CN108034703A - Digital pcr system based on EWOD drivings and constant temperature source - Google Patents

Digital pcr system based on EWOD drivings and constant temperature source Download PDF

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Publication number
CN108034703A
CN108034703A CN201711207094.XA CN201711207094A CN108034703A CN 108034703 A CN108034703 A CN 108034703A CN 201711207094 A CN201711207094 A CN 201711207094A CN 108034703 A CN108034703 A CN 108034703A
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China
Prior art keywords
electrode
ewod
constant temperature
temperature source
drop
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Inventor
杜林�
章凯迪
周嘉
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Fudan University
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Fudan University
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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6844Nucleic acid amplification reactions
    • C12Q1/686Polymerase chain reaction [PCR]
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00Constructional details, e.g. recesses, hinges
    • C12M23/02Form or structure of the vessel
    • C12M23/16Microfluidic devices; Capillary tubes
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/12Means for regulation, monitoring, measurement or control, e.g. flow regulation of temperature

Abstract

The invention discloses it is a kind of based on EWOD driving and constant temperature source digital pcr system, it includes:Control unit;The EWOD chips being electrically connected with control unit, it is made of reservoir portion, drop formation part, drive part and the waste liquid part for including some electrodes respectively;The constant temperature source being arranged on directly over EWOD chips, it is not contacted with EWOD chips, is made of heating part, ground electrode part and the transducing part for including some electrodes respectively;The detection unit being electrically connected with control unit;The control unit includes drive circuit, the control circuit of constant temperature source and the control interface of detection unit of EWOD chips.The present invention utilizes EWOD technologies, can accurately control drop staying-time and transfer time, makes drop reaction abundant, coordinate detection unit, the extensive fast transfer of batch drop can be achieved, the reaction temperature for coordinating constant temperature source to provide, makes reaction solution fully be reacted under high and low temperature environment.Moreover, apparatus structure is simple, temperature-controllable, rapid reaction, small, easy to use.

Description

Digital pcr system based on EWOD drivings and constant temperature source
Technical field
The present invention relates to a kind of control device of biochemistry, and in particular to a kind of number based on EWOD drivings and constant temperature source Word PCR system.
Background technology
PCR (Polymerase Chain Reaction, polymerase chain reaction) is commonly applied to biomolecular science and gene A key technology of engineering, the technology are that one kind expands making choice property of templet gene under the effect such as polymerase, primer The method of fragment, by high-temperature denatured, process annealing(Renaturation)And a few step reaction composition a cycles such as thermophilic extension, circulation carry out So that target gene expands rapidly.
After drop diminishes, single drop includes a DNA molecular, using mathematics Poisson distribution computational methods, according to liquid Drop sends that amount of fluorescence is counter to release DNA concentration.This computation model comparative maturity, digital pcr biologic applications are substantially this Computational methods principle.
Third generation digital pcr technology has been obtained for Preliminary Applications at present, it is in copy number variation, abrupt climatic change, gene Relative expression studies(Expressed as allele is uneven), the verification of two generation sequencing results, miRNA expression analysis, unicellular gene Expression analysis etc. has the incomparable advantage of traditional PCR technique.
However, existing digital pcr technology needs accurate temperature cycles control, temperature control system is proposed very high It is required that moreover, the temperature cycles time constrain the whole reaction time of PCR.Micro-fluidic circulating round pcr is for high/low temperature Reaction time control is inaccurate, there is a situation where that reaction process is insufficient, and be difficult to test annealing temperature.
For system in digital pcr technology forms complicated, reaction time consumption length, drop controllability is poor, reaction is insufficient Deficiency, it would be highly desirable to need that a kind of temperature control is accurate, the digital pcr system schema of rapid reaction.
The content of the invention
In order to solve prior art problem, it is an object of the present invention to overcome the deficiencies of the prior art, and to provide one kind Digital pcr system based on EWOD drivings and constant temperature source, generation, mixing and the movement of drop are controlled using EWOD drive systems, Enough power is provided for microlayer model movement, suitable reaction temperature region is provided using heated at constant temperature source, is inside microlayer model Reaction provides suitable reaction temperature condition.The present invention is using integrated circuit planar technique processing Array microelectrode, it can be achieved that criticizing The extensive fast transfer of drop is measured, the reaction temperature for coordinating constant temperature source to provide, makes reaction solution abundant under high and low temperature environment Reaction.Apparatus of the present invention composition is simple, temperature-controllable, rapid reaction, it is small, easy to use the advantages of.
In order to achieve the above object, should the present invention provides a kind of digital pcr system based on EWOD drivings and constant temperature source System includes:
Control unit;
The EWOD chips being electrically connected with control unit, the EWOD chips by including the reservoir portion of some electrodes respectively, drop is given birth to Formed into part, drop drive part and waste liquid part;
The constant temperature source being arranged on directly over EWOD chips, the constant temperature source are not contacted with EWOD chips;PCR reaction solution is located at EWOD cores Between piece and constant temperature source;The constant temperature source is made of heating part, ground electrode part and the transducing part for including some electrodes respectively; And
The detection unit being electrically connected with control unit, this is used for detection unit to the droplet morphology on EWOD chips, position and glimmering Luminous intensity is observed, and control unit is fed back;
Wherein, the control unit include the drive circuits of EWOD chips, constant temperature source control circuit and detection unit control Interface processed.
It is preferred that the reservoir portion includes first electrode, for storing drop.
It is preferred that the drop formation part includes second electrode, the 3rd electrode and the 4th electrode, for generating liquid Drop.
It is preferred that the drop drive part includes the 5th electrode, the 6th electrode and the 7th electrode, generated for driving Drop.
It is preferred that the waste liquid part includes the 8th electrode, for collecting waste liquid drop.
It is preferred that the heating part includes the 9th electrode, the tenth electrode, the 11st electrode, the 12nd electrode, part It is covered on drive part region, for heating EWOD chips.
It is preferred that the ground electrode part includes the 13rd electrode, it covers the reservoir portion of all drops, drop life Into part, drop drive part, waste liquid part, for causing drop driving more to stablize.
It is preferred that the transducing part includes the 14th electrode, the 15th electrode, the 16th electrode, the 17th electrode, It is partially covered on drive part region, for detecting the temperature on EWOD chips.
It is preferred that the detection unit includes light source, the first optical filter and image acquisition device.
It is preferred that the detection unit also includes the second optical filter.
EWOD (electrowetting-on-dielectric, electrowetting on dielectric) is that a kind of automatically controlled surface tension is driven Flowing mode, the EWOD processed using integrated circuit technology are had the advantages that driving is accurate, can be mass.
The present invention compared with prior art, has following remarkable advantage:
1. the present invention utilizes EWOD actuation techniques, generation droplet size is homogeneous, avoids outside contamination, can accurately control drop Residence time and transfer time, make drop reaction abundant, coordinate detection unit to realize feedback control, reduce empty drop(Can not Produce drop)And droplet coalescence.As drop is stretched, if the cutting-off process time is too short, cause sky drop, and the time is too long, drop Low drop generation efficiency.Reduce fusion and may be such that droplet size is homogeneous, so that DNA molecular enters the probability of each drop It is equal.
2. the present invention utilizes constant temperature source control technology, temperature control is accurate, coordinates EWOD actuation techniques to realize greatly The fast PCR reaction of batch drop, and primer annealing temperature can be measured.Generally use experimental measurement method, concrete operations It is:Different cryogenic temperatures is first set, then finds out optimum annealing temperature.Idea of the invention is that drop is moved to low-temperature space not Same temperature province.And be detected respectively, realize measurement annealing temperature purpose.
3. the present invention uses integrated circuit planar processing technology(EWOD is made using ultraviolet photolithographic and metal etch process Chip)It can be mass-produced, reduce use cost, the array electrode of processing, can in high volume transport drop, realize that high pass measures Examination.
Brief description of the drawings
Fig. 1 is the structure diagram of the digital pcr system based on EWOD drivings and constant temperature source of the present invention.
Fig. 2 is the EWOD chip and the structure diagram of constant temperature source assembling of the present invention.
Fig. 3 is the structure diagram of the EWOD chip electrodes of the present invention.
Fig. 4 is the structure diagram of the constant temperature source electrode of the present invention.
Fig. 5 is drop driving and heating schematic diagram in the embodiment of the present invention 1.
Fig. 6 is drop driving and heating schematic diagram in the embodiment of the present invention 2.
Embodiment
Technical scheme is described further below in conjunction with drawings and examples.
As shown in Figure 1, the digital pcr system based on EWOD drivings and constant temperature source is by control unit 10, EWOD chips 20, perseverance Warm source 30 and detection unit 40 form.The constant temperature source 30 is and spaced apart directly over EWOD chips 20(Such as 50 μm, Numerical value is simultaneously not specifically limited);PCR reaction solution is between EWOD chips and constant temperature source;Detection unit 40 is located at constant temperature source 30 Top, can be observed the droplet morphology on EWOD chips 20, position and fluorescence intensity.
Described control unit 10 includes the drive circuit of EWOD chips 20, the control circuit and detection unit 40 of constant temperature source 30 Control interface.
The EWOD chips 20 are made of substrate 21, electrode 22 and insulating hydrophobic layer 23, including reservoir portion 201, drop Generating portion 202, drop drive part 203 and waste liquid part 204, see Fig. 2.Reservoir portion 201 includes first electrode 2011, liquid Dripping generating portion 202 includes second electrode 2021, the 3rd electrode 2022, the 4th electrode 2023, and drop drive part 203 includes the Five electrodes 2031, the 6th electrode 2032, the 7th electrode 2033, waste liquid part 204 include the 8th electrode 2041, as shown in Figure 3.
The second electrode 2021 is the pull-out electrode of drop formation part, its function is that reservoir portion is pulled out first Step;3rd electrode 2022 is the transition electrode of drop formation part, and function is turned off the drop elongated;Described the 4th Electrode 2023 is the storage electrode of drop formation part, and function is the drop that storage pulls out.
The constant temperature source 30 is made of constant temperature source substrate 31, constant temperature source electrode 32 and constant temperature source insulating hydrophobic layer 33, including Heating part 301, ground electrode part 302 and transducing part 303.Heating part 301 includes the 9th electrode 3011, the tenth electrode 3012nd, the 11st electrode 3013, the 12nd electrode 3014, ground electrode part 302 include the 13rd electrode 3021, transducing part 303 include the 14th electrode 3031, the 15th electrode 3032, the 16th electrode 3033, the 17th electrode 3034.The constant temperature Source electrode can not only connect voltage difference fever, but also can cause that drop driving is more stable as ground electrode, and be provided with sensing electrode, Reaction temperature can accurately be detected.
The detection unit 40 includes light source 41, the first optical filter 42, spectroscope 43, the second optical filter 44, Image Acquisition Device 45, as shown in Figure 1.Two pieces of optical filters, a piece of excitation, a piece of receiving.Accurate as video surveillance drop formation and movement When, a tablet filter is removed, so as to it was observed that droplet morphology.During work, after opening light source 41, the light launched passes through First optical filter 42 filters out veiling glare, only the exciting light of surplus excitation bandwidth wavelength.Exciting light is reflected to by spectroscope 43 On EWOD chips 20, exciting light is irradiated to above drop, since fluorescent effect inspires the transmitting light of specific bandwidth wavelength.Transmitting Light can pass through the second optical filter 44 and enter image acquisition device 45.
Embodiment 1
EWOD chips 20 are as follows to drop formation and mobile operation:The reaction solution prepared is poured into the liquid storage of EWOD chips 20 Part 201, while by the 13rd electrode 3021 of the ground electrode part 302 of constant temperature source 30, the 9th electrode of heating part 301 3011st, the ground electrode that the tenth electrode 3012, the 11st electrode 3013, the 12nd electrode 3014 lead to negative electricity to be driven as EWOD, First electrode 2011, which leads to positive electricity, makes reaction solution be fixed on reservoir portion, opens light source 41, removes the second optical filter 44.Drop is given birth to Lead to positive electricity successively into the second electrode 2021 of part 202, the 3rd electrode 2022, the 4th electrode 2023, first electrode power-off, passes through After the observation liquid of image acquisition device 45 is drawn out, the 3rd electrode 2022 powers off, and produces the first dropping liquid drop at this time.Then, drop is given birth to The 4th electrode 2023 into part 202 powers off, and the 5th electrode 2031 of drop drive part 203 leads to positive electricity, and drop is at this time Move in five electrodes, 2031 direction.5th electrode 2031 of drop drive part 203 powers off, and the 6th electrode 2032 leads to positive electricity, at this time Drop is continued to move to 2032 direction of the 6th electrode.6th electrode 2032 powers off, and the 7th electrode 2033 leads to positive electricity, at this time drop to 7th electrode, 2033 direction continues to move to.When the 7th electrode 2033 powers off, and the 5th electrode 2031 leads to positive electricity, drop continues forward It is mobile.
Above-mentioned electrode power on/off order is repeated, drop continues to generate and moves;When the electrode power on/off of drop drive part When sequentially opposite, the movement of drop opposite direction.When the electrode no longer power on/off of drop drive part, drop stops in situ no longer It is mobile.When drop is moved adjacent to the proximal most position of waste liquid part, the 5th electrode 2031 powers off, and the 8th of waste liquid part 204 the Electrode 2041 leads to positive electricity, and drop is moved to waste liquid part and is collected at this time.
Constant temperature source 30 is as follows to temperature controlled operation:13rd electrode 3021 of ground electrode part 302 is used as ground electrode All the time negative electricity is led to.When the 9th electrode 3011, the tenth electrode 3012 when heating part 301 lead to different voltages respectively so that two electricity There is pressure difference between pole(Pressure difference is certain, then quantity of heat production is certain, and external environment is the same, then heterogeneity phantom is constant), the 11st electrode 3013rd, when the 12nd electrode 3014 leads to different voltages respectively so that there is pressure difference between two electrodes, heat can be produced, with right EWOD chips 20 are heated, and when reaching thermal balance, voltage difference is certain, and the temperature province of EWOD chips 20 is constant.Detecting means Divide 303 the 14th electrode 3031 and the 15th electrode 3032, and the 16th electrode 3033, the 17th electrode 3034 can be right The temperature of EWOD chips 20 measures.
The operation of second optical filter 44 is as follows in detection unit 40:When drop formation and movement, the second optical filter is not filled 44, detection unit 40 can be acquired Liquid particle image, and the control as control unit 10 is fed back.When drop is static, install additional Second optical filter 44, detection unit 40 can record the fluorescence intensity of drop.
When producing and mobile drop, the 9th electrode 3011 of 301 parts is heated, the tenth electrode 3012 makes as ground electrode With.At this time, it may be necessary to produce drop and convey drop to heating the 11st electrode 3013 of 301 parts, the 12nd electrode 3014 Upright projection position.In the present embodiment, the 9th electrode 3011, the tenth electrode 3012 connect negative electricity all the time, realize gradient temperature environment, Measure annealing temperature function.
In the present embodiment, referring to Fig. 5, the 9th electrode 3011, the tenth electrode 3012 of heating part 301 in constant temperature source 30 Negative electricity is connect, the 11st electrode 3013, the 12nd electrode 3014 lead to positive electricity and negative electricity, the 16th electrode of transducing part 303 respectively 3031st, the 17th electrode 3032, after detection temperature reaches 95 DEG C, the 11st electrode 3013, the 12nd electrode 3014 power off and same When connect negative electricity(When connecing negative electricity at the same time, driving droplet effect is best).Because the front and rear arrangement of number discharge opeing drop, therefore after temperature reaches, stop Only heating connects negative electricity, to ensure that drop moves effect.After drop is moved to heating part, then connect above-mentioned voltage(Keep voltage Difference)Continue to heat.After the warm of 2 minutes(PCR reaction solutions are preheated), the 11st electrode the 3013, the tenth The power-off of two electrodes 3014 connects negative electricity, and drop is driven to another extreme direction movement of chip in EWOD chips 20, when being moved to EWOD The second temperature region 205 of 20 heating part of chip(50-62 DEG C of temperature province, corresponding 9th electrode in temperature province lower section 3011st, the tenth electrode 3012)Afterwards, 40s is stopped, while the 11st electrode 3013, the 12nd electrode 3014 connect above-mentioned positive electricity and bear Electricity.After 40s, after the 11st electrode 3013, the 12nd electrode 3014 connect negative electricity, drop is by fast driving in EWOD chips 20 Back to the first temperature province of heating part 206,15s is stopped.Afterwards, respectively in heating part second temperature region, the first temperature Spend region and stop 40s and 15s.And so on circulate, realize that templet gene expands in reaction solution.When drop rests on same temperature When under degree, detection unit 40 measures drop fluorescence intensity, according to measured value carry out analysis draw primer annealing temperature, The data such as Ct values, to realize the measurement to optimum annealing temperature.Wherein, C represents Cycle, and t represents threshold, Ct values Implication is:Fluorescence signal in each reaction tube reaches the period undergone during the thresholding of setting.Above-mentioned same temperature is Refer at room temperature or heating-up temperature region is less than 95 degrees Celsius of a certain temperature(Generally take 62 DEG C of annealing temperature).
In the present embodiment, by the natural conduction pattern such as heat radiation thermal convection current, second temperature region is set to reach a temperature Gradient.The first temperature province of specific design and the distance and use environment in second temperature region, guarantee reach 50-62 degrees Celsius About scope, specific how many degree can be monitored.According to the change sequencing of fluorescence intensity signals, which discharge opeing drop judged Fluorescence signal take-off at first, the temperature where finally drawing discharge opeing drop is annealing temperature.
Embodiment 2
The present embodiment is substantially the same manner as Example 1, is particular in that:
In the present embodiment, referring to Fig. 6, the 9th electrode 3011, the tenth electrode 3012 of heating part lead to respectively in constant temperature source 30 Positive electricity and negative electricity so that the 14th electrode 3031 of transducing part, 3032 detection temperature of the 15th electrode reach 62 DEG C(Second temperature Spend region 205), the 11st electrode 3013, the 12nd electrode 3014 lead to positive electricity and negative electricity, the 16th electrode of transducing part respectively 3033rd, 3034 detection temperature of the 17th electrode reaches 95 DEG C(First temperature province 206).Afterwards, react molten in EWOD chips 20 Liquid forms few drops of drops side by side and moves quickly into the different temperatures region of heating part, is stopped 2 minutes in 95 DEG C of temperature provinces. 40s is stopped in 62 DEG C of temperature provinces, 95 DEG C of temperature provinces stop 15s, and reciprocation cycle, realizes that templet gene expands in reaction solution Increase.When drop rests on a certain temperature province(Generally use 62 DEG C of temperature provinces), detection unit 40 is to drop fluorescence intensity Measure, carrying out analysis according to measured value draws the data such as Ct values, realizes to the DNA cloning under the optimum annealing temperature.
The embodiment of the present invention is illustrated above in conjunction with attached drawing, but the invention is not restricted to above-described embodiment, such as also The quantity of heating part in constant temperature source 30 can be increased, realize three temperature cycles PCR amplifications etc., the mesh of innovation and creation of the invention Make a variety of changes, change, modification, replacement, the combination made under all Spirit Essences and principle according to technical solution of the present invention Or simplify, equivalent substitute mode is should be, as long as meeting the goal of the invention of the present invention, EWOD is based on without departing from the present invention Technical principle and inventive concept of the digital pcr system of driving and constant temperature source by control device, belong to the protection model of the present invention Enclose.
Although present disclosure is discussed in detail by above preferred embodiment, but it should be appreciated that above-mentioned Description is not considered as limitation of the present invention.After those skilled in the art have read the above, for the present invention's A variety of modifications and substitutions all will be apparent.Therefore, protection scope of the present invention should be limited to the appended claims.

Claims (10)

1. a kind of digital pcr system based on EWOD drivings and constant temperature source, it is characterised in that the system includes:
Control unit;
The EWOD chips being electrically connected with control unit, the EWOD chips by including the reservoir portion of some electrodes respectively, drop is given birth to Formed into part, drop drive part and waste liquid part;
The constant temperature source being arranged on directly over EWOD chips, the constant temperature source are not contacted with EWOD chips;PCR reaction solution is located at EWOD cores Between piece and constant temperature source, which is made of heating part, ground electrode part and the transducing part for including some electrodes respectively; And
The detection unit being electrically connected with control unit, the detection unit are used for the droplet morphology on EWOD chips, position and glimmering Luminous intensity is observed, and control unit is fed back;
Wherein, the control unit include the drive circuits of EWOD chips, constant temperature source control circuit and detection unit control Interface processed.
2. the digital pcr system based on EWOD drivings and constant temperature source as claimed in claim 1, it is characterised in that the storage Liquid part includes first electrode.
3. the digital pcr system based on EWOD drivings and constant temperature source as claimed in claim 1, it is characterised in that the liquid Drop generating portion includes second electrode, the 3rd electrode and the 4th electrode.
4. the digital pcr system based on EWOD drivings and constant temperature source as claimed in claim 1, it is characterised in that the liquid Drop drive part includes the 5th electrode, the 6th electrode and the 7th electrode.
5. the digital pcr system based on EWOD drivings and constant temperature source as claimed in claim 1, it is characterised in that described is useless Liquid part includes the 8th electrode.
6. the digital pcr system based on EWOD drivings and constant temperature source as claimed in claim 1, it is characterised in that described adds Hot part includes the 9th electrode, the tenth electrode, the 11st electrode, the 12nd electrode.
7. the digital pcr system based on EWOD drivings and constant temperature source as claimed in claim 1, it is characterised in that the ground Electrode section includes the 13rd electrode.
8. the digital pcr system based on EWOD drivings and constant temperature source as claimed in claim 1, it is characterised in that the biography Sense part includes the 14th electrode, the 15th electrode, the 16th electrode, the 17th electrode.
9. the digital pcr system based on EWOD drivings and constant temperature source as claimed in claim 1, it is characterised in that the detection Unit includes light source, the first optical filter and image acquisition device.
10. the digital pcr system based on EWOD drivings and constant temperature source as claimed in claim 1, it is characterised in that the detection Unit also includes the second optical filter.
CN201711207094.XA 2017-11-27 2017-11-27 Digital pcr system based on EWOD drivings and constant temperature source Pending CN108034703A (en)

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CN114870915A (en) * 2022-04-24 2022-08-09 复旦大学 Method for controlling liquid drops in multiple directions on single-plane light-control electrowetting device

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WO2019230566A1 (en) * 2018-05-31 2019-12-05 キヤノン株式会社 Analysis system
WO2020142938A1 (en) * 2019-01-09 2020-07-16 京东方科技集团股份有限公司 Chip used for polymerase chain reaction and operation method therefor, and reaction device
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CN109999929A (en) * 2019-03-28 2019-07-12 上海天马微电子有限公司 Micro fluidic device and its driving method
CN112175815A (en) * 2019-07-05 2021-01-05 京东方科技集团股份有限公司 PCR substrate, chip, system and droplet drawing method
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CN114870915A (en) * 2022-04-24 2022-08-09 复旦大学 Method for controlling liquid drops in multiple directions on single-plane light-control electrowetting device

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Application publication date: 20180515