016-08-09 | 2017-08-11 | 深圳信炜科技有限公司 | Biological information sensing device and electronic equipment |
| CN109855657A (en) * | 2019-02-28 | 2019-06-07 | 京东方科技集团股份有限公司 | Signal supervisory instrument and sensor |
| CN110168364A (en) * | 2019-03-27 | 2019-08-23 | 京东方科技集团股份有限公司 | Biological detection chip, biological monitor and its detection method |
| CN110243277A (en) * | 2019-06-28 | 2019-09-17 | 上海天马微电子有限公司 | A kind of array substrate, its driving method and display device |
| CN110568053A (en) * | 2019-08-12 | 2019-12-13 | 浙江大学 | Non-contact type cell membrane potential sensor based on field effect tube sensing structure |
| CN110580434A (en) * | 2018-06-11 | 2019-12-17 | 鸿富锦精密工业（深圳）有限公司 | Array substrate, display panel and display device |
| US20200152141A1 (en) * | 2018-11-13 | 2020-05-14 | Xianyang Caihong Optoelectronics Technology Co.,Ltd | Display panel and display method |
| CN111167531A (en) * | 2020-02-11 | 2020-05-19 | 京东方科技集团股份有限公司 | Detection chip and detection system |
| CN111175367A (en) * | 2020-02-21 | 2020-05-19 | 京东方科技集团股份有限公司 | Biosensor, biomolecule detection circuit and biochip |
-
2020
- 2020-06-15 CN CN202010543207.9A patent/CN111521546B/en active Active
Patent Citations (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040110277A1 (en) * | 2002-04-12 | 2004-06-10 | Seiko Epson Corporation | Sensor cell, bio-sensor, capacitance element manufacturing method, biological reaction detection method and genetic analytical method |
| CN1981192A (en) * | 2004-05-14 | 2007-06-13 | 拜尔健康护理有限责任公司 | Voltammetric systems for assaying biological analytes |
| TW200702777A (en) * | 2005-07-07 | 2007-01-16 | Chunghwa Picture Tubes Ltd | Liquid crystal display panel, thin film transistor array substrate and examining method thereof |
| US20070030408A1 (en) * | 2005-08-08 | 2007-02-08 | Kuang-Hsiang Lin | Liquid crystal display panel, thin film transistor array substrate and detection methods therefor |
| US20100270174A1 (en) * | 2006-01-20 | 2010-10-28 | Agency For Science, Technology And Research | Biosensor cell and biosensor array |
| JP2012078180A (en) * | 2010-09-30 | 2012-04-19 | Dainippon Printing Co Ltd | Biosensor |
| CN103412676A (en) * | 2013-07-29 | 2013-11-27 | 合肥京东方光电科技有限公司 | Touch screen and display device. |
| US20160034745A1 (en) * | 2014-08-01 | 2016-02-04 | General Electric Company | High sensitivity flat panel microbiology detection and enumeration system |
| CN105301858A (en) * | 2015-11-06 | 2016-02-03 | 深圳市华星光电技术有限公司 | Display panel, preparation method of display panel and array substrate |
| CN105425486A (en) * | 2015-12-11 | 2016-03-23 | 厦门天马微电子有限公司 | Array substrate and display panel |
| CN105527738A (en) * | 2016-02-17 | 2016-04-27 | 京东方科技集团股份有限公司 | Array substrate, data drive circuit, data drive method and display device |
| CN106047678A (en) * | 2016-05-20 | 2016-10-26 | 江苏大学 | Cell activity detection method and device based on impedance spectroscopy |
| CN106462753A (en) * | 2016-08-09 | 2017-02-22 | 深圳信炜科技有限公司 | Biological information sensing device and electronic device |
| CN206400570U (en) * | 2016-08-09 | 2017-08-11 | 深圳信炜科技有限公司 | Biological information sensing device and electronic equipment |
| CN106200183A (en) * | 2016-09-27 | 2016-12-07 | 昆山龙腾光电有限公司 | Thin-film transistor array base-plate and manufacture method and display panels |
| CN106405963A (en) * | 2016-10-31 | 2017-02-15 | 厦门天马微电子有限公司 | Array substrate and display panel comprising same |
| CN106970127A (en) * | 2017-03-28 | 2017-07-21 | 扬州大学 | One kind is used for bacterial community signaling molecule detection cell sensor and its preparation method and application |
| CN110580434A (en) * | 2018-06-11 | 2019-12-17 | 鸿富锦精密工业（深圳）有限公司 | Array substrate, display panel and display device |
| US20200152141A1 (en) * | 2018-11-13 | 2020-05-14 | Xianyang Caihong Optoelectronics Technology Co.,Ltd | Display panel and display method |
| CN109855657A (en) * | 2019-02-28 | 2019-06-07 | 京东方科技集团股份有限公司 | Signal supervisory instrument and sensor |
| CN110168364A (en) * | 2019-03-27 | 2019-08-23 | 京东方科技集团股份有限公司 | Biological detection chip, biological monitor and its detection method |
| CN110243277A (en) * | 2019-06-28 | 2019-09-17 | 上海天马微电子有限公司 | A kind of array substrate, its driving method and display device |
| CN110568053A (en) * | 2019-08-12 | 2019-12-13 | 浙江大学 | Non-contact type cell membrane potential sensor based on field effect tube sensing structure |
| CN111167531A (en) * | 2020-02-11 | 2020-05-19 | 京东方科技集团股份有限公司 | Detection chip and detection system |
| CN111175367A (en) * | 2020-02-21 | 2020-05-19 | 京东方科技集团股份有限公司 | Biosensor, biomolecule detection circuit and biochip |
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|---|---|
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