CN115475669A - Droplet micro-fluidic chip - Google Patents

Droplet micro-fluidic chip Download PDF

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Publication number
CN115475669A
CN115475669A CN202211124391.9A CN202211124391A CN115475669A CN 115475669 A CN115475669 A CN 115475669A CN 202211124391 A CN202211124391 A CN 202211124391A CN 115475669 A CN115475669 A CN 115475669A
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China
Prior art keywords
electrode
electrodes
droplet
microfluidic chip
insulating substrate
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Chinese (zh)
Inventor
刘一凡
周乐乐
张蓉
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ShanghaiTech University
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ShanghaiTech University
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502769Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements
    • B01L3/502784Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/10Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/06Auxiliary integrated devices, integrated components
    • B01L2300/0627Sensor or part of a sensor is integrated
    • B01L2300/0645Electrodes

Abstract

The application discloses micro-fluidic chip, including the insulating substrate, be formed with the electrode pattern on the insulating substrate, the electrode pattern includes a plurality of electrodes, sets up the clearance between the adjacent electrode, and each electrode is equipped with power connection element respectively to be suitable for the polarity and the voltage of controlling each electrode respectively. The application also discloses a driving method of the micro-fluidic chip, wherein the liquid drop is placed on the electrodes of the micro-fluidic chip to be in contact with at least two electrodes, and the liquid drop moves from one electrode to the other electrode along the preset movement route by adjusting the voltage of the electrodes on the preset movement route. The application also discloses application of the microfluidic chip in a microfluidic control system, biological detection and chemical detection.

Description

Droplet micro-fluidic chip
Technical Field
The present description relates to fluidic devices, and more particularly to droplet microfluidic chips.
Background
The microfluidic chip is a chip that integrates basic operation units related to sample preparation, separation, reaction, detection and the like in the biological or chemical field into a few square centimeters or even smaller to construct a biological or chemical analysis platform, thereby realizing various functions of a conventional biological or chemical laboratory. The microfluidic technology has the characteristics of small sample volume, high integration level and easy realization of automatic control and high-flux analysis, so that the biochemical detection on the microfluidic chip is more convenient and faster than the conventional biochemical detection, and the cost is low. The micro-fluidic chip generally completes the reaction automatically through a matched instrument, the internal reaction process is completely controllable, the technical requirements on users are reduced, and the human errors of detection are reduced, so that more accurate detection data are obtained.
Digital microfluidics is a fluid control technology that performs a series of operations such as movement, mixing, splitting, etc. by manipulating droplets on a substrate by applying an electrical signal, and is now widely used in the fields of biomedicine, optics, thermal and electrical. The direct resulting commercial products include optical displays, biomedical detection and diagnostic devices. The main digital microfluidic device is characterized in that a dielectric layer and a hydrophobic layer are added between a liquid drop and an electrode, and then the surface tension of a liquid-solid interface is changed under the action of an external electric field through the electric double layer capacitance, so that the contact angle of the liquid drop is changed, and the liquid drop is manipulated.
Most of the digital microfluidic devices that have been widely studied and used at present adopt a dual-substrate structure, in which the bottom substrate is changed from a hydrophobic state to a hydrophilic state, i.e., electrowetting, by adjusting the electric fields of the upper and lower substrates. However, the voltage for driving the droplet is increased, usually over 100V, due to the dielectric layer between the droplet and the substrate electrode, and the dielectric layer and the hydrophobic layer need to be deposited on the bottom electrode, which not only increases the cost, but also causes many problems, such as breakdown of the dielectric layer, instability of the device, and the like.
Therefore, there is a need for a microfluidic device that is simple, cost effective, and stable.
Disclosure of Invention
In one aspect of the present application, a microfluidic chip is provided, which includes an insulating substrate, an electrode pattern formed on the insulating substrate, the electrode pattern including a plurality of electrodes, a gap being provided between adjacent electrodes, and each electrode being provided with a power connection element respectively, so as to be suitable for controlling the polarity and voltage of each electrode respectively.
The application also provides a driving method of the microfluidic chip, the liquid drop is placed on the electrodes of the microfluidic chip to be in contact with at least two electrodes, and the liquid drop moves from one electrode to the other electrode along the preset movement path by adjusting the voltage of the electrodes on the preset movement path.
The application also provides the application of the microfluidic chip in a microfluidic control system, biological detection and chemical detection.
The microfluidic chip disclosed by the application brings the following beneficial effects that but not limited to: (1) The micro-fluidic chip can realize the huge change of the contact angle of the liquid drop based on the double electric effect, the change of the contact angle is completely reversible, and the efficiency of driving the liquid drop to move can be improved. (2) The micro-fluidic chip has an open structure, can run in the air, and has the characteristics of simple structure, easiness in manufacturing, convenience in operation, low cost and the like. (3) The working voltage required by the micro-fluidic chip is 1V-20V, so that the problem of device instability caused by high voltage is greatly reduced, the energy is saved, and the cost is reduced. (4) The liquid drops used by the microfluidic chip only need to dissolve ionic surfactant with extremely low concentration, which greatly expands the application range of the device.
Drawings
The present description will be further explained by way of exemplary embodiments, which will be described in detail by way of the accompanying drawings. These embodiments are not intended to be limiting, and in these embodiments like numerals are used to indicate like structures, wherein:
FIG. 1 isbase:Sub>A cross-sectional view ofbase:Sub>A microfluidic chip taken along A-A according to some embodiments of the present application;
FIG. 2 is an exemplary block diagram of a microfluidic chip according to some embodiments of the present application;
FIG. 3 is a schematic top view of droplet movement according to some embodiments of the present application;
FIG. 4 is a schematic side view of droplet movement according to some embodiments of the present application;
figure 5 is a schematic diagram illustrating dual electrical effects according to some embodiments of the present application.
Reference numerals:
10. a microfluidic chip; 11. an insulating substrate; 12. dielectric layer, 13, electrode pattern; 130. an electrode; 131. a first electrode; 132 a second electrode; 133. a wire; 134. a gap; 14. a power source; 15. a droplet.
Detailed Description
In order to more clearly illustrate the technical solutions of the embodiments of the present disclosure, the drawings used in the description of the embodiments will be briefly described below. It is obvious that the drawings in the following description are only examples or embodiments of the present description, and that for a person skilled in the art, the present description can also be applied to other similar scenarios on the basis of these drawings without inventive effort. Unless otherwise apparent from the context, or stated otherwise, like reference numbers in the figures refer to the same structure or operation.
As used in this specification and the appended claims, the terms "a," "an," "the," and/or "the" are not intended to be inclusive in the singular, but rather are intended to be inclusive in the plural, unless the context clearly dictates otherwise. In general, the terms "comprises" and "comprising" merely indicate that steps and elements are included which are explicitly identified, that the steps and elements do not form an exclusive list, and that a method or apparatus may include other steps or elements.
The traditional micro-fluidic system is a micro total analysis system which integrates functional components such as a micro-channel, a micro pump, a micro valve, a micro liquid storage device, a micro electrode, a detection element, a window, a connector and the like on a chip material through a micro machining technology. In a digital microfluidic system, a digital microfluidic chip mainly operates on discrete fluids, and has many advantages: the micro-channel is not needed, the micro-pump and the micro-valve are functional elements, the micro-construction is more favorably realized, and the consumption of the sample and the reaction reagent is reduced, so that the cost is saved, the reaction time is shortened, the efficiency is improved, and the like. However, many current digital microfluidic devices require the initial surface of the substrate to be very hydrophilic (contact angles typically below 20 °), which also limits its application and the contact angles do not vary much, reducing the efficiency of droplet driving.
Embodiments of the present description provide a microfluidic chip that may include an insulating substrate. In some embodiments, an electrode pattern may be formed on the insulating substrate. The electrode pattern comprises a plurality of electrodes, gaps are arranged between every two adjacent electrodes, and each electrode is provided with a power supply connecting element so as to be suitable for respectively controlling the polarity and the voltage of each electrode.
In order to isolate the electrical conduction between the insulating substrate and the electrode pattern, in some embodiments, a dielectric layer may be disposed between the insulating substrate and the electrode pattern.
In some embodiments, the electrodes may include at least two electrodes of different surface areas. In some embodiments, the electrodes may be used for droplet operations. In particular, in some embodiments, a large electrode may be used to store a droplet. In some embodiments, small electrodes can provide a field for manipulating droplets to perform operations such as movement, splitting, and mixing.
The term "droplet manipulation" means any manipulation of one or more droplets on a droplet microfluidic chip. Droplet operations may include, for example: loading the droplets into a droplet microfluidic chip; dispensing one or more droplets from a droplet source, splitting, separating or dividing the droplets into two or more droplets; transporting a droplet from one location to another in any direction; combining or combining two or more droplets into a single droplet; diluting the droplets; mixing the droplets; agitating the droplets; deforming the droplets; holding the droplet in place; disposing of the droplets; other droplet operations described herein; and/or any combination of the foregoing. The terms "merge", "combine", and the like are used to describe the formation of one droplet from two or more droplets. It should be understood that when such terms are used with reference to two or more droplets, any combination of droplet operations sufficient to cause two or more droplets to be combined into one droplet may be used. For example, "merging droplet a with droplet B" can be achieved by transporting droplet a to contact static droplet B, transporting droplet B to contact static droplet a, or transporting droplet a and droplet B to contact each other. The terms "split," "separate," and "divide" are not intended to imply any particular outcome with respect to the volume of the resulting droplets (i.e., the volume of the resulting droplets may be the same or different) or the number of resulting droplets (the number of resulting droplets may be 2, 3, 4, 5, or more). The term "mixing" refers to droplet operations that result in a more uniform distribution of one or more components within one droplet. Examples of "loading" droplet operations include microdialysis loading, pressure assisted loading, robotic loading, passive loading and pipette loading. Droplet operations may be electrode-mediated. In some cases, droplet manipulation is further facilitated by the use of hydrophilic and/or hydrophobic regions on the surface and/or by physical barriers.
In some embodiments, a top surface of the electrode pattern may be exposed. So set up, not only make things convenient for scientific research personnel to operate, save material simultaneously, be convenient for manufacturing.
In some embodiments, the electrodes and/or power connection elements may be formed by photolithography or etching after forming a conductive layer on an insulating substrate.
In some embodiments, the resistivity of the electrode may be less than 0.003 Ω · cm, which may provide better electrical conductivity with less electrical energy loss.
In some embodiments, the microfluidic chip may further include a control element and a power supply, the electrodes are respectively connected to the power supply through power supply connection elements, and the control element is electrically connected to the electrodes. In some embodiments, the control element may be used to control the polarity and voltage magnitude of the electrodes. In some embodiments, the power connection element may be a wire. In some embodiments, the control element may be located on the microfluidic chip or may be located outside the microfluidic chip.
In some embodiments, referring to fig. 1 and 2, the microfluidic chip 10 may include an insulating substrate 11. In some embodiments, the insulating substrate 11 may have an electrode pattern 13 formed thereon. The electrode pattern 13 includes a plurality of electrodes 130, a gap 134 is disposed between adjacent electrodes 130, and each electrode 130 is provided with a power supply 14 connecting element 133 adapted to control the polarity and voltage of each electrode 130.
In some embodiments, the width of the gap 134 may be between 1 μm and 100 μm. In some embodiments, the width of gap 134 may be 5 μm to 95 μm. In some embodiments, the width of the gap 134 may be between 10 μm and 90 μm. In some embodiments, the width of the gap 134 may be 15 μm to 85 μm. In some embodiments, the width of the gap 134 may be 20 μm to 80 μm. In some embodiments, the width of the gap 134 may be 25 μm to 75 μm. In some embodiments, the width of the gap 134 may be 30 μm to 70 μm. In some embodiments, the width of gap 134 may be 35 μm to 65 μm. In some embodiments, the width of the gap 134 may be 40 μm to 60 μm. In some embodiments, the width of gap 134 may be 45 μm to 55 μm. In some embodiments, the width of the gap 134 may be 45 μm to 50 μm. It should be noted that the width of the gap 134 should not be too large to prevent droplets from remaining therein.
In some embodiments, the electrodes 130 include at least two electrodes (a first electrode 131 and a second electrode 132) of different surface areas. In some embodiments, the surface area of the first electrode 131 may be greater than the surface area of the second electrode 132. In some embodiments, the surface area of the electrode 130 may be 0.01mm 2 ~100mm 2 . In some embodiments, the surface area of the electrode 130 may be 0.05mm 2 ~99mm 2 . In some embodiments, the surface area of the electrode 130 may be 0.1mm 2 ~98mm 2 . In some embodiments, the surface area of the electrode 130 may be 0.5mm 2 ~97mm 2 . In some embodiments, the surface area of the electrode 130 may be 1mm 2 ~96mm 2 . In some embodiments, the surface area of the electrode 130 may be 5mm 2 ~95mm 2 . In some embodiments, the surface area of the electrode 130 may be 10mm 2 ~90mm 2 . In some embodiments, the surface area of the electrode 130 may be 15mm 2 ~85mm 2 . In some embodiments, the surface area of the electrode 130 may be 20mm 2 ~80mm 2 . In some embodiments, the surface area of the electrode 130 may be 25mm 2 ~75mm 2 . In some embodiments, the surface area of the electrode 130 may be 30mm 2 ~70mm 2 . In some embodiments, the surface area of the electrode 130 may be 35mm 2 ~65mm 2 . In some embodiments, the surface area of the electrode 130 may be 40mm 2 ~60mm 2 . In some embodiments, the surface area of the electrode 130 may be 45mm 2 ~55mm 2 . In some embodiments, the surface area of the electrode 130 may be 45mm 2 ~50mm 2
In some embodiments, the resistivity of the electrode 130 may be less than 0.003 Ω -cm, such as 0.002 Ω -cm or 0.001 Ω -cm.
The term "resistivity" refers to the ratio of the product of the resistance and the cross-sectional area of an original made of a substance (20 ℃ C. At normal temperature) to the length, and is a physical quantity used to represent the resistance characteristics of various substances. The resistivity is independent of the length, cross-sectional area, etc. of the conductor, is the electrical property of the conductor material itself, is determined by the material of the conductor, and is temperature dependent.
In some embodiments, a dielectric layer 12 may be disposed between the insulating substrate 11 and the electrode pattern 13.
To facilitate the processing of the electrode pattern 13 On the insulating substrate 11, in some embodiments, the insulating substrate 11 may be made of an SOI (Silicon-On-Insulator) material. Specifically, the insulating substrate 11 may be a low-doped substrate silicon. The insulating substrate 11 mainly plays a role of supporting, and the dielectric layer 12 is attached to the insulating substrate 11 and is not easily broken or damaged.
In some embodiments, the relative permittivity of the dielectric layer 12 may be greater than 3. The relative dielectric constant is a physical parameter characterizing dielectric properties or polarization properties of the dielectric material. The relative dielectric constant of different materials at different temperatures is different, and the capacitor or related components with different performance pairs can be manufactured by utilizing the characteristic.
In some embodiments, the dielectric layer 12 may be an oxide layer. In some embodiments, the dielectric layer 12 may also be a silicon dioxide layer. In some embodiments, the dielectric layer 12 may have a thickness of 0.1 μm to 10 μm. In some embodiments, the thickness of the dielectric layer 12 may be 0.5 μm to 9.5 μm. In some embodiments, the thickness of the dielectric layer 12 may be 1 μm to 9 μm. In some embodiments, the thickness of the dielectric layer 12 may be 1.5 μm to 8.5 μm. In some embodiments, the thickness of the dielectric layer 12 may be 2 μm to 8 μm. In some embodiments, the thickness of the dielectric layer 12 may be 2.5 μm to 7.5 μm. In some embodiments, the thickness of the dielectric layer 12 may be 3 μm to 7 μm. In some embodiments, the thickness of the dielectric layer 12 may be 3.5 μm to 6.5 μm. In some embodiments, the thickness of the dielectric layer 12 may be 4 μm to 6 μm. In some embodiments, the thickness of the dielectric layer 12 may be 4.5 μm to 5.5 μm. In some embodiments, the thickness of the dielectric layer 12 may be 5 μm to 5.5 μm.
In some embodiments, the electrode pattern 13 may be machined from conductive silicon. In some embodiments, the thickness of the electrode pattern 13 may be 0.1 μm to 10 μm. In some embodiments, the thickness of the electrode pattern 13 may be 0.5 μm to 9.5 μm. In some embodiments, the thickness of the electrode pattern 13 may be 1 μm to 9 μm. In some embodiments, the thickness of the electrode pattern 13 may be 1.5 μm to 8.5 μm. In some embodiments, the thickness of the electrode pattern 13 may be 2 μm to 8 μm. In some embodiments, the thickness of the electrode pattern 13 may be 2.5 μm to 7.5 μm. In some embodiments, the thickness of the electrode pattern 13 may be 3 μm to 7 μm. In some embodiments, the thickness of the electrode pattern 13 may be 3.5 μm to 6.5 μm. In some embodiments, the thickness of the electrode pattern 13 may be 4 μm to 6 μm. In some embodiments, the thickness of the electrode pattern 13 may be 4.5 μm to 5.5 μm. In some embodiments, the thickness of the electrode pattern 13 may be 5 μm to 5.5 μm.
It should be noted that the inclusion of conductive silicon in the electrode patterns 13 in fig. 1-2 and the related description is for illustrative purposes only and is not intended to limit the scope of the present application to the illustrated embodiments.
In some embodiments, the microfluidic chip can be processed by: a, cleaning a silicon wafer for 10 minutes at 120 ℃ by using piranha solution; b, putting the silicon chip obtained in the step a into hydrofluoric acid with the mass fraction of 50% for cleaning for 15-30 seconds; c, washing and spin-drying the silicon wafer obtained in the step b by using deionized water to finish the washing step; and d, processing the top conductive silicon of the silicon wafer obtained in the step c into an electrode pattern through photoetching and etching. The finished silicon wafer is cut to a proper size, packaged and connected with a power supply, and then the chip of the microfluidic device can be finished, but the material is not limited by the invention.
In some embodiments, both the electrode 130 and the conductive line 133 may be fabricated from top conductive silicon. In some embodiments, the first electrode 131 may be used to store a droplet. In some embodiments, the second electrode 132 may be used to provide a field for manipulating the droplet 15 to perform operations such as movement, break-up, and mixing. In some embodiments, the electrode 130 and the power source 14 may be connected by a wire 133.
In an embodiment of the present specification, there is also provided a driving method of the above microfluidic chip, where a droplet is placed on an electrode of the microfluidic chip so as to contact at least two electrodes, and a voltage is adjusted to the electrode on a preset movement path, so that the droplet moves from one electrode to another electrode along the preset movement path.
In order to avoid the problems of breakdown of the dielectric layer, instability of the device, and the like, in some embodiments, the voltage applied to the electrodes may be 1V to 20V. In some embodiments, the voltage applied to the electrodes may be between 2.5V and 17.5V. In some embodiments, the voltage applied to the electrodes may be between 5V and 15V. In some embodiments, the voltage applied to the electrodes may be 7.5V to 12.5V. In some embodiments, the voltage applied to the electrodes may be between 10V and 12.5V. In some embodiments, voltages of opposite polarities, such as +3V and-3V, +4V and-4V, +2V and-2V or +1V and-1V, may be applied between adjacent electrodes on the preset motion path. In some embodiments, voltages with different magnitudes, such as 4V and 1V, 4V and 2V, or 4V and 3V, may be applied between adjacent electrodes on the predetermined moving path.
In order to reduce the driving voltage when the microfluidic chip operates, in some embodiments, the droplet may include an ionic surfactant. In some embodiments, the ionic surfactant may include a cationic surfactant and an anionic surfactant. In some embodiments, the cationic surfactant may include one or more of dodecyltrimethylammonium bromide, hexadecyltrimethylammonium bromide, tetradecyltrimethylammonium bromide, octadecyltrimethylammonium chloride, distearylmethylammonium methylsulfate, ceteareth-21. In some embodiments, the anionic surfactant may include one or more of sodium lauryl sulfate, sodium lauryl polyoxyethylene ether sulfate, ammonium lauryl sulfate, dodecylbenzene sulfonic acid, triethanolamine lauryl sulfate, sodium secondary alkyl sulfonate, sodium fatty alcohol isethionate, sodium N-lauroyl sarcosinate, sodium cocoyl methyl taurate, sodium N-lauroyl glutamate, magnesium amidopolyoxyethylene ether sulfate, sodium laureth carboxylate, lauryl phosphate, potassium lauryl phosphate, triethanolamine lauryl phosphate, disodium lauryl polyoxyethylene ether sulfosuccinate, sodium alpha-alkenyl sulfonate.
In some embodiments, the final concentration of ionic surfactant in the droplets may be between 0.005 and 0.5CMC. In some embodiments, the final concentration of ionic surfactant in the droplets may be between 0.0075 and 0.49CMC. In some embodiments, the final concentration of ionic surfactant in the droplets may be between 0.01 and 0.475CMC. In some embodiments, the final concentration of ionic surfactant in the droplets may be between 0.025 and 0.45CMC. In some embodiments, the final concentration of ionic surfactant in the droplets may be between 0.05 and 0.425CMC. In some embodiments, the final concentration of ionic surfactant in the droplets may be from 0.075 to 0.4CMC. In some embodiments, the final concentration of ionic surfactant in the droplets may be between 0.1 and 0.375CMC. In some embodiments, the final concentration of ionic surfactant in the droplets may be between 0.125 and 0.35CMC. In some embodiments, the final concentration of ionic surfactant in the droplets may be between 0.15 and 0.325CMC. In some embodiments, the final concentration of ionic surfactant in the droplets may be between 0.175 and 0.3CMC. In some embodiments, the final concentration of ionic surfactant in the droplets may be between 0.2 and 0.275CMC. In some embodiments, the final concentration of ionic surfactant in the droplets may be between 0.225 and 0.25CMC.
The term "droplet" means a volume of liquid on a droplet actuator. In some embodiments, the droplet driver may be a droplet microfluidic chip. Typically, the droplet is at least partially bounded by the fill fluid. For example, the droplet may be completely surrounded by the fill fluid or may be bounded by the fill fluid and one or more surfaces of the droplet driver. As another example, a droplet may be bounded by a fill fluid, one or more surfaces of a droplet actuator, and/or the atmosphere. As yet another example, the droplets may be bounded by a fill fluid and the atmosphere. The droplets may for example be aqueous or non-aqueous or may be a mixture or emulsion comprising aqueous and non-aqueous components. The droplets can take a wide variety of shapes; non-limiting examples generally include disc-shaped, bullet-shaped, truncated spherical, ellipsoidal, spherical, partially compressed spheres, hemispherical, ovoid, cylindrical, combinations of such shapes, and various shapes formed during droplet operations such as merging or splitting, or due to contact of such shapes with one or more surfaces of a droplet drive. In some embodiments, the droplets may be aqueous droplets.
In some embodiments, the droplet can include a biological sample, such as whole blood, lymph, serum, plasma, sweat, tears, saliva, sputum, cerebrospinal fluid, amniotic fluid, semen, vaginal secretions, serous fluid, synovial fluid, pericardial fluid, ascites, pleural fluid, exudates, secretions, cystic fluid, bile, urine, gastric fluid, intestinal fluid, fecal samples, fluids containing single or multiple cells, fluids containing organelles, fluidized tissues, fluidized organisms, fluids containing multicellular organisms, biological swabs, and biological washes. In addition, the droplets may include reagents such as water, deionized water, saline solutions, acidic solutions, basic solutions, cleaner solutions, and/or buffers. The droplets may contain proteins or enzymes. The droplets may contain nucleic acids, such as DNA, genomic DNA, RNA, mRNA, or analogs thereof; nucleotides such as deoxyribonucleotides, ribonucleotides, or analogs thereof such as analogs having a terminator moiety.
In some embodiments, the droplet may include an enzyme such as a polymerase, ligase, recombinase, or transposase; binding partners such as antibodies, epitopes, streptavidin, avidin, biotin, lectins or carbohydrates; or other biochemically active molecules. In some embodiments, the droplets may include reagents, such as reagents for biochemical protocols, nucleic acid amplification protocols, affinity-based assay protocols, enzymatic assay protocols, sequencing protocols, and/or biological fluid analysis protocols. In some embodiments, a droplet may comprise one or more beads.
In some embodiments, referring to fig. 3 and 4, the droplet 15 is placed on the electrodes 130 of the microfluidic chip 10 such that it contacts at least two electrodes (130 a, 130 b), and the droplet 15 is moved from one electrode 130a to the other electrode 130b by adjusting the voltage (+ 3V and-3V) to the electrodes on the preset movement path.
The movement of the droplet 15 on the electrode 130 is controlled by applying a voltage to the electrode 130. In some embodiments, referring to FIGS. 4 and 5, a voltage of +3V may be applied to electrode 130a and a voltage of-3V may be applied to electrode 130b by a power supply. Electrical dehumidification of the droplet 15 on the electrode 130a will occur resulting in an increase in the contact angle. The droplet 15 will be electrowetting on the electrode 130b resulting in a decrease of the contact angle. The droplet will move from electrode 130a towards electrode 130b.
As used herein, the term "contact angle" refers to an angle measured through a liquid where the liquid interface contacts a solid surface. A solid with a small contact angle is easily wetted by a liquid, whereas a solid with a large contact angle is not easily wetted by a liquid. The magnitude of the contact angle can therefore be used as an intuitive measure of wetting.
As used herein, the term "electrowetting" refers to the process in which the contact angle between a droplet and an electrode becomes smaller and the electrode becomes more hydrophilic.
As used herein, the term "electrical dehumidification" refers to the process by which the contact angle between a droplet and an electrode becomes larger and the electrode becomes more hydrophobic.
In some embodiments, the initial contact angle of the droplet 15 with the electrode pattern 13 may be between 15 ° and 35 ° to achieve droplet driving by the dual electrical effect. In some embodiments, droplet actuation may be achieved by electrical dehumidification when the initial contact angle of the droplet 15 with the electrode pattern 13 is below 20 °. In some embodiments, droplet actuation may be achieved by electrowetting when the initial contact angle of the droplet 15 with the electrode pattern 13 is higher than 30 °.
The term "dual electrical effect" refers to the change of the electrode pattern from an original hydrophilic state to hydrophobic (electro-dehumidification), or from an original hydrophilic state to more hydrophilic (electro-wetting), by changing the direction of the electric field.
The embodiment of the specification also provides application of the microfluidic chip in a microfluidic control system, biological detection and chemical detection. In some embodiments, the microfluidic chip can be used as an independent reaction unit to implement qualitative or quantitative applications in molecular diagnosis, immunochemistry, cell culture, polymer synthesis, single cell analysis, drug delivery, and the like, in combination with fluorescence imaging analysis, spectroscopy, electrochemistry, capillary electrophoresis, mass spectrometry, nuclear magnetic resonance spectroscopy, chemiluminescence, and the like.
Having thus described the basic concept, it will be apparent to those skilled in the art that the foregoing detailed disclosure is to be regarded as illustrative only and not as limiting the present specification. Various modifications, improvements and adaptations to the present description may occur to those skilled in the art, although not explicitly described herein. Such modifications, improvements and adaptations are proposed in the present specification and thus fall within the spirit and scope of the exemplary embodiments of the present specification.
Also, the description uses specific words to describe embodiments of the description. Reference throughout this specification to "one embodiment," "an embodiment," and/or "some embodiments" means that a particular feature, structure, or characteristic described in connection with at least one embodiment of the specification is included. Therefore, it is emphasized and should be appreciated that two or more references to "an embodiment" or "one embodiment" or "an alternative embodiment" in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, some features, structures, or characteristics of one or more embodiments of the specification may be combined as appropriate.
Numerals describing the number of components, attributes, etc. are used in some embodiments, it being understood that such numerals used in the description of the embodiments are modified in some instances by the use of the modifier "about", "approximately" or "substantially". Unless otherwise indicated, "about", "approximately" or "substantially" indicates that the number allows a variation of ± 20%. Accordingly, in some embodiments, the numerical parameters used in the specification and claims are approximations that may vary depending upon the desired properties of the individual embodiments. In some embodiments, the numerical parameter should take into account the specified significant digits and employ a general digit-preserving approach. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the range in some embodiments of the specification are approximations, in specific embodiments, such numerical values are set forth as precisely as possible within the practical range.
Finally, it should be understood that the embodiments described herein are merely illustrative of the principles of the embodiments described herein. Other variations are also possible within the scope of the present description. Thus, by way of example, and not limitation, alternative configurations of the embodiments of the specification can be considered consistent with the teachings of the specification. Accordingly, the embodiments of the present description are not limited to only those embodiments explicitly described and depicted herein.

Claims (10)

1. The micro-fluidic chip is characterized by comprising an insulating substrate, wherein an electrode pattern is formed on the insulating substrate, the electrode pattern comprises a plurality of electrodes, gaps are formed between every two adjacent electrodes, and each electrode is provided with a power supply connecting element so as to be suitable for respectively controlling the polarity and the voltage of each electrode.
2. The microfluidic chip of claim 1, wherein:
a dielectric layer is arranged between the insulating substrate and the electrode pattern;
and/or, the electrodes comprise at least two electrodes of different surface areas;
and/or, a top surface of the electrode pattern is exposed;
and/or the electrode and/or the power supply connecting element are formed by photoetching or etching after a conducting layer is formed on the insulating substrate;
and/or the width of the gap is 1-100 μm;
and/or the resistivity of the electrode is lower than 0.003 ohm cm;
and/or the microfluidic chip further comprises a control element and a power supply, the electrodes are respectively connected with the power supply through power supply connecting elements, and the control element is electrically connected with the electrodes and used for controlling the polarity and voltage of the electrodes.
3. The microfluidic chip of claim 2, wherein the dielectric layer has a relative dielectric constant greater than 3.
4. A method for driving a microfluidic chip according to any one of claims 1 to 3,
and placing the liquid drop on the electrodes of the microfluidic chip to enable the liquid drop to contact at least two electrodes, and adjusting the voltage of the electrodes on the preset movement path to enable the liquid drop to move from one electrode to the other electrode along the preset movement path.
5. The driving method according to claim 4, wherein the voltage applied to the electrode is 1V to 20V.
6. The driving method according to claim 4, wherein voltages of opposite polarities are applied between adjacent electrodes on the preset movement path; and/or voltages with different magnitudes are applied between adjacent electrodes on the preset motion path.
7. The driving method as claimed in claim 4, wherein said liquid droplet contains therein an ionic surfactant including a cationic surfactant and an anionic surfactant.
8. The driving method as claimed in claim 4, wherein the cationic surfactant comprises one or more of dodecyl trimethyl ammonium bromide, hexadecyl trimethyl ammonium bromide, tetradecyl trimethyl ammonium bromide, octadecyl trimethyl ammonium chloride, distearyl hydroxyethyl methyl ammonium methylsulfate, ceteareth-21; the anionic surfactant comprises one or more of sodium dodecyl sulfate, lauryl alcohol polyoxyethylene ether sodium sulfate, ammonium dodecyl sulfate, dodecyl benzene sulfonic acid, lauryl sulfate triethanolamine, secondary alkyl sodium sulfonate, fatty alcohol hydroxyethyl sodium sulfonate, N-lauroyl sarcosine sodium salt, cocoyl methyl taurate, N-lauroyl sodium glutamate, amide polyoxyethylene ether magnesium sulfate, lauryl alcohol polyoxyethylene ether sodium carboxylate, dodecyl phosphate potassium salt, dodecyl phosphate triethanolamine, lauryl alcohol polyoxyethylene ether disodium sulfosuccinate and alpha-alkenyl sodium sulfonate.
9. The driving method as claimed in claim 4, wherein the final concentration of the ionic surfactant in the liquid droplet is 0.005 to 0.5CMC.
10. Use of the microfluidic chip according to any of claims 1 to 3 in microfluidic control systems, biological assays, chemical assays.
CN202211124391.9A 2022-09-15 2022-09-15 Droplet micro-fluidic chip Pending CN115475669A (en)

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