CN1239961C - Method and system for preparing high polymer group biochip micro flow path structure adopting quasi molecule laser - Google Patents
Method and system for preparing high polymer group biochip micro flow path structure adopting quasi molecule laser Download PDFInfo
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Abstract
The present invention relates to a method and a system for preparing a high polymer group biochip micro flow path structure by a quasi-molecule laser, which belongs to the technical field of the fine processing of a laser. The method comprises that the area of a light spot is determined; work voltage is set; processing parameters and a mask pattern are set according to the size of a micro flow path and the shape of the cross section; a pattern is drawn according to the structure of the micro flow path, and a generated data file is stored for use; after the data file is read, and the processing parameters are detected, a working table and the laser are driven to work so that base sheet processing is finished; a cover sheet is processed according to the steps or conventional drilling; a base sheet and the cover sheet are bonded. The system comprises a control computer 1, the quasi-molecule laser 2, a drive motor 7, the working table 8 and a workpiece 6, wherein the quasi-molecule laser and the drive motor are controlled by the control computer; the working table is controlled by the drive motor; the workpiece is arranged on the working table. The optical path of an emergent light beam of the quasi-molecule laser 2 is changed by a reflector 3, and the workpiece 6 is processed by the mask rotary table 4 and an imaging objective lens 5. The present invention realizes the rapid forming of a biochip, enhances processing flexibility and reliability and reduces production cost.
Description
Technical field
The method and system that adopts excimer laser to prepare superpolymer base biological chip miniflow line structure belongs to the laser fine processing technique field, and relating generally to the superpolymer is microfluidic circuit processing on the microfluidic circuit class biochip of matrix.
Background technology
Biochip technology is an emerging technology that has developed since the initial stage nineties.It is the cross products of subjects such as molecular biology and microelectronics, little processing, micromechanics.The essence of biochip is exactly the biochemical analysis device that has dwindled, and the biochip of making by micro-processing technology is handled micrometer structure and biological chemistry to combine being integrated on the chip that material such as very little monox, glass or plastics makes.Initial biochip mainly is that therefore the chip that is used for the latticed form of aspects such as dna sequence dna detection, gene expression profile evaluation is also referred to as genetic chip, microfluidic circuit class chip is just being paid attention in the research of biochip at present, its main type has PCR micro-fluidic chip, CE electrophoresis chip, principal character is: the capacity that will constitute by the microfluidic circuit of etching on substrate only for receive the upgrading the microfluidic circuit structural unit combine with various electronic control units, detecting unit, thereby realize corresponding integrated biochemical analytic function.The size of microfluidic circuit and configuration of surface feature will directly have influence on the result of biochemical reaction in the chip.Therefore in the manufacturing process of microfluidic circuit chip, being mainly used in microfluidic circuit, partly to make micro-processing technology be key in the research.
Past people adopts the material that extensively adopts in the integrated circuit such as silicon, glass to manufacture the microfluidic circuit chip usually, although little processing of silicon is more convenient and ripe, and has a good heat conductivity, but the poor compatibility of used biological sample in these materials and the experiment, and their optics and electrical properties have also limited their further application in the microfluidic circuit chip.And by comparison, it is good that the superpolymer organic material then has with biological sample liquid compatibility, biological preferably bonding properties, and hot isolated form is good, and can degrade automatically in vivo and get rid of advantages such as electrical insulating property by body fluid circulation.Simultaneously high polymer material is cheap, but helps realizing the manufacturing of the biochip of low cost disposal type.Therefore, more and more researchers begins to pay close attention to the matrix of employing superpolymer organic material as biochip.
At present, be that the job operation that the matrix biochip mainly adopts has photoetching, wet chemical etch, galvanic corrosion, reactive ion etching etc. with silicon, glass.But these methods can only be confined to the extensive material that adopts in the integrated circuit such as above-mentioned silicon, glass, and need through multiple working procedures such as gluing, exposure, development, photographic fixing, solarization plates, so long processing time, and complex process requires the operational degree height.Be difficult to adapt to the requirement that chip is produced in enormous quantities and reduced cost.In addition, at present the job operation at the biochip of superpolymer mainly contains pressure sintering, injection moulding, stamped method etc., and these methods need rely on mould, and process flexibility is poor.Can't satisfy the demand of the microfluidic circuit class biochip fast development of different structure.
Defective at the said method existence, and consider that excimer laser photon energy height is suitable for the characteristic of etch polymers, we have proposed to utilize the new method of microfluidic circuit on the processing superpolymer base biochip that Excimer Laser combines with the CAD/CAM technology, and this method is not only convenient, fast but also guaranteed good processing effect.
Summary of the invention
The object of the present invention is to provide a kind of excimer laser to prepare the method and system of superpolymer base biological chip miniflow line structure: data file and excimer laser microfabrication system that the CAD figure of drawing based on microfluidic circuit structure in the biochip is generated, realized the rapid shaping of microfluidic circuit class biochip, improved processing flexibility, reliability and reduce production costs.
Technical thought of the present invention is:
(1) workpiece is placed on the worktable, in worktable Z-direction range of movement, set arbitrarily the position of Z axle, promptly set the laser facula area that the workpiece that is positioned on the worktable and the distance between the object lens are determined surface of the work;
(2) according to the threshold energy density of laser facula area of determining and known material, the area of mask pattern, obtain the threshold value operating voltage; According to this threshold value, when being higher than threshold energy density, the laser energy density on the workpiece could realize that the principle of etching is provided with operating voltage to material;
(3) according to laser energy density and the etching rate of determining surface of the work by formula;
(4) according to the size and the shape of cross section of the microfluidic circuit that usually adopts in the biochip, set machined parameters and mask pattern, the speed, laser instrument trigger pulse frequency and the number that comprise working table movement in the machined parameters, the pattern of microfluidic circuit xsect is by selected mask pattern decision;
(5) according to the microfluidic circuit structure of biochip to be processed, utilize AUTOCAD software rendering architecture figure, and graphic file generated the data file include the dat form of move distance and moving line information on the X-Y both direction, storage this document is in order to calling;
(6) read data files is obtained the move distance and the moving line of X, Y-axis, they and the machined parameters that is provided with are detected the back drive little processing worktable and laser instrument by move distance and moving line, mask pattern and the parameter work set, realize the processing of microfluidic circuit structure on the substrate by control computer;
(7) according to the starting point of microfluidic circuit on the substrate and the position of terminal point, be used to inject via hole with outgoing liquid at the correspondence position of cover plate with quasi-molecule laser etching or with conventional drilling method processing by above step, finish processing to cover plate;
(8) according to the bonding method of existing high polymer material,, form the microfluidic circuit structure of complete sealing, finish the making of biological chip miniflow line structure of the present invention substrate and the cover plate bonding that processes.
The preparation method of the biological chip miniflow line structure of the superpolymer base of employing excimer laser, its ultimate principle is a very high photon energy of utilizing excimer laser to have, is higher than the characteristic in conjunction with bond energy of partial polymer.Based on this character, within the scope of excimer laser radiation, the workpiece of high polymer material realizes that after the photon flow surpasses threshold value effective photodissociation causes the fracture of chemical bond owing to absorb photon.When the quantity of scission of link constantly increases, when the fragment of generation reached certain concentration, the pressure and temperature in the material bodies that is etched sharply raise, and causes the generation of body blast, makes fragment leave matrix, forms etching.Therefore excimer laser processing is counted as a kind of cold working, can access level and smooth etching surface.Cooperating upper table again is moving of the location of workpiece, just can realize the processing of the microfluidic circuit of difformity and parameter.The control of microfluidic circuit shape of cross section can make things convenient for realization by changing mask.The degree of depth of stream and surface quality can be controlled by change laser energy, laser pulse frequency, these machined parameters of moving speed of table in the microfluidic circuit.
The concrete steps of the inventive method are:
(1) workpiece to be machined is placed on the worktable, and aim at, in worktable Z-direction range of movement, set the position of Z axle arbitrarily, determine the distance between workpiece and object lens, thereby determine the facula area S on the surface of the work with laser beam;
(2) 1. can calculate F according to formula
0 *: the threshold energy density of laser emitting,
F
0/F
0 *＝S
*/S ①
F wherein
0: the threshold energy density of workpiece material; F
0 *: the threshold energy density of laser emitting;
S: the laser facula area of surface of the work; S
*: the area of mask pattern
And F
0: the threshold energy density of workpiece material is by workpiece material itself decision,
(3) 2. can calculated threshold laser emitting ENERGY E according to formula
0
E
0=F
0* S
02., thus obtain corresponding threshold value operating voltage;
(4) according to this threshold value operating voltage, when being higher than threshold energy density, could realize the laser energy density on the workpiece material principle of etching to material, the operating voltage of laser greater than the threshold value operating voltage is set, thereby obtains corresponding laser emitting ENERGY E;
(5) 3. according to formula
F
*＝E/S
0 ③
F wherein
*Be by laser emitting ENERGY E and laser emitting facula area S
0Decision;
Laser emitting facula area S
0Be by laser instrument decision itself,
(6) according to formula F/F
*=S
*4./S calculates the laser energy density F on workpiece material surface;
F wherein: the laser energy density on workpiece material surface; F
*: the energy density of shoot laser;
S: the laser facula area of surface of the work; S
*: the laser energy density F of the area surface of the work of mask pattern is by the decision of the laser facula area of laser operating voltage and surface of the work,
(7) 5. can calculate etching rate x according to the etching rate formula
f
x
f＝ln(F/F
0)/α ⑤
Wherein: x
f: etching rate; F: the laser energy density of surface of the work;
F
0: the threshold energy density of workpiece material; α: workpiece material is to the absorption coefficient of laser
F
0Determine by workpiece material that is adopted and optical maser wavelength with α;
(8) according to the size and the shape of cross section of the microfluidic circuit that usually adopts in the biochip, set machined parameters and mask pattern, the speed, laser instrument trigger pulse frequency and the number that comprise working table movement in the machined parameters, the pattern of microfluidic circuit xsect is by selected mask pattern decision;
According to h, x
f6. determine n with formula,
n＝h/x
f ⑥
N wherein: each processing place needs the pulse number of etching; H: the degree of depth of microfluidic circuit to be processed;
7. calculate the value of f/v according to 1 known value substitution formula, select the laser frequency and the moving speed of table numerical value that are fit to according to this relation; The working range of f is by laser instrument decision itself, and the working range of v is determined by worktable itself;
n＝6*l*f/v ⑦
L: the length of the mask that uses; F: laser pulse frequency; V: moving speed of table is selected corresponding mask pattern according to the shape of cross section of the microfluidic circuit of processing request;
(9), adopt AUTOCAD software to draw the microfluidic circuit structure graph, and the data file that this graphic file is converted to the dat form in AUTOCAD software store in the control computer in order to calling according to the structure and the size of microfluidic circuit to be processed;
(10) read data files is obtained the move distance and the moving line of X, Y-axis, moving speed of table, laser operating voltage, these machined parameters of laser pulse frequency of setting in they and the above-mentioned steps are sent to control computer after detecting, realize the configuration of system's machined parameters; Drive worktable and laser instrument by route, mask pattern and the parameter work set, realize the processing of microfluidic circuit structure on the substrate;
(11) according to the starting point of microfluidic circuit on the substrate and the position of terminal point, the method of (1) set by step-(10) is used to inject via hole with outgoing liquid at the correspondence position of cover plate with quasi-molecule laser etching or with conventional drilling method processing, finishes the processing to cover plate;
(12) substrate and the cover plate that processes is bonded together with existing superpolymer bonding techniques, thereby the making of biological chip miniflow line structure of the present invention is finished in the sealing of realization microfluidic circuit structure.
A kind of system that adopts excimer laser to prepare superpolymer base biological chip miniflow line structure, it is characterized in that including: control computer 1 and excimer laser 2 and the drive motor 7 controlled respectively by it, the X-Y-Z three-D displacement worktable 8 of drive motor 7 control and on worktable 8 place work piece 6, excimer laser 2 outgoing beams adopt catoptron 3 to change the direction light path, are radiated at the preparation of carrying out superpolymer base biological chip miniflow line structure on the workpiece 6 by mask universal stage 4 and image-forming objective lens 5 successively.
Mask swivel plate 4 in this system includes multiple mask pattern, and the difference of mask pattern will cause processing the difference of the microfluidic circuit xsect of gained.
The present invention has dirigibility in the preparation of microfluidic circuit class biochip, accuracy can satisfy the needs of different microfluidic circuit structures with high efficiency.
Description of drawings
Fig. 1 the inventive method main flow chart;
Fig. 2 system of the present invention embodiment synoptic diagram
Among the figure: 1 control computer, 2 excimer lasers, 3 catoptrons, 4 rotation mask plates, 5 image-forming objective lens, 6 workpiece, 7 drive motor, 8 worktable;
The microfluidic circuit manuscript of the substrate that Fig. 3 draws in AUTOCAD;
The cover plate manuscript that Fig. 4 draws in AUTOCAD;
Fig. 5 microfluidic circuit one-piece construction and sample introduction effect;
The inner pattern of the microfluidic circuit that Fig. 6 microscopically is observed.
Embodiment
Utilize the technology of the present invention, can on COC (cyclenes copolymer), PDMS (dimethyl silicone polymer), polymethylmethacrylate superpolymer materials such as (PMMA), process the microfluidic circuit of biochip;
The present invention adopts embodiment to introduce we have carried out CE (Capillary Electrophoresis) biological chip miniflow road on polymethylmethacrylate (PMMA) material processing and sample introduction experiment; System of processing is made according to a conventional method, Installation and Debugging, and wherein, the model of excimer laser 2 is Lambda physik LPX305IF, and optical maser wavelength is 248nm; Computing machine 1 is a Pentium 586PC machine; Be equipped with in the computing machine 1 to excimer laser 2, X-Y-Z three-D displacement table drive motor 7 and send signal and reach, the general stepper motor of drive motor 7 employings of displacement work table from the general input of drive motor 7 received signals, the built-in laser-processing system control card of output interface; Concrete steps are as follows:
(1) will position and aim at according to the processing needs through polymethylmethacrylate (PMMA) the material workpiece (area 20mm*20mm, thickness 1mm) of ultrasonic cleaning in ethanolic solution as on the worktable; By regulating the Z axle, determine that workpiece is in mask pattern by on the image planes of object lens imaging, because the imaging multiplying power of these object lens is 1/10, so the facula area S of radiation on surface of the work and the area S of mask pattern
*Ratio be 1/100, according to formula 1. the ratio of threshold value laser energy density and the threshold energy density of shoot laser of workpiece material be 100;
(2) because polymethylmethacrylate (PMMA) is 0.05 μ m to the absorption coefficient of 248nm laser
-1, the laser of this wavelength begins the threshold value laser energy density F of etching PMMA material
0Be 5000mJ/cm
2According to formula 1. the shoot laser threshold energy density of this threshold value correspondence be 50mJ/cm
2, because the shoot laser facula area of this laser instrument is 8cm
2With formula 2. corresponding threshold shoot laser energy be 400mJ, therefore the operating voltage for this laser instrument of PMMA material all can satisfy processing request; Setting operating voltage in the present embodiment is 20kv, and corresponding laser energy is 1000mJ; According to the shoot laser energy value 1000mJ that sets, the laser facula area is 8cm
2, calculate the energy density F of outgoing laser
*Therefore, placing the laser energy density F on the workpiece of mask image planes is 12500mJ/cm
2According to 5. x of formula
f=ln (F/F
0)/α calculates etching rate x
fBe 18 μ m/ laser pulses;
(3) because the xsect of required microfluidic circuit is semicircle, therefore having chosen diameter is the circular hole mask of 1mm; Because the microfluidic circuit degree of depth to be processed is 100 μ m, etching rate x
fBe 18 μ m/ laser pulses, thus according to formula 6. each processing place all 6 laser pulses of needs just can reach needed etching depth 100 μ m; Because the mask that adopts in this example is that diameter is the circular hole of 1mm, the value that 7. draws laser pulse frequency f/ moving speed of table v according to formula is 1, and therefore f being set is 5hz, and v is 5mm/min;
(4) according to needed microfluidic circuit structure, in AUTOCAD software with the on-chip microfluidic circuit structural drawing of 1: 1 scale such as Fig. 3, and this document converted in the control computer 1 that data file stores excimer laser microfabrication system into, the data file that generates according to figure by the Control work platform on the x-y both direction moving line and the processing instruction sequences of move distance form;
(5) all parameters to input detect, because the laser works frequency of present embodiment is 0-50hz, operating voltage is that the laser energy of 13-23kv correspondence is at 500-1200mJ, any parameter that surpasses this scope all can cause damage to laser instrument, the translational speed of same worktable is between 0-60mm/min, also need input value checked in order to avoid cause damage,, as exceed effective range and will quit work if running parameter effectively will continue next step;
(6) the various machined parameters that will set of CPU are sent to respectively on the channel address corresponding on the hardware, finish the configuration of machined parameters; The operating voltage of laser instrument, pulsed frequency parameter values are transferred into control laser operating voltage, 2 channel address of pulsed frequency, and setting laser pulse and worktable this working method corresponding parameters value synchronously are transferred into laser pulse number control channel; The numerical value of X-axis movement velocity is transferred into the channel address of control X-axis movement velocity; The numerical value of Y-axis movement velocity is transferred into the channel address of control Y-axis movement velocity; Then according to the order of the processing on the data file that is read (dat file) instruction, every corresponding X-Y axle move distance of instruction wherein is sent to the channel address of control X-axis move distance and the channel address of control Y-axis move distance respectively, direction of motion is transferred into the channel address of Control work platform direction, carries out the processing instruction under the various machined parameters that set one by one; By computer data bus, steering order is transferred to the control corresponding passage, again control signal is sent to stepper motor, drive the running of worktable and laser instrument, carry out movement instruction successively and finish whole processing route;
(7) channel address of the machined parameters that transmit to be provided with to the relevant hardware is about to this numerical value of moving speed of table 5mm/min and is sent to x axle movement velocity control channel address 310H and y axle movement velocity control channel address 311H; The numerical value of laser pulse frequency 5hz is sent to pulsed frequency control channel address 319H; The synchronous instruction of laser pulse and movable workbench is sent to laser pulse number control channel address 31bH; Instruct according to the processing that the reading of data processed file obtains, to control x axle displacement passage 313H, y axle displacement passage 314H, direction of motion passage 31cH, send corresponding movement instruction by document order, the movement instruction of carrying out this document one by one is until covering whole processing route; Thereby drive the etching that worktable and laser instrument are realized microfluidic circuit on the substrate;
(8), need 3 via holes of etching on the cover plate as injection orifice and perforation hole according to the structure of microfluidic circuit on the substrate; In AUTOCAD, draw cover plate manuscript such as Fig. 4, generate corresponding data file; According to the step identical with process substrates, it is 23kv that laser operating voltage is set, and pulsed frequency is 20hz, and moving speed of table is 2mm/min, and read data files is finished the processing of cover plate; Via diameter on the cover plate is 500um;
(9) with the substrate that processes and cover plate with methenyl choloride organic adhesion agent bonding, at first cover plate is fixed on the sol evenning machine, the running parameter that sol evenning machine is set is rotation time 6 seconds; 3000 rev/mins of velocities of rotation, beginning to splash into the methenyl choloride organic solvent at the center of rotation place after the rotation, rotate and finish the back because this tackifier of action of centrifugal force is covered on the cover plate uniformly, apply certain pressure together with substrate and cover plate secured in alignment, after treating this adhesive solidification, can realize the sealing of microfluidic circuit structure, finish the making of biological chip miniflow line structure of the present invention.
After finishing whole microfluidic circuit structure preparations, inject red pigment by syringe pump and check the sample introduction effect, to verify the actual effect of this microfluidic circuit structure, not only guaranteed the evenly level and smooth of stream but also realized real airtight microfluidic circuit by Fig. 5,6 visible these structures; The main body that can be used as biochip is used for various biochemical tests.
This shows that the manufacturing process according to above preparation method can simplify biochip greatly obviously improves the dirigibility of making, and guaranteed processing effect.
The present invention and system thereof only need adopt different data files as processed file with the microfluidic circuit structure that different machined parameters can obtain coming in every shape is set, and utilized the cold worked characteristic of excimer laser to guarantee good processing effect; Realize the structure processing of three-dimensional microfluidic circuit class biochips such as PCR (polymerase chain amplified reaction) chip and CE (Capillary Electrophoresis) chip.
Claims (1)
1, a kind of method that adopts excimer laser to prepare superpolymer base biological chip miniflow line structure is characterized in that it may further comprise the steps:
(1) workpiece to be machined is placed on the worktable, and aim at, in worktable Z-direction range of movement, set the position of Z axle arbitrarily, determine the distance between workpiece and object lens, thereby determine the facula area S on the surface of the work with laser beam;
(2) 1. can calculate F according to formula
0 *: the threshold energy density of laser emitting,
F
0/F
0 *＝S
*/S ①
F wherein
0: the threshold energy density of workpiece material; F
0 *: the threshold energy density of laser emitting;
S: the laser facula area of surface of the work; S
*: the area of mask pattern
And F
0: the threshold energy density of workpiece material is by workpiece material itself decision,
(3) 2. can calculated threshold laser emitting ENERGY E according to formula
0
E
0=F
0 *S
02., thus obtain corresponding threshold value operating voltage;
(4) according to this threshold value operating voltage, when being higher than threshold energy density, could realize the laser energy density on the workpiece material principle of etching to material, the operating voltage of laser greater than the threshold value operating voltage is set, thereby obtains corresponding laser emitting ENERGY E;
(5) 3. according to formula
F
*＝E/S
0 ③
F wherein
*Be by laser emitting ENERGY E and laser emitting facula area S
0Decision;
Laser emitting facula area S
0Be by laser instrument decision itself,
(6) according to formula F/F
*=S
*4./S calculates the laser energy density F on workpiece material surface;
F wherein: the laser energy density on workpiece material surface; F
*: the energy density of shoot laser;
S: the laser facula area of surface of the work; S
*: the area of mask pattern
The laser energy density F of surface of the work is by the decision of the laser facula area of laser operating voltage and surface of the work,
(7) 5. can calculate etching rate x according to the etching rate formula
f
x
f＝ln(F/F
0)/α ⑤
Wherein: x
f: etching rate; F: the laser energy density of surface of the work;
F
0: the threshold energy density of workpiece material; α: workpiece material is to the absorption coefficient of laser
F
0Determine by workpiece material that is adopted and optical maser wavelength with α;
(8) according to the size and the shape of cross section of the microfluidic circuit that usually adopts in the biochip, set machined parameters and mask pattern, the speed, laser instrument trigger pulse frequency and the number that comprise working table movement in the machined parameters, the pattern of microfluidic circuit xsect is by selected mask pattern decision;
According to h, x
f6. determine n with formula,
n＝h/x
f ⑥
N wherein: each processing place needs the pulse number of etching; H: the degree of depth of microfluidic circuit to be processed;
7. calculate the value of f/v according to known l value substitution formula, select the laser frequency and the moving speed of table numerical value that are fit to according to this relation; The working range of f is by laser instrument decision itself, and the working range of v is determined by worktable itself;
n＝6*l*f/v ⑦
L: the length of the mask that uses; F: laser pulse frequency; V: moving speed of table
Shape of cross section according to the microfluidic circuit of processing request is selected corresponding mask pattern;
(9), adopt AUTOCAD software to draw the microfluidic circuit structure graph, and the data file that this graphic file is converted to the dat form in AUTOCAD software store in the control computer in order to calling according to the structure and the size of microfluidic circuit to be processed;
(10) read data files is obtained the move distance and the moving line of X, Y-axis, moving speed of table, laser operating voltage, these machined parameters of laser pulse frequency of setting in they and the above-mentioned steps are sent to control computer after detecting, realize the configuration of system's machined parameters; Drive worktable and laser instrument by route, mask pattern and the parameter work set, realize the processing of microfluidic circuit structure on the substrate;
(11) according to the starting point of microfluidic circuit on the substrate and the position of terminal point, the method of (1) set by step-(10) is used to inject via hole with outgoing liquid at the correspondence position of cover plate with quasi-molecule laser etching or with conventional drilling method processing, finishes the processing to cover plate;
(12) substrate and the cover plate that processes is bonded together with existing superpolymer bonding techniques, thereby the making of biological chip miniflow line structure of the present invention is finished in the sealing of realization microfluidic circuit structure.
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| CN 200410000670 CN1239961C (en) | 2004-01-16 | 2004-01-16 | Method and system for preparing high polymer group biochip micro flow path structure adopting quasi molecule laser |
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| CN 200410000670 CN1239961C (en) | 2004-01-16 | 2004-01-16 | Method and system for preparing high polymer group biochip micro flow path structure adopting quasi molecule laser |
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| CN1239961C true CN1239961C (en) | 2006-02-01 |
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| CN101468423B (en) * | 2007-12-29 | 2011-12-07 | 深圳市大族激光科技股份有限公司 | laser cutting control method |
| CN104552679B (en) * | 2015-01-12 | 2017-01-11 | 北京同方生物芯片技术有限公司 | Preparation method of mold core of mold, mold core of mold and biochip |
| CN109317228B (en) * | 2018-11-01 | 2021-02-26 | 北京工业大学 | Micro-fluidic chip preparation method based on laser inner carving micro-machining |
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