CN100582743C - Optical biochip for disease diagnosis and preparation method thereof - Google Patents
Optical biochip for disease diagnosis and preparation method thereof Download PDFInfo
- Publication number
- CN100582743C CN100582743C CN200610165543A CN200610165543A CN100582743C CN 100582743 C CN100582743 C CN 100582743C CN 200610165543 A CN200610165543 A CN 200610165543A CN 200610165543 A CN200610165543 A CN 200610165543A CN 100582743 C CN100582743 C CN 100582743C
- Authority
- CN
- China
- Prior art keywords
- detector array
- vertical cavity
- emitting laser
- sio
- silicon detector
- 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.)
- Active
Links
Images
Abstract
An optical biochip for disease diagnosis and preparation method is based on the self advantages of a vertical cavity surface emitting laser array, the high sensitivity of a silicon detector array and the micro-electronic mechanical system technology. The specific proposal is as follows: firstly processing a plurality of micron level reaction pools and a plurality of micron level fluid transmission grooves on the light emitting surface of the vertical cavity surface emitting laser array which emits light from the bottom surface, then spreading a layer of SiO2, and at last directly linking with the silicon detector array which has a thin layer of SiO2 on a photo surface. The detector array is used for detecting the fluorescence given off by a biomolecule target which is labeled by specific fluorescent material, thereby quickly detecting whether a patient has a certain disease. The peak wavelength of each laser is 650-980nm, and the sensitive wavelength of each detector is 400-1100nm.
Description
Technical field
The present invention is a kind of optical biochip that is used for medical diagnosis on disease.
The invention still further relates to the preparation method of above-mentioned biochip.
Background technology
The design of optical biochip (Optical Biochips) and technology of preparing are breadboard gordian techniquies on a kind of sheet based on laser instrument, it has made full use of semiconductor technology, integrated demarcation, detect the microsystem with analysis, can spend and seldom measure sample and reagent to finish a large amount of testings in the very short time simultaneously to biomolecule.
Require the chip microminiaturization based on laboratory (Lab-on-a-chip) on the sheet of laser instrument, it is complete that the while chip also should have function, and speed is fast, the characteristics that precision is high.
Vertical cavity surface emitting laser (VCSEL) has the following advantages, as: the little angle of divergence and the hot spot of circular symmetry; The light direction vertical substrates can realize the integrated of high density two-dimensional array; Can greatly reduce cost of development at built-in testing.From integrated viewpoint, VCSEL has following advantage: the little size of devices of (1) area occupied is compared littler for a few to tens of microns with 300 μ m of stripe laser; (2) from around all directions can access, and stripe laser is only limited to both sides, and its size is subjected to the length restriction of resonator cavity; (3) integrated again after stacked, can make full use of the vertical features of resonator cavity; (4) can constitute two-dimensional array.The most attracting is its manufacturing process and light emitting diode (LED) compatibility, and the extensive cost of making is very low.
Summary of the invention
The object of the present invention is to provide a kind of optical biochip that is used for medical diagnosis on disease.
Another purpose of the present invention is to provide a kind of method for preparing above-mentioned optical biochip.
For achieving the above object, the optical biochip that is used for medical diagnosis on disease provided by the invention, its structure is carried out bonding by the light-sensitive surface of the exiting surface of a face battle array vertical cavity surface emitting laser and a silicon detector array and is formed;
The exiting surface of the face battle array vertical cavity surface emitting laser of bottom surface bright dipping is provided with at least one reaction pond, microchannel, this reaction pond, microchannel connects two input slots and an output magazine respectively, and this reaction pond, microchannel is relative with the light hole of face battle array vertical cavity surface emitting laser;
Reaction pond, microchannel, input slot and output magazine array accordingly on the exiting surface with face battle array vertical cavity surface emitting laser is arranged on the light-sensitive surface of silicon detector array.
Described optical biochip, wherein, the depth ratio of reaction tank input groove depth 1 μ m.
Described optical biochip wherein, deposits one deck SiO on the exiting surface of face battle array vertical cavity surface emitting laser and the light-sensitive surface of silicon detector array
2Film.
The method of the above-mentioned optical biochip of preparation provided by the invention, its step is as follows:
A) input slot and the output magazine that on the corresponding position of light hole on the exiting surface of the face battle array vertical cavity surface emitting laser of bottom surface bright dipping, etches reaction pond, a microchannel and be attached thereto;
B) extension one SiO on reaction pond, microchannel
2Film is to improve the bio-compatibility of optical biochip;
C) according to reaction pond, microchannel and the input slot that is attached thereto and the particular location of output magazine of steps A preparation, make the silicon detector array on the light-sensitive surface of silicon detector array;
D) deposition one SiO on the light-sensitive surface of the silicon detector array that step C prepares
2Film as the photosensitive window of detector, improves the bio-compatibility of optical biochip simultaneously;
E) with the SiO on the silicon detector array light-sensitive surface
2SiO on the exiting surface of film and face battle array vertical cavity surface emitting laser
2The film Direct Bonding, make between the bonding face of the exiting surface of face battle array vertical cavity surface emitting laser and detector array input slot, output magazine and reaction pond, microchannel are arranged, wherein the photosensitive window of silicon detector array is corresponding with input slot and output magazine, surveys with the fluorescence that the target biological molecules of being demarcated by specific fluorescent material is sent.
Described preparation method, wherein, etching is to utilize focused ion beam system.
Described preparation method, wherein, the SiO2 film thickness on the exiting surface of face battle array vertical cavity surface emitting laser is 1-10 μ m.
Described preparation method, wherein, the SiO on the light-sensitive surface of silicon detector array
2Film thickness is 0.6-1 μ m.
Described preparation method, wherein, the operation wavelength of silicon detector array is 400-1100nm, has wavelength to reply the peak in the 800nm-900nm scope.
Described preparation method, wherein, the bonding between the exiting surface of face battle array vertical cavity surface emitting laser and the light-sensitive surface of silicon detector array is SiO
2-SiO
2Between bonding.
The present invention induces fluorescent material light source (laser instrument) and fluorescent probe to be integrated in a structure on the chip, can finish demarcation, detection and analysis to sample on chip piece.Structural design of the present invention and preparation method thereof, it has, and cost is low, structure and manufacturing process simple, applied range, required sample are little with amount of reagent, makes things convenient for portative advantage.
Description of drawings
Fig. 1 is the planimetric map of the structure of making on the exiting surface of face battle array vertical cavity surface emitting laser;
Fig. 2 is the lower section figure of optical biochip;
Fig. 3 is the side cross-sectional view of optical biochip;
Fig. 4 is the upper section figure of optical biochip;
Fig. 5 is the relative position figure of vertical cavity surface emitting laser in the optical biochip and reaction tank and transfusion groove;
Fig. 6 is the relative position figure of silicon detector array in the optical biochip and reaction tank and transfusion groove;
Fig. 7 is the integrally-built three-dimensional cross-sectional figure of optical biochip.
Embodiment
The fluorescence induction light source (laser instrument) of optical biochip of the present invention is selected vertical cavity surface emitting laser for use.Need make transfusion groove and reaction tank at exiting surface, the face battle array vertical cavity surface emitting laser with back side bright dipping is an example here
The structure that is used for the optical biochip of medical diagnosis on disease of the present invention, its structure comprise that the face battle array vertical cavity surface emitting laser of a bottom surface bright dipping and a silicon detector array reach the reaction pond, microchannel that makes on face battle array vertical cavity surface emitting laser exiting surface.Microchannel reaction pond be with the light-emitting window of vertical cavity surface emitting laser over against substrate on process reaction tank with focused ion beam system, and some transfusion grooves that are attached thereto cover one deck SiO then
2Film, again with deposited one deck SiO
2The light-sensitive surface of the silicon detector array of film carries out bonding and makes, and wherein the photosensitive window of silicon detector array is just corresponding with the transfusion groove, and bonding is at SiO
2-SiO
2Between bonding.
The membraneous material of face battle array vertical cavity surface emitting laser exiting surface preparation is SiO
2, thickness is 1 μ m-10 μ m, it has the membraneous material SiO of good chemical stability
2, mainly be in order to improve the bio-compatibility of whole optical biochip, while SiO
2Film has played anti-reflection effect, has improved the luminous power that of laser instrument;
The position of the reaction tank just light hole with face battle array vertical cavity surface emitting laser is relative, and processing covers one deck SiO then on backing material
2Film;
Face battle array vertical cavity surface emitting laser mainly rises and excites the target biological molecules of being demarcated by fluorescent material, make it send fluorescence, can control simultaneously the luminous power that of laser instrument by the input current that changes laser instrument, required condition when combining with fluorescent material to satisfy biomolecule;
The operation wavelength of silicon detector array is 400-1100nm, has wavelength to reply the peak in the 800-900nm scope;
The SiO that the light-sensitive surface of silicon detector array is capped
2Film thickness is about 1 μ m, SiO
2The main bio-compatibility that works to improve chip, the while is as the photosensitive window of silicon detector array;
Bonding between the exiting surface of face battle array vertical cavity surface emitting laser and the light-sensitive surface of silicon detector array is SiO
2-SiO
2Between bonding;
The structure of optical biochip is face battle array vertical cavity surface emitting laser and detector array Direct Bonding, has between bonding face to be carved with the reaction pond, microchannel that input slot, output magazine and biomolecule are reacted.
The preparation method of optical biochip of the present invention (Optical Biochips) may further comprise the steps:
1) on the exiting surface of the face battle array vertical cavity surface emitting laser of bottom surface bright dipping, utilize focused ion beam system with the corresponding SiO of the light hole of each laser instrument
2Several inputs, the output magazine that process a reaction tank on the pellicular front and be attached thereto;
2) the thicker SiO that good chemical stability is arranged of preparation one deck
2Film is to improve the bio-compatibility of optical biochip;
3) according to the particular location needs of step 2, make the silicon detector array.
4) deposition one deck SiO on the light-sensitive surface of silicon detector array
2Film as the photosensitive window of detector, mainly is in order to improve the bio-compatibility of optical biochip;
5) having deposited one deck SiO
2The SiO that is deposited on the exiting surface of the light-sensitive surface of the silicon detector array of film and face battle array vertical cavity surface emitting laser
2The film Direct Bonding, wherein the photosensitive window of silicon detector array is corresponding with input slot and output magazine, surveys with the fluorescence that the target biological molecules of being demarcated by specific fluorescent material is sent.
Among the above-mentioned preparation method:
Step 1: according to the domain of designing requirement design reaction tank and coupled transfusion groove, plate-making; Utilize photoetching technique or directly utilize focused ion beam system on the exiting surface of face battle array vertical cavity surface emitting laser, to process microchannel reaction pond and input slot, output magazine, as shown in Figure 1.
Step 2: utilizing ion assistant chemical vapor deposition (PECVD) technology deposit thickness on the exiting surface of vertical cavity surface emitting laser according to designing requirement is the SiO of 1-10 μ m
2Film;
Step 3: corresponding with the position of reaction tank, input slot and the output magazine of the design of step 1 according to designing requirement; Design silicon detector array domain, plate-making; Produce photodetector;
Step 4: utilize ion assistant chemical vapor deposition (PECVD) technology on the light-sensitive surface of silicon detector array, to deposit the SiO that a layer thickness is about 1 μ m according to designing requirement
2Film;
Step 5: utilize the low-temperature-direct-bonding technology to carry out bonding with the exiting surface of the vertical cavity surface emitting laser of transfusion groove and the light-sensitive surface of silicon detector array to being carved with reaction tank according to designing requirement, wherein the photosensitive window of silicon detector array is corresponding with the transfusion groove, as shown in Figure 6.
Put it briefly, the optical biochip that is used for medical diagnosis on disease of the present invention, this structure comprises a bottom surface exiting surface battle array vertical cavity surface emitting laser and a silicon detector array, laser instrument light-emitting window in face battle array vertical cavity surface emitting laser over against backing material on some transfusion grooves (being input slot and output magazine) processing microchannel reaction pond and be attached thereto with focused ion beam system, deposition one deck SiO on the exiting surface of the face battle array vertical cavity surface emitting laser of the transfusion groove that etches reaction pond, microchannel and be attached thereto then
2Material has deposited one deck SiO at last and
2The light-sensitive surface Direct Bonding of the silicon detector array of film and making, wherein the photosensitive window of silicon detector array is just corresponding with input slot and output magazine.
For further specifying content of the present invention and characteristics, below in conjunction with drawings and Examples the present invention is done a detailed description, wherein:
See also Fig. 1-Fig. 7, a kind of design and preparation that is used for the optical biochip of medical diagnosis on disease of the present invention, comprising following steps:
1) utilizes photoetching technique or directly utilize focused ion beam system on the exiting surface of face battle array vertical cavity surface emitting laser 1, to etch microchannel shown in Figure 1 reaction pond 8, input slot 5,6 and output magazine 7, wherein pond 8 depth ratio input slots 5,6 and output magazine 7 dark about 1 μ m are reacted in the microchannel, be beneficial to sample molecules 11 and enter in the reaction pond 8, microchannel from input slot 5,6 respectively with fluorescent material 12 and react more fully, the sample molecules 13 of being demarcated by fluorescent material flows out from output magazine 7; Wherein microchannel reaction pond 8 be with the light hole 9 of face battle array vertical cavity surface emitting laser over against substrate on;
2) use ion auxiliary chemical vapor deposition method (PECVD) to deposit the SiO that a layer thickness is 1-10 μ m as shown in Figure 1 at the exiting surface of the face battle array vertical cavity surface emitting laser 1 of bottom surface bright dipping
2 Film 2;
3) corresponding according to the position of microchannel reaction pond, input slot and the output magazine of designing requirement and the design of step 1, the domain of design silicon detector array layer 10, make a plate, produce photodetector;
4) on the light-sensitive surface of silicon detector array 4, deposit the SiO that a layer thickness is about 1 μ m with ion auxiliary chemical vapor deposition method (PECVD)
2Film 3 is to improve the bio-compatibility of chip, Chen Ji SiO simultaneously
2Film 3 can be used as the photosensitive window of detector, and wherein the photosensitive window of silicon detector array is corresponding with input slot 5,6 and output magazine 7 (as shown in Figure 1);
5) use the method for low-temperature-direct-bonding the SiO of the exiting surface of face battle array vertical cavity surface emitting laser deposition
2The SiO that deposits on the light-sensitive surface of film and silicon detector array 10
2The film Direct Bonding is got up, as shown in Figure 6.
Claims (7)
1, a kind of optical biochip that is used for medical diagnosis on disease, its structure carry out bonding by the light-sensitive surface of the exiting surface of a face battle array vertical cavity surface emitting laser and a silicon detector array and form;
The exiting surface of the face battle array vertical cavity surface emitting laser of bottom surface bright dipping is provided with at least one reaction pond, microchannel, this reaction pond, microchannel connects two input slots and an output magazine respectively, and this reaction pond, microchannel is relative with the light hole of face battle array vertical cavity surface emitting laser;
Deposit one deck SiO on the exiting surface of face battle array vertical cavity surface emitting laser and the light-sensitive surface of silicon detector array
2Film;
Bonding between the exiting surface of face battle array vertical cavity surface emitting laser and the light-sensitive surface of silicon detector array is SiO
2-SiO
2Between bonding;
The photosensitive window of silicon detector array is corresponding with input slot and output magazine position.
2, optical biochip as claimed in claim 1, wherein, the depth ratio of reaction tank input groove depth 1 μ m.
3, prepare the method for optical biochip according to claim 1, its step is as follows:
A) input slot and the output magazine that on the corresponding position of light hole on the exiting surface of the face battle array vertical cavity surface emitting laser of bottom surface bright dipping, etches reaction pond, a microchannel and be attached thereto;
B) extension one SiO on reaction pond, microchannel
2Film is to improve the bio-compatibility of optical biochip;
C) according to reaction pond, microchannel and the input slot that is attached thereto and the particular location of output magazine of steps A preparation, make the silicon detector array;
D) deposition one SiO on the light-sensitive surface of the silicon detector array that step C prepares
2Film as the photosensitive window of detector, improves the bio-compatibility of optical biochip simultaneously;
E) with the SiO on the light-sensitive surface of silicon detector array
2SiO on the exiting surface of film and face battle array vertical cavity surface emitting laser
2The film Direct Bonding, make between the bonding face of the exiting surface of face battle array vertical cavity surface emitting laser and detector array input slot, output magazine and reaction pond, microchannel are arranged, wherein the photosensitive window of silicon detector array is corresponding with input slot and output magazine, surveys with the fluorescence that the target biological molecules of being demarcated by specific fluorescent material is sent.
4, the etching preparation method as claimed in claim 3, wherein, steps A) utilizes focused ion beam system to finish.
5, preparation method as claimed in claim 3, wherein, the SiO on the exiting surface of face battle array vertical cavity surface emitting laser
2Film thickness is 1-10 μ m.
6, preparation method as claimed in claim 3, wherein, the SiO on the light-sensitive surface of silicon detector array
2Film thickness is 0.6-1 μ m.
7, preparation method as claimed in claim 3, wherein, the operation wavelength of silicon detector array is 400-1100nm, has wavelength to reply the peak in the 800nm-900nm scope.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200610165543A CN100582743C (en) | 2006-12-21 | 2006-12-21 | Optical biochip for disease diagnosis and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200610165543A CN100582743C (en) | 2006-12-21 | 2006-12-21 | Optical biochip for disease diagnosis and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101206175A CN101206175A (en) | 2008-06-25 |
| CN100582743C true CN100582743C (en) | 2010-01-20 |
Family
ID=39566542
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200610165543A Active CN100582743C (en) | 2006-12-21 | 2006-12-21 | Optical biochip for disease diagnosis and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100582743C (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103824813B (en) * | 2014-03-05 | 2016-05-11 | 陈龙 | A kind of single chip integrated micro-system of fluorescence analysis and preparation method thereof |
| CN104483498A (en) * | 2014-12-24 | 2015-04-01 | 中国科学院半导体研究所 | Sensing chip and preparation method thereof |
| CN115989406A (en) * | 2021-05-31 | 2023-04-18 | 京东方科技集团股份有限公司 | Detection chip, preparation method and sample introduction method thereof |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5784396A (en) * | 1996-09-17 | 1998-07-21 | Xerox Corporation | VCSEL integral feedback assembly two-etch structure |
| US6424418B2 (en) * | 1998-05-29 | 2002-07-23 | Canon Kabushiki Kaisha | Surface plasmon resonance sensor apparatus using surface emitting laser |
| US20020148982A1 (en) * | 2001-04-12 | 2002-10-17 | Tatum Jimmy A. | Systems and methods for optically identifying objects |
| US20030021732A1 (en) * | 2001-07-25 | 2003-01-30 | Motorola, Inc. | Apparatus for analyzing target materials and methods for fabricating an apparatus for analyzing target materials |
| CN1472526A (en) * | 2002-07-31 | 2004-02-04 | 中国科学院生态环境研究中心 | Tunnel capillary electrophoretic chemiluminescence testing microfluid control chip |
| CN1591001A (en) * | 2003-08-29 | 2005-03-09 | 中国科学院生态环境研究中心 | Laser induced fluorescence and light absorption bifunction detecting microflow controlled electrophoresis ehip |
| US20050264817A1 (en) * | 2004-05-27 | 2005-12-01 | Envision Instruments, Llc | Systems and methods for in situ spectroscopic measurements |
-
2006
- 2006-12-21 CN CN200610165543A patent/CN100582743C/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5784396A (en) * | 1996-09-17 | 1998-07-21 | Xerox Corporation | VCSEL integral feedback assembly two-etch structure |
| US6424418B2 (en) * | 1998-05-29 | 2002-07-23 | Canon Kabushiki Kaisha | Surface plasmon resonance sensor apparatus using surface emitting laser |
| US20020148982A1 (en) * | 2001-04-12 | 2002-10-17 | Tatum Jimmy A. | Systems and methods for optically identifying objects |
| US20030021732A1 (en) * | 2001-07-25 | 2003-01-30 | Motorola, Inc. | Apparatus for analyzing target materials and methods for fabricating an apparatus for analyzing target materials |
| CN1472526A (en) * | 2002-07-31 | 2004-02-04 | 中国科学院生态环境研究中心 | Tunnel capillary electrophoretic chemiluminescence testing microfluid control chip |
| CN1591001A (en) * | 2003-08-29 | 2005-03-09 | 中国科学院生态环境研究中心 | Laser induced fluorescence and light absorption bifunction detecting microflow controlled electrophoresis ehip |
| US20050264817A1 (en) * | 2004-05-27 | 2005-12-01 | Envision Instruments, Llc | Systems and methods for in situ spectroscopic measurements |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101206175A (en) | 2008-06-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7879598B2 (en) | Multianalyte determination system and methods | |
| Schumacher et al. | Highly-integrated lab-on-chip system for point-of-care multiparameter analysis | |
| US7170050B2 (en) | Apparatus and methods for optical analysis of molecules | |
| CA2881823C (en) | Method and system for fluorescence lifetime based sequencing | |
| CN210037611U9 (en) | Light detection device and biosensor using the same | |
| EP1078248A1 (en) | Sensing unit provided with separated detection light guiding | |
| US11747263B2 (en) | Flow cells and methods related to same | |
| JP2003527580A (en) | Flow cell array and its use for multiple analyte measurements | |
| CN101395463B (en) | Luminescence sensor comprising at least two wire grids | |
| CN101467027A (en) | Integrated biosensing device having photo detector | |
| US20220120684A1 (en) | Waveguide integration with optical coupling structures on light detection device | |
| TWI722673B (en) | Flow cell systems and methods related to same | |
| CN100582743C (en) | Optical biochip for disease diagnosis and preparation method thereof | |
| TW202115382A (en) | Optical nanostructure rejecter for an integrated device and related methods | |
| US20090284746A1 (en) | Radiation detectors using evanescent field excitation | |
| US11247207B2 (en) | Microfluidic systems having photodetectors disposed therein and methods of producing the same | |
| KR101563688B1 (en) | Integrated bio-chip and method of fabricating the integrated bio-chip | |
| TW201802455A (en) | A biosensor | |
| KR101569833B1 (en) | Integrated bio-chip and method of fabricating the integrated bio-chip | |
| Petrou et al. | Silicon optocouplers for biosensing | |
| JP2009210316A (en) | Emission measuring device | |
| Misiakos et al. | Monolithic silicon optoelectronic devices for protein and DNA detection | |
| JP2021535405A (en) | A device with an optically readable liquid reservoir | |
| CN114632557A (en) | Opposed substrate of micro-fluidic chip and micro-fluidic chip | |
| Le et al. | Design, simulation and fabrication of a monolithic total internal reflection (TIR) chip for fluorescent-based bio detection |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |