CN110398528A - A kind of antituberculosis drugs screening plant and method based on liquid grid-type IGZO thin film transistor (TFT) - Google Patents
A kind of antituberculosis drugs screening plant and method based on liquid grid-type IGZO thin film transistor (TFT) Download PDFInfo
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Abstract
The present invention discloses a kind of antituberculosis drugs screening plant and method based on liquid grid-type IGZO thin film transistor (TFT), described device includes substrate, the substrate surface and the successively source electrode of laid out in parallel, indium gallium zinc oxygen thin film channel layer and drain electrode are set, the reservoir on the source electrode and drain electrode surface is set, the bottom surface of the reservoir is the indium gallium zinc oxygen thin film channel layer, electrolyte is stored in the reservoir, inserted with gate electrode in the electrolyte, the source electrode, drain electrode and gate electrode are electrically connected same electrical signal detection device.The features such as antituberculosis drugs screening plant provided by the invention has high sensitivity, detection speed fast, and stability is strong, structure is simple low with operating voltage is highly suitable for screening antituberculosis drugs.
Description
Technical field
The present invention relates to field of biosensors more particularly to a kind for the treatment of tuberculosis based on liquid grid-type IGZO thin film transistor (TFT)
Class medicament screening apparatus and method.
Background technique
Tuberculosis is a kind of several chronic diseases as caused by mycobacterium tuberculosis, relatively conventional with pulmonary tuberculosis, is had every year
Millions of people suffers from tuberculosis, is the ninth-largest cause of the death in the whole world.Know from " report of the whole world 2018WHO tuberculosis ", 2017, is estimated to be
10000000 people's new infection tuberculosis: 5,800,000 males, 3,200,000 women, 1,000,000 children, wherein China is estimated to be 88.9 ten thousand people's new infections
Tuberculosis.In addition, drug resistance tuberculosis is the public health crisis more to merit attention, estimate that the whole world in 2017 there are 45.8 ten thousand people to suffer from
Multiple-drug resistance tuberculosis disease (MDR-TB), mycobacterium tuberculosis is to the enhancing of first-line drug drug resistance so that curing becomes very spine
Hand.It, every year can be to avoid millions of people's death, in early diagnosis detection and newly although diagnosis lungy and successful treatment
Very big gap is still had in type medicament research and development compared with expected.
Macrophage is the main parasitic place of mycobacterium tuberculosis, frequently as research object lungy.General tuberculosis
After mycobacteria invades human body, macrophage can be swallowed.Mycobacterium tuberculosis is by preventing the fusion of phagolysosome, dropping
Low macrophage escapes the immunosurveillance and attack of macrophage to approach such as the sensibility of stimulation responses, allows in macrophage
Intracellular survival and proliferation are prepared for new round infection.By understanding the mechanism of macrophage and tubercle bacillus, both may be used
To provide new approaches for prevention and treatment lungy, and help to develop newtype drug.
Efficiently easily drug screening method is the research and development vital ring of newtype drug.Currently used drug screening
Experimental technique has affine flicker detection method (SPA), time-resolved fluorescence Resonance energy transfer detection method (TR-FRET) etc..These
On the one hand detection technique requires more harshness to experiment condition, generally require some specific large-scale experiment equipment and special examination
Agent；Another aspect experimentation is quite cumbersome, and to the more demanding of operator.In addition, current most drugs are screened
Technology is all confined to end-point method detection, is difficult to realize the tracking and detection to entire drug effect process.
In recent years, indium gallium zinc oxygen (IGZO) thin film transistor (TFT) is because it is high with mobility, on-off ratio is big, job stability
By force, can low temperature preparation and the good characteristic of bio-compatibility, received more and more attention in biochemistry sensory field.
Have been reported that IGZO thin film transistor (TFT) for various biomolecule detections such as DNA detection, enzyme detection and Ag-Ab detections.It is examined
Surveying principle is the size for inducing charge in active layer by charge entrained by biomolecule, and then changing channel current.
IGZO thin film transistor (TFT) biosensor have high sensitivity, detection speed are fast, high throughput micro-scale detection can be achieved and
The advantages such as real-time monitoring hold promise as the detection platform of drug screening.However, the IGZO thin film transistor (TFT) biology reported at present
There are still some shortcomings for sensor, in terms of being mainly manifested in following two: first is that existing IGZO thin film transistor (TFT) biology passes
The operating voltage of sensor is very high (generally tens volts)；Second is that the device junction of existing IGZO thin film transistor (TFT) biosensor
Structure is complex.
Therefore, the existing technology needs to be improved and developed.
Summary of the invention
In view of above-mentioned deficiencies of the prior art, the purpose of the present invention is to provide one kind to be based on liquid grid-type IGZO film crystal
The antituberculosis drugs screening plant and method of pipe, it is intended to it is multiple to solve the existing medicament screening apparatus structure based on thin film transistor (TFT)
The problem that miscellaneous and operating voltage is higher, detection sensitivity is poor.
Technical scheme is as follows:
A kind of antituberculosis drugs screening plant based on liquid grid-type IGZO thin film transistor (TFT), wherein including substrate, be arranged in institute
Substrate surface and the successively source electrode of laid out in parallel, indium gallium zinc oxygen thin film channel layer and drain electrode are stated, is arranged in the source electrode
With the reservoir of drain electrode surface, the bottom surface of the reservoir is the indium gallium zinc oxygen thin film channel layer, the reservoir memory
Contain electrolyte, inserted with gate electrode in the electrolyte, the source electrode, drain electrode and gate electrode are electrically connected same telecommunications
Number detector.
The antituberculosis drugs screening plant based on liquid grid-type IGZO thin film transistor (TFT), wherein in the reservoir
Electrolyte be cell culture fluid, the cell culture fluid be the DMED culture solution containing 10%FBS.
The antituberculosis drugs screening plant based on liquid grid-type IGZO thin film transistor (TFT), wherein the reservoir material
Material is dimethyl silicone polymer.
The antituberculosis drugs screening plant based on liquid grid-type IGZO thin film transistor (TFT), wherein the electric signal inspection
Survey the probe station that device includes semi-conductor test instrument and is electrically connected with the semi-conductor test instrument.
The antituberculosis drugs screening plant based on liquid grid-type IGZO thin film transistor (TFT), wherein the substrate is glass
One of glass substrate, polyimide substrate or dimethyl silicone polymer substrate.
A kind of screening technique of antituberculosis drugs screening plant, which comprises the following steps:
Set the voltage V between source electrode and drain electrodeDSAnd the voltage V between source electrode and gate electrodeGS, into reservoir
Cell culture fluid is added, channel current is measured by electrical signal detection device and is denoted as I1；
Macrophage is added into reservoir and carries out the culture predetermined time, channel current is measured by electrical signal detection device and is denoted as
I2, I2Less than I1；
Tubercle bacillus is added into reservoir and carries out cell infection to the predetermined time, channel current is measured by electrical signal detection device
And it is denoted as I3, I3Greater than I2；
Drug to be detected is added into reservoir to continue to cultivate the predetermined time, channel current is measured by electrical signal detection device and is remembered
For I4If I4Less than I3, then determine that the drug to be detected is antituberculosis drugs.
The antituberculosis drugs screening technique, wherein if I4More than or equal to I3, then determine that the drug to be detected is
Non- antituberculosis drugs.
The antituberculosis drugs screening technique, wherein the voltage V between the source electrode and drain electrodeDS=0.3V。
The antituberculosis drugs screening technique, wherein the voltage V between the source electrode and gate electrodeGS=-0.5-
1V。
The antituberculosis drugs screening technique, wherein the addition macrophage into reservoir cultivate pre-
It fixes time, channel current is measured by electrical signal detection device and is denoted as I2The step of include:
Macrophage is added into the reservoir for be stored with cell culture fluid and is put into cell incubator and is cultivated, setting temperature
Degree is 37 °C, gas concentration lwevel 5%；
When culture is paved with indium gallium zinc oxygen channel layer to macrophage, then channel current at this time is measured by electrical signal detection device
And it is denoted as I2。
The utility model has the advantages that the antituberculosis drugs screening plant tool provided by the invention based on liquid grid-type IGZO thin film transistor (TFT)
There is high sensitivity, detect the features such as speed is fast, and stability is strong, structure is simple low with operating voltage, it is anti-to be highly suitable for screening
Tuberculosis class drug.Drug is converted to the change of electric signal by the antituberculosis drugs screening plant to infection cell mechanism
Change, and electric signal can directly be read from electrical signal detection device, be evaluated by change in electric degree drug effect, this will
Previous operating process is greatly simplified, and of less demanding to experiment condition.In addition, liquid grid-type IGZO thin film transistor (TFT) pair
Drug effect process can be monitored in real time, compensate for the deficiency of conventional medicament screening technique well.
Detailed description of the invention
Fig. 1 is that a kind of structure of the antituberculosis drugs screening plant based on liquid grid-type IGZO thin film transistor (TFT) of the present invention is shown
It is intended to.
Fig. 2 is that a kind of work of the antituberculosis drugs screening plant based on liquid grid-type IGZO thin film transistor (TFT) of the present invention is former
Reason.
Fig. 3 is the flow diagram of antituberculotic screening in the embodiment of the present invention 1.
Fig. 4 is the change in electric figure in the embodiment of the present invention 1 in drug screening process.
Specific embodiment
The present invention provides a kind of antituberculosis drugs screening plant and method based on liquid grid-type IGZO thin film transistor (TFT), is
Keep the purpose of the present invention, technical solution and effect clearer, clear, the present invention is described in more detail below.It should manage
Solution, the specific embodiments described herein are merely illustrative of the present invention, is not intended to limit the present invention.
Referring to Fig. 1, Fig. 1 is a kind of antituberculosis drugs based on liquid grid-type IGZO thin film transistor (TFT) provided by the invention
The structural schematic diagram of screening plant preferred embodiment, wherein as shown, the antituberculosis drugs screening plant includes substrate
1,1 surface of substrate and the successively source electrode 2 of laid out in parallel, indium gallium zinc oxygen thin film channel layer 3 and drain electrode 4 are set, if
The reservoir 5 on 4 surface of the source electrode 2 and drain electrode is set, the bottom surface of the reservoir 5 is the indium gallium zinc oxygen channel layer 3,
Be stored with electrolyte 6 in the reservoir 5, inserted with gate electrode 7 in the electrolyte, the source electrode 2, drain electrode 4 and
Gate electrode 7 is electrically connected same electrical signal detection device 8.
Antituberculosis drugs screening plant provided in this embodiment based on liquid grid-type IGZO thin film transistor (TFT) is using electrolysis
Liquid is instead of common solid dielectric layer in traditional IGZO thin film transistor (TFT) biosensor.Ion in electrolyte is easier
Separation of charge is carried out under the action of electric field, when applying a positive gate voltage, accumulation of positive ions to indium gallium zinc oxygen (IGZO) channel layer
On, it will increase the electron concentration in indium gallium zinc oxygen channel layer, so that the channel current of device increases rapidly, working principle is as schemed
Shown in 2.Therefore, the work of the antituberculosis drugs screening plant provided in this embodiment based on liquid grid-type IGZO thin film transistor (TFT)
Voltage in 1 V or so, the biological detection that dramatically reduces the power consumption of device, and be more advantageous under solution environmental and
The practical application of sensor.
In some embodiments, the antituberculosis drugs screening plant based on liquid grid-type IGZO thin film transistor (TFT) is logical
Following methods are crossed to be prepared:
The deposit metal electrodes on substrate first by way of hot evaporation, as an example, can deposit respectively 10nm Cr and
The Au of 100nm prepares the Cr/Au electrode that channel width-over-length ratio is 30:1, the source electrode and drain electrode as transistor；Then lead to
The physical vapour deposition (PVD)s mode such as extra pulse laser deposition or magnetron sputtering deposition thickness between source electrode and drain electrode is 60nm left
Right indium gallium zinc oxygen (IGZO) film is as indium gallium zinc oxygen channel layer；
Prepare reservoir on the source electrode and drain electrode surface, the reservoir prepared by dimethyl silicone polymer (PDMS) and
At, the volume and shape of the reservoir can be adjusted according to actual needs, the bottom of reservoir through oxygen plasma at
Reason, can be bonded more preferably with glass substrate, guarantee that the solution in reservoir does not outflow.The reservoir be both needed to before use into
Row cleaning treatment and ultraviolet irradiation sterilization treatment avoid impurity or other pathogenic microorganisms from influencing testing result；
Electrolyte is added into the reservoir, then selects metals or other conductive film material conducts such as Au, Ag, Pt, ITO
Gate electrode, the shape of gate electrode can be Filamentous, rodlike or sheet, the gate electrode are placed in electrolyte, then by source electrode,
Drain electrode and gate electrode are electrically connected with external electrical signal detection device, are obtained described based on liquid grid-type IGZO film crystal
The antituberculosis drugs screening plant of pipe.
In some embodiments, the substrate is glass substrate, polyimide substrate or dimethyl silicone polymer substrate
One of, but not limited to this.
In some embodiments, the electrical signal detection device include semi-conductor test instrument and with the semiconductor test
The probe station of instrument electrical connection.In the present embodiment, the fixture on the probe station passes liquid grid-type IGZO thin film transistor (TFT) biology
Source electrode, drain electrode and the gate electrode of sensor are connected on semi-conductor test instrument.Semi-conductor test instrument will be in source electrode and leakage
Apply voltage V between electrodeDSAnd apply voltage V between gate electrode and source electrodeGS, and the channel current I of deviceDSIt can be from half
It is directly read on conductor tester.
In some embodiments, cell culture fluid is also stored in the reservoir, the cell culture fluid is containing 10%
The DMED culture solution of FBS.When macrophage adherent growth in the reservoir for being stored with cell culture fluid in reservoir, by
It is negatively charged in Macrophage Surface in the solution, the electron concentration in indium gallium zinc oxygen (IGZO) thin film channel can be reduced, so that ditch
Road electric current IDSReduce, after macrophage is infected, activity and adhered state are deteriorated, so that channel current IDSIncrease, when
After applying drug, macrophage activity and adhered state are restored, then channel current IDSIt can reduce.In the present embodiment, lead to
The variation that mechanism of the drug to infection cell can be converted to electric signal by the antituberculosis drugs screening plant is crossed, and it is electric
Signal can directly be read from electrical signal detection device, be evaluated by change in electric degree drug effect, this will greatly
Previous operating process is simplified, and of less demanding to experiment condition.
From manufacture craft, the production of the liquid grid-type IGZO thin film transistor (TFT) is more simple, because only needing two steps
Device can be prepared, that is, prepares source electrode and drain electrode and deposition indium gallium zinc oxygen film, this advantageously reduces cost, and popularization is answered
With.The liquid grid-type IGZO thin film transistor (TFT) Antituberculous class drug screens in which can realize sensitive fast, economical, compared to tradition
Drug screening technology, have in terms of screening sensitivity and detection efficiency and significantly improve.And biological respinse is directly turned
It is melted into the variation of electric signal, the variation of electric signal can be directly read from semi-conductor test instrument, is not necessarily to other macro-organism instrument
Device equipment participates in, this greatly reduces the requirement to technical staff.It is provided by the invention to be based on liquid grid-type IGZO thin film transistor (TFT)
Antituberculosis drugs screening plant, can make up well conventional medicament screening technique drug effect process cannot be carried out it is real
When the deficiency that monitors.
In some embodiments, a kind of antituberculosis drugs sieve based on liquid grid-type IGZO thin film transistor (TFT) is additionally provided
Choosing method, which comprises the following steps:
Voltage V between S10, setting source electrode and drain electrodeDSAnd the voltage V between source electrode and gate electrodeGS, to liquid storage
Cell culture fluid is added in slot, channel current is measured by electrical signal detection device and is denoted as I1；
S20, into reservoir, addition macrophage carries out the culture predetermined time, measures channel current simultaneously by electrical signal detection device
It is denoted as I2, I2Less than I1；
S30, the tubercle bacillus progress cell infection predetermined time is added into reservoir, channel electricity is measured by electrical signal detection device
It flows and is denoted as I3, I3Greater than I2；
S40, be added into reservoir drug to be detected continue cultivate the predetermined time, channel current is measured by electrical signal detection device
And it is denoted as I4If I4Less than I3, then determine that the drug to be detected is antituberculosis drugs；If I4More than or equal to I3, then determine institute
Stating drug to be detected is non-antituberculosis drugs.
In the present embodiment, when using the antituberculosis drugs screening of the invention based on liquid grid-type IGZO thin film transistor (TFT)
When device screens drug, the parameter on semiconductor analysis instrument is first set, is respectively set between source electrode and drain electrode
Voltage VDSAnd the voltage V between source electrode and gate electrodeGS.Preferably, since the present invention uses electrolyte instead of biography
Common solid dielectric layer in system IGZO thin film transistor (TFT) biosensor, and the ion in electrolyte is easier the work in electric field
Separation of charge is carried out under, therefore can set the voltage V between the source electrode and drain electrodeDS=0.3V；The source electrode and grid
Voltage V between electrodeGS=-0.5-1V。
In some embodiments, the macrophage that is added into reservoir carries out the culture predetermined time, passes through telecommunications
Number detector measures channel current and is denoted as I2The step of include: into the reservoir for be stored with cell culture fluid be added macrophage it is thin
Born of the same parents and being put into cell incubator cultivate, and set temperature is 37 °C, gas concentration lwevel 5%；When culture to macrophage
When being paved with indium gallium zinc oxygen channel layer, then channel current at this time is measured by electrical signal detection device and be denoted as I2。
Below by specific embodiment the present invention will be further explained explanation:
Embodiment 1
1, the preparation process of the antituberculosis drugs screening plant based on liquid grid-type IGZO thin film transistor (TFT) the following steps are included:
The preparation of the source electrode and drain electrode of transistor: glass substrate is after Piranha solution is handled, AZ1512 photoetching in spin coating
Glue is transferred to glass in 100 °C of warm table front baking 10 minutes, then by designed array device figure by way of photolithographic exposure
On glass, after end exposure, develop 45 seconds in AZ developer solution, then rinse glass with deionized water and remove remaining developer solution,
By hot evaporation deposit metal electrodes after being dried with nitrogen, the Au of the Cr and 100 nm of 10 nm are deposited respectively, and metal Cr increases metal
The adhesiveness of Au and glass, glass is put remove after having deposited in acetone, and finally obtaining channel width-over-length ratio is 30:1's
Source electrode and drain electrode；
The preparation of active layer indium gallium zinc oxygen (IGZO) film: the place that deposition is not needed in above-mentioned electrode is carried out with high temperature gummed tape
Encapsulation, then deposited to indium gallium zinc oxygen (IGZO) on packaged electrode by pulse laser depositional mode, it is taken after deposition
Device out removes high temperature gummed tape, puts into corundum crucible with cover, anneals 2 hours at 400 °C of Muffle furnace, finally obtains IGZO
Film transistor device；
The preparation of reservoir: dimethyl silicone polymer (PDMS) and curing agent, the two mixing are weighed respectively for 10:1 in mass ratio
After mixing evenly, it vacuumize until fluid is transparent to clarify not bubbles, by dimethyl silicone polymer (PDMS)
It pours into designed mold, the mold equipped with dimethyl silicone polymer (PDMS) is placed on warm table and heats 30 points for 80 °C
Clock, heating can accelerate the solidification of dimethyl silicone polymer (PDMS).Then it needs to the dimethyl silicone polymer solidified
(PDMS) it is demoulded, finally obtains reservoir；
Reservoir and device assemble: reservoir and IGZO film transistor device are carried out oxygen plasma (O2Plasma at)
Reason, the two is bonded later, and the antituberculosis drugs screening plant based on liquid grid-type IGZO thin film transistor (TFT) is made.
2, antituberculosis drugs screening technique based on liquid grid-type IGZO thin film transistor (TFT) the following steps are included:
Cell culture is carried out in reservoir: cleaning and ultraviolet radiation sterilization first being carried out to reservoir inside, then into reservoir
The Raw macrophage of certain cell concentration is added, puts into cell incubator later, temperature and gas concentration lwevel are set, point
It Wei not be 37 °C and 5 %；
The electric signal of cell adherent growth monitors: be placed in tungsten wire as gate electrode in reservoir, then by source electrode, drain electrode and
Gate electrode is connected by conducting wire with semi-conductor test instrument 4200.According to cell habit, select suitable time interval into
Horizontal electrical signal test.By testing transfer curve IDS-VGS, observe channel current IDSVariation to realize to cell grow shape
The monitoring of state because in the solution cell surface be it is electronegative, the adherent meeting of cell is so that channel current IDSReduce.When thin
After born of the same parents are paved with the entire channel portion of device, channel current IDSIt can stablize near a certain current value；
The electrical signal detection of infected cell: after cell adherent growth is paved with entire device, tubercle bacillus is added into reservoir
Infection macrophage is removed, infection after a certain period of time, is cleaned multiple times reservoir with the PBS solution of 0.01M, removes thinless
The tubercle bacillus that endocytosis is bitten adds the fresh DMEM culture medium containing 10%FBS, and device is put into cell culture after cleaning
Case.Due to being changed by the form of mycobacterium tuberculosis infection, macrophage, activity and adhered state are deteriorated, so that channel is electric
Flow IDSIncrease；
Electrical signal detection after drug-treated: apply drug to infected macrophage, drug enters cell and kills intracellular
Tubercle bacillus so that cell activity and adhered state have a degree of recovery, at this time carry out electric signal test, channel electricity
Flow IDSHave reduces to a certain extent.
3, with Raw macrophage frequently as the phthisical model of research, the method packet that Antituberculous class drug is screened
Include following steps:
With Raw macrophage frequently as phthisical model is studied, select Raw macrophage as research object.First set
The voltage V between source-drain electrode is respectively set in parameter on semiconductor analysis instrumentDS=0.3V and gate voltage VGS1V is measured from -0.5V.
The step of tuberculosis drugs screen measures channel current after device is stablized as shown in figure 3, culture medium is first added in reservoirI 1 , as shown in Figure 4.Then it again by Raw macrophage culture into reservoir, is put into cell incubator and cultivates, raw macrophage is thin
Born of the same parents can on indium gallium zinc oxygen (IGZO) film adherent growth, since Macrophage Surface is negatively charged, when cell is paved with entire device
Channel current is reduced to after partI 2 , as shown in Figure 4.Then tubercle bacillus is added into reservoir and goes infection macrophage, infection
After a certain period of time, the form of macrophage changes, and activity and adhered state are deteriorated, so that channel current is increased toI 3 ,
As shown in Figure 4.It is added followed by drug, after drug-treated, the activity and adhered state of macrophage have a degree of extensive
It is multiple, so that channel current is reduced toI 4 , as shown in Figure 4.
In conclusion the antituberculosis drugs screening plant tool provided by the invention based on liquid grid-type IGZO thin film transistor (TFT)
There is high sensitivity, detect the features such as speed is fast, and stability is strong, structure is simple low with operating voltage, it is anti-to be highly suitable for screening
Tuberculosis class drug.Drug is converted to the change of electric signal by the antituberculosis drugs screening plant to infection cell mechanism
Change, and electric signal can directly be read from electrical signal detection device, be evaluated by change in electric degree drug effect, this will
Previous operating process is greatly simplified, and of less demanding to experiment condition.In addition, liquid grid-type IGZO thin film transistor (TFT) pair
Drug effect process can be monitored in real time, compensate for the deficiency of conventional medicament screening technique well.
It should be understood that the application of the present invention is not limited to the above for those of ordinary skills can
With improvement or transformation based on the above description, all these modifications and variations all should belong to the guarantor of appended claims of the present invention
Protect range.
Claims (10)
1. a kind of antituberculosis drugs screening plant based on liquid grid-type IGZO thin film transistor (TFT), which is characterized in that including substrate,
The substrate surface and the successively source electrode of laid out in parallel, indium gallium zinc oxygen thin film channel layer and drain electrode are set, are arranged in institute
The reservoir on source electrode and drain electrode surface is stated, the bottom surface of the reservoir is the indium gallium zinc oxygen thin film channel layer, the storage
Electrolyte is stored in liquid bath, inserted with gate electrode, the source electrode, drain electrode and gate electrode electrical connection in the electrolyte
Same electrical signal detection device.
2. the antituberculosis drugs screening plant according to claim 1 based on liquid grid-type IGZO thin film transistor (TFT), feature
It is, the electrolyte in the reservoir is cell culture fluid, and the cell culture fluid is the DMED culture solution containing 10%FBS.
3. the antituberculosis drugs screening plant according to claim 1 based on liquid grid-type IGZO thin film transistor (TFT), feature
It is, the reservoir material is dimethyl silicone polymer.
4. the antituberculosis drugs screening plant according to claim 1 based on liquid grid-type IGZO thin film transistor (TFT), feature
It is, the electrical signal detection device includes semi-conductor test instrument and the probe station that is electrically connected with the semi-conductor test instrument.
5. the antituberculosis drugs screening plant according to claim 1 based on liquid grid-type IGZO thin film transistor (TFT), feature
It is, the substrate is one of glass substrate, polyimide substrate or dimethyl silicone polymer substrate.
6. just like the screening technique of any antituberculosis drugs screening plant of claim 1-5, which is characterized in that including with
Lower step:
Set the voltage V between source electrode and drain electrodeDSAnd the voltage V between source electrode and gate electrodeGS, into reservoir
Cell culture fluid is added, channel current is measured by electrical signal detection device and is denoted as I1；
Macrophage is added into reservoir and cultivates to the predetermined time, channel current is measured by electrical signal detection device and is denoted as
I2, I2Less than I1；
Tubercle bacillus is added into reservoir and carries out cell infection to the predetermined time, channel current is measured by electrical signal detection device
And it is denoted as I3, I3Greater than I2；
Drug to be detected is added into reservoir and continues culture to the predetermined time, channel current is measured simultaneously by electrical signal detection device
It is denoted as I4If I4Less than I3, then determine that the drug to be detected is antituberculosis drugs.
7. antituberculosis drugs screening technique according to claim 6, which is characterized in that if I4More than or equal to I3, then determine
The drug to be detected is non-antituberculosis drugs.
8. antituberculosis drugs screening technique according to claim 6, which is characterized in that the source electrode and drain electrode it
Between voltage VDS=0.3V。
9. antituberculosis drugs screening technique according to claim 6, which is characterized in that the source electrode and gate electrode it
Between voltage VGS=-0.5-1V。
10. antituberculosis drugs screening technique according to claim 6, which is characterized in that described to be added into reservoir
Macrophage was cultivated to the predetermined time, is measured channel current by electrical signal detection device and is denoted as I2The step of include:
Macrophage is added into the reservoir for be stored with cell culture fluid and is put into cell incubator and is cultivated, setting temperature
Degree is 37 °C, gas concentration lwevel 5%；
When culture is paved with indium gallium zinc oxygen channel layer to macrophage, then channel current at this time is measured by electrical signal detection device
And it is denoted as I2。
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111307912A (en) * | 2020-03-05 | 2020-06-19 | 苏州微湃医疗科技有限公司 | Field-effect tube biosensor and preparation method thereof |
| CN113466301A (en) * | 2021-07-29 | 2021-10-01 | 武汉大学 | Biochip for rapidly screening bladder cancer markers and preparation method and application thereof |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100053624A1 (en) * | 2008-08-29 | 2010-03-04 | Kyung-Hwa Yoo | Biosensor |
| CN102435653A (en) * | 2011-09-05 | 2012-05-02 | 湖南大学 | Field effect transistor-based antibiotic medicine screening device and antibiotic medicine screening method |
| US20130075793A1 (en) * | 2010-06-14 | 2013-03-28 | Dai Nippon Printing Co., Ltd. | Field effect transistor type biosensor |
| KR20130101295A (en) * | 2012-03-05 | 2013-09-13 | 충남대학교산학협력단 | Screening method for anti-mycobacterial drugs |
| CN204422470U (en) * | 2015-01-07 | 2015-06-24 | 融智生物科技（青岛）有限公司 | Microbial detection device |
| CN105552123A (en) * | 2016-01-25 | 2016-05-04 | 南开大学 | Silk-screen printing type self-referencing-graphene field effect transistor biochemical sensor |
| CN106770566A (en) * | 2016-11-25 | 2017-05-31 | 深圳大学 | The detection method of Salmonella sensor, preparation method and salmonella concentration |
| CN109585567A (en) * | 2018-11-22 | 2019-04-05 | 武汉大学 | High-performance indium gallium zinc oxygroup double-layer structure thin film transistor (TFT) and preparation method thereof |
| CN109801975A (en) * | 2019-01-15 | 2019-05-24 | 天津大学 | Flexible thin-film transistor and its manufacturing method based on amorphous indium gallium zinc film |
-
2019
- 2019-06-10 CN CN201910497417.6A patent/CN110398528B/en active Active
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100053624A1 (en) * | 2008-08-29 | 2010-03-04 | Kyung-Hwa Yoo | Biosensor |
| US20130075793A1 (en) * | 2010-06-14 | 2013-03-28 | Dai Nippon Printing Co., Ltd. | Field effect transistor type biosensor |
| CN102435653A (en) * | 2011-09-05 | 2012-05-02 | 湖南大学 | Field effect transistor-based antibiotic medicine screening device and antibiotic medicine screening method |
| KR20130101295A (en) * | 2012-03-05 | 2013-09-13 | 충남대학교산학협력단 | Screening method for anti-mycobacterial drugs |
| CN204422470U (en) * | 2015-01-07 | 2015-06-24 | 融智生物科技（青岛）有限公司 | Microbial detection device |
| CN105552123A (en) * | 2016-01-25 | 2016-05-04 | 南开大学 | Silk-screen printing type self-referencing-graphene field effect transistor biochemical sensor |
| CN106770566A (en) * | 2016-11-25 | 2017-05-31 | 深圳大学 | The detection method of Salmonella sensor, preparation method and salmonella concentration |
| CN109585567A (en) * | 2018-11-22 | 2019-04-05 | 武汉大学 | High-performance indium gallium zinc oxygroup double-layer structure thin film transistor (TFT) and preparation method thereof |
| CN109801975A (en) * | 2019-01-15 | 2019-05-24 | 天津大学 | Flexible thin-film transistor and its manufacturing method based on amorphous indium gallium zinc film |
Non-Patent Citations (4)
| Title |
|---|
| MYUNG-SIC CHAE ET AL: "IGZO-based electrolyte-gated field-effect transistor for in situ biological sensing platform", 《SENSORS AND ACTUATORS B: CHEMICAL》 * |
| NARENDRA KUMAR ET AL: "Back-Channel Electrolyte-Gated a-IGZO Dual-Gate Thin-Film Transistor for Enhancement of pH Sensitivity Over Nernst Limit", 《IEEE ELECTRON DEVICE LETTERS》 * |
| NARENDRA KUMAR等: "Enhanced pH sensitivity over the Nernst limit of electrolyte gated a-IGZO thin film transistor using branched polyethylenimine", 《RSC ADVANCES》 * |
| 吴虢东等: "抗结核天然药物筛选的巨噬细胞模型研究", 《昆明医学院学报》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111307912A (en) * | 2020-03-05 | 2020-06-19 | 苏州微湃医疗科技有限公司 | Field-effect tube biosensor and preparation method thereof |
| CN111307912B (en) * | 2020-03-05 | 2022-08-09 | 苏州微湃医疗科技有限公司 | Field-effect tube biosensor and preparation method thereof |
| CN113466301A (en) * | 2021-07-29 | 2021-10-01 | 武汉大学 | Biochip for rapidly screening bladder cancer markers and preparation method and application thereof |
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