CN1187601C - Micro fluid control chip detecting system - Google Patents
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- CN1187601C CN1187601C CNB021451710A CN02145171A CN1187601C CN 1187601 C CN1187601 C CN 1187601C CN B021451710 A CNB021451710 A CN B021451710A CN 02145171 A CN02145171 A CN 02145171A CN 1187601 C CN1187601 C CN 1187601C
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Abstract
The present invention discloses a micro-fluid control chip detection system which comprises an optical part, an interface circuit used for processing electrical signals output by a photomultiplier tube and an embedded system with display, storage and printing functions, wherein the optical part comprises a laser excitation unit and a detection unit; the laser excitation unit is vertical to an optical axis of the detection unit. Through a signal processing and data conversion unit, the embedded system is connected to the detection unit and controls electrophoresis voltage and the negative high-voltage output of the photomultiplier tube. The whole detection unit adopts an inverse structure, and an optical system keeps still with a folded optical path so as to realize the miniaturization of the whole system. In addition, the detection system is convenient for placing chips and regulating chip positions, meets the confocal principle to obtain signals with high a signal-to-noise ratio, and can be independently operated or can communicate with a computer.
Description
Technical field
The present invention relates to a kind of fluidic chip detecting system.
Background technology
Micro-total analysis system (Micro Total Analysis Systems, μ-TAS) is a frontier interdisciplinary, and its target is to realize that by micro electronmechanical processing (MEMS) technology and biotechnology chemical analysis system handles whole microminiaturized, the integrated and portability that detects from sample.It has become the important directions and the forward position of present analytical instrument development.
Current micro-total analysis system can be divided into chip type and non-chip type two big classes.The current chip formula is a development priority, wherein can be divided into two big classes again according to chip structure and working mechanism: micro-array chip (Microarraychip) and micro-fluidic chip (Microfluidic chip), though have a small amount of intersection to experience evolution separately substantially between two kinds of technology.
Micro-array chip also claims biochip, mainly based on biotechnology, is core with affine combination technology, is architectural feature to fix a series of addressable identification molecular array at chip surface.It is easy to use, measures fast, but generally is disposable use, and very strong specificity is arranged.Another kind of chip is that micro-fluidic chip then mainly is based on chemical analysis and analytical biochemistry, is support with micro electronmechanical process technology, is architectural feature with the microchannel network, is the emphasis of current micro-total analysis system development.It is integrated on the chip sampling, dilute, add reagent, reaction, separation etc., and can repeatedly use, and therefore has applicability widely.
The appearance of microchip analysis system not only can make precious Biosample and reagent consumption be reduced to microlitre greatly even receive upgrading, and hundred times of ground of operational analysis speed tenfold improve, expense tenfold, hundred times decline.
Biomedicine is the main application fields of current microfluidic analysis system, at the research of human gene and disease relationship, development is applicable to that the Capillary Electrophoresis micro-fluidic chip of single nucleotide polymorphism (SNP) detection, dna sequencing and the protein sequencing of genome times afterwards comprehensively is the task of top priority.The micro-fluidic chip that is used for clinical examination will have market the most widely in China.Synthetic and the screening of novel drugs is another field that can play a significant role of micro-fluidic chip.Other important applied field comprise food and commodity inspection, environmental monitoring, criminal science and space science etc.
The micro-fluidic chip that the present invention is directed to is the integrated capillary electrophoretic cake core, and its detection method has uv absorption detection, fluoroscopic examination, Mass Spectrometer Method, Amperometric Detection Coupled etc.Wherein, fluoroscopic examination is called laser-induced fluorescence (LIF) (Laser Induced Fluorescence is called for short LIF) detection method again, is used for detecting the fluorescigenic compound of energy, is a kind of highly sensitive selectivity detection method.After some compound with special construction is subjected to ultraviolet light or laser radiation, can send the long light of wavelength ratio ultraviolet light or laser, generally in visible-range, this light is called fluorescence, short ultraviolet light or the laser of wavelength becomes exciting light, and the fluorescence of generation is called emission light.Fluorescence detector is exactly a kind of system of measuring fluorescence intensity, and fixedly the time, fluorescence intensity and sample concentration are linear at experiment condition.Because fluorescence detection is directly measured fluorescence intensity, sensitivity is very high, suit especially to do trace analysis, and equipment is fairly simple, therefore when considering to select the detection method of Capillary Electrophoresis cake core, selects fluorescence detection usually.
Fig. 1 is the synoptic diagram of a fluorescence detector.Laser that laser instrument 1 sends is through the convergence of lens 2, produces a hot spot in the fixed position of the capillary channel of micro-fluidic chip 3.When the fluid in the kapillary was flowed through this facula position, the fluorescent material that carry the inside was subjected to exciting of laser, launches fluorescence.These fluorescence signals are collected by microcobjective 4, through the unwanted wavelength information of emission light narrow-cut filter 5 filterings, by photomultiplier 6 (PMT) fluorescence signal that receives are changed into electric signal, output in the follow-up equipment to show.
The specific implementation light path has three kinds: oblique incidence formula, transmission-type and reflective detection light path.Early stage to use more be oblique incidence formula light path, and laser beam is oblique incidence at a certain angle, and the fluorescent material fluorescence signal that the laser facula place produces of flowing through is directly collected by object lens, handles, shows by photomultiplier.This relatively simple for structure, but the adjusting angle inconvenience, and also the signal to noise ratio (S/N ratio) of signal is not high yet, uses seldom now.
Fig. 2 is reflective light path synoptic diagram, and transmission-type detection light path is similar to reflective detection light channel structure, and the transmission-type light path that is not both of both maximums is not used dichroscope, and the luminous energy loss is lower.In the transmission-type light path, laser by catoptron and convergent lens from chip bottom incident, the principal goods mirror is collected the fluorescence that send the appointed area on chip top, chip is respectively the fluorescence signal light path up and down and laser is introduced light path, can directly build light path on the microscopical basis of common biology.
In reflective light path (Fig. 2), laser instrument 1 emitted laser bundle is reflected by dichroscope 7, and the fixed position at micro-fluidic chip 3 under the effect of principal goods mirror 8 produces a focused light spot.In the time of electrophoresis, fluorescent material this laser facula generation fluorescence signal that is excited of flowing through.The fluorescence signal of these scatterings is collected by principal goods mirror 8, sees through dichroscope 7, is assembled by tube lens 9, by the non-fluorescence signal of color filter 5 filterings, receives and convert to electric signal by photomultiplier 6.The electric signal that photomultiplier 6 produces is sent into computer recording, demonstration by subsequent treatment such as electronic filterings.The reflecting light line structure realizes that with dichroscope 7 laser is introduced light path and the fluorescence signal light path is partially folded, and principal goods mirror 8 had both played the effect of convergent laser light beam, can collect fluorescence signal again, made the total system smaller volume, had reached the requirement of instrument miniaturization.Therefore but, dichroscope brings optical energy loss to a certain degree, has reduced signal, considers to introduce the signal to noise ratio (S/N ratio) that confocal technology improves signal, like this, even system loss a part of luminous energy, still can obtain signal than good quality.
Fig. 3 is a confocal principle synoptic diagram.Confocal technology, promptly light source, photographed object point and point probe three are in corresponding optics object-image conjugate position in twos.Reflect by dichroscope 7 behind the laser bundle-enlarging collimation that laser instrument 1 sends, on micro-fluidic chip 3, be focused into diffraction limit hot spot (spot diameter d=1.22* λ/NA) through principal goods mirror 8 (numerical aperture is NA), excite the fluorescence of generation to be collected by principal goods mirror 8, see through dichroscope 7, by tube lens 9 at spatial filter 10 (detecting pinhole) planar imaging, and by reflection (scattering) signal that receives micro-fluidic chip 3 near the photodetector of image planes position.In the confocal technology,, receive only reflection (scattering) signal of micro-fluidic chip 3 focal planes by detecting pinhole 10 filter actions, and its non-focal plane reflection (scattering) signal of filtering.This shows that confocal technology is effectively to reduce noise for the great advantage of fluidic chip detecting system, improve signal quality.Compare with common light path, the maximum characteristics of introducing confocal technology are uses of detecting pinhole 10, and there is fundamental influence its size and position to the performance of total system, are to derive theoretically or all embodied this point in experiment.
Summary of the invention
The purpose of this invention is to provide a kind of fluidic chip detecting system of introducing confocal technology, optics employing inverted structure.
The technical solution used in the present invention is as follows:
It comprises optics, is used for handling the electric signal of photomultiplier output, has the interface circuit of amplification, filtering, A/D sampling and D/A control high-pressure modular output voltage function and has the embedded system of demonstration, storage, printing function.Said optics is made up of laser excitation unit and probe unit, and the laser excitation unit is vertical with the optical axis of probe unit; The laser excitation unit comprises semiconductor laser, the exciting light narrow-cut filter that connects at same optical axis successively from a right left side, expansion bundle object lens and collimator objective; Probe unit comprises dichroscope tilting on the same optical axis, above dichroiscopic the principal goods mirror is housed, the catoptron that tube lens is housed from top to down successively, can rotates below dichroiscopic, eyepiece, detecting pinhole, emission light narrow-cut filter and photomultiplier.
The beneficial effect that the present invention has is:
The laser excitation unit is vertical with the optical axis of probe unit, and embedded system links to each other with probe unit with Date Conversion Unit by signal Processing, also exports by the negative high voltage of signal Processing and Date Conversion Unit control electrophoretic voltage and photomultiplier simultaneously.Whole probe unit adopts inverted structure, and optical system keeps transfixion, not only light path folding, realize the miniaturization of total system, and be convenient to place chip, regulated the position of chip, satisfy confocal principle, obtain the signal to noise ratio (S/N ratio) higher signal, but independent operation or and compunication.
Description of drawings
Fig. 1 is the principle schematic of fluoroscopic examination;
Fig. 2 is that reflective micro-fluidic chip detects the light path synoptic diagram;
Fig. 3 is the confocal principle synoptic diagram;
Fig. 4 is a directional light light path synoptic diagram of the present invention;
Fig. 5 is the overall framework figure of Circuits System;
Fig. 6 is the refinement of circuit among the little empty frame I of Fig. 5.
The number in the figure explanation:
1-semiconductor laser 2-lens
3-micro-fluidic chip 4-microcobjective
5-emission light narrow-cut filter 6-photomultiplier
7-dichroscope 8-principal goods mirror
9-tube lens 10-detecting pinhole
11-exciting light narrow-cut filter 12-expands the bundle object lens
13-collimator objective 14-catoptron
The 15-eyepiece
Embodiment
As shown in Figure 4, it comprises optics, be used for handling the electric signal of photomultiplier output, have the interface circuit of amplification, filtering, A/D sampling and D/A control high-pressure modular output voltage function and have the embedded system of demonstration, storage, printing function.Said optics is made up of laser excitation unit and probe unit, and the laser excitation unit is vertical with the optical axis of probe unit; The laser excitation unit comprises semiconductor laser 1, the exciting light narrow-cut filter 11 that connects at same optical axis successively from a right left side, expansion bundle object lens 12 and collimator objective 13; Probe unit comprises dichroscope tilting on the same optical axis 7, and principal goods mirror 8 is housed above dichroscope 7, the catoptron 14 that below dichroscope 7 tube lens 9 is housed successively from top to down, can rotate, eyepiece 15, detecting pinhole 10, emission light narrow-cut filter 5, photomultiplier 6.
What the present invention adopted is the light path of Fig. 4 structure.Based on the principle of Fig. 2, adopt inverted structure, and, make more reasonable, the more realistic needs of its structure in conjunction with confocal technology.The laser beam that laser instrument 1 sends, is reflected by dichroscope 7 by expansion bundle object lens 12 expansion bundles and after by collimator objective 13 collimations through exciting light narrow-cut filter 11, and principal goods mirror 8 is converged to a hot spot to light beam on micro-fluidic chip 3.Fluorescent material this hot spot of flowing through excites the fluorescence of generation still to be collected by principal goods mirror 8, sees through dichroscope 7 through tube lens 9 and focuses on.If catoptron 14 is in solid line position shown in Figure 4, then fluorescence mirror 14 reflection that is reflected enters eyepiece 15, and the operator can directly observe the particular location that whether produce fluorescence and regulate the hot spot of laser beam on chip by eyepiece 15; If catoptron 14 switches to dotted line position shown in Figure 4, fluorescence signal through the signal of the non-wavelength of fluorescence of emission light narrow-cut filter 5 filterings, is received by photomultiplier 6 more at last by the non-test surface information of detecting pinhole 10 filterings.
Adopted inverted structure among the present invention, micro-fluidic chip is placed on the dedicated platform, and this platform can move in X, Y direction, makes the installation chip convenient, and the aligning that also helps the iontophoretic electrode position is simultaneously regulated.The introducing of catoptron 14 both can guarantee that photomultiplier received fluorescence signal, can help the operator to observe whether fluorescence signal produces again, whether facula position wrong, the experiment whether normal.
Circuit part comprises signal Processing and Date Conversion Unit (interface circuit) and embedded system unit.The module map of circuit part is seen Fig. 5 and Fig. 6.Signal Processing and Date Conversion Unit mainly are that the electric signal to photomultiplier 6 output amplifies, filtering, sampling.In addition, also comprise the negative high voltage control of photomultiplier 6 and the output high voltage control of chip electrophoresis high-pressure modular.In order to reach the requirement of instrumentation, miniature portableization, adopt embedded system, fluid,matching crystal display screen and special liquid crystal driving circuit, make instrument itself have demonstration, storage, printing function, can use separately, also can adopt standardized communication interface and computing machine interconnected, further can transmit testing result by the internet, more convenient to operate.
Its principle of work is: photomultiplier 6 is converted to electric signal to the light signal of collecting, and after these electric signal preposition amplifications of process and the Filtering Processing, is carried out the A/D sampling by data collecting card, and its result sends into the embedded system storage or shows.Embedded system is sent signal according to instruction, by the high voltage package output and the electrophoresis high pressure of D/A conversion back control photomultiplier 6, regulates the performance of photomultiplier and the situation of carrying out of electrophoresis.
In the circuit module, signalling channel is concrete diagram such as Fig. 7 of preposition amplification and electronic filtering part.What photomultiplier 6 was exported is current signal, by the current-voltage modular converter it is converted to voltage signal and amplification, then by the buffering follower, enters instrumentation amplifier again and carries out the secondary amplification, and adopt voltage-controlled mode filter filtering.According to the performance of the data collecting card of selecting, filtered signal is carried out the correspondent voltage bias treatment, by cushioning follower by data collecting card collection, conversion.
Claims (1)
1. fluidic chip detecting system, it comprises optics, be used for handling the electric signal of photomultiplier output, interface circuit with amplification, filtering, A/D sampling and D/A control high-pressure modular output voltage function, with embedded system with demonstration, storage, printing function, it is characterized in that: said optics is made up of laser excitation unit and probe unit, and the laser excitation unit is vertical with the optical axis of probe unit; The laser excitation unit comprises semiconductor laser (1), the exciting light narrow-cut filter (11) that connects at same optical axis successively from a right left side, expansion bundle object lens (12) and collimator objective (13); Probe unit comprises dichroscope tilting on the same optical axis (7), in the top of dichroscope (7) principal goods mirror (8) is housed, the catoptron (14) that below at dichroscope (7) is equipped with tube lens (9) from top to down successively, can be rotated, eyepiece (15), detecting pinhole (10), emission light narrow-cut filter (5), photomultiplier (6).
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| Application Number | Priority Date | Filing Date | Title |
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| CNB021451710A CN1187601C (en) | 2002-11-08 | 2002-11-08 | Micro fluid control chip detecting system |
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| CNB021451710A CN1187601C (en) | 2002-11-08 | 2002-11-08 | Micro fluid control chip detecting system |
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| CN1410760A CN1410760A (en) | 2003-04-16 |
| CN1187601C true CN1187601C (en) | 2005-02-02 |
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Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102628017B (en) * | 2012-04-09 | 2015-05-06 | 盛司潼 | Nucleic acid detection device, gene sequencing equipment and gene sequencing system |
| CN103217405B (en) * | 2013-03-21 | 2015-03-04 | 浙江大学 | Microfluidic contrast optical path detection system |
| CN103837515A (en) * | 2014-03-17 | 2014-06-04 | 北京理工大学 | Confocal automatic regulation device |
| CN104101588A (en) * | 2014-07-25 | 2014-10-15 | 山东省科学院海洋仪器仪表研究所 | Integrated seawater chlorophyll microfluidic chip sensor and manufacturing method thereof |
| CN105583014B (en) * | 2015-12-18 | 2019-01-22 | 中国电子科技集团公司第五十四研究所 | The photon miniflow detection chip integrated based on LTCC |
| CN106841042B (en) * | 2017-04-01 | 2019-12-03 | 广东永诺医疗科技有限公司 | Micro-fluidic chip focusing control system and micro-fluidic chip fluorescence detecting system |
| CN107254406B (en) * | 2017-05-23 | 2019-07-05 | 北京大学 | Biological cell chip high throughput, high intension, parallel imaging arrangement and screening system |
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