CN103604785A - Fluorescence detection system - Google Patents
Fluorescence detection system Download PDFInfo
- Publication number
- CN103604785A CN103604785A CN201310542526.8A CN201310542526A CN103604785A CN 103604785 A CN103604785 A CN 103604785A CN 201310542526 A CN201310542526 A CN 201310542526A CN 103604785 A CN103604785 A CN 103604785A
- Authority
- CN
- China
- Prior art keywords
- fluorescence
- signal
- array
- photoelectric sensing
- chip body
- 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.)
- Pending
Links
Images
Landscapes
- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
Abstract
The invention discloses a fluorescence detection system which comprises a chip body, a pulse excitation light source and a singlechip data storage processing module, wherein the pulse excitation light source is connected with a micro reaction pool of the chip body through a coupling optical fiber; the chip body is in signal connection with the singlechip data storage processing module; the chip body comprises a silicon substrate, SU-8 thick rubber, a signal processing circuit, a photoelectric sensing array, an active preprocessing amplification array and an asynchronous sequential control circuit. The fluorescence detection system has the beneficial effects that 1, the time resolution technology is combined with a fluorescence detection technology, the fluorescence detection system is optimized, a complex optical path structure is not needed, and the fluorescence can be effectively detected; 2, the fluorescence detection system can be compatible with a standard complementary metal oxide semiconductor (CMOS) process, namely a current mainstream microelectronic process, and a photoelectric sensing unit, a subsequent active pixel amplifier circuit and the signal processing circuit are in monolithic integration; 3, the micro reaction pool is integrated on the chip, and multi-channel different samples can be simultaneously detected.
Description
Technical field
The present invention relates to a kind of fluorescence detecting system.
Background technology
Fluorescence analysis is to utilize the excited fluorescence characterisitic parameter of sample the characteristic of material to be carried out to the method for qualitative or quantitative test, for example utilize cancer cell and the normal cell affinity difference to the photosensitive fluorescence probe of hematoporphyrin, obtain cancer cell and Normocellular fluorescence lifetime characteristic and the time dependent curve difference of Insulin, can be used for early diagnosis of cancer and treatment effectiveness evaluation.In fluoroscopic examination at present, conventional detection system is the detection system that adopts light channel structure, as shown in Figure 1, traditional fluorescence detecting system comprises burst of ultraviolel light source (1 '), exciting light optical filter (2 '), sample cell (3 '), fluorescent optical filter (4 '), fluorescent probe (5 ') and record display system (6 ').Described burst of ultraviolel light source is positioned on the optical axis of exciting light, by shown in exciting light optical filter enter described sample cell, form an exciting light light path; The fluorescence that described sample cell sends arrives described fluorescent probe by described fluorescent optical filter, forms a fluorescence light path; Described fluorescent probe converts the fluorescence signal detecting to current/voltage output, by described, records the fluorescence characteristic that display system obtains predetermined substance.
Traditional fluorescence detecting system needs complicated light path system, fluorescence and exciting light that material stimulated luminescence in described sample cell sends after irradiating mix, in order effectively excited fluorescence to be screened from mixed light, between described sample cell and described photodetector, must add the above fluorescent optical filter, the fluorescence producing has larger decay through fluorescent optical filter, reduce detection sensitivity, complicated light path system adopts discrete component to build simultaneously, system is huge, can not meet integrated, the microminiaturized requirement of fluorescence detecting system.
Summary of the invention
While the present invention is directed to current fluorescence detection device test, fluorescence can produce the problem of the sensitivity of loss, reduction fluoroscopic examination between fluorescence reaction pond and fluorescent probe, has proposed the fluorescence detecting system based on TIME RESOLVED TECHNIQUE that a kind of measurement sensitivity is high, loss is little.
Fluorescence detecting system of the present invention, is characterized in that: comprise chip body, pulse excitation light source, single-chip data stores processor module, described pulse excitation light source is connected with the micro reaction pool of described chip body by coupled fiber; Described chip body is connected with described single-chip data stores processor module by signal;
Described chip body comprises silicon substrate, the thick glue of SU-8, signal processing circuit, photoelectric sensing array, active pre-service amplification array and asynchronous sequential control circuit, the thick glue of described SU-8 is fixed on described silicon substrate upper surface, at least one fluorescence reaction pond group is set on the thick glue of described SU-8, and the fluorescence reaction pond group described in each consists of at least one micro reaction pool; Be positioned at and on the silicon substrate under the group of fluorescence reaction pond, lay corresponding signal processing circuit, photoelectric sensing array, active pre-service and amplify array and asynchronous sequential control circuit; The signal input part that the signal input part of described photoelectric sensing array is connected with the signal output part signal of described asynchronous sequential control circuit, the signal output part of described photoelectric sensing array amplifies array with described active pre-service is connected; The signal output part that array is amplified in described active pre-service is connected with the signal input part signal of described signal processing circuit and the signal output part of described signal processing circuit is fixed by press welding block and pcb board, and described pcb board is connected with the signal input part signal of described single-chip data stores processor module.
Between described photoelectric sensing array and described signal processing circuit, metal screen layer is set.
Described photoelectric sensing array is to form four-way light sensation array with the PN junction photodiode of CMOS process compatible.
The thick glue of described SU-8 is provided with four symmetrical fluorescence reaction pond groups, and each fluorescence reaction pond group Jun You tetra-road micro reaction pool symmetric offset spread.
The described micro reaction pool degree of depth is 100 μ m.
The consistent size of described coupled fiber diameter and described micro reaction pool.
The micro reaction pool of described coupled fiber and described chip body is by insulating gel adhesion.
Principle of work, the thick glue Shang tetra-road micro reaction pools of SU-8, in micro reaction pool, designed four-way photoelectric sensing array, be time origin that time that the light-pulse generator of take excites, postpone after a period of time (being greater than light source pulse width time delay), the fluorescence signal that measurement is excited, can effectively avoid exciting light noise to the impact of measuring, the fluorescence intensity of different time points is read in asynchronous sequential control circuit timesharing, obtain the die-away curve of fluorescence signal, then photoelectric sensing array is converted into proportional current signal by the fluorescence signal of generation; Now active pixel amplifies array faint photo-signal is changed into voltage transmission that amplitude is larger to signal processing circuit, signal processing circuit is transferred to single-chip microcomputer single-chip data stores processor module by press welding block after reading the fluorescence intensity signals voltage in the fluorescence decay process of four-way photoelectric sensing array, and the fluorescence signal of measuring is processed.
The invention has the beneficial effects as follows: 1, can convert faint fluorescence to photocurrent with the photoelectricity PN junction diode of CMOS process compatible, photoelectricity PN junction diode is Array Design as required; 2, photoelectricity PN junction diode can be integrated with follow-up active signal treatment circuit monolithic, reduced signal slippages and realized the microminiaturization detecting; 3, integrated SU-8 micro reaction pool on sheet, can carry out single or multiple passage samples and detect simultaneously.The present invention produces fluorescence signal, detect and processes with the sensing chip of monolithic and realize.
Accompanying drawing explanation
Fig. 1 is traditional fluorescence detecting system.
Fig. 2 be chip body of the present invention structural drawing (wherein: arrow represents the incident direction of nanoscale pulse excitation light; p
+for P type source, leak and inject; n
+for N-type source, leak and inject; N-well is N-type light dope trap).
Fig. 3 is chip body cut-away view of the present invention.
Fig. 4 is structural drawing of the present invention.
Embodiment
Below in conjunction with accompanying drawing, further illustrate the present invention
With reference to accompanying drawing:
Described chip body 1 comprises silicon substrate 11, the thick glue 12 of SU-8, signal processing circuit 13, photoelectric sensing array 14, active pre-service amplification array and asynchronous sequential control circuit, the thick glue 12 of described SU-8 is fixed on described silicon substrate 11 upper surfaces, at least one fluorescence reaction pond group 121 is set on the thick glue 12 of described SU-8, and the fluorescence reaction pond group 121 described in each becomes 1211 by least one micro reaction pool; Be positioned at and on the silicon substrate 11 under fluorescence reaction pond group 121, lay corresponding signal processing circuit 13, photoelectric sensing array 14, active pre-service and amplify array and asynchronous sequential control circuit; The signal input part that the signal input part of described photoelectric sensing array 14 is connected with the signal output part signal of described asynchronous sequential control circuit, the signal output part of described photoelectric sensing array 14 amplifies array with described active pre-service is connected; The signal output part that array is amplified in described active pre-service is connected with the signal input part signal of described signal processing circuit and the signal output part of described signal processing circuit 13 is fixed by press welding block 15 and pcb board 16, and described pcb board is connected with the signal input part of described single-chip data stores processor module 3.
Between described photoelectric sensing array 14 and described signal processing circuit 13, metal screen layer 17 is set.
Described photoelectric sensing array 14 is to form four-way light sensation array with the PN junction photodiode of CMOS process compatible.
The thick glue 12 of described SU-8 is provided with four symmetrical fluorescence reaction pond groups 121, and each fluorescence reaction pond group Jun You tetra-road micro reaction pool 1211 symmetric offset spread.
Described micro reaction pool 1211 degree of depth are 100 μ m.
The consistent size of described coupled fiber diameter and described micro reaction pool.
The micro reaction pool of described coupled fiber and described chip body is by insulating gel adhesion.
Principle of work, the thick glue 12 Shang tetra-road micro reaction pools 1211 of SU-8, in micro reaction pool 1211, designed four-way photoelectric sensing array 14, be time origin that time that the light-pulse generator of take excites, postpone after a period of time (being greater than light source pulse width time delay), the fluorescence signal that measurement is excited, can effectively avoid exciting light noise to the impact of measuring, the fluorescence intensity of different time points is read in asynchronous sequential control circuit timesharing, obtain the die-away curve of fluorescence signal, then photoelectric sensing array is converted into proportional current signal by the fluorescence signal of generation; Now active pixel amplifies array faint photo-signal is changed into voltage transmission that amplitude is larger to signal processing circuit, signal processing circuit is transferred to single-chip microcomputer single-chip data stores processor module by press welding block after reading the fluorescence intensity signals voltage in the fluorescence decay process of four-way photoelectric sensing array, and the fluorescence signal of measuring is processed.
Content described in this instructions embodiment is only enumerating the way of realization of inventive concept; protection scope of the present invention should not be regarded as only limiting to the concrete form that embodiment states, protection scope of the present invention also comprises that those skilled in the art conceive the equivalent technologies means that can expect according to the present invention.
Claims (7)
1. fluorescence detecting system, is characterized in that: comprise chip body, pulse excitation light source, single-chip data stores processor module, described pulse excitation light source is connected with the micro reaction pool of described chip body by coupled fiber; Described chip body is connected with described single-chip data stores processor module by signal;
Described chip body comprises silicon substrate, the thick glue of SU-8, signal processing circuit, photoelectric sensing array, active pre-service amplification array and asynchronous sequential control circuit, the thick glue of described SU-8 is fixed on described silicon substrate upper surface, at least one fluorescence reaction pond group is set on the thick glue of described SU-8, and the fluorescence reaction pond group described in each consists of at least one micro reaction pool; Be positioned at and on the silicon substrate under the group of fluorescence reaction pond, lay corresponding signal processing circuit, photoelectric sensing array, active pre-service and amplify array and asynchronous sequential control circuit; The signal input part that the signal input part of described photoelectric sensing array is connected with the signal output part signal of described asynchronous sequential control circuit, the signal output part of described photoelectric sensing array amplifies array with described active pre-service is connected; The signal output part that array is amplified in described active pre-service is connected with the signal input part signal of described signal processing circuit and the signal output part of described signal processing circuit is fixed by press welding block and pcb board, and described pcb board is connected with the signal input part signal of described single-chip data stores processor module.
2. fluorescence detecting system as claimed in claim 1, is characterized in that: between described photoelectric sensing array and described signal processing circuit, metal screen layer is set.
3. fluorescence detecting system as claimed in claim 2, is characterized in that: described photoelectric sensing array is the PN junction photodiode formation four-way light sensation array with CMOS process compatible.
4. fluorescence detecting system as claimed in claim 3, is characterized in that: the thick glue of described SU-8 is provided with four symmetrical fluorescence reaction pond groups, and each fluorescence reaction pond group Jun You tetra-road micro reaction pool symmetric offset spread.
5. fluorescence detecting system as claimed in claim 4, is characterized in that: the described micro reaction pool degree of depth is 100 μ m.
6. fluorescence detecting system as claimed in claim 5, is characterized in that: the consistent size of described coupled fiber diameter and described micro reaction pool.
7. fluorescence detecting system as claimed in claim 6, is characterized in that: the micro reaction pool of described coupled fiber and described chip body is by insulating gel adhesion.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310542526.8A CN103604785A (en) | 2013-11-05 | 2013-11-05 | Fluorescence detection system |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310542526.8A CN103604785A (en) | 2013-11-05 | 2013-11-05 | Fluorescence detection system |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103604785A true CN103604785A (en) | 2014-02-26 |
Family
ID=50123030
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310542526.8A Pending CN103604785A (en) | 2013-11-05 | 2013-11-05 | Fluorescence detection system |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103604785A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112812954A (en) * | 2020-12-29 | 2021-05-18 | 中国科学院长春光学精密机械与物理研究所 | Gene sequencing chip |
| CN114594592A (en) * | 2022-05-10 | 2022-06-07 | 中国科学技术大学 | Imaging method and device for measuring higher harmonics, electronic equipment and storage medium |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030175987A1 (en) * | 2002-03-18 | 2003-09-18 | Edward Verdonk | Biochemical assay with programmable array detection |
| CN1865932A (en) * | 2005-05-19 | 2006-11-22 | 清华大学 | Fluorometric detector for micro-fluidic chip system |
| US20070097364A1 (en) * | 2005-05-09 | 2007-05-03 | The Trustees Of Columbia University In The City Of New York | Active CMOS biosensor chip for fluorescent-based detection |
| CN102483427A (en) * | 2009-06-15 | 2012-05-30 | 茨瓦内科技大学 | CMOS moems sensor device |
| CN103219342A (en) * | 2013-04-07 | 2013-07-24 | 浙江工业大学 | Double-junction depth photodiode for fluorescence detection |
| CN103380500A (en) * | 2010-11-30 | 2013-10-30 | 茨瓦内科技大学 | CMOS based micro-photonic systems |
| CN203643339U (en) * | 2013-11-05 | 2014-06-11 | 浙江工业大学 | Fluorescence detection system |
-
2013
- 2013-11-05 CN CN201310542526.8A patent/CN103604785A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030175987A1 (en) * | 2002-03-18 | 2003-09-18 | Edward Verdonk | Biochemical assay with programmable array detection |
| US20070097364A1 (en) * | 2005-05-09 | 2007-05-03 | The Trustees Of Columbia University In The City Of New York | Active CMOS biosensor chip for fluorescent-based detection |
| CN1865932A (en) * | 2005-05-19 | 2006-11-22 | 清华大学 | Fluorometric detector for micro-fluidic chip system |
| CN102483427A (en) * | 2009-06-15 | 2012-05-30 | 茨瓦内科技大学 | CMOS moems sensor device |
| CN103380500A (en) * | 2010-11-30 | 2013-10-30 | 茨瓦内科技大学 | CMOS based micro-photonic systems |
| CN103219342A (en) * | 2013-04-07 | 2013-07-24 | 浙江工业大学 | Double-junction depth photodiode for fluorescence detection |
| CN203643339U (en) * | 2013-11-05 | 2014-06-11 | 浙江工业大学 | Fluorescence detection system |
Non-Patent Citations (8)
| Title |
|---|
| HONGHAO JI ET AL.: "Contact Imaging: Simulation and Experiment", 《IEEE TRANSACTIONS ON CIRCUITS AND SYSTEMS—I: REGULAR PAPERS》 * |
| KHALED SALAMA ET AL.: "Modeling and simulation of luminescence detection platforms", 《BIOSENSORS AND BIOELECTRONICS》 * |
| M. AGIRREGABIRIA ET AL.: "Fabrication of SU-8 multilayer microstructures based on successive CMOScompatible adhesive bonding and releasing steps", 《LAB ON A CHIP》 * |
| TA-CHIEN D.HUANG ET AL.: "A 0.18-µm CMOS Array Sensor for Integrated Time-Resolved Fluorescence Detection", 《IEEE JOURNAL OF SOLID-STATE CIRCUITS》 * |
| TA-CHIEN D.HUANG ET AL.: "A 0.18-µm CMOS Array Sensor for Integrated Time-Resolved Fluorescence Detection", 《IEEE JOURNAL OF SOLID-STATE CIRCUITS》, vol. 44, no. 5, 31 May 2009 (2009-05-31), XP011256793, DOI: doi:10.1109/JSSC.2009.2016994 * |
| Y.MARUYAMA ET AL.: "An all-digital, time-gated 128*128 SPAD array for on-chip, filterless fluorescence detector", 《SOLID-STATE SENSORS, ACTUATORS AND MICROSYSTEMS CONFERENCE,2011 16TH INTERNATIONAL》 * |
| ZHIYONG ZHAN ET AL.: "Filterless optical oxygen sensor based on a CMOS buried double junction photodiode", 《SENSORS AND ACTUATORS B:CHEMICAL》 * |
| 刘楠 等: "用于生物荧光检测的CMOS光电探测器涉及", 《光电工程》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112812954A (en) * | 2020-12-29 | 2021-05-18 | 中国科学院长春光学精密机械与物理研究所 | Gene sequencing chip |
| CN114594592A (en) * | 2022-05-10 | 2022-06-07 | 中国科学技术大学 | Imaging method and device for measuring higher harmonics, electronic equipment and storage medium |
| CN114594592B (en) * | 2022-05-10 | 2022-07-29 | 中国科学技术大学 | Imaging method and device for measuring higher harmonics, electronic equipment and storage medium |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103529006B (en) | A kind of Portable fluorescence based on micro-fluidic chip detection device | |
| CN207318734U (en) | A kind of linear array double energy X-ray detector | |
| CN107462566B (en) | Raman spectrometer for detecting specific narrow wavenumber range | |
| CN101868727A (en) | Fluorescent biochip diagnosis device | |
| CN105675497B (en) | A kind of optical fiber sensing system of while quick detection contents of many kinds of heavy metal ion | |
| CN104568927A (en) | Electrochemical luminescence device and method | |
| CN201583666U (en) | Double-energy X-ray array detector | |
| CN107255710A (en) | Multichannel micro-fluidic fluorescence detection device and method | |
| CN102147365A (en) | Handheld bioluminescent detector and detection method | |
| CN103219342A (en) | Double-junction depth photodiode for fluorescence detection | |
| CN203116857U (en) | High-speed gate-mode detection circuit applicable to MPPCs | |
| CN101009192A (en) | Photoncounting methods and devices | |
| CN105388132A (en) | fluorescence detection apparatus, test substance detection apparatus, and fluorescence detection method | |
| CN106290286A (en) | Time-resolved fluorescence assay system and detection device | |
| CN103604785A (en) | Fluorescence detection system | |
| CN203643339U (en) | Fluorescence detection system | |
| CN103604784B (en) | Array sensing chip is analyzed in the fluoroscopic examination of CMOS contact | |
| EP1698911B1 (en) | Radiation detector | |
| CN103901009A (en) | Optical fiber scanning type laser-induced fluorescence detection system | |
| CN110100315A (en) | Charge avalanche photodetector system | |
| CN103940707A (en) | Method and device for counting insoluble particles | |
| CN107490432A (en) | A kind of Feebleness Light Signal Examining system | |
| CN113466113B (en) | Measuring method for position distribution of flow type fluorescent light spots | |
| CN203643338U (en) | CMOS (complementary metal oxide semiconductor) contact type fluorescent detection analysis array sensing chip | |
| CN212111140U (en) | Portable optical detector |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20140226 |