CN106018775A - Micro-via array cancer cell detection biological chip and manufacturing method thereof - Google Patents
Micro-via array cancer cell detection biological chip and manufacturing method thereof Download PDFInfo
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- CN106018775A CN106018775A CN201610298065.8A CN201610298065A CN106018775A CN 106018775 A CN106018775 A CN 106018775A CN 201610298065 A CN201610298065 A CN 201610298065A CN 106018775 A CN106018775 A CN 106018775A
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5091—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing the pathological state of an organism
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/65—Raman scattering
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Abstract
The invention provides a micro-via array cancer cell detection biological chip and a manufacturing method thereof. The chip is composed of a high-molecular polymer substrate, micro-via arrays distributed on the substrate and a metal film. The manufacturing method mainly includes the steps of photoetching, plasma etching and film plating. The controllable manufacturing of the high-molecular polymer micro-via array cancer cell detection chip can be achieved. The chip filters out normal red blood cells and blocks cancerous cells with enlarged size through the micro-via arrays, and then determines the number and types of cancer cells through the Raman spectrum imaging technology, thereby providing an effective solution for early detection, determination and diagnosis of cancer cells.
Description
Technical field
The present invention relates to a kind of novel micro nanometer structure devices micro through hole array cancerous cell detection biochip, with
And the micro-nano processing method of this kind of chip.
Background technology
World Health Organization's survey result shows, cancer is one of main reason directly resulting in human death,
In the death toll that the whole world is annual, 40% comes from cancer, annual newly-increased cancer patient 14,000,000 people, cancer
Lethal number more than 820 ten thousand people.And suffer from cancer number every year close to 1.3% speed increment.
Existing blood cancer cell detection method mainly includes microscopic examination, biochemistry detection, micro-fluidic
Diagnosis etc..Accuracy and the speed of conventional optical microscope observation cancerous cell pattern are the most poor, Er Qiejian
Survey result and affected bigger by operator's technical merit.The method that biochemical Ag-Ab combines, false negative
False-positive misdiagnosis rate is more, and needs to consume substantial amounts of high cost auxiliary biochemical reagents, processes
Journey is complicated, and efficiency is low.The micro-fluidic diagnostic method of existing physics is similar with the principle of the present invention, mainly
Use the mode filtered according to cancerous cell size, diagnosis efficiency is higher, but existing micro-fluidic diagnostic method
Accuracy not enough, it is impossible to differentiate the leukocyte mixed, and chip cost be higher, every market price
Reach more than 1000 yuan.
At present, chip manufacturing technology mainly has nucleopore membranes technology, and nucleopore membranes uses synchrotron radiation light source to irradiate,
Then development is made, but the pore size prepared differs, and based filtration precision is relatively low；Chip structure mainly has stone
English micro through hole array structure, quartz micro through hole array is also to use lithographic etch process to make, due to quartz thickness
Being difficult to persistently reduce, it is difficult to make high aspect ratio vias, the gap in hole is relatively big, and density is less, and quartz is micro-simultaneously
Hole only possesses filtration, it is impossible to carry out subsequent cell degree of depth examination.
Summary of the invention
The problem relatively low, inefficient, relatively costly in order to solve existing cancerous cell filtrating chip accuracy of detection,
The invention provides a kind of micro through hole array cancerous cell detection biochip and preparation method thereof, when using this chip
Utilize syringe to be expelled on chip by blood cell, by negative pressure, its normal cell is sifted out from through hole, stay
Cancerous cell, then utilizes the alignment of Raman spectrum imaging system to carry out spectrum analysis.
The present invention provides a kind of micro through hole array cancerous cell detection biochip, and chip base is high molecular polymerization
Thing, thickness is distributed micro through hole array on below 100um, high molecular polymer, and hole is all-pass structure, hole
Footpath size is 4um～100um, and hole and gap size ratio are 1:1～1:20, and high molecular polymer surface is one
Layer metal film, thickness is 10nm～500nm.
Described high molecular polymer can be PI, PMMA, PET.
The arrangement mode of described micro through hole array can be positive direction, hexagon and any arrangement mode.
Described metal membrane material is silver, gold or copper.
The present invention also provides for the manufacture method of a kind of micro through hole array cancerous cell detection biochip, the method step
As follows:
(1) photoetching: be attached to smooth for high molecular polymer thin film in hard silicon or quartz substrate, coats photoresist,
Baked and cured, then photoetching development makes photoresist masking figure；
(2) etching: utilize plasma etching machine that the high molecular polymer thin film with photoetching offset plate figure is done
Method etches, and etches micro through hole array structure；
(3) plated film: use chemical deposition by high molecular polymer thin film with micro through hole array structure after sensitization
Metal-coated membrane.
The biochip test cancerous cell that the present invention provides, it is not necessary to high cost reagent and complex process,
On the basis of traditional microfluidic chip technology, introducing Raman enhancement techniques, specificity is higher, can realize cancer
Being precisely separating and the accurate calculating of quantity of cell category, it is excellent to have that accuracy is high, speed is high and simple to operate etc.
Point, in sides such as prevention in time, the most timely discovery of cancer and cancer return controls that cancer patient's focus shifts
Mask is significant.The macromolecular material price that the present invention uses is more cheap, and it is relatively low that processing technique realizes cost,
Being suitable for large-scale production, monolithic cost can be down to less than 10 yuan, it is ensured that the technology of a large amount of blood examination of low cost
Demand.
Accompanying drawing explanation
Fig. 1 is that micro through hole array cancerous cell detects biochip structural representation, and wherein, 1 is high molecular polymerization
Thing substrate, 2 is metal film, and 3 is micro through hole array.
Fig. 2 is micro through hole array fabrication processing schematic diagram.
Fig. 3 is that micro through hole array cancerous cell detects biochip sample drawing.
Fig. 4 is that micro through hole array cancerous cell detects biochip microcosmic microgram.
Detailed description of the invention
The present invention is discussed in detail below in conjunction with the accompanying drawings with embodiment, but following example is only limitted to explain the present invention,
Protection scope of the present invention should include the full content of claim.
Embodiment 1
The present embodiment offer a kind of micro through hole array cancerous cell detection biochip and preparation method thereof, specially one
Kind micro through hole array chip with PI material as substrate and preparation method thereof.
The material of the present embodiment chips high molecular polymer substrate 1 is PI, and thickness is to divide on 25um, PI film
Cloth micro through hole array 3, hole is all-pass structure, and pore size is 10um, and hole and gap size ratio are 1:5,
Array arrangement mode is square, and PI film upper surface metal film 2 is layer of metal silver, concrete structure such as accompanying drawing 1
Shown in.
The chip manufacture method step that the present embodiment provides is as shown in Figure 2, specific as follows:
(1) being fixed on silicon chip by 25um thickness PI film, spin coating photoresist AZ92600, glue thickness 10um, in heat
100 degree of front bakings 10min on plate, then under 365nm ultraviolet exposure machine, utilize contact exposure method,
Exposure dose 100mJ/cm2, develop 30s, and mask graph is copied into photoetching offset plate figure.
(2) exposure imaging is complete, is put in plasma etching machine by the PI film with photoetching offset plate figure, uses oxygen
Gas, fluoroform, three kinds of gas etchings of sulfur hexafluoride, gas flow is 3sccm, 40sccm, 10sccm respectively,
Etching power 100W, etch period 90min, etch micro through hole array structure.
(3) the PI film with micro through hole array is used chemical deposition plating silver.First by PI film in sensitization
Hydrophilic treated in liquid, has then configured silver ammino solution and glucose solution, puts after the PI Membrane cleaning after sensitization
In vessel, silver ammino solution and glucose solution are fallen after vessel, reaction 30s, PI film is taken out, dry
After dry, complete chip manufacturing.
The micro through hole array cancerous cell detection biochip sample such as accompanying drawing prepared by method described in the present embodiment
Shown in 3, microcosmic microgram is as shown in Figure 4.
Embodiment 2
The present embodiment offer a kind of micro through hole array cancerous cell detection biochip and preparation method thereof, specially one
Kind micro through hole array chip with PMMA material as substrate and preparation method thereof.
The present embodiment chips high molecular polymer base material is PMMA, and thickness is 50um, PMMA
Being distributed micro through hole array on film, hole is all-pass structure, and pore size is 4um, and hole with gap size ratio is
1:10, array arrangement mode is hexagon, and PMMA film upper surface metal film is layer of metal gold.
The chip manufacture method step that the present embodiment provides is specific as follows:
(1) 50um thickness PMMA film is fixed on silicon chip, spin coating photoresist AZ92600, glue thickness 10um,
100 degree of front bakings 10min on hot plate, then under 365nm ultraviolet exposure machine, utilize contact exposure side
Method, exposure dose 100mJ/cm2, develop 30s, and mask graph is copied into photoetching offset plate figure.
(2) exposure imaging is complete, by being put in plasma etching machine with the PMMA film of photoetching offset plate figure, adopts
With oxygen, fluoroform, three kinds of gas etchings of sulfur hexafluoride, gas flow is 3sccm, 40sccm respectively,
10sccm, etches power 100W, etch period 90min, etches micro through hole array structure.
(3) PMMA film with micro through hole array is used chemical deposition gold metallization.First by PMMA
Film is hydrophilic treated in sensitizing solution, has then configured AuCl3Solution and oxalic acid solution, by the PMMA after sensitization
It is put in after Membrane cleaning in vessel, AuCl3Solution and oxalic acid solution fall after vessel, reaction 60s, by PMMA
Film takes out, and after drying, completes chip manufacturing.
Embodiment 3
The present embodiment offer a kind of micro through hole array cancerous cell detection biochip and preparation method thereof, specially one
Kind micro through hole array chip with PET material as substrate and preparation method thereof.
The present embodiment chips high molecular polymer base material is PET, and thickness is 80um, and PET film divides
Cloth micro through hole array, hole is all-pass structure, and pore size is 20um, and hole and gap size ratio are 1:20,
Array arrangement mode is annular, and PET film upper surface metal film is layer of metal copper.
The chip manufacture method step that the present embodiment provides is specific as follows:
(1) 80um thickness PET film is fixed on a quartz substrate, spin coating photoresist AZ92600, glue thickness 10um,
100 degree of front bakings 10min on hot plate, then under 365nm ultraviolet exposure machine, utilize contact exposure side
Method, exposure dose 100mJ/cm2, develop 30s, and mask graph is copied into photoetching offset plate figure.
(2) exposure imaging is complete, will be put in plasma etching machine with the PET film of photoetching offset plate figure, uses
Oxygen, fluoroform, three kinds of gas etchings of sulfur hexafluoride, gas flow is 3sccm, 40sccm respectively,
10sccm, etches power 100W, etch period 90min, etches micro through hole array structure.
(3) same, the PET film with micro through hole array is used chemical deposition plating copper, finally by PET
Film takes out dried, completes chip manufacturing.
Claims (5)
1. a micro through hole array cancerous cell detection biochip, it is characterised in that chip base is high molecular polymerization
Thing, thickness is distributed micro through hole array on below 100um, high molecular polymer, and hole is all-pass structure,
Pore size is 4um～100um, and hole and gap size ratio are 1:1～1:20, high molecular polymer surface
For layer of metal film, thickness is 10nm～500nm.
Micro through hole array cancerous cell the most according to claim 1 detection biochip, it is characterised in that described
High molecular polymer can be PI, PMMA, PET.
Micro through hole array cancerous cell the most according to claim 1 detection biochip, it is characterised in that described
The arrangement mode of micro through hole array can be positive direction, hexagon and any arrangement mode.
Micro through hole array cancerous cell the most according to claim 1 detection biochip, it is characterised in that described
Metal membrane material is silver, gold or copper.
5. a manufacture method for micro through hole array cancerous cell as claimed in claim 1 detection biochip, it is special
Levying and be, the method step is as follows:
(1) photoetching: be attached to smooth for high molecular polymer thin film in hard silicon or quartz substrate, coats photoetching
Glue, baked and cured, then photoetching development makes photoresist masking figure；
(2) etching: utilize plasma etching machine that the high molecular polymer thin film with photoetching offset plate figure is carried out
Dry etching, etches micro through hole array structure；
(3) plated film: use chemical deposition by thin with the high molecular polymer of micro through hole array structure after sensitization
Film metal-coated membrane.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610298065.8A CN106018775A (en) | 2016-05-06 | 2016-05-06 | Micro-via array cancer cell detection biological chip and manufacturing method thereof |
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| CN201610298065.8A CN106018775A (en) | 2016-05-06 | 2016-05-06 | Micro-via array cancer cell detection biological chip and manufacturing method thereof |
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| CN201610298065.8A Pending CN106018775A (en) | 2016-05-06 | 2016-05-06 | Micro-via array cancer cell detection biological chip and manufacturing method thereof |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106754720A (en) * | 2016-11-14 | 2017-05-31 | 中国科学院重庆绿色智能技术研究院 | A kind of circulating tumor cell enrichment and micro-imaging sample producing device |
| CN106769693A (en) * | 2016-11-14 | 2017-05-31 | 中国科学院重庆绿色智能技术研究院 | A kind of circulating tumor cell automatic checkout system based on Raman spectrum |
| CN107907529A (en) * | 2017-12-29 | 2018-04-13 | 中国科学院重庆绿色智能技术研究院 | Chip of Raman trace detection and preparation method thereof and application method a kind of environment suitable for complex sample |
| CN108313976A (en) * | 2017-12-29 | 2018-07-24 | 西北工业大学 | A kind of polyimide surface micro-structure preparation method |
| CN109652308A (en) * | 2018-12-20 | 2019-04-19 | 中国科学院微电子研究所 | Cell sorting device |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070025883A1 (en) * | 2005-04-21 | 2007-02-01 | California Institute Of Technology | Uses of parylene membrane filters |
| CN103189122A (en) * | 2010-05-03 | 2013-07-03 | 柯丽安缇维微技术公司 | Polymer microfilters and methods of manufacturing the same |
-
2016
- 2016-05-06 CN CN201610298065.8A patent/CN106018775A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070025883A1 (en) * | 2005-04-21 | 2007-02-01 | California Institute Of Technology | Uses of parylene membrane filters |
| CN103189122A (en) * | 2010-05-03 | 2013-07-03 | 柯丽安缇维微技术公司 | Polymer microfilters and methods of manufacturing the same |
Non-Patent Citations (1)
| Title |
|---|
| 俞爱斌等: "O2 反应离子深刻蚀PMMA", 《微细加工技术》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106754720A (en) * | 2016-11-14 | 2017-05-31 | 中国科学院重庆绿色智能技术研究院 | A kind of circulating tumor cell enrichment and micro-imaging sample producing device |
| CN106769693A (en) * | 2016-11-14 | 2017-05-31 | 中国科学院重庆绿色智能技术研究院 | A kind of circulating tumor cell automatic checkout system based on Raman spectrum |
| CN107907529A (en) * | 2017-12-29 | 2018-04-13 | 中国科学院重庆绿色智能技术研究院 | Chip of Raman trace detection and preparation method thereof and application method a kind of environment suitable for complex sample |
| CN108313976A (en) * | 2017-12-29 | 2018-07-24 | 西北工业大学 | A kind of polyimide surface micro-structure preparation method |
| CN109652308A (en) * | 2018-12-20 | 2019-04-19 | 中国科学院微电子研究所 | Cell sorting device |
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Application publication date: 20161012 |
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