CN114414531A - In-situ on-line detection method and device for metabolic molecules of organoid - Google Patents
In-situ on-line detection method and device for metabolic molecules of organoid Download PDFInfo
- Publication number
- CN114414531A CN114414531A CN202210114102.0A CN202210114102A CN114414531A CN 114414531 A CN114414531 A CN 114414531A CN 202210114102 A CN202210114102 A CN 202210114102A CN 114414531 A CN114414531 A CN 114414531A
- Authority
- CN
- China
- Prior art keywords
- detection
- module
- molecules
- metabolic
- organoid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Classifications
-
- 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
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/41—Refractivity; Phase-affecting properties, e.g. optical path length
- G01N21/45—Refractivity; Phase-affecting properties, e.g. optical path length using interferometric methods; using Schlieren methods
-
- 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
- G01N21/01—Arrangements or apparatus for facilitating the optical investigation
-
- 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
- G01N21/01—Arrangements or apparatus for facilitating the optical investigation
- G01N2021/0106—General arrangement of respective parts
- G01N2021/0112—Apparatus in one mechanical, optical or electronic block
Abstract
The invention relates to an in-situ online detection method and a device for metabolic molecules of organoid, which firstly establish the corresponding relation between the concentration of metabolic molecules and the phase change of interference signals, then collect various metabolic molecules generated by the organoid in situ in different regions by adopting a detection chip, measure the phase change of the interference signals caused by the combination of the metabolic molecules in each region and probe molecules on the surface of the detection chip in real time by an optical interference area array detection system, and further obtain the concentration information of the metabolic molecules in each region, thereby realizing the in-situ, online and high-flux quantitative detection of the metabolic molecules of the organoid. The method and the device are beneficial to saving the detection time and labor cost, avoiding the artificial interference on the detection and improving the detection efficiency and effectiveness.
Description
Technical Field
The invention belongs to the technical field of detection, and particularly relates to an in-situ online detection method and device for metabolic molecules of organoid.
Background
In the prior art, the detection method of the organoid metabolic molecules comprises a conventional fluorescence labeling method, a mass spectrum, a chromatogram and the like, and the methods have high detection sensitivity, but all the methods need to manually sample from a culture cavity, so that the organoid metabolic molecule detection cannot be continuously carried out for a long time in real time, and the continuous and real-time monitoring of the organoid metabolic molecules is the basic requirement of the organoid detection. Meanwhile, the manual sampling not only influences the normal growth of the organoids, but also consumes a great deal of time and labor cost. Therefore, it is necessary to develop a real-time in-situ on-line detection method for real-time detection of organoid metabolic molecules.
Disclosure of Invention
The invention aims to provide an in-situ online detection method and device for metabolic molecules of organoid, which are beneficial to saving detection time and labor cost, avoiding artificial interference on detection and improving detection efficiency and effectiveness.
In order to achieve the purpose, the invention adopts the technical scheme that: the method comprises the steps of establishing a corresponding relation between the concentration of metabolic molecules and the phase change of an interference signal, collecting various metabolic molecules generated by the organoid in situ in different regions by adopting a detection chip, measuring the phase change of the interference signal caused by the combination of the metabolic molecules in different regions and probe molecules on the surface of the detection chip in real time by an optical interference area array detection system, and further obtaining the concentration information of the metabolic molecules in different regions, thereby realizing the in-situ, on-line and high-flux quantitative detection of the metabolic molecules of the organoid.
Further, the specific method for establishing the corresponding relation between the metabolic molecule concentration and the interference signal phase change is as follows:
under the condition of not placing organoids, a concentration gradient experiment is carried out on pure solution of metabolic molecules by adopting a detection chip and an optical interference area array detection system, probe molecules capable of being specifically combined with the metabolic molecules are modified on the surface of the detection chip in advance, the phase change of interference signals in detection of different concentrations is measured, and a calibration curve of the concentration of the metabolic molecules and the phase change of the interference signals is established.
Furthermore, the detection chip is composed of a glass sheet, the surface of the glass sheet is divided into a plurality of areas, each area is modified with the same probe molecule, and different areas are modified with different types of probe molecules for collecting different types of metabolic molecules, so that high-flux detection of various metabolic molecules is realized.
Furthermore, the detection chip is in a rectangular, circular, oval, quadrilateral or pentagonal structure, and the thickness of the detection chip is between 0.02 mm and 20 mm.
The invention also provides an in-situ online detection device for the organoid metabolic molecules for realizing the method, which comprises a runner module, an organoid culture module, a detection chip and an optical interference area array detection system, wherein the runner module, the organoid culture module and the detection chip are sequentially arranged from top to bottom, the runner module is connected with a liquid inlet pipe and a liquid outlet pipe, the runner module is used for providing nutrients for the organoid and discharging metabolic waste, nutrient solution flows into the organoid culture module from the liquid inlet pipe through a runner, the culture solution flows out from the organoid culture module through the liquid outlet pipe through the runner during liquid change, the organoid culture module is used for culturing the organoid, the detection chip is used for in-situ collection of the metabolic molecules of the organoid, and different types of probe molecules are modified on the detection chip in different regions to collect different types of metabolic molecules; the optical interference area array detection system is arranged on the lower side of the detection chip and used for measuring the phase variation of interference signals introduced by combination of metabolic molecules in each subarea of the detection chip and probe molecules on the surface of the chip, then selecting the average phase variation of a plurality of measurement sites in each subarea as the interference signals in the area, and finally acquiring the concentration information of various metabolic molecules according to the established corresponding relation between the molecular concentration and the phase variation of the interference signals.
Furthermore, the flow channel module, the organoid culture module and the detection chip are clamped together by supporting pieces arranged on the upper side and the lower side of the flow channel module, the organoid culture module and the detection chip and are fastened by fasteners.
Furthermore, the optical interference area array detection system is a spectral Michelson interference detection system, and two paths of interference light are reflected by the upper surface and the lower surface of the detection chip; the optical interference area array detection system comprises a light source module, a light splitting module, a collimation module, a scanning module, a microscopic module and a spectrometer, wherein light emitted by the light source module is focused on a detection chip after passing through the light splitting module, the collimation module, the scanning module and the microscopic module, light reflected from the upper surface and the lower surface of the detection chip is reversely collected by the same microscopic module, and the reverse light is collected by the spectrometer after passing through the light splitting module; the interference spectrum acquired by the spectrometer is processed by data including fast Fourier transform, phase extraction and initial phase subtraction to obtain the phase variation of metabolic molecule detection; and further, sequentially scanning different subareas by using a galvanometer to obtain the average phase variation of interference signals of different subareas as a detection result of the subarea.
Compared with the prior art, the invention has the following beneficial effects: the method and the device overcome the problems of the existing organoid metabolic molecule detection method, do not need manual sampling, save the detection time and labor cost, do not interfere with organoid culture, can automatically and continuously track and monitor the metabolic molecules generated by the organoids for a long time, have the advantages of real-time, high efficiency, sensitivity, in-situ, high flux and the like, and have strong practicability and wide application prospect.
Drawings
FIG. 1 is a flow chart of a method implementation of an embodiment of the present invention.
FIG. 2 is a schematic diagram of a process for manufacturing a detection chip according to an embodiment of the present invention.
Fig. 3 is a schematic diagram of the structure of the device according to the embodiment of the present invention.
Detailed Description
The invention is further explained below with reference to the drawings and the embodiments.
It should be noted that the following detailed description is exemplary and is intended to provide further explanation of the disclosure. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs.
It is noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of example embodiments according to the present application. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, and it should be understood that when the terms "comprises" and/or "comprising" are used in this specification, they specify the presence of stated features, steps, operations, devices, components, and/or combinations thereof, unless the context clearly indicates otherwise.
As shown in fig. 1, the embodiment provides an in-situ online detection method for metabolic molecules of an organoid, which includes establishing a corresponding relationship between the concentration of metabolic molecules and the phase change of an interference signal, collecting multiple metabolic molecules generated by the organoid in situ in different regions of a detection chip, measuring the phase change of the interference signal caused by the combination of the metabolic molecules in different regions and probe molecules on the surface of the detection chip in real time by an optical interference area array detection system, and obtaining the concentration information of the metabolic molecules in different regions according to the corresponding relationship between the concentration of the metabolic molecules and the phase change of the interference signal, thereby implementing in-situ, online, and high-flux quantitative detection of the metabolic molecules of the organoid.
The specific method for establishing the corresponding relation between the metabolic molecule concentration and the interference signal phase change comprises the following steps: under the condition of not placing organoids, a concentration gradient experiment is carried out on pure metabolic molecule solutions by adopting a detection chip and an optical interference area array detection system, namely, the pure metabolic molecule solutions only containing one metabolic molecule but with different concentrations are subjected to an experiment, probe molecules capable of being specifically combined with the metabolic molecule are modified on the surface of the detection chip in advance, the phase change of interference signals in detection of different concentrations is measured, and a calibration curve of the metabolic molecule concentration and the interference signal phase change is established.
The preparation process of the detection chip in this embodiment is shown in fig. 2. The detection chip is composed of a glass sheet, the surface of the glass sheet is divided into a plurality of areas, the same probe molecules are modified on each sub-area, different types of probe molecules are modified on different sub-areas, and the detection chip is used for collecting different types of metabolic molecules, so that high-flux detection of various metabolic molecules is realized. The detection chip can be in a rectangular, circular, oval, quadrilateral or pentagonal structure, and the thickness of the detection chip is between 0.02 and 20 mm.
As shown in fig. 3, the present embodiment provides an in-situ online detection apparatus for organoid metabolic molecules for implementing the above method, including a flow channel module 1, an organoid culture module 2, an in-situ detection chip 5, and an optical interference area array detection system, where the flow channel module 1, the organoid culture module 2, and the detection chip 5 are sequentially arranged from top to bottom, the flow channel module is connected to a liquid inlet pipe 8 and a liquid outlet pipe 9, the flow channel module 1 is configured to provide nutrients for organoids and discharge metabolic waste, a nutrient solution flows into the organoid culture module from the liquid inlet pipe through a flow channel, a culture solution flows out from the organoid culture module through the flow channel during liquid change, the organoid culture module 2 is configured to culture organoids, the detection chip 5 is configured to collect in-situ metabolic molecules of the organoids, and different types of probe molecules are modified on the detection chip by different regions, to collect different kinds of metabolic molecules. The flow channel module and the organoid culture module can be different specific structures in the prior art. The solution containing various metabolic molecules simultaneously reaches each subarea, and different probe molecules only react with corresponding metabolic molecules. The size of the organoid is larger than the total area of molecular detection, so that metabolic molecules can uniformly reach each subarea and are combined with probe molecules in each subarea to finish specific detection. The optical interference area array detection system is arranged on the lower side of the detection chip and used for measuring the phase variation of interference signals introduced by combination of metabolic molecules in each subarea of the detection chip and probe molecules on the surface of the chip, then selecting the average phase variation of a plurality of measurement sites in each subarea as the interference signals in the area, and finally acquiring the concentration information of various metabolic molecules according to the established corresponding relation between the molecular concentration and the phase variation of the interference signals. The flow channel module 1, the organoid culture module and the detection chip 5 are clamped together by the supporting pieces 6 and 7 arranged on the upper side and the lower side of the flow channel module and are fastened by the fastening pieces.
The optical interference area array detection system is a spectral Michelson interference detection system, and two paths of interference light are reflected by the upper surface and the lower surface of a detection chip. The optical interference area array detection system comprises a light source module 10, a light splitting module 11, a collimation module 12, a scanning module 13, a microscopic module 14 and a spectrometer 15. The light source module is a broadband light source, light emitted by the light source is focused on the detection chip after passing through the light splitting module, the collimation module, the scanning module and the microscope module, light reflected from the upper surface and the lower surface of the detection chip is reversely collected by the same microscope module, and the light is collected by the spectrometer after reversely passing through the light splitting module, namely is interfered on the spectrometer and is recorded; the interference spectrum acquired by the spectrometer is processed by data including fast Fourier transform, phase extraction and initial phase subtraction to obtain the phase variation of metabolic molecule detection; and further, sequentially scanning different subareas by using a galvanometer to obtain the average phase variation of interference signals of different subareas as a detection result of the subarea.
The following describes the implementation of the present invention with reference to a specific embodiment.
FIG. 1 shows the implementation steps of the in-situ online detection method for organoid metabolic molecules provided in this embodiment, including:
1) and preparing an in-situ detection chip and finishing the surface functional modification of the chip.
2) And constructing an in-situ online detecting device for the organoid metabolic molecules.
3) And (3) carrying out a calibration experiment, carrying out a concentration gradient experiment on pure solution of the metabolic molecules by using a detection chip and an optical interference area array detection system under the condition of not placing organoids, and establishing a corresponding relation between the concentration of the metabolic molecules and the phase change of an interference signal.
4) Carrying out in-situ on-line detection on metabolic molecules of the organoid, putting the organoid into an organoid culture module for culture, measuring the phase change of an interference signal introduced by the combination of the metabolic molecules and probe molecules on the surface of a chip by using a detection chip and an optical interference area array detection system, and finally determining the concentration of the metabolic molecules according to the established relationship between the molecular concentration and the phase change of the interference signal.
5) And scanning different partitions of the chip to finish the quantitative detection of various metabolic molecules.
The preparation process of the in-situ detection chip is shown in fig. 2:
a glass plate having a rectangular parallelepiped shape and a thickness of 0.33mm is preferable as the detection chip. This example illustrates the detection of human IgG metabolic molecules. The surface modification process of the detection chip comprises the following steps: firstly, soaking a sensing chip with piranha washing liquor overnight, and then washing the sensing chip clean with deionized water; further dropwise adding 2mg/ml dopamine solution to the surface of the sensor chip for reaction for 20 minutes, and then washing the sensor chip clean with deionized water; further dropwise adding 1mg/ml Protein A solution to the surface of the sensor chip for reaction for 1 hour, then washing the sensor chip clean with deionized water, wherein the Protein A is used as a probe molecule for specifically capturing a target molecule, namely human IgG, and different probe molecules can be selected for modification according to different metabolic molecules; and further dripping the protein-free blocking liquid onto the surface of the sensor chip for reaction for 1 hour for blocking, and then washing the sensor chip clean by deionized water.
The organoid metabolism molecule detection device comprises a flow channel module, an organoid culture module, an in-situ detection chip and an optical interference area array detection system. As shown in fig. 3, 1 is a flow channel module made of PDMS with a through hole engraved on the surface; 2 is organoid culture module, the middle layer of which is tissue engineering membrane for supporting organoid growth; 5 is a modified in-situ detection chip; 6-7 are supporting parts; 8-9 are liquid inlet and outlet pipes. The optical interference area array detection system performs real-time interference measurement on the chip from the lower part. The optical interference area array detection system comprises a light source module 10, a light splitting module 11, a collimation module 12, a scanning module 13, a microscopic module 14 and a spectrometer 15. Light emitted by the light source is focused on the detection chip after passing through the light splitting module, the collimation module, the scanning module and the microscopic module, light reflected from the upper surface and the lower surface of the chip is reversely collected by the same microscopic module 14, and the light is finally collected by the spectrometer 15 after reversely passing through the light splitting module 11. The acquired interference spectrum is subjected to fast Fourier transform to obtain a complex spatial domain interference signal, the phase of the interference signal at the position where the optical path difference is equal to the optical thickness of the chip is further extracted, and the optical thickness of the chip is equal to the geometric thickness of the chip multiplied by the refractive index. The phase at the time of the initial measurement is further subtracted from the phase of the interference signal, which is the amount of phase change introduced by the molecular detection.
And further carrying out a concentration calibration experiment, carrying out a measurement experiment on pure solutions of human IgG with different concentrations by using a detection chip and an optical interference area array detection system under the condition of not placing organoids, establishing a calibration curve of the human IgG concentration and the phase quantity of an interference signal, and determining the detection limit of the system according to a 3 delta theory. Further carrying out in-situ on-line detection of metabolic molecules of the organoid, putting the organoid into a culture module for culture, carrying out measurement of human IgG by using a detection chip and an optical interference area array detection system, and further calculating the actual concentration of the IgG molecules from the measured phase quantity according to the established corresponding relation between the concentration of the IgG molecules and the phase of an interference signal.
For the detection of various metabolic molecules, the chip modification and detection process is similar to the detection of a single molecule, except that the surface of the chip needs to modify different types of probe molecules in different regions, so that each region detects one metabolic molecule. And further sequentially scanning different subareas by using a galvanometer, selecting 8 points in each subarea, and obtaining the average phase variation of interference signals of the 8 points as an interference measurement result of the subarea. And further calculating the concentration information of various metabolic molecules according to the established calibration curve of the concentration of the metabolic molecules and the phase quantity of the interference signal. Assuming that the chip size is 3mm × 3mm and each small partition is 0.1mm × 0.1mm (the length and width of the chip are respectively divided into 30 parts), the simultaneous quantitative detection of 900 metabolic molecules can be theoretically realized.
The foregoing is directed to preferred embodiments of the present invention, other and further embodiments of the invention may be devised without departing from the basic scope thereof, and the scope thereof is determined by the claims that follow. However, any simple modification, equivalent change and modification of the above embodiments according to the technical essence of the present invention are within the protection scope of the technical solution of the present invention.
Claims (7)
1. The in-situ on-line detection method of the organ-like metabolic molecules is characterized by firstly establishing a corresponding relation between the concentration of the metabolic molecules and the phase change of an interference signal, then collecting a plurality of metabolic molecules generated by the organ-like by adopting a detection chip in a regional in-situ manner, and measuring the phase change of the interference signal caused by the combination of the metabolic molecules in each regional region and probe molecules on the surface of the detection chip in real time through an optical interference area array detection system so as to obtain the concentration information of the metabolic molecules in each regional region, thereby realizing the in-situ, on-line and high-flux quantitative detection of the organ-like metabolic molecules.
2. The in-situ on-line detection method of metabolic molecules of an organoid according to claim 1, wherein the specific method for establishing the corresponding relationship between the concentration of metabolic molecules and the phase change of the interference signal comprises:
under the condition of not placing organoids, a concentration gradient experiment is carried out on pure solution of metabolic molecules by adopting a detection chip and an optical interference area array detection system, probe molecules capable of being specifically combined with the metabolic molecules are modified on the surface of the detection chip in advance, the phase change of interference signals in detection of different concentrations is measured, and a calibration curve of the concentration of the metabolic molecules and the phase change of the interference signals is established.
3. The in-situ on-line detection method of metabolic molecules of an organ-like body according to claim 1, wherein the detection chip is composed of a glass sheet, the surface of the glass sheet is divided into a plurality of regions, each region is modified with the same probe molecule, and different regions are modified with different probe molecules for collecting different metabolic molecules, thereby realizing high-throughput detection of various metabolic molecules.
4. The in-situ on-line detection method of metabolic molecules of an organoid according to claim 3, wherein the detection chip has a rectangular, circular, elliptical, quadrilateral or pentagonal structure, and the thickness of the detection chip is between 0.02 mm and 20 mm.
5. An in situ on-line detection device for organoid metabolic molecules for implementing the method according to any of claims 1-4, it is characterized by comprising a flow channel module, an organoid culture module, a detection chip and an optical interference area array detection system, the flow channel module, the organoid culture module and the detection chip are sequentially arranged from top to bottom, the flow channel module is connected with a liquid inlet pipe and a liquid outlet pipe, the flow channel module is used for providing nutrients for the organoid and discharging metabolic waste, nutrient solution flows into the organoid culture module from the liquid inlet pipe through the flow channel, culture solution flows out from the organoid culture module through the flow channel and the liquid outlet pipe during solution replacement, the organoid culture module is used for culturing organoids, the detection chip is used for collecting metabolic molecules of the organoids in situ, modifying different types of probe molecules on the detection chip in different areas so as to collect different types of metabolic molecules; the optical interference area array detection system is arranged on the lower side of the detection chip and used for measuring the phase variation of interference signals introduced by combination of metabolic molecules in each subarea of the detection chip and probe molecules on the surface of the chip, then selecting the average phase variation of a plurality of measurement sites in each subarea as the interference signals in the area, and finally acquiring the concentration information of various metabolic molecules according to the established corresponding relation between the molecular concentration and the phase variation of the interference signals.
6. The in-situ on-line detection device for the metabolic molecules of the organoid according to claim 5, wherein the flow channel module, the organoid culture module and the detection chip are clamped together by the supporting members disposed at the upper and lower sides thereof and fastened by the fastening members.
7. The in-situ on-line detection device of a organoid metabolic molecule according to claim 5, wherein the optical interference area array detection system is a spectral Michelson interference detection system, and two paths of interference light are reflected from the upper and lower surfaces of the detection chip; the optical interference area array detection system comprises a light source module, a light splitting module, a collimation module, a scanning module, a microscopic module and a spectrometer, wherein light emitted by the light source module is focused on a detection chip after passing through the light splitting module, the collimation module, the scanning module and the microscopic module, light reflected from the upper surface and the lower surface of the detection chip is reversely collected by the same microscopic module, and the reverse light is collected by the spectrometer after passing through the light splitting module; the interference spectrum acquired by the spectrometer is processed by data including fast Fourier transform, phase extraction and initial phase subtraction to obtain the phase variation of metabolic molecule detection; and further, sequentially scanning different subareas by using a galvanometer to obtain the average phase variation of interference signals of different subareas as a detection result of the subarea.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210114102.0A CN114414531B (en) | 2022-01-30 | 2022-01-30 | In-situ on-line detection method and device for organoid metabolic molecules |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210114102.0A CN114414531B (en) | 2022-01-30 | 2022-01-30 | In-situ on-line detection method and device for organoid metabolic molecules |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114414531A true CN114414531A (en) | 2022-04-29 |
| CN114414531B CN114414531B (en) | 2023-07-28 |
Family
ID=81279613
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210114102.0A Active CN114414531B (en) | 2022-01-30 | 2022-01-30 | In-situ on-line detection method and device for organoid metabolic molecules |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114414531B (en) |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101893563A (en) * | 2010-04-19 | 2010-11-24 | 清华大学 | Phase measurement method of variable exposure time imaging phase shift |
| CN101915750A (en) * | 2010-07-07 | 2010-12-15 | 清华大学 | Biomolecule interaction detection method and system based on SPR interference imaging |
| CN104826676A (en) * | 2015-05-04 | 2015-08-12 | 清华大学深圳研究生院 | Microfluidic chip, microfluidic chip system and applications of microfluidic chip system |
| CN106483117A (en) * | 2016-09-28 | 2017-03-08 | 中国科学院重庆绿色智能技术研究院 | A kind of sensor chip for Microcystin detection and its mobile monitoring equipment |
| CN110283724A (en) * | 2019-07-09 | 2019-09-27 | 汇芯(北京)科技有限公司 | A kind of high throughput organoid phenotype screening system and method |
| CN110927121A (en) * | 2019-12-05 | 2020-03-27 | 深圳大学 | Phase type SPR detection device and method based on white light interference spectrum |
| CN113941378A (en) * | 2021-10-14 | 2022-01-18 | 浙江大学 | Multi-cavity electrophysiological micro-nano detection-based neural organoid chip and detection method |
-
2022
- 2022-01-30 CN CN202210114102.0A patent/CN114414531B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101893563A (en) * | 2010-04-19 | 2010-11-24 | 清华大学 | Phase measurement method of variable exposure time imaging phase shift |
| CN101915750A (en) * | 2010-07-07 | 2010-12-15 | 清华大学 | Biomolecule interaction detection method and system based on SPR interference imaging |
| CN104826676A (en) * | 2015-05-04 | 2015-08-12 | 清华大学深圳研究生院 | Microfluidic chip, microfluidic chip system and applications of microfluidic chip system |
| CN106483117A (en) * | 2016-09-28 | 2017-03-08 | 中国科学院重庆绿色智能技术研究院 | A kind of sensor chip for Microcystin detection and its mobile monitoring equipment |
| CN110283724A (en) * | 2019-07-09 | 2019-09-27 | 汇芯(北京)科技有限公司 | A kind of high throughput organoid phenotype screening system and method |
| CN110927121A (en) * | 2019-12-05 | 2020-03-27 | 深圳大学 | Phase type SPR detection device and method based on white light interference spectrum |
| CN113941378A (en) * | 2021-10-14 | 2022-01-18 | 浙江大学 | Multi-cavity electrophysiological micro-nano detection-based neural organoid chip and detection method |
Non-Patent Citations (3)
| Title |
|---|
| CHULMIN JOO 等: "Spectral-domain optical coherence phase microscopy for label-free multiplexed protein microarray assay", 《BIOSENSORS AND BIOELECTRONICS》, vol. 25, pages 275 - 281, XP026600420, DOI: 10.1016/j.bios.2009.06.028 * |
| CUIXIA GUO 等: "A Fluidic Biosensor Based on a Phase-Sensitive Low-Coherence Spectral-Domain Interferometer", 《SENSORS》, vol. 18, pages 1 - 10 * |
| CUIXIA GUO 等: "Spectral-Domain Phase Microscopy for Thickness Encoded Suspension Array", 《IEEE PHOTONICS TECHNOLOGY LETTERS》, vol. 32, no. 8, pages 461 - 464, XP011779177, DOI: 10.1109/LPT.2020.2971508 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN114414531B (en) | 2023-07-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Li et al. | Plasmonic nanohole array biosensor for label-free and real-time analysis of live cell secretion | |
| US20210208033A1 (en) | Diffusive gradients in thin films (dgt) test device for lake water and test method using same | |
| US20120129723A1 (en) | System and method for carrying out multiple binding reactions in an array format | |
| US20120214707A1 (en) | Method for detection of an analyte in a fluid sample | |
| CN105527397B (en) | Pb based on intelligent gel2+Pb in micro-fluidic detection chip and water sample2+Detection method | |
| Wolken et al. | Capillary isoelectric focusing of individual mitochondria | |
| US20200103343A1 (en) | Measuring System, Such as an Interaction Measuring System and a Measuring Method | |
| WO2017050940A1 (en) | Biosensor and use thereof | |
| ATE541048T1 (en) | METHOD AND DEVICE FOR DETECTING AND/OR DETERMINING THE BACTERIA CONTAINED IN A SAMPLE | |
| Liu et al. | Real-time monitoring of single-cell secretion with a high-throughput nanoplasmonic microarray | |
| CN114414531B (en) | In-situ on-line detection method and device for organoid metabolic molecules | |
| KR101992612B1 (en) | Autosampler for continuous water monitoring equipment | |
| Xu et al. | A general method to regenerate arrayed gold microelectrodes for label-free cell assay | |
| WO2019035462A1 (en) | Method for position-specific determination of undifferentiated state of pluripotent stem cells cultured in a cell culture container, method for subculturing pluripotent stem cells, and device used in said methods | |
| CN101514986A (en) | Label-free biochemical detection method reinforced by utilizing local surface plasma | |
| US20210302312A1 (en) | Integrated Microfluidic Device for Capture and Spectroscopic Characterization of Live Cells Under Various Treatment Conditions | |
| CN103645332B (en) | Multifunctional workstation for automatically detecting outflow of cholesterol and other analyte cells with high throughput | |
| CN203881776U (en) | Multifunctional workstation for automatically detecting outflow of cholesterol and other analytes from cells at high throughput | |
| CN109540846B (en) | Method for measuring glycated protein | |
| WO2005001472A1 (en) | Method of screening substance with anticancerous activity and apparatus therefor | |
| US20040096930A1 (en) | Method for monitoring biotechnological processes | |
| US8557609B1 (en) | Imaging electrophoresis system | |
| Sonnleitner | Real‐time measurement and monitoring of bioprocesses | |
| Gudermann et al. | CeDEX: Automated Cell Density Determination | |
| CN203551561U (en) | Detection device for trace target material measurement |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |