CN1412545A - Spectiogram biological chip detector - Google Patents
Spectiogram biological chip detector Download PDFInfo
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- CN1412545A CN1412545A CN 02156891 CN02156891A CN1412545A CN 1412545 A CN1412545 A CN 1412545A CN 02156891 CN02156891 CN 02156891 CN 02156891 A CN02156891 A CN 02156891A CN 1412545 A CN1412545 A CN 1412545A
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Abstract
The spectral image biological chip detection apparatus includes a line light source excitation unit capable of producing line light source for exciting biological chip to send fluorescent light; slitless spectral image apparatus for receiving fluorescent light sent by biological chip and forming spectral image; chip carrier and moving mechanism for bearing chip and moving under the control of the computer; and computer system for controlling movement of chip carrier, collecting spectral image signal, controlling exposure time, processing data and giving out judgement and detection result about disease and medicine. Said invention can promote the application of biological chip in diagnosis of diseases and medicine.
Description
Technical field
The invention belongs to the biological chip testing technology field, particularly adopt the pick-up unit of spectral image technology biochip.
Background technology
Biochip finger protein biochip and DNA biochip etc.Existing a lot of reports of the use of biochip on diagnosing the illness and propaganda.At present from one bleed by biochip diagnose multiple disease be reality.In addition, biochip being used for the anti-depressant inspection of physical culture also is a vast field.The development of biochip, production and application will bring a revolution to the diagnosis of disease, medicine, and this revolution will be in recent generation.Biochip will become an industry, at present a lot of a large amount of manpowers of unit input, and material resources are developed, are developed biochip.
A biochip has very multiple-unit: be used for the medical treatment and the low-density biochip of pharmacodiagnosis, the area of each unit is 50 μ m * 50 μ m, is 10 * 10mm as the area of biochip
240,000 unit are just arranged.If a kind of disease is diagnosed in each unit inspection.A biochip can check that all diseases of human body also may become a reality.There is different bioprotein/dna moleculars each unit of biochip, and this molecule is with the very high selectivity that is combined with of other albumen/dna moleculars.If the molecule of a unit is only with the albumen/dna molecular combination of certain disease, and the molecule of certain disease is only with this unit molecule combination, and different other unit molecule combinations.As long as having, the molecule of this unit of detection do not have this disease so in conjunction with just having diagnosed.Therefore, the development of biochip mainly is the molecule that finds with certain disease molecule combination, and it is placed on the chip.The detection of biochip is to measure whether the molecule combination is arranged, have or not interaction in other words.
Biochip test mainly contains two kinds of methods at present: a kind of light excitation surface plasma wave technology that utilizes, the method is used less, and irrelevant with the present invention.Another is to utilize the optical excitation fluorescent technique.With the molecule of a unit of the optical excitation biochip of certain light source, the fluorescence that the molecule of different other molecule combinations sends can use f (λ) expression, can use g (λ) to represent with the molecular fluorescence of certain disease combination.F (λ) is exactly to detect principle with the different of g (λ).
Be each unit that light (550nm green glow or 415nm blue streak) with a specific wavelength is distinguished the irradiating biological chip at present based on the detection method of optical excitation fluorescence, measure all fluorescence and variation.With mathematical notation is to measure
The difference (1) of ∫ f (λ) d λ and ∫ g (λ) d λ
Another kind method is to adopt the spectral image technology, and the spectral image technology is a spectrum to each unit measurement, is to measure with mathematical notation.
The difference (2) of f (λ) and g (λ)
With spectral image method detection method relatively, though the detection method of existing optical excitation fluorescence has simple advantage, but have significant disadvantages: on principle, f (λ) and g (λ) may be easy to difference, and ∫ f (λ (λ) d λ and ∫ g (λ) d λ can become and be difficult to difference.D λ and ∫ g (λ) d λ only provide an information respectively because ∫ is f (λ), and f (λ) and g (λ) provide respectively above 100 information.Thereby, just very low with present fluorescence method detection sensitivity, just difficult to the judgement of disease medicament.This shortcoming not only is reflected in the application, and is reflected in the development of biochip: in development, if detect with the spectral image technology, as long as the molecule that finds f (λ) and g (λ) to distinguish easily is just much of that.And, must find ∫ f (λ) d λ and ∫ g (λ) the d λ molecule of difference easily with the detection method of existing optical excitation fluorescence.Work brings difficulty to the development biochip for this.
Adopt spectral image technology for detection biochip also not obtain practical application at present, the key of problem is not have suitable spectral image instrument.
The spectral image instrument is mainly grown up by imager at present, and this instrument mostly has very high spatial resolution, and spatial resolution is about 1 μ m, or better.This instrument price is very high.All surpass 1,000,000 yuan.In addition, this instrument mostly spectral resolution is very low, can only obtain the picture of several different colours fluorescence.Here be meant that with the color showing wavelength resolution is on duty mutually.This spectral image instrument is not developed for biochip.
Also have a kind of spectral image instrument that is used for space: it is imaged on a slit with thing, and slit is pressed light spectrum image-forming.This spectral image instrument structure is very huge, also is not suitable for the detection to biochip.
Summary of the invention
The objective of the invention is for overcoming the weak point of prior art, a kind of spectral image biochip supplies analysis is proposed, cost with detection sensitivity height, instrument is low, volume is little, in light weight, advantage such as a complete set of equipment can be carried, help reducing biochip development and application cost, promote biochip diagnose the illness and medicine on application.
The present invention proposes a kind of spectral image biochip supplies analysis, it is characterized in that it comprises:
The line source that produces a line source excites the unit, sends fluorescence in order to a column unit that excites biochip, and its length requirement is more than or equal to the length of biochip one row, and its width is less than the width of 1 unit of biochip;
No slit spectral image instrument, the fluorescence that is used for biochip one row are sent is by light spectrum image-forming and reception, and the fluorescence that each biochip unit sends is in line by wavelength, obtains a spectrum, and the fluorescence of biochip one column unit is formed the spectral image of a face;
Chip microscope carrier and travel mechanism, it is used for carries chips, and under computer control to the displacement of chip microscope carrier;
Computing machine, be used for moving of control chip microscope carrier, gather the time shutter of the spectral image signal and the control spectral image instrument of spectral image instrument, utilize database data and program in the computing machine that the data of gathering are handled, provide judgement at last, provide testing result disease, medicine etc.
Characteristics of the present invention:
Spectral image biochip supplies analysis of the present invention has the high advantage of detection sensitivity, make biochip research unit be easy to development and be disease, the biomolecule that medicine etc. combine reduces the biochip cost, can make application units to disease, medicine etc. are made accurate judgement.In addition, the cost of this instrument is low, and volume is little, and is in light weight.A complete set of equipment can be carried.
Description of drawings
Fig. 1 is a general structure block diagram of the present invention.
Fig. 2 excites unit example structure synoptic diagram for line source of the present invention.
Fig. 3 is a no slit spectral image instrument structural representation of the present invention.
Fig. 4 is an A-A direction diagrammatic sketch among Fig. 3.
Embodiment
A kind of spectral image biochip supplies analysis of the present invention's design reaches accompanying drawing in conjunction with the embodiments and is described in detail as follows:
Spectral image biochip supplies analysis of the present invention is a kind of no slit spectral image biochip supplies analysis, its general structure embodiment as shown in Figure 1, it comprises four chief components:
Line source excites the unit, and its effect is to produce a line source, is used for exciting a column unit of biochip to send fluorescence, and its length requirement is more than or equal to the length 10mm of biochip one row, and its width requirement is less than the width 50 μ m of 1 unit.
No slit spectral image instrument, its effect are that fluorescence that biochip one row are sent is by light spectrum image-forming.The fluorescence that each biochip unit sends is in line by wavelength, obtains a spectrum.The fluorescence of biochip one column unit is formed a face, the i.e. spectral image of a column unit.The unit fluorescence of different lines is in different spectral images.
The spectral image instrument should guarantee that the fluorescence that sends each unit only images in the row of oneself.
Chip microscope carrier and travel mechanism, it is used for carries chips, and under computer control to the displacement of chip microscope carrier, amount of movement is the distance between biochip two row, after the data of biochip one column unit are finished by collection, in order to the following fluorescence data of spectral image instrument collection of biological chip.
Computing machine (comprising database, data processing and the judgement, the display routine that set within it), be used for moving of control chip microscope carrier, gather the time shutter of the spectral image signal and the control spectral image instrument of spectral image instrument, utilize database data and program in the computing machine that the data of gathering are handled, provide judgement at last, provide testing result disease, medicine etc.
Embodiment to each ingredient is described in detail below:
The example structure that line source of the present invention excites the unit comprises as shown in Figure 2: total solidifying laser device 21, and be successively set on optical fiber 25 on the laser output light path and the suitable lens 26 of refractive index collimation (also can), concavees lens 22, post lens 23; Its course of work is; Laser instrument output light is coupled on the suitable lens 26 of refractive index collimation with fiber coupler 25, is directional light from refractive index collimation lens output beam, and spot diameter is 1mm; Directional light expands bundle through concavees lens 22, continues to expand bundle at column direction through post lens 23, focuses on line direction.Shining one of biochip L4 at last lists.
The laser instrument of present embodiment adopts commercially available product, its wavelength is the green glow of single transverse mode of 550mm, power is 50mw, Concave Mirrors Focus is-15mm, the post focal length of lens is 40mm, can obtain a length greater than 10mm (column direction), width is less than the Line beam (at line direction beam focus place) of 10 μ m.Shine on the chip from oblique 45 degree, then width guarantees to satisfy the requirement of only shining row less than 15 μ m..Even small out of focus also can meet the demands.
No slit spectral image instrument example structure of the present invention is shown in Fig. 3,4, by collecting fluorescence lens L31, grating g32, becoming spectral image lens L33 and CCD receiver to form; Wherein, collect fluorescence lens L31 and be separately positioned on the input path and emitting light path of grating g32 with becoming spectral image lens L33, the CCD receiver is in the opposite side of spectral image lens L33 and be arranged in parallel with these spectral image lens.Its course of work is:
Biochip L4 is on the focal plane of lens L31, the fluorescence that each unit of biochip sends becomes directional light directive grating g32 behind lens L31, behind grating g32, press different wavelength diffraction, the light of different wave length is directional light in different directions, after becoming spectral image lens L33, these different wavelength will be imaged on respectively on the different lines of delegation.The unit of the same row different rows of biochip will become spectral image on different row, totally obtain the spectral image of biochip one row.Lens L31 utilizes the camera lens of camera f=50mm to get final product in the present embodiment.Grating g32 can select the common grating of 700/mm, area 30mm * 30mm for use.Become spectral image lens L33 can select identical lens with L31.Select 550nm/415nm as excitation wavelength.The CCD useful area is got 10mm * 14mm, can receive the fluorescence of 600nm ~ 1000nm/500nm ~ 900nm, dynamic range 400nm.Because of luminous live width is 15 μ m, by the spectral resolution of grating property calculation much smaller than 1nm.So spectrum is divided into 100 parts without a doubt.
Chip microscope carrier of the present invention and mobile system embodiment can adopt stepper motor to drive the precision optical machinery worktable and finish, because total kilometres are less than 20mm, bearing accuracy is a few μ m, can adopt existing mature technology to realize.
Computer system of the present invention can adopt general commercially available PC, also configurable notebook computer so that whole device be easy to carry.At present computer sampling one width of cloth figure is guaranteed fully with 0.1 second, and Measuring Time is mainly by the signal intensity decision, as the light that incides on the sample is about ten milliwatts, and the photon of each unit reception of per second CCD on average can reach 10
5~ 10
6Individual photon, thereby can realize the per second width of cloth spectrum image pattern of sampling.Measured a biochip sample in about like this three minutes.
Data stock in the computing machine and data processor and determining program can adopt routine techniques to realize that the specific implementation technology of this part content is not in the present patent application protection domain in conjunction with application requirements.
In the present embodiment optical maser wavelength, the focal length of lens, grating constant all just be used to illustrate and with, their change does not all influence enforcement of the present invention, can select when specific design, reasonable combination.
Claims (4)
1, a kind of spectral image biochip supplies analysis is characterized in that it comprises:
The line source that produces a line source excites the unit, sends fluorescence in order to a column unit that excites biochip, and its length requirement is more than or equal to the length of biochip one row, and its width is less than the width of 1 unit of biochip;
No slit spectral image instrument, the fluorescence that is used for biochip one row are sent is by light spectrum image-forming and reception, and the fluorescence that each biochip unit sends is in line by wavelength, obtains a spectrum, and the fluorescence of biochip one column unit is formed the spectral image of a face;
Chip microscope carrier and travel mechanism, it is used for carries chips, and under computer control to the displacement of chip microscope carrier;
Computing machine, be used for moving of control chip microscope carrier, gather the time shutter of the spectral image signal and the control spectral image instrument of spectral image instrument, utilize database data and program in the computing machine that the data of gathering are handled, provide judgement at last, provide testing result disease, medicine etc.
2, spectral image biochip supplies analysis as claimed in claim 1 is characterized in that, said line source excites the unit to comprise: laser instrument, and be successively set on concavees lens, post lens on the laser output light path.
3, spectral image biochip supplies analysis as claimed in claim 1 is characterized in that, said no slit spectral image instrument is formed by collecting fluorescence lens, grating, one-tenth spectral image lens and CCD receiver; Wherein, said collection fluorescence lens are separately positioned on the input path and emitting light path of grating with becoming the spectral image lens, and said CCD receiver is in the opposite side of spectral image lens and be arranged in parallel with these spectral image lens.
4, spectral image biochip supplies analysis as claimed in claim 1 is characterized in that, the precision optical machinery worktable that said chip microscope carrier and mobile system adopt stepper motor to drive.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB02156891XA CN1174239C (en) | 2002-12-20 | 2002-12-20 | Spectiogram biological chip detector |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB02156891XA CN1174239C (en) | 2002-12-20 | 2002-12-20 | Spectiogram biological chip detector |
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| Publication Number | Publication Date |
|---|---|
| CN1412545A true CN1412545A (en) | 2003-04-23 |
| CN1174239C CN1174239C (en) | 2004-11-03 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB02156891XA Expired - Fee Related CN1174239C (en) | 2002-12-20 | 2002-12-20 | Spectiogram biological chip detector |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106501219A (en) * | 2016-10-19 | 2017-03-15 | 中国科学院电子学研究所 | A kind of Portable, multiple parameter surface plasma resonance biochemical analyzer |
-
2002
- 2002-12-20 CN CNB02156891XA patent/CN1174239C/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106501219A (en) * | 2016-10-19 | 2017-03-15 | 中国科学院电子学研究所 | A kind of Portable, multiple parameter surface plasma resonance biochemical analyzer |
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| CN1174239C (en) | 2004-11-03 |
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