CN209451867U - Step biochip and gene sequencing device for detecting the biochip - Google Patents
Step biochip and gene sequencing device for detecting the biochip Download PDFInfo
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- CN209451867U CN209451867U CN201821965022.1U CN201821965022U CN209451867U CN 209451867 U CN209451867 U CN 209451867U CN 201821965022 U CN201821965022 U CN 201821965022U CN 209451867 U CN209451867 U CN 209451867U
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- biochip
- gene sequencing
- sequencing device
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- fluorescence
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- 238000000018 DNA microarray Methods 0.000 title claims abstract description 49
- 238000012163 sequencing technique Methods 0.000 title claims abstract description 31
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 30
- 239000011324 bead Substances 0.000 claims abstract description 26
- 239000000758 substrate Substances 0.000 claims abstract description 19
- 239000008188 pellet Substances 0.000 claims abstract description 6
- 230000003247 decreasing effect Effects 0.000 claims abstract description 4
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 7
- 230000003287 optical effect Effects 0.000 abstract description 9
- 238000003384 imaging method Methods 0.000 abstract description 7
- 238000010586 diagram Methods 0.000 description 3
- 238000005286 illumination Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000001427 coherent effect Effects 0.000 description 1
- 239000006059 cover glass Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
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- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
Abstract
The utility model discloses a kind of step biochip, which includes substrate and carries the fluorescence beads of biological information positioned at substrate top, and height of the adjacent phosphor center of pellet point away from substrate bottom edge A is to wait numerical value increasing or decreasing.The invention also discloses the gene sequencing devices for detecting above-mentioned step biochip, the gene sequencing device includes chip placement platform and the step biochip being placed on platform, further includes microcobjective above chip placement platform and is radiated at the lighting source on step biochip with certain incident angle.The utility model gene sequencing device is without using high-resolution microcobjective, as long as high-resolution imaging can be obtained using the microcobjective of standard, and without using optical filter in device, so that the cost of gene sequencing device be made to substantially reduce.
Description
Technical field
A kind of gene sequencing device the utility model relates to step biochip and for detecting the biochip,
Belong to field of optical measuring technologies.
Background technique
Gene sequencing is a kind of novel medical detection technique, and meaning is very great, therefore temperature is high both at home and abroad.
How to realize that the gene sequencing of low cost high rate always is the research direction of numerous companies.
The gene sequencing device for realizing industrialization at present is all the 20X microcobjective using the high NA of carrying (in order to realize height
Resolution ratio, usual resolution ratio is in submicron order), realize fluorescence signal collection；And coaxial-illuminating is used, while high-precision by cooperating
Degree inhibition laser enters the signal-to-noise ratio of optical filter (cut-off depth is greater than 6) Lai Tigao gene sequencing device of camera, to realize
The imaging analysis of fluorescence signal.Therefore existing gene sequencing equipment cost is very high, and the requirement to each device is also extremely harsh.
Utility model content
Purpose of utility model: the technical problem to be solved by the utility model is to provide a kind of step biochips, should
The biochip of step, step biochip can make gene sequencing device by shooting several in same field range
Image obtains information, and piece image represents a step depth, it is assumed that the chip has N number of step, then can in same visual field
N width image (by mobile Z axis) is shot, by the number of records photographing, can accurately know the position of these images.If should
The resolution ratio for the object lens that device uses is δ, by using step biochip, the resolution ratio of object lens can be made to be increased to δ/N.
The utility model also technical problems to be solved are to provide a kind of for detecting the base of above-mentioned step biochip
Because of sequencing device, the gene sequencing device is without using high-resolution microcobjective, as long as the microcobjective using standard is
High-resolution imaging can be obtained, and without using optical filter in device, so that the cost of gene sequencing equipment be made to substantially reduce.
In order to solve the above technical problems, the technology employed by the present utility model is
Step biochip carries the fluorescence beads of biological information including substrate and positioned at substrate top, adjacent
Height of the fluorescence beads central point away from substrate bottom edge A is to wait numerical value increasing or decreasing.
Wherein, the stepped arrangement of adjacent phosphor bead, the fluorescence beads of multiple stepped arrangements are one group, biological core
On piece is successively placed with the fluorescence beads of the stepped arrangement of multiple groups.
For detecting the gene sequencing device of above-mentioned step biochip, including chip placement platform and it is placed on flat
Step biochip on platform further includes the microcobjective being located above chip placement platform and is shone with certain incident angle
Penetrate the lighting source on step biochip；Wherein, the step biochip include substrate and be located at substrate top
End carries the fluorescence beads of biological information, height of the adjacent phosphor center of pellet point away from substrate bottom edge A be equal numerical value be incremented by or
Successively decrease.
Wherein, in the fluorescence beads of every group of stepped arrangement, the difference in height of adjacent phosphor bead is greater than the 2 of microcobjective
Times depth of focus.
Wherein, the angle of the lighting source issues incident light and biochip is greater than 0 ° less than 90 °, specially illuminates
The incident angle of light source is greater than arctan (D/2L)；Wherein, D is the diameter of microcobjective, and L is object lens to the vertical of biochip
Distance.
The horizontal interval of adjacent phosphor bead be submicron order, step depth (adjacent phosphor center of pellet point it is vertical
Difference in height) be greater than object lens 2 times of depths of focus, prevent the fluorescence picture of different step depths from influencing each other, guarantee once photo taking just for
The fluorescence signal of one depth confirms coherent signal (i.e. express delivery navigates to corresponding luminous fluorescence beads) by bench information,
Realize low NA object lens high-resolution imaging.
Compared with prior art, technical solutions of the utility model have the beneficial effect that
The utility model gene sequencing device is far longer than tradition using low range standard microcobjective, field range
20X object lens, to improve the scanning speed of device；The utility model gene sequencing device uses oblique incidence lighting method,
Illumination light cannot be introduced into system as background miscellaneous light, to greatly improve the signal-to-noise ratio of system, while also no longer need to end sharp
The high-precision filters of light；The biochip of the utility model gene sequencing device uses step structure, to realize use
The low NA objective of low range can also obtain the effect of high-resolution imaging.
Detailed description of the invention
Fig. 1 is the structural schematic diagram of existing gene sequencing device；
Fig. 2 is the structural schematic diagram of the utility model gene sequencing device；
Fig. 3 is the structural schematic diagram of the utility model step biochip.
Specific embodiment
The technical solution of the utility model is described further below in conjunction with attached drawing.
As shown in figure 3, the utility model step biochip, including substrate and it is fixed on substrate top and carries life
The fluorescence beads of object information, the number decrements such as the vertical height of adjacent phosphor center of pellet point away from substrate bottom edge A, every five are in rank
The fluorescence beads of scalariform arrangement are one group, and the fluorescence that three groups of stepped arrangements are horizontally successively placed on biochip is small
Ball (three groups of fluorescence beads are arranged on a horizontal line), in the fluorescence beads of every group of stepped arrangement, adjacent phosphor bead
Central point vertical drop is greater than 2 times of depths of focus of microcobjective.
Number of steps (fluorescence beads of every group of stepped arrangement have several) and the step depth (center of adjacent phosphor bead
Difference in height) selection it is related to microcobjective used in equipment.The microcobjective that the utility model is chosen is 5X, and NA is
0.15.If resolution ratio needs to reach the level that 0.9um is equal to the 20X/0.75 object lens of traditional approach, due to 5X object lens
Resolution ratio only has 4.5um, then we need using 5 steps, i.e., the number of the fluorescence beads of every group stepped arrangement is 5
It is a.Influence each other in order to avoid being imaged between two steps, difference in height between two steps needs guarantee 2 times of depths of focus about
100um.Similarly the test speed of the utility model gene sequencing device will also greatly improve.The true field of 5X object lens is ф
5mm (the standard object lens that number of fields is 25mm), and the 20X object lens of traditional approach, true field are ф 1.25mm, therefore compared to existing
Have gene sequencing device, the Polaroid area of the utility model gene sequencing device totally increases 16 times, chip it is mobile,
When auto-focusing and the time taken pictures are all the same, the chip of same area, the speed of the utility model gene sequencing device are tested
Improve 8 times.
As shown in Fig. 2, the utility model is used to detect the gene sequencing device of above-mentioned step biochip, including chip
Placement platform and the step biochip being placed on platform further include the microcobjective above chip placement platform
And the lighting source of step biology core is radiated at certain incident angle；The incident angle of lighting source, i.e. incident light with
The angle of biochip be greater than 0 degree less than 90 degree, specifically, after having selected the microcobjective in device, lighting source
Incident angle is greater than arctan (D/2L)；Wherein, D is the diameter of microcobjective, and L is vertical range of the object lens to biochip.
The utility model gene sequencing device is using being oblique incidence illumination, then the illumination light for being not converted into fluorescence passes through mirror
Face reflection cannot be introduced into imaging system as background miscellaneous light, inhibit the optical filtering of lighting source without being arranged in a device
Piece.Compared with traditional coaxial-illuminating, oblique incidence illuminates the noise for the system that greatly reduces, while inhibiting the optical filtering of lighting source
Piece is not also needing, and thus greatly reduces cost.The outer diameter and operating distance of the object lens of the angle and selection of oblique incidence are related.
Assuming that the diameter of object lens is D, operating distance (vertical ranges of object lens to biochip) is L, then the oblique incidence of lighting source
Angle (oblique incidence angle refers to that incident light and biochip are a certain included angle) needs to be greater than arctan (D/2L).
Traditional mode, the course of work are as follows: light is issued from lighting source, by the system that is reflected into of color separation film, then
By light splitting piece and object lens, biochip is reached, is radiated in biological tissue and excites fluorescence.Fluorescence is collected by object lens, is passed through
Light splitting piece, color separation film and cylinder mirror, optical filter enter camera.The size of biochip is larger, and the field range of object lens is small, therefore
Need a high-precision XY mobile platform, it is primary that each movement once requires auto-focusing, guarantees biochip always in object
On the focal plane of mirror.Since lighting source energy is very high, and fluorescent energy is extremely weak, the light energy of the reflections such as object lens and light splitting piece
It needs to end the very high optical filter of depth to be inhibited.
And the utility model device course of work is as follows: light enters in biochip from lighting source oblique incidence, then logical
The light for crossing substrate and cover glass reflection belongs to regular reflection, cannot be introduced into fluorescence gathering system, therefore optical filter and color separation film are all
It can remove, substantially reduce cost.Fluorescence is similarly excited, is collected by object lens and cylinder mirror and enters camera.Automatic focusing module
It is when guaranteeing that XY mobile platform is mobile, biochip is in always on the focal plane of object lens.Need to acquire several figures in same visual field
Picture needs between adjacent two images one to have a displacement in Z-direction, which is the depth between two steps
Difference.Since the utility model microcobjective field range is big, all information under same field on biochip are obtained, this
The imaging that utility model device only needs to carry out corresponding to number of steps to biochip in Z-direction (can be imaged on i.e. each step
Once), and prior-art devices need biochip on the direction XY it is mobile repeatedly, and every movement is primary, needs to focus one
It is secondary, all information under same field on biochip can be just obtained, so that the test speed of utility model device is much high
In existing apparatus.
Claims (4)
1. step biochip, it is characterised in that: carry the fluorescence of biological information including substrate and positioned at substrate top
Bead, vertical height of the adjacent phosphor center of pellet point away from substrate bottom edge A are to wait numerical value increasing or decreasing；Adjacent phosphor bead is in
Ladder-like arrangement, the fluorescence beads of multiple stepped arrangements are one group, and it is stepped that multiple groups are successively placed on biochip
The fluorescence beads of arrangement.
2. a kind of for detecting the gene sequencing device of step biochip described in claim 1, it is characterised in that: including
Chip placement platform and the step biochip being placed on platform further include micro- above chip placement platform
Object lens and the lighting source on step biochip is radiated at certain incident angle；Wherein, the step biology core
Piece includes substrate and carries the fluorescence beads of biological information positioned at substrate top, and adjacent phosphor center of pellet point is away from substrate bottom
The height of side A is to wait numerical value increasing or decreasing.
3. according to claim 2 for detecting the gene sequencing device of step biochip, it is characterised in that: every group
In the fluorescence beads of stepped arrangement, the difference in height of adjacent phosphor bead is greater than 2 times of depths of focus of microcobjective.
4. according to claim 2 for detecting the gene sequencing device of step biochip, it is characterised in that: described
The angle of incident light and biochip that lighting source issues is greater than 0 ° less than 90 °.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201821965022.1U CN209451867U (en) | 2018-11-27 | 2018-11-27 | Step biochip and gene sequencing device for detecting the biochip |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201821965022.1U CN209451867U (en) | 2018-11-27 | 2018-11-27 | Step biochip and gene sequencing device for detecting the biochip |
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| Publication Number | Publication Date |
|---|---|
| CN209451867U true CN209451867U (en) | 2019-10-01 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201821965022.1U Withdrawn - After Issue CN209451867U (en) | 2018-11-27 | 2018-11-27 | Step biochip and gene sequencing device for detecting the biochip |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109433282A (en) * | 2018-11-27 | 2019-03-08 | 茂莱（南京）仪器有限公司 | A kind of step biochip and the gene sequencing device for detecting the biochip |
-
2018
- 2018-11-27 CN CN201821965022.1U patent/CN209451867U/en not_active Withdrawn - After Issue
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109433282A (en) * | 2018-11-27 | 2019-03-08 | 茂莱（南京）仪器有限公司 | A kind of step biochip and the gene sequencing device for detecting the biochip |
| WO2020108664A1 (en) * | 2018-11-27 | 2020-06-04 | 茂莱（南京）仪器有限公司 | Stepped biological chip and gene sequencing device for testing same |
| CN109433282B (en) * | 2018-11-27 | 2024-02-13 | 茂莱（南京）仪器有限公司 | Step biochip and gene sequencing device for detecting same |
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| AV01 | Patent right actively abandoned |
Granted publication date: 20191001 Effective date of abandoning: 20240213 |
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| AV01 | Patent right actively abandoned |
Granted publication date: 20191001 Effective date of abandoning: 20240213 |
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| AV01 | Patent right actively abandoned | ||
| AV01 | Patent right actively abandoned |