CN108148757A - A kind of integrated ITO and piezoelectric pump micro-fluidic chip - Google Patents
A kind of integrated ITO and piezoelectric pump micro-fluidic chip Download PDFInfo
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- CN108148757A CN108148757A CN201611102248.4A CN201611102248A CN108148757A CN 108148757 A CN108148757 A CN 108148757A CN 201611102248 A CN201611102248 A CN 201611102248A CN 108148757 A CN108148757 A CN 108148757A
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- C12M23/00—Constructional details, e.g. recesses, hinges
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- C12M23/16—Microfluidic devices; Capillary tubes
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- C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
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- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/12—Means for regulation, monitoring, measurement or control, e.g. flow regulation of temperature
- C12M41/18—Heat exchange systems, e.g. heat jackets or outer envelopes
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Abstract
A kind of integrated ITO and piezoelectric pump micro-fluidic chip, can perfusion culture cell, and cell state can be observed in real time in cell processes are cultivated, which forms as follows：Piezoelectric pump (1), microfluidic channel (2) and substrate (3)；Three stacks arrangement successively from top to bottom；Piezoelectric pump (1) forms as follows：Culture solution entrance (7), the second check valve (10), piezoelectricity shake sub (8), the first check valve (9), Cell infusion mouth (5) and culture solution outlet (4)；Substrate (3) forms as follows：First electrode (13), second electrode (16), ITO (14) and temperature sensor (15)；External power supply is connected between first electrode (13) and second electrode (16) makes ITO (14) that can heat monoblock micro-fluidic chip, and temperature sensor (15) can control the temperature of the environment of cell culture.The present invention is applied widely, it can be achieved that high-throughput, and observation cell in real time for a long time；It is simple in structure, it is small, it is at low cost.It is with expected more huge economic value and social value.
Description
Technical field
The present invention relates to the microfluidic chip structure designs and applied technical field of biomedical sector, specifically provide one
The integrated ITO of kind and piezoelectric pump micro-fluidic chip.
Background technology
Biomedical sector micro-fluidic chip is biology, the sample preparation of medical analysis process, reaction, separation, detection
Basic operation units is waited to be integrated on the chip of one piece of micro-meter scale, complete analytic process.Due to it great potential,
Develop into the brand-new research field of the subject crossings such as biology, chemistry, medicine, fluid, electronics, material, a machinery.It is micro- at present
Fluidic chip trend is：Integrated assembly of elements is more and more, and integrated scale is increasing.Including for fluid control
The components such as micro-valve, Micropump, separation and the detection of system, integrated microfluidic chip have that raw material consumption is low, and run time is short, and price is low
Honest and clean, safe to use, flux is high, pollutes the features such as small, these are obviously advantages.
A kind of cell culture apparatus for having the function of to cultivate fluid exchange is disclosed in 104169413 A of patent document 1CN,
In the small-scale cell culture apparatus that the mode of cell is cultivated in a small number of culture dishes, culture solution can be carried out in identical intracavitary
It is automatic replace and cell culture, this device cannot provide environmental condition needed for cell culture, culture cell processes cannot be real
When observe.
One kind is disclosed in 103667053 A of patent document 2CN and automatically continuously changes liquid cell culture apparatus, has both had company
Continuous changing liquid automatically control ability, and can provide cell culture required condition, realize that cell culture fluid is automatic in incubation
It is continuous to replace.This apparatus structure is complicated, and cell is needed to take out culture environment, could be observed.
Cell culture is scientific research and field of biological pharmacy basic technology and important research means, currently with micro-fluidic
Chip culture cell can not need to manually replace, but the growing environment of cell also needs to incubator with continuous perfusion culture liquid
It providing, culture environment chip must be taken out when observing cell, the influence of the variation of environment to cell sample cannot be ignored, and
Syringe pump needed for perfusion or peristaltic pump, volume is larger, and attended operation and setting flow control are cumbersome, in addition, cell is being cultivated
It needs to be observed in real time in the process.
People are highly desirable to obtain a kind of excellent integrated ITO of technique effect and piezoelectric pump micro-fluidic chip.
Invention content
The object of the present invention is to provide a kind of excellent integrated ITO of technique effect and piezoelectric pump micro-fluidic chips.For mesh
Preceding cell cultivation instrument there are the defects of, the present invention can be realized in cell culture and experimentation for a long time and high throughput, grasp
Make convenient and cell can be observed in real time for a long time.
The present invention provides a kind of integrated ITO and piezoelectric pump micro-fluidic chips, it is characterised in that：It can perfusion culture it is thin
Born of the same parents, and cell state can be observed in real time in cell processes are cultivated, which forms as follows：Piezoelectric pump 1, microfluidic channel
2 and substrate 3；Three stacks arrangement successively from top to bottom；Wherein：
Structure on 1 matrix of piezoelectric pump forms as follows：Culture solution entrance 7, the second check valve 10, piezoelectricity shake 8, the
One check valve 9, Cell infusion mouth 5 and culture solution outlet 4；Wherein：Cell infusion mouth 5 and culture solution outlet 4 are all perforation plates
The fluid flow paths and the two of 1 thickness direction of piezoelectric pump are on the length direction of 1 matrix of piezoelectric pump of rectangle tabular structure
It separates far from arrangement；Culture solution entrance 7 connects culture solution temporary storage cavity by the second check valve 10, and culture solution temporary storage cavity lower part is set
The channel to close 2 one side opening of microfluidic channel in 1 downside of piezoelectric pump is equipped with, the first check valve 9 is provided on the channel；
The groove structure of following perforation matrix thickness is provided on 2 matrix of microfluidic channel：Culture solution channel 11；Training
Cell culture area 12 is provided on nutrient solution channel 11；
The substrate 3 forms as follows：First electrode 13, second electrode 16, ITO14 and temperature sensor 15；Wherein：
ITO14 is N-type oxide semiconductor material, and material is tin indium oxide, is layer structure；First electrode 13 and second electrode
16 are arranged in the both ends proximal end of ITO14；Temperature sensor 15 is arranged close to ITO14；
External power supply is connected between first electrode 13 and second electrode 16 enables ITO14 to heat monoblock micro-fluidic chip, temperature
Degree sensor 15 can control the temperature of the environment of cell culture；
Cell infusion mouth 5 all connects culture solution channel 11 with culture solution outlet 4；Culture solution is connected in piezoelectric pump 1 to keep in
Chamber lower part and it is provided with the training that the channel of the first check valve 9 connects 5 lower section of Cell infusion mouth by culture solution channel 11
Nutrient solution channel 11；
The piezoelectric pump 1 drives culture solution that it is made to be entered in microfluidic channel 2 by culture solution entrance 7, flows through cell culture
Area 12, the cell that nutrition is cultivated；And metabolite is discharged with culture solution through culture solution outlet 4.
The integrated ITO and piezoelectric pump micro-fluidic chip, also following preferably claimed contents：
The piezoelectric pump 6 is following one of several：Piezoelectricity chip has valve piezoelectric pump, piezo-stack type to have valve piezoelectric pump, more
Cavity has valve piezoelectric pump, cone-shaped tube Valveless piezoelectric pump, shape tube Valveless piezoelectric pump, temperature control Valveless piezoelectric pump, piezoelectric ultrasonic pump；Pressure
Electric pump 6 control range of flow for 0.001 microlitre per hour~1 liter per hour.
The quantity in cell culture area 12 is 2~1000, culture solution entrance 7, culture solution outlet 4 and Cell infusion mouth 5
Equal quantity is also 2~1000.
The shape in cell culture area 12 is following one of several or its certain combination：Rectangle, square, circle, ellipse
Shape, diamond shape, triangle and number of edges are more than four certain polygon；Or the integrated ITO and piezoelectric pump micro-fluidic chip it is direct
Using microfluidic channel 2 itself as cell culture area 12.
The areal extent in cell culture area 12 can be 1 square micron~100 square millimeter.
The substrate 3 is ITO heating films or ito glass with heating function, and thickness can be 10 microns~10 lis
Rice.
There are two types of the 2 preferred structures of microfluidic channel：
First, following annulars and perforation matrix thickness groove structure is provided on 2 matrix of microfluidic channel：Training
Nutrient solution channel 11 and cell culture area 12；Cell culture area 12 has 2 and the two is set in the length direction of matrix, 2 cells
Groove structure that cultivation region 12 is circularized by 11 serial communication of culture solution channel and perforation matrix thickness.Referring to Fig. 4；
Second, strip is provided on 2 matrix of microfluidic channel and penetrates through the groove structure in matrix thickness direction：Culture
Liquid channel 11；Cell culture area 12 is additionally provided at 11 middle part of culture solution channel.Referring to Fig. 6.
The chip is capable of providing the environmental condition and experiment condition for meeting culture cell, and core is adjusted by temperature sensor
Piece internal conditions.
The present invention provides a kind of integrated ITO and piezoelectric pump micro-fluidic chip, cell culture and micro-fluidic can be carried out
Perfusion experiment, and cell is being cultivated and can observed in real time in experimentation.Chip uses ITO mode of heatings and miniature temperature
Degree sensor control provides temperature condition for cell culture；Cell is filled into carefully by Cell infusion mouth 5 first when cultivating cell
Born of the same parents cultivation region 12 after cell is adherent, conveys culture solution nutrition using piezoelectric pump 1 and cultivates cell.
The invention has the advantages that：
(1) it suitable for chip culture cell or micro-fluidic chip perfusion experiment, is also applied for using fungi, microorganism, carefully
Bacterium and the culture of nematode.
(2) during culture cell or micro-fluidic chip perfusion experiment, it can be achieved that high-throughput, and observation in real time for a long time
Cell.
(3) apparatus structure is simple, small, at low cost.
In terms of comprehensive, the present invention has expected more huge economic value and social value.
Description of the drawings
Below in conjunction with the accompanying drawings and embodiment the present invention is described in further detail：
Fig. 1 is that integrated ITO and piezoelectric pump micro-fluidic chip are integrally formed STRUCTURE DECOMPOSITION relationship simplified schematic diagram；
Fig. 2 is the structure schematic diagram stereogram of piezoelectric pump 1；
Fig. 3 is the lateral view of structure schematic diagram of piezoelectric pump 1 (dotted line expression is internally provided with structure)；
Fig. 4 is the structural principle simplified schematic diagram of microfluidic channel 2；
Fig. 5 is the structural principle simplified schematic diagram of substrate 3；
Fig. 6 is the structural principle simplified schematic diagram of another microfluidic channel 2.
Specific embodiment
Embodiment 1
A kind of integrated ITO and piezoelectric pump micro-fluidic chip, can perfusion culture cell, and in cell processes are cultivated
Cell state can be observed in real time, which forms as follows：Piezoelectric pump 1, microfluidic channel 2 and substrate 3；Three from top to bottom according to
It is secondary to stack arrangement；Wherein：
Structure on 1 matrix of piezoelectric pump forms as follows：Culture solution entrance 7, the second check valve 10, piezoelectricity shake 8, the
One check valve 9, Cell infusion mouth 5 and culture solution outlet 4；Wherein：Cell infusion mouth 5 and culture solution outlet 4 are all perforation plates
The fluid flow paths and the two of 1 thickness direction of piezoelectric pump are on the length direction of 1 matrix of piezoelectric pump of rectangle tabular structure
It separates far from arrangement；Culture solution entrance 7 connects culture solution temporary storage cavity by the second check valve 10, and culture solution temporary storage cavity lower part is set
The channel to close 2 one side opening of microfluidic channel in 1 downside of piezoelectric pump is equipped with, the first check valve 9 is provided on the channel；
Following annulars and perforation matrix thickness groove structure is provided on 2 matrix of microfluidic channel：Culture solution
Channel 11 and cell culture area 12；Cell culture area 12 has 2 and the two is set in the length direction of matrix, 2 cell culture
Groove structure that area 12 is circularized by 11 serial communication of culture solution channel and perforation matrix thickness；Referring to Fig. 4；
The substrate 3 forms as follows：First electrode 13, second electrode 16, ITO14 and temperature sensor 15；Wherein：
ITO14 is N-type oxide semiconductor material, and material is tin indium oxide, is layer structure；First electrode 13 and second electrode
16 are arranged in the both ends proximal end of ITO14；Temperature sensor 15 is arranged close to ITO14；
External power supply is connected between first electrode 13 and second electrode 16 enables ITO14 to heat monoblock micro-fluidic chip, temperature
Degree sensor 15 can control the temperature of the environment of cell culture；
Cell infusion mouth 5 all connects culture solution channel 11 with culture solution outlet 4；Culture solution is connected in piezoelectric pump 1 to keep in
Chamber lower part and it is provided with the training that the channel of the first check valve 9 connects 5 lower section of Cell infusion mouth by culture solution channel 11
Nutrient solution channel 11；
The piezoelectric pump 1 drives the microfluidic channel 2 that culture solution makes it be entered by culture solution entrance 7 in microfluidic channel 2,
Flow through cell culture area 12, the cell that nutrition is cultivated；And metabolite is discharged with culture solution through culture solution outlet 4.
The integrated ITO and piezoelectric pump micro-fluidic chip, also following preferably claimed contents：
The piezoelectric pump 6 is following one of several：Piezoelectricity chip has valve piezoelectric pump, piezo-stack type to have valve piezoelectric pump, more
Cavity has valve piezoelectric pump, cone-shaped tube Valveless piezoelectric pump, shape tube Valveless piezoelectric pump, temperature control Valveless piezoelectric pump, piezoelectric ultrasonic pump；Pressure
Electric pump 6 control range of flow for 0.001 microlitre per hour~1 liter per hour.
The quantity in cell culture area 12 is 2~1000, culture solution entrance 7, culture solution outlet 4 and Cell infusion mouth 5
Equal quantity is also 2~1000.
The shape in cell culture area 12 is following one of several or its certain combination：Rectangle, square, circle, ellipse
Shape, diamond shape, triangle and number of edges are more than four certain polygon；Or the integrated ITO and piezoelectric pump micro-fluidic chip it is direct
Using microfluidic channel 2 itself as cell culture area 12.
The areal extent in cell culture area 12 can be 1 square micron~100 square millimeter.
The substrate 3 is ITO heating films or ito glass with heating function, and thickness can be 10 microns~10 lis
Rice.
The chip is capable of providing the environmental condition and experiment condition for meeting culture cell, and core is adjusted by temperature sensor
Piece internal conditions.
A kind of integrated ITO and piezoelectric pump micro-fluidic chip are present embodiments provided, cell culture and miniflow can be carried out
Perfusion experiment is controlled, and cell is being cultivated and can observed in real time in experimentation.Chip uses ITO mode of heatings and miniature
Temperature sensor control provides temperature condition for cell culture；Cell is filled by Cell infusion mouth 5 first when cultivating cell
Cell culture area 12 after cell is adherent, conveys culture solution nutrition using piezoelectric pump 1 and cultivates cell.
The present embodiment has the advantages that：
(2) it suitable for chip culture cell or micro-fluidic chip perfusion experiment, is also applied for using fungi, microorganism, carefully
Bacterium and the culture of nematode.
(2) during culture cell or micro-fluidic chip perfusion experiment, it can be achieved that high-throughput, and observation in real time for a long time
Cell.
(3) apparatus structure is simple, small, at low cost.
In terms of comprehensive, the present embodiment has expected more huge economic value and social value.
Embodiment 2
The present embodiment content and embodiment 1 are essentially identical, and difference is mainly：
Strip is provided on 2 matrix of microfluidic channel and penetrates through the groove structure in matrix thickness direction：Culture solution leads to
Road 11；Cell culture area 12 is additionally provided at 11 middle part of culture solution channel.Referring to Fig. 6.
Embodiment 3
A kind of integrated ITO and piezoelectric pump micro-fluidic chip primary structure include：Piezoelectric pump 1, microfluidic channel 2 and substrate 3,
With reference to Fig. 1, the piezoelectric pump includes sub 8, first check valve 9 of piezoelectricity shake, the second check valve 10, culture solution entrance 7, culture solution and goes out
Mouth 4 and Cell infusion entrance 5；Wherein culture solution entrance 7, culture solution outlet 4 and Cell infusion entrance 5 and culture fluid course 11
It is connected, culture solution is driven from culture solution entrance 7 by piezoelectric pump and enters microfluidic channel, then by 4 outflow of culture solution outlet；It fills
When noting cell the cell to be cultivated is poured into from Cell infusion entrance 5 to the cell culture area 12 of microfluidic channel 2.Reference Fig. 1,
With reference to shown in Fig. 2 and Fig. 3.
The microfluidic channel 2 includes culture solution channel 11 and cell culture area 12；Wherein culture solution channel 11 is used for defeated
Culture solution is sent to cell culture area 12, the cell that nutrition is cultivated.With reference to Fig. 1 and Fig. 4.
The substrate includes electrode 13, ITO14 and temperature sensor 15；Wherein electrode 13 is connect with external power supply；ITO14
Monoblock chip and culture solution can be heated after energization；Temperature sensor 15 can control the temperature of cell culture environment.With reference to Fig. 1 and
Fig. 5.
The piezoelectric pump 1 has valve piezoelectric pump, piezo-stack type to have valve piezoelectric pump, Multicarity to have valve piezoelectricity for piezoelectricity chip
Pump, cone-shaped tube Valveless piezoelectric pump, shape tube Valveless piezoelectric pump, temperature control Valveless piezoelectric pump and piezoelectric ultrasonic pump one of which；Piezoelectricity
Pump control range of flow for 0.001 microlitre per hour~1 liter per hour.
The quantity of the culture solution channel 11 and cultivation region 12 is 2~1000, and culture solution entrance 7, culture solution export 4 and
The equal quantity of Cell infusion entrance 5 is also 2~1000；Wherein the shape in cell culture area 12 can be rectangle, pros
Shape, circle, ellipse, diamond shape, triangle and polygon one or more combinations therein or microfluidic channel are in itself；Carefully
The areal extent of born of the same parents cultivation region can be 1 square micron~100 square millimeter.With reference to figure 4 and Fig. 6.
The substrate 3 is ITO14 heating films or ITO14 glass with heating function, and thickness can be 10 microns~10
Centimetre.
The chip is capable of providing the environmental condition and experiment condition for meeting culture cell, and core is adjusted by temperature sensor
Piece internal conditions.
A kind of integrated ITO and piezoelectric pump micro-fluidic chip are present embodiments provided, cell culture and micro-fluidic can be carried out
Perfusion experiment, and cell is being cultivated and can observed in real time in experimentation.Chip uses ITO mode of heatings and miniature temperature
Degree sensor control provides temperature condition for cell culture；Cell is filled into cell by Cell infusion mouth first when cultivating cell
After cell is adherent, cell is cultivated using piezoelectric pump conveying culture solution nutrition for cultivation region.
Claims (8)
1. a kind of integrated ITO and piezoelectric pump micro-fluidic chip, it is characterised in that：It can perfusion culture cell, and cultivating
Cell state can be observed in cell processes in real time, which forms as follows：Piezoelectric pump (1), microfluidic channel (2) and substrate
(3)；Three stacks arrangement successively from top to bottom；Wherein：
Structure on piezoelectric pump (1) matrix forms as follows：Culture solution entrance (7), the second check valve (10), piezoelectricity shake
(8), the first check valve (9), Cell infusion mouth (5) and culture solution outlet (4)；Wherein：Cell infusion mouth (5) and culture solution outlet
(4) all be penetrate through plate piezoelectric pump (1) thickness direction fluid flow paths and the two rectangle tabular structure piezoelectric pump
(1) it is separated on the length direction of matrix far from arrangement；It is temporary that culture solution entrance (7) by the second check valve (10) connects culture solution
Chamber is deposited, culture solution temporary storage cavity lower part is provided with the channel to close (2) one side opening of microfluidic channel in piezoelectric pump (1) downside,
The first check valve (9) is provided on the channel；
The groove structure of following perforation matrix thickness is provided on microfluidic channel (2) matrix：Culture solution channel (11)；Training
Cell culture area (12) is provided on nutrient solution channel (11)；
The substrate (3) forms as follows：First electrode (13), second electrode (16), ITO (14) and temperature sensor (15)；Its
In：ITO (14) is layer structure；First electrode (13) and second electrode (16) are arranged in the both ends proximal end of ITO (14)；
Temperature sensor (15) is arranged close to ITO (14)；
External power supply is connected between first electrode (13) and second electrode (16) makes ITO (14) that can heat monoblock micro-fluidic chip,
Temperature sensor (15) can control the temperature of the environment of cell culture；
Cell infusion mouth (5) all connects culture solution channel (11) with culture solution outlet (4)；Connection culture solution in piezoelectric pump (1)
It temporary storage cavity lower part and is provided with the channel of the first check valve (9) Cell infusion mouth is connected by culture solution channel (11)
(5) the culture solution channel (11) below；
The piezoelectric pump (1) driving culture solution makes it by culture solution entrance (7) into the microfluidic channel in microfluidic channel (2)
(2), cell culture area (12), the cell that nutrition is cultivated are flowed through；And metabolite is exported with culture solution through culture solution
(4) it discharges.
2. according to ITO and piezoelectric pump micro-fluidic chip is integrated described in claim 1, it is characterised in that：
The piezoelectric pump (6) is following one of several：Piezoelectricity chip has valve piezoelectric pump, piezo-stack type to have valve piezoelectric pump, multi-cavity
Body has valve piezoelectric pump, cone-shaped tube Valveless piezoelectric pump, shape tube Valveless piezoelectric pump, temperature control Valveless piezoelectric pump, piezoelectric ultrasonic pump；Piezoelectricity
(6) control range of flow is pumped as 0.001 microlitre per hour~1 liter per hour.
3. according to ITO and piezoelectric pump micro-fluidic chip is integrated described in claim 1, it is characterised in that：
The quantity in cell culture area (12) is 2~1000, culture solution entrance (7), culture solution outlet (4) and Cell infusion mouth
(5) equal quantity is also 2~1000.
4. according to ITO and piezoelectric pump micro-fluidic chip is integrated described in claim 1, it is characterised in that：
The shape in cell culture area (12) is following one of several or its certain combination：Rectangle, square, circle, ellipse,
Diamond shape, triangle and number of edges are more than four certain polygon；
Or the integrated ITO and piezoelectric pump micro-fluidic chip are directly using microfluidic channel (2) itself as cell culture area
(12)。
5. according to ITO and piezoelectric pump micro-fluidic chip is integrated described in claim 1, it is characterised in that：Cell culture area (12)
Areal extent can be 1 square micron~100 square millimeter.
6. according to ITO and piezoelectric pump micro-fluidic chip is integrated described in claim 1, it is characterised in that：
The substrate (3) is ITO heating films or ito glass with heating function, and thickness can be 10 microns~10 centimetres.
7. according to one of the claim 1-6 integrated ITO and piezoelectric pump micro-fluidic chip, it is characterised in that：It is described micro-
Following annulars and perforation matrix thickness groove structure is provided on flow control channel (2) matrix：Culture solution channel (11) and thin
Born of the same parents cultivation region (12)；Cell culture area (12) has 2 and the two is set in the length direction of matrix, 2 cell culture areas (12)
Groove structure circularized by culture solution channel (11) serial communication and perforation matrix thickness.
8. according to one of the claim 1-6 integrated ITO and piezoelectric pump micro-fluidic chip, it is characterised in that：It is described micro-
Strip is provided on flow control channel (2) matrix and penetrates through the groove structure in matrix thickness direction：Culture solution channel (11)；It is cultivating
Cell culture area (12) is additionally provided in the middle part of liquid channel (11).
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108893411A (en) * | 2018-06-15 | 2018-11-27 | 杭州电子科技大学 | Micro-fluidic chip and its manufacturing method based on photocuring printing |
| CN112501020A (en) * | 2020-12-04 | 2021-03-16 | 西北大学 | Biological tissue culture system based on micro-fluidic chip and implementation operation method thereof |
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