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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- 238000000034 method Methods 0.000 title claims abstract description 29
- 239000007788 liquid Substances 0.000 title abstract description 22
- 230000003287 optical effect Effects 0.000 claims abstract description 39
- 238000001514 detection method Methods 0.000 claims description 86
- 239000003153 chemical reaction reagent Substances 0.000 claims description 75
- 238000004458 analytical method Methods 0.000 claims description 15
- 108091034117 Oligonucleotide Proteins 0.000 claims description 5
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 5
- 230000008878 coupling Effects 0.000 claims description 4
- 238000010168 coupling process Methods 0.000 claims description 4
- 238000005859 coupling reaction Methods 0.000 claims description 4
- 230000001678 irradiating effect Effects 0.000 claims description 3
- 238000002493 microarray Methods 0.000 abstract description 25
- 230000001360 synchronised effect Effects 0.000 abstract 1
- 238000000018 DNA microarray Methods 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 235000012431 wafers Nutrition 0.000 description 7
- 238000010586 diagram Methods 0.000 description 5
- 230000007547 defect Effects 0.000 description 4
- 238000009826 distribution Methods 0.000 description 4
- 238000003908 quality control method Methods 0.000 description 4
- 238000006073 displacement reaction Methods 0.000 description 3
- 238000000203 droplet dispensing Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000013307 optical fiber Substances 0.000 description 1
- 238000011897 real-time detection Methods 0.000 description 1
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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 present invention relates to a biochip measuring platform, and more particularly, to an optical droplet measuring system and a measuring method thereof.
Background
The reagent distribution of the biochip can be done in many ways, for example: the contact type micro-droplet dropper method or the non-contact type liquid spraying method, and the reagent droplets just laid on the surface of the wafer are in a three-dimensional droplet shape. Usually, the reagent solution is dispensed before the wafer is cleaned, and a droplet dispensing test is performed to determine whether each reagent solution is properly dispensed in the corresponding position. The current manner of droplet placement detection will be described below.
As shown in fig. 1, U.S. Pat. No. 6,232,072 discloses an optical droplet detection method, which uses incident light 4 generated by an optical fiber bundle 2 to irradiate a droplet 8, and uses a light detector 6 to receive signal light reflected or transmitted by the droplet 8 to detect whether the droplet 8 is present, i.e. whether the droplet 8 is located at a correct position is detected by using the change of the reflection angle of the light after the droplet 8 is irradiated. However, the number of droplets 8 detected at a time is limited, and a large number of droplets cannot be detected, so that the detection speed is long.
U.S. Pat. No. 6,558,623 also discloses an optical drop detection method, which utilizes a light source and a light detector to detect the placement of drops in real time, wherein the light source and the light detector are on the same side, and a reflective structure is used to obtain the images of the drops on the chip, but the detection time is the real-time detection during placement, which takes time and increases the production cost.
U.S. Pat. No. 5,601,980 discloses a liquid droplet detection method, which is to arrange liquid droplets in a contact manner and detect the state of each liquid droplet by an optical method while arranging the liquid droplet, which is time consuming and very inefficient. These techniques can detect the placement of droplets, but only to a small extent, for example, the detection of a single droplet.
U.S. Pat. No. 6,587,579 discloses another droplet detection method, in which images of a plurality of adjacent droplets are obtained each time, and then an algorithm map is used to compose an image of the entire wafer surface to determine the overall droplet placement. However, the image of the wafer surface formed by this method requires a powerful computing device and is time consuming and not suitable for mass production processes.
Therefore, it is an urgent problem to provide a high-efficiency detection method capable of detecting the distribution state of a large amount of droplets and taking a short time.
Disclosure of Invention
The main objective of the present invention is to provide an optical droplet detecting system and a detecting method thereof, so as to rapidly detect the reagent solution disposed on the biochip and perform quality control and management processing in real time.
Another objective of the present invention is to provide an optical droplet detecting system and a detecting method thereof, so as to provide a simple and efficient detecting mechanism to reduce the cost of mass production.
According to a feature of the present invention, an optical droplet detecting system for detecting a target sample with a plurality of reagent solutions disposed therein is provided, which includes:
a carrier for carrying the target sample;
a light source for providing a bright light to irradiate the target sample; and
a light detector, which is positioned at one side of the carrying platform and is used for detecting the reagent solutions of the target sample; wherein,
the target sample of the carrying platform is positioned between the light detector and the light source, so that the light detector can detect the reagent solutions of the target sample through the irradiation of the bright light to obtain a detection result.
According to a feature of the present invention, an optical droplet detecting system for detecting a target sample with a plurality of reagent solutions disposed therein is provided, which includes:
a carrier for carrying the target sample;
a light source for providing a bright light;
a light guide plate for receiving the bright light and irradiating the target sample with the bright light; and
a light detector, which is positioned at one side of the carrying platform and is used for detecting the reagent solutions of the target sample; wherein,
the target sample of the carrying platform is positioned between the light detector and the light guide plate, so that the light detector can detect the reagent solutions of the target sample through the irradiation of the light guide plate to obtain a detection result.
Wherein, the light source and the light detector move relatively and synchronously to the target sample during detection so as to scan the reagent solutions on the target sample.
The light source, the light guide plate and the light detector move relatively and synchronously to the target sample during detection so as to scan the reagent solutions on the target sample.
The light detector is connected with an electronic device to output the detection result of the light detector to the electronic device and display the detection result.
The electronic device is provided with an analysis program, and the analysis program is provided with a plurality of detection preset values, so that after the electronic device receives the detection result, the detection result is analyzed through the detection preset values of the analysis program.
The electronic device stores a plurality of detection preset values, and when the light detector outputs the detection result to the electronic device, the electronic device judges the droplet states of the reagent solutions through the detection preset values.
Wherein the detection preset values are diameters of the dispensed droplets, areas of the dispensed droplets, or positions of the dispensed droplets.
Wherein the photodetector is a CCD detector.
Wherein the photodetector is a linear scanning electric coupling element detector.
The light guide plate is used for converting the bright light into a linear light source and irradiating the target sample by the linear light source.
Wherein the detection result is the reagent solution images of the target sample.
Wherein the reagent solution is a biological molecule.
Wherein the biological molecule is an oligonucleotide, a peptide, or a derivative thereof.
According to a feature of the present invention, a method for detecting an optical drop detection system is characterized by comprising the following steps:
providing a target sample distributed with a plurality of reagent solutions; and
scanning the target sample by moving the target sample synchronously with a light source and a photodetector; wherein,
the target sample is located between the light detector and the light source, and the light source can provide bright light to irradiate the target sample so that the light detector can detect the reagent solutions on the target sample to obtain a detection result.
According to a feature of the present invention, a method for detecting an optical drop detection system is characterized by comprising the following steps:
providing a target sample distributed with a plurality of reagent solutions; and
using a light source, a light guide plate and a photodetector to synchronously move the target sample, and scanning the target sample; the target sample is located between the light detector and the light guide plate, and the light guide plate can irradiate the bright light provided by the light source to the target sample so that the light detector can detect the reagent solutions on the target sample to obtain a detection result.
The method also comprises an analysis step of comparing the detection result with a plurality of detection preset values respectively to obtain at least one analysis judgment result after obtaining a detection result, and then carrying out corresponding processing on the target sample according to the at least one analysis judgment result.
Wherein the detection preset values are diameters of the dispensed droplets, areas of the dispensed droplets, or positions of the dispensed droplets.
Wherein the detection preset values are diameters of the distributed liquid drops, areas of the distributed liquid drops or positions of the distributed liquid drops, and if the at least one analysis judgment result shows that the number of the position errors of the liquid drops distributed on the reagents is larger than a preset value, the target sample is marked to be removed.
Wherein the photodetector is a CCD detector.
Wherein the photodetector is a linear scanning electric coupling element detector.
Wherein the reagent solution is a biological molecule.
Wherein the biological molecule is an oligonucleotide, a peptide, or a derivative thereof.
According to the optical droplet detecting system and the detecting method thereof provided by the invention, the related information of the position, the shape, the size, the diameter and the like of the droplets just distributed on the surface of the wafer is measured, so as to achieve the purpose of controlling the production quality of the biochip.
Drawings
To further illustrate the technical content of the present invention, the following detailed description is provided in conjunction with the embodiments and the accompanying drawings, in which:
FIG. 1 is a schematic diagram of a known optical drop detection scheme.
FIG. 2 is a schematic system architecture diagram of a first embodiment of the optical drop detection system of the present invention.
FIG. 3 is a schematic system architecture diagram of a second embodiment of the optical drop detection system of the present invention.
FIG. 4 is a flow chart of a detection method of the optical drop detection system of the present invention.
Detailed Description
Referring to the schematic system architecture shown in fig. 2, a first embodiment of the present invention is composed of a carrier 11, a light source 12, a photodetector 13, a computer 14, a microarray chip 15, and a light guide plate 16, wherein a plurality of reagent solutions 151 are distributed on the microarray chip 15, and the reagent solutions 151 are distributed on a biochip by spraying.
In this embodiment, the carrier 11 is preferably a machine having a transparent conveyor belt 111, and the light source 12 is a continuous light source; the light guide plate 16 can convert the continuous light source generated by the light source 12 into a linear light source (linear light source), which is uniformly distributed on the back of the microarray chip 15 to match with the linear scanning photodetector 13 for detection; the photodetector 13 is a Charge Coupled Device (CCD) detector, preferably a line-scan CCD (line-scan CCD). In the optical droplet detecting system and the detecting method thereof of the present invention, the light detector 13 is preferably a linear light source scanner, and cooperates with the operation of the light guide plate 16 to obtain continuous images, and the following description is provided. Of course, if the photodetector 13 is only a CCD detector, the embodiment does not need the guiding plate 16, so as to save the system cost.
The microarray chip 15 is placed on the transparent conveyor belt 111 of the carrier 11, and the microarray chip 15 is located between the light detector 13 and the light guide plate 16, i.e. the light detector 13 is above the microarray chip 15, so as to capture the image of the reagent solutions 151 on the surface of the microarray chip 15; the light guide plate 16 is located under the transparent conveyor 111 and the microarray chip 15, and uses the continuous light source generated by the light source 12 as a backlight source, so that the image captured by the light detector 13 is clearer. The reagent solution 151 is a biological molecule, and the biological molecule can be an oligonucleotide, a peptide, or a derivative thereof.
When the light source penetrates through the liquid drop, the center of the protruded liquid drop has a lens effect, so that the captured image has the effects of bright center and dark edge, the boundary of the liquid drop is determined, and the related information such as the liquid flowing position, the shape, the size, the diameter and the like is accurately obtained, so as to judge whether the distribution condition of each liquid drop meets the preset production condition.
The light detector 13 is connected to the computer device 14 for transmitting the captured image to the computer device 14 for analysis. The computer device 14 is installed with a quality control (QoS) program and a database for analyzing the received image. The description of the image of the reagent solutions 151 captured by the light detector 13 and the processing of the image by the computer device for analyzing will be described in detail below.
FIG. 4 is a flow chart of the present invention for detecting the biological crystal plane 15, and the description thereof is related to the system architecture diagram shown in FIG. 2. First, the microarray wafer 15 on which the plurality of reagent solutions 151 are disposed is placed on the transparent conveyor belt 111 of the stage 11, wherein the number of the microarray wafers 15 placed is not limited (step S201).
Next, the carrier 11 is controlled to move the transparent conveyor belt 111 to the right, so that the backlight source and the photodetector 13 move relatively in synchronization with the microarray chip 15, and the photodetector 13 scans the reagent solutions 151 on the surface of the microarray chip 15 (step S202). Therefore, the photo detector 13 will take the images of the reagent solutions 151 on the surface of the microarray chip 15 at a time and transmit them to the computer device 14 for analysis (step S203).
The computer device 14 analyzes the detected images according to the built-in database and the analysis procedure thereof. First, the computer device 14 compares the detected image with a predetermined image (e.g., a perfect droplet dispensing image) to determine whether the dispensed reagent solutions 151 are located at corresponding positions, and if the reagent solutions 151 are greater than a certain amount (e.g., 20 reagent solutions) and not located at correct positions, the computer device 14 displays relocation information or serious defect information (step S204), and meanwhile, the computer device 14 counts the amount of the abnormal reagent solutions 151 to serve as a parameter for adjusting a machine (not shown) on which the reagent solutions 151 are dispensed.
Then, the computer device 14 analyzes the diameters of the disposed reagent solutions 151 again, which compares the preset diameters of the droplets in the database with the diameters of the reagent solutions 151 to ensure the disposing quality of the machine for disposing the reagent solutions, and if the diameters of the reagent solutions 151 are much smaller than the preset diameters of the droplets, or the diameters of the reagent solutions 151 are much larger than the preset diameters of the droplets, and the number of the reagent solutions exceeds a certain number (for example, 20 reagent solutions), the computer device 14 displays the re-disposing information or the serious defect information (step S205).
Finally, the computer device 14 analyzes the area of the disposed reagent solution 151 on the surface of the microarray chip 15, compares the area of the liquid drop preset in the database with the area of the reagent solution 151 to ensure the disposing quality of the apparatus for disposing the reagent solution, if the area of the reagent solution 151 is smaller than the area of the liquid drop preset or the diameter of the reagent solution 151 is larger than the area of the liquid drop preset and the number of the reagent solution exceeds a certain number (for example, 20 reagent solutions), the computer device 14 displays the re-disposing information or the serious defect information, the computer device 14 also counts the results of the diameter analysis and the area analysis to obtain a plurality of parameters to adjust the apparatus for disposing all the liquid drops successfully disposed at one time in the next disposing, and the state of the disposed liquid drops is optimized to improve the disposing efficiency (step S206).
Therefore, the computer device 14 compares and analyzes the states of the reagent solutions 151 from the stored default values or the built-in database. Since the distribution state of the reagent solutions 151 will affect the bonding of the reagents in the reagent solutions 151 to the microarray chip 15, the detection method of the present invention first confirms the state of the reagent solutions 151, and then performs a cleaning step on the microarray chip 15 to complete the production of the biochip (step S207).
Referring to fig. 3, a system structure diagram of a second embodiment of the present invention is shown, which is composed of a carrier 11, a light source 12, a light detector 13, a computer device 14, a microarray chip 15, a light guide plate 16, and a displacement device 17, wherein the displacement device 17 is used for moving the light detector 13, the light source 12, and the light guide plate 16. The main difference from the first embodiment of the present invention is that the carrier 11 is a fixed carrier, which is used to support only the microarray chip 15, and the relative positions of the light detector 13, the light source 12 and the light guide plate 16 are kept unchanged by the movement of the displacement device 17, so that the light detector 13 can scan the reagent solutions 151 on the surface of the microarray chip 15 and perform the subsequent processing. Since the operation of the second embodiment of the present invention is similar to that of the first embodiment of the present invention, and the flowchart for inspecting the biochip 15 is also similar to that of fig. 3, it is not explained much.
From the above description, the present invention utilizes a backlight optical scanning structure composed of a light source and a light detector to detect the states of the reagent solutions on the microarray chip to obtain a droplet image with a better resolution, wherein the detection time is batch processing, that is, after the reagent solutions are distributed, at least one microarray chip is observed on the surface again, and then a plurality of preset values or built-in databases stored in a computer device are utilized to analyze the droplet image to judge the states of the reagent solutions, and a quality control process (such as redistribution, defect marking, etc.) is performed according to the analysis result, so as to perform a quality control process in real time, and provide a simple and efficient detection mechanism to reduce the mass production cost.
The above-mentioned embodiments are merely exemplary for convenience of description, and the claimed invention should not be limited to the above-mentioned embodiments, but should be limited only by the claims.
Claims (23)
1. An optical drop detection system for detecting a target sample containing a plurality of reagent solutions, the optical drop detection system comprising:
a carrier for carrying the target sample;
a light source for providing a bright light to irradiate the target sample; and
a light detector, which is positioned at one side of the carrying platform and is used for detecting the reagent solutions of the target sample; wherein,
the target sample of the carrying platform is positioned between the light detector and the light source, so that the light detector can detect the reagent solutions of the target sample through the irradiation of the bright light to obtain a detection result.
2. An optical drop detection system for detecting a target sample containing a plurality of reagent solutions, the optical drop detection system comprising:
a carrier for carrying the target sample;
a light source for providing a bright light;
a light guide plate for receiving the bright light and irradiating the target sample with the bright light; and
a light detector, which is positioned at one side of the carrying platform and is used for detecting the reagent solutions of the target sample; wherein,
the target sample of the carrying platform is positioned between the light detector and the light guide plate, so that the light detector can detect the reagent solutions of the target sample through the irradiation of the light guide plate to obtain a detection result.
3. The optical drop detection system of claim 1 wherein the light source and the light detector are moved synchronously relative to the target sample during detection to scan the reagent solutions on the target sample.
4. The optical drop detection system of claim 2 wherein the light source, the light guide plate, and the light detector are moved synchronously relative to the target sample during detection to scan the reagent solutions on the target sample.
5. The optical drop detection system according to claims 1 and 2, wherein the light detector is connected to an electronic device for outputting the detection result of the light detector to the electronic device and displaying the detection result.
6. The optical drop detection system of claim 5 wherein the electronic device has an analysis process with a plurality of default detection values, such that the electronic device receives the detection result and analyzes the detection result according to the default detection values of the analysis process.
7. The optical drop detection system according to claims 1 and 2, wherein the light detector is connected to an electronic device, and the electronic device stores a plurality of preset detection values, and when the light detector outputs the detection result to the electronic device, the electronic device determines the drop status of the reagent solutions according to the preset detection values.
8. The optical drop detection system of claim 7 wherein the detection presets are drop diameter, drop area, or drop placement location.
9. The optical drop detection system of claim 1 wherein the photodetector is a charge coupled device detector.
10. The optical drop detection system of claim 2 wherein the photodetector is a linear scanning electric coupling element detector.
11. The optical drop detection system of claim 10 wherein the light guide plate is configured to convert bright light into a line light source and illuminate the target sample with the line light source.
12. The optical droplet detection system of claims 1 and 2, wherein the detection result is the reagent solution images of the target sample.
13. The optical drop detection system according to claims 1 and 2, wherein the reagent solution is a biological molecule.
14. The optical drop detection system of claim 13, wherein the biological molecule is an oligonucleotide, a peptide, or a derivative thereof.
15. A method of detection in an optical drop detection system, comprising the steps of:
providing a target sample distributed with a plurality of reagent solutions; and
scanning the target sample by moving the target sample synchronously with a light source and a photodetector; wherein,
the target sample is located between the light detector and the light source, and the light source can provide bright light to irradiate the target sample so that the light detector can detect the reagent solutions on the target sample to obtain a detection result.
16. A method of detection in an optical drop detection system, comprising the steps of:
providing a target sample distributed with a plurality of reagent solutions; and
using a light source, a light guide plate and a photodetector to synchronously move the target sample, and scanning the target sample; the target sample is located between the light detector and the light guide plate, and the light guide plate can irradiate the bright light provided by the light source to the target sample so that the light detector can detect the reagent solutions on the target sample to obtain a detection result.
The detecting method of claim 15 and 16, further comprising an analyzing step of comparing the detection results with a plurality of preset detection values to obtain at least one analysis determination result after obtaining a detection result, and performing a corresponding process on the target sample according to the at least one analysis determination result.
18. The detecting method of claim 17, wherein the preset detecting values are diameters of the dispensed droplets, areas of the dispensed droplets, or positions of the dispensed droplets.
19. The detecting method of claim 17, wherein the predetermined detecting values are diameters, areas or positions of the dispensed droplets, and if the at least one analysis result indicates that the number of position errors of the droplets dispensed on the reagents is greater than a predetermined value, the target sample is marked for rejection.
20. The method of claim 15, wherein the light detector is a CCD detector.
21. The method of claim 16, wherein the light detector is a linear scan electric coupling element detector.
The method of detecting in an optical drop detection system according to claims 15 and 16, wherein the reagent solution is a biological molecule.
23. The method of detecting in an optical drop detection system according to claims 15 and 16, wherein the biological molecule is an oligonucleotide, a peptide, or a derivative 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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| CN1641338A true CN1641338A (en) | 2005-07-20 |
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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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