CN1641338A - Optica liquid drop detecting system and its detecting method - Google Patents
Optica liquid drop detecting system and its detecting method Download PDFInfo
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- CN1641338A CN1641338A CN 200410001211 CN200410001211A CN1641338A CN 1641338 A CN1641338 A CN 1641338A CN 200410001211 CN200410001211 CN 200410001211 CN 200410001211 A CN200410001211 A CN 200410001211A CN 1641338 A CN1641338 A CN 1641338A
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Abstract
The invention relates to an optical liquid drop detecting system and method, including bearing platform, light source, light detector, computer unit, and microarray wafer distributed with plural agent solutions, where the microarray wafer is on the bearing platform and between the light source and the light detector, the light source, the light detector and the microarray wafer make synchronous and relative movement to scan the video of these agent solutions on the surface of the microarray wafer so as to send the video to the computer unit for analyzing and comparing to confirm arranged state of each agent solution.
Description
Technical field
The invention relates to a kind of biochip detection platform, refer to a kind of optical drop detection system and detection method thereof especially.
Background technology
The reagent mode of laying of biochip has many kinds, for example: and little drop tube side formula of contact, or contactless hydrojet mode, and firm cloth is put in the reagent droplet of wafer surface, can present three-dimensional drops.Usually, finish the reagent solution that lays and before wafer cleans, must carry out a drop and lay to detect and move, whether have correctly to detect each reagent solution that cloth is placed on relative position.Followingly will introduce the mode that present drop lays detection.
As shown in Figure 1, United States Patent (USP) case numbers 6,232, the 072nd, disclose a kind of optical drop detection mode, it is that the incident light 4 that utilizes optical fiber boundling 2 to be produced shines drop 8, and receive by drop 8 reflection or the flashlight that penetrates with optical detector 6, detecting having or not of drop 8, that is it is to utilize the variation of the reflection angle of irradiate light behind drop 8 to detect drop 8 whether cloth to be arranged in correct position.Yet its each drop 8 limited amounts that detect can't detect in a large number, make that the detection speed time is more of a specified duration.
United States Patent (USP) case numbers 6,558,623 also disclose a kind of optical drop detection mode, it is to utilize light source and optical detector to detect drop immediately to lay situation, and wherein, light source and optical detector are in the same side, and utilize reflective framework to obtain the image of these drops on the wafer, yet its detection is to detect immediately when laying opportunity, spended time comparatively, and increase production cost.
United States Patent (USP) case numbers 5,601,980 discloses a kind of drop detection mode, and it is to utilize contact to lay drop, and when laying each drop, promptly utilizes optical mode to detect the state of this drop, not only loses time and does not have very much efficient.Though these technology can detect the situation that drop lays, can only carry out among a small circle, for example the detection of single drop.
United States Patent (USP) case numbers 6,587,579 discloses another kind of drop detection mode, obtains the image of adjacent a plurality of drops at every turn, utilizes the mode of calculation pinup picture again, forms the image on entire wafer surface, with the situation of judging that whole drop lays.Yet, utilize the formed wafer surface image of this mode, need the equipment of powerful arithmetic capability, and expend time in, be unfavorable for mass-produced processing procedure.
Therefore, how to provide a kind of high-level efficiency detection mode that detects the state that lays of a large amount of drops and can spend the short period, become the problem of needing solution badly.
Summary of the invention
Fundamental purpose of the present invention is that a kind of optical drop detection system and detection method thereof are being provided, so that can detect the reagent solution that is laid on the biochip apace, and carries out the quality keyholed back plate immediately and handles.
Another object of the present invention is that a kind of optical drop detection system and detection method thereof are being provided, so that a simple and easy efficient again testing mechanism can be provided, to reduce the volume production cost.
According to a characteristic of the present invention, a kind of optical drop detection system of the present invention is to detect in order to the target sample that a cloth is placed with plural reagent solution, it is characterized in that this optical drop detection system comprises:
One microscope carrier is in order to carry this target sample;
One light source is in order to provide a light to shine this target sample; And
One optical detector is a side that is positioned at this microscope carrier, to detect these reagent solutions of this target sample; Wherein,
This target sample of this microscope carrier is between this optical detector and this light source, and these reagent solutions of this target sample are detected in the irradiation that sees through this light for this optical detector, to obtain a detecting result.
According to a characteristic of the present invention, a kind of optical drop detection system of the present invention is to detect in order to the target sample that a cloth is placed with plural reagent solution, it is characterized in that this optical drop detection system comprises:
One microscope carrier is in order to carry this target sample;
One light source is in order to a light to be provided;
One light guide plate is in order to receive this light also with this target sample of this bright light exposure; And
One optical detector is a side that is positioned at this microscope carrier, to detect these reagent solutions of this target sample; Wherein,
This target sample of this microscope carrier is between this optical detector and this light guide plate, and these reagent solutions of this target sample are detected in the irradiation that sees through this light guide plate for this optical detector, to obtain a detecting result.
Wherein, this light source and this optical detector are that this target sample is carried out the same moved further of relativity when detecting, to scan these reagent solutions on this target sample.
Wherein, this light source, this light guide plate, and this optical detector when detecting, be that this target sample is carried out the same moved further of relativity, to scan these reagent solutions on this target sample.
Wherein, this optical detector is to be connected with an electronic installation, to this electronic installation, and shows this detecting result for the detecting result of this optical detector of output.
Wherein, this electronic installation has a routine analyzer, and this routine analyzer has plural number and detects preset value, receive this detecting result for this electronic installation after, be that these detection preset values that see through this routine analyzer come this detecting result is analyzed.
Wherein, this optical detector is to be connected with an electronic installation, and this electronic installation stores plural number and detects preset value, and when this optical detector was exported this detecting result to this electronic installation, this electronic installation saw through these detection preset values and judges the drop state that these reagent solutions present.
Wherein, these detection preset values are to be the diameter that lays drop, the position that lays the area of drop or lay drop.
Wherein, this optical detector is to be the charge coupled cell detector.
Wherein, this optical detector is to scan the charge coupled device detector for linearity.
Wherein, this light guide plate is in order to light is converted to line source, and shines this target sample with line source.
Wherein, this detecting result is these reagent solution images for this target sample.
Wherein, this reagent solution is biological molecule.
Wherein this biological molecule is oligonucleotides, victory peptide, or derivatives thereof.
According to a characteristic of the present invention, the detection method of a kind of optical drop detection system of the present invention is characterized in that, comprises the steps:
One target sample that is furnished with plural reagent solution is provided; And
With a light source, and an optical detector this target sample is carried out same moved further, scan this target sample; Wherein,
This target sample is between this optical detector and this light source, and this light source can provide light exposing to this target sample, detects these reagent solutions on this target sample for this optical detector, to obtain a detecting result.
According to a characteristic of the present invention, the detection method of a kind of optical drop detection system of the present invention is characterized in that, comprises the steps:
One target sample that is furnished with plural reagent solution is provided; And
With a light source, a light guide plate, and an optical detector this target sample is carried out same moved further, scan this target sample; Wherein, this target sample is between this optical detector and this light guide plate, and this light guide plate can be with bright light exposure that this light source provided to this target sample, detects these reagent solutions on this target sample for this optical detector, to obtain a detecting result.
It also comprises one after obtaining a detecting result, analytical procedure, be to detect the result to compare with plural number detection preset value respectively,, according to this at least one analysis and judgement result this target sample carried out a corresponding processing then to obtain at least one analysis and judgement result.
Wherein, these detection preset values are to be the diameter that lays drop, the position that lays the area of drop or lay drop.
Wherein, these detect preset value is to be the diameter that lays drop, the position that lays the area of drop or lay drop, if this at least one analysis and judgement result is put in the quantity of drop positional fault of these reagent greater than a preset value for cloth, then this target sample is given annotation, to reject it.
Wherein, this optical detector is to be the charge coupled cell detector.
Wherein, this optical detector is to scan the charge coupled device detector for linearity.
Wherein, this reagent solution is biological molecule.
Wherein this biological molecule is oligonucleotides, victory peptide, or derivatives thereof.
According to optical drop detection system provided by the invention and detection method thereof, relevent informations such as the position of the drop that the measurement wafer surface has just laid, external form, size, diameter are to reach the purpose of biochip production quality keyholed back plate.
Description of drawings
For further specifying technology contents of the present invention, below in conjunction with embodiment and accompanying drawing describes in detail as after, wherein:
Fig. 1 is the synoptic diagram of known optical drop detection mode.
Fig. 2 is the system architecture synoptic diagram of first embodiment of optical drop detection system of the present invention.
Fig. 3 is the system architecture synoptic diagram of second embodiment of optical drop detection system of the present invention.
Fig. 4 is the process flow diagram of optical drop detection system detection method of the present invention.
Embodiment
The relevant first embodiment of the present invention, please be with reference to the system architecture synoptic diagram of Fig. 2 demonstration, its by microscope carrier 11, light source 12, optical detector 13, computer apparatus 14, micro array chip 15, and main member such as light guide plate 16 formed, wherein, be to be furnished with plural reagent solution 151 on this micro array chip 15, and these reagent solutions 151 are to utilize hydrojet mode cloth to be put on the biochip.
In present embodiment, microscope carrier 11 is preferably a board with transparent travelling belt 111, and light source 12 is a continuous light source; The continuous light source that light guide plate 16 can be produced light source 12 is converted to line source (linear light source), is uniformly distributed into the back side of micro array chip 15, and the optical detector 13 that scans with the linearity of arranging in pairs or groups detects; Optical detector 13 is that (preferably scans CCD (line-scan CCD) for linearity to charge coupled cell for Charged Coupled Device, CCD) detector.Optical drop detection system provided by the invention and detection method thereof, optical detector 13 are preferably and are the linear light sorurce scanner, and the running that cooperates light guide plate 16 to be obtaining successional image, and carry out following explanation.Certainly, if optical detector 13 only is the charge coupled cell detector, then present embodiment promptly need not use and lead first plate 16, can save the cost of system thus.
Above-mentioned micro array chip 15 is to be placed on the transparent travelling belt 111 of microscope carrier 11, and micro array chip 15 is between optical detector 13 and light guide plate 16, that is optical detector 13 is above micro array chip 15, with the image of these reagent solutions 151 of being used for capturing micro array chip 15 surfaces; 16 of light guide plate are below transparent travelling belt 111 and micro array chip 15, and the continuous light source that light source 12 is produced makes that as a back light 13 picked image of optical detector are comparatively clear.Wherein, these reagent solutions 151 are to be biological molecule, and biological molecule can be oligonucleotides, wins peptide, or derivatives thereof.
Backlight type light source of the present invention, when light source sees through this drop, the drop central authorities of projection have a lens effect, make institute's picked image present the effect that central authorities are bright, the limit is dark, border with clear and definite drop, and then accurately obtain liquid and drop down relevent informations such as position, external form, size, diameter, to judge laying situation and whether satisfying default working condition of each drop.
Optical detector 13 is to be connected with computer apparatus 14, for its picked image is sent to computer apparatus 14, to carry out analyzing and processing.Computer apparatus 14 be equipped with a quality control (QoS) program and in have the related data storehouse, so that the image that it was received is carried out analyzing and processing.The explanation of the image of relevant optical detector 13 these reagent solutions 151 of acquisition and the processing how computer apparatus analyzes these images will explain orally in detail in following.
Fig. 4 shows that the present invention detects the process flow diagram of this biology crystal face 15, the system architecture diagram that relevant its explanation please show with reference to Fig. 2 in the lump.At first, the micro array chip 15 that cloth is placed with plural reagent solution 151 is placed on the transparent travelling belt 111 of microscope carrier 11, wherein, and the quantity of the micro array chip of being settled 15 and unrestricted (step S201).
Then, control microscope carrier 11, make its transparent travelling belt 111 toward moving right, relatively synchronously relatively move for back light and optical detector 13, so that optical detector 13 scans lip-deep these reagent solutions 151 (step S202) of micro array chip 15 with micro array chip 15.Therefore, optical detector 13 will once be obtained the image of these reagent solutions 151 on micro array chip 15 surfaces, and be sent to computer apparatus 14, to carry out analyzing and processing (step S203).
14 of computer apparatus are according to the data bank of The built-in and utilize its routine analyzer to come these detecting images are analyzed.At first, computer apparatus 14 will be compared a detecting image and a default image (for example: perfectly lay the drop image), to judge whether these reagent solutions that lay 151 are positioned on the opposite position, if reagent solution 151 greater than some (for example: 20 reagent solutions) be not positioned at the tram, then computer apparatus 14 demonstrates the information that lays again or serious flaw information (step S204), simultaneously, computer apparatus 14 will be added up the quantity of unusual reagent solution 151, with the parameter of the board (figure does not show) that lays reagent solution 151 as adjustment.
Then, computer apparatus 14 is analyzed the diameter of these reagent solutions that lay 151 once again, it is that the liquid-drop diameter default in the data bank and the diameter of these reagent solutions 151 are compared, to guarantee to lay the quality that lays of reagent solution board, if the diameter of these reagent solutions 151 is many less than default liquid-drop diameter, or its diameter is many greater than default liquid-drop diameter, and its quantity surpasses some, and (for example: 20 reagent solutions), then computer apparatus 14 demonstrates the information that lays again or serious flaw information (step S205).
At last, computer apparatus 14 is analyzed these reagent solutions that lay 151 in the area on the surface of micro array chip 15, it is that the drop area default in the data bank and the area of these reagent solutions 151 are compared, to guarantee to lay the quality that lays of reagent solution board, if the area of these reagent solutions 151 is many less than default drop area, or its diameter is many greater than default drop area, and its quantity (for example: 20 reagent solutions) surpasses some, then computer apparatus 14 demonstrates the information that lays again or serious flaw information, computer apparatus 14 is the result of statistic diameters analysis and areal analysis also, adjust and lay board to obtain complex parameter, can once lay successfully all drops when laying for next time, and make that the state of the drop that these lay is best, lay efficient (step S206) with lifting.
Therefore, computer apparatus 14 state that comes these reagent solutions 151 of compare of analysis by the preset value or the built-in data bank of its storage.Because, the state of laying of these reagent solutions 151 will influence engaging of reagent and micro array chip 15 in these reagent solutions 151, so, by detection method of the present invention, confirm the state of these reagent solutions 151 earlier, then, again micro array chip 15 is carried out cleaning step, with the making (step S207) of finishing biochip.
The relevant second embodiment of the present invention, please be with reference to the system architecture synoptic diagram of Fig. 3 demonstration, its by microscope carrier 11, light source 12, optical detector 13, computer apparatus 14, micro array chip 15, light guide plate 16, and gearshift 17, etc. main member formed, gearshift 17 is in order to mobile optical detector 13, mobile light source 12 and light guide plate 16.The main difference of itself and first embodiment of the invention is to be that microscope carrier 11 is to be fixed carrier, only in order to support micro array chip 15, and moving by gearshift 17, making the optical detector 13 and the relative position of light source 12 and light guide plate 16 is for constant, make optical detector 13 be scanned lip-deep these reagent solutions 151 of micro array chip 15, and carry out follow-up processing.Because the running of second embodiment of the invention is similar to the running of first embodiment of the invention, and its process flow diagram that detects this biochip 15 is also similar to the process flow diagram of Fig. 3, so seldom explain.
By above explanation as can be known, the present invention is the state that the backlight type optical storage device framework that utilizes light source and optical detector to form detects these reagent solutions above the micro array chip, to obtain the drop image of preferable resolution, wherein, its detection opportunity is to be batch processed, that is, after reagent solution lays and finishes, again at least one micro array chip is carried out surface observation, then utilize plural preset value stored on the computer apparatus or built-in data bank to carry out the drop image analysing computer again, to judge the state of these reagent solutions, and carry out a quality control according to its analysis result and (for example: lay again handle, processing such as mark defective part), handle to carry out the quality keyholed back plate immediately, and a simple and easy efficient again testing mechanism is provided, to reduce the volume production cost.
The foregoing description only is to give an example for convenience of description, and the interest field that the present invention advocated should be as the criterion so that claim is described certainly, but not only limits to the foregoing description.
Claims (23)
1. an optical drop detection system is to detect in order to the target sample that a cloth is placed with plural reagent solution, it is characterized in that this optical drop detection system comprises:
One microscope carrier is in order to carry this target sample;
One light source is in order to provide a light to shine this target sample; And
One optical detector is a side that is positioned at this microscope carrier, to detect these reagent solutions of this target sample; Wherein,
This target sample of this microscope carrier is between this optical detector and this light source, and these reagent solutions of this target sample are detected in the irradiation that sees through this light for this optical detector, to obtain a detecting result.
2. an optical drop detection system is to detect in order to the target sample that a cloth is placed with plural reagent solution, it is characterized in that this optical drop detection system comprises:
One microscope carrier is in order to carry this target sample;
One light source is in order to a light to be provided;
One light guide plate is in order to receive this light also with this target sample of this bright light exposure; And
One optical detector is a side that is positioned at this microscope carrier, to detect these reagent solutions of this target sample; Wherein,
This target sample of this microscope carrier is between this optical detector and this light guide plate, and these reagent solutions of this target sample are detected in the irradiation that sees through this light guide plate for this optical detector, to obtain a detecting result.
3. optical drop detection system as claimed in claim 1 is characterized in that, wherein, this light source and this optical detector are that this target sample is carried out the same moved further of relativity when detecting, to scan these reagent solutions on this target sample.
4. optical drop detection system as claimed in claim 2 is characterized in that, wherein, this light source, this light guide plate, and this optical detector when detecting, be that this target sample is carried out the same moved further of relativity, to scan these reagent solutions on this target sample.
5. as claim 1 and 2 described optical drop detection system, it is characterized in that wherein, this optical detector is to be connected with an electronic installation, to this electronic installation, and show this detecting result for the detecting result of this optical detector of output.
6. optical drop detection system as claimed in claim 5, it is characterized in that, wherein, this electronic installation has a routine analyzer, this routine analyzer has plural number and detects preset value, after receiving this detecting result for this electronic installation, be that these that see through this routine analyzer detect preset values and come this detecting result is analyzed.
7. as claim 1 and 2 described optical drop detection system, it is characterized in that, wherein, this optical detector is to be connected with an electronic installation, and this electronic installation stores plural number and detects preset value, when this optical detector was exported this detecting result to this electronic installation, this electronic installation saw through these detection preset values and judges the drop state that these reagent solutions present.
8. optical drop detection system as claimed in claim 7 is characterized in that, wherein, these detect preset value is to be the diameter that lays drop, the position that lays the area of drop or lay drop.
9. optical drop detection system as claimed in claim 1 is characterized in that, wherein, this optical detector is to be the charge coupled cell detector.
10. optical drop detection system as claimed in claim 2 is characterized in that, wherein, this optical detector is to scan the charge coupled device detector for linearity.
11. optical drop detection system as claimed in claim 10 is characterized in that, wherein, this light guide plate is in order to light is converted to line source, and shines this target sample with line source.
12., it is characterized in that wherein, this detecting result is these reagent solution images for this target sample as claim 1 and 2 described optical drop detection system.
13., it is characterized in that wherein, this reagent solution is biological molecule as claim 1 and 2 described optical drop detection system.
14. optical drop detection system as claimed in claim 13 is characterized in that, wherein this biological molecule is oligonucleotides, victory peptide, or derivatives thereof.
15. the detection method of an optical drop detection system is characterized in that, comprises the steps:
One target sample that is furnished with plural reagent solution is provided; And
With a light source, and an optical detector this target sample is carried out same moved further, scan this target sample; Wherein,
This target sample is between this optical detector and this light source, and this light source can provide light exposing to this target sample, detects these reagent solutions on this target sample for this optical detector, to obtain a detecting result.
16. the detection method of an optical drop detection system is characterized in that, comprises the steps:
One target sample that is furnished with plural reagent solution is provided; And
With a light source, a light guide plate, and an optical detector this target sample is carried out same moved further, scan this target sample; Wherein, this target sample is between this optical detector and this light guide plate, and this light guide plate can be with bright light exposure that this light source provided to this target sample, detects these reagent solutions on this target sample for this optical detector, to obtain a detecting result.
17, detection method as claim 15 and 16 described optical drop detection system, it is characterized in that, it also comprises one after obtaining a detecting result, analytical procedure, be to detect the result to compare with plural number detection preset value respectively,, according to this at least one analysis and judgement result this target sample carried out a corresponding processing then to obtain at least one analysis and judgement result.
18. the detection method of optical drop detection system as claimed in claim 17 is characterized in that, wherein, these detect preset value is to be the diameter that lays drop, the position that lays the area of drop or lay drop.
19. the detection method of optical drop detection system as claimed in claim 17, it is characterized in that, wherein, these detect preset value is to be the diameter that lays drop, the position that lays the area of drop or lay drop, if this at least one analysis and judgement result is put in the quantity of drop positional fault of these reagent greater than a preset value for cloth, then this target sample is given annotation, to reject it.
20. the detection method of optical drop detection system as claimed in claim 15 is characterized in that, wherein, this optical detector is to be the charge coupled cell detector.
21. the detection method of optical drop detection system as claimed in claim 16 is characterized in that, wherein, this optical detector is to scan the charge coupled device detector for linearity.
22, the detection method as claim 15 and 16 described optical drop detection system is characterized in that, wherein, this reagent solution is biological molecule.
23. the detection method as claim 15 and 16 described optical drop detection system is characterized in that, wherein this biological molecule is oligonucleotides, victory peptide, or derivatives thereof.
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| CN 200410001211 CN1641338A (en) | 2004-01-02 | 2004-01-02 | Optica liquid drop detecting system and its detecting method |
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| Application Number | Priority Date | Filing Date | Title |
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| CN 200410001211 CN1641338A (en) | 2004-01-02 | 2004-01-02 | Optica liquid drop detecting system and its detecting method |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101256092B (en) * | 2007-02-26 | 2011-02-16 | 精工爱普生株式会社 | Method of measuring landed dot, measuring apparatus for landed dot, liquid droplet ejection apparatus |
| CN104406689A (en) * | 2014-11-28 | 2015-03-11 | 江门市宏丰电子科技有限公司 | Light guide bar detection device |
| CN105358958A (en) * | 2013-01-22 | 2016-02-24 | 泰肯贸易股份公司 | Optical measuring apparatus and method for the analysis of samples contained in liquid drops |
| CN105861299A (en) * | 2016-05-05 | 2016-08-17 | 广东顺德工业设计研究院(广东顺德创新设计研究院) | Micro-drop digital PCR (polymerase chain reaction) fluorescent detection system and fluorescent detection device |
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2004
- 2004-01-02 CN CN 200410001211 patent/CN1641338A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101256092B (en) * | 2007-02-26 | 2011-02-16 | 精工爱普生株式会社 | Method of measuring landed dot, measuring apparatus for landed dot, liquid droplet ejection apparatus |
| CN105358958A (en) * | 2013-01-22 | 2016-02-24 | 泰肯贸易股份公司 | Optical measuring apparatus and method for the analysis of samples contained in liquid drops |
| CN105358958B (en) * | 2013-01-22 | 2018-07-31 | 泰肯贸易股份公司 | Optical gauge and method for contained sample in analysis of the droplet |
| CN104406689A (en) * | 2014-11-28 | 2015-03-11 | 江门市宏丰电子科技有限公司 | Light guide bar detection device |
| CN104406689B (en) * | 2014-11-28 | 2016-06-22 | 江门市宏丰电子科技有限公司 | Light-strip detecting device |
| CN105861299A (en) * | 2016-05-05 | 2016-08-17 | 广东顺德工业设计研究院(广东顺德创新设计研究院) | Micro-drop digital PCR (polymerase chain reaction) fluorescent detection system and fluorescent detection device |
| CN105861299B (en) * | 2016-05-05 | 2018-05-22 | 广东顺德工业设计研究院(广东顺德创新设计研究院) | Droplet type digital pcr fluorescence detecting system and fluorescence detection device |
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