CN110244050A - A kind of cell cracking original position optical sensing detection chip and its preparation and application - Google Patents
A kind of cell cracking original position optical sensing detection chip and its preparation and application Download PDFInfo
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Abstract
The present invention provides a kind of cell cracking original position optical sensing detection chip and its preparation and application, when the chip is applied, antibody conjugate is carried out on nanostructure sensor array surface by the polydimethylsiloxane cover plate with microfluidic channel first, then piezoelectric substrate is made to generate surface acoustic wave by interdigital transducer, with drive cell of the drop in the drop of nanostructure sensor array surface and for lytic cell microballoon high-speed motion and mutually collide, to make cell cracking.The antibody of marker to be measured and nanostructure sensor array surface after cell cracking forms specific reaction substance, local surface using metal Nano structure etc. carries out the test of metallic particles fluorescence enhancement, local surface plasma resonance LSPR spectrum test or surface-enhanced Raman SERS spectra by optical detecting instrument and tests from resonance effects.The present invention can carry out optical detection in situ to the marker to be measured after cell cracking, so that easy to detect, quick, accurate.
Description
Technical field
The present invention relates to biomedical sensing detection fields more particularly to a kind of cell cracking original position optical sensing to detect core
Piece and its preparation and application.
Background technique
In recent years, in clinical medicine under the great demand of liquid detecting, micro-nano technology of preparing and microflow control technique are fast
Speed development, biochemical sensitive chip have also obtained corresponding development, and the detection method of use and sensitivity have also obtained fast lifting, such as
Electrochemical sensor, nanophotonics sensor, colorimetric sensor etc. have all obtained certain application, in conjunction with novel nano enhanced sensitivity
Material and new principle, highly sensitive and portable sensor chip and detection device are rapidly developed, these sensors and detection
Equipment is diagnosed in major disease early stage becomes possibility, so as to take medical means to prevent and treat as soon as possible,
Reduce disease as far as possible to the injury of human body.And multiple technologies combine, realize that same sample is in situ, multifunctional examining survey technology
Patent or product are seldom.Although there are many single medicine sensing detection methods, because of the sensitivity of sensing detection technology, detection
The reasons such as limit, amount of samples and cost and be unable to satisfy major disease early stage precisely diagnosis require.Therefore, have it is highly sensitive,
The novel sensing chip and detection technique and analysis instrument that extremely low detection limit, a variety of detection methods are integrated in one, and it is used for cancer
Disease early stage, precisely diagnosis was to meet the demand of people's livelihood needs and health industry development.
Novel Biosensor is for analyzing the stigmatas such as the various DNA, RNA, the protein that are present in human body fluid
Object, thus detection or identification various diseases.But these markers have and are greatly present in cell interior, when biochemistry detection
A large amount of blood samples are needed, using traditional equipment by cell cracking, obtain inhereditary material, protein, vesica and organelle etc., are then received
Sample after collection cracking, then is detected and analyzed, and this usual sample consumption of traditional method is big or even Partial key disease
Sick marker is lost, so that disease markers can not be detected, this will make testing result inaccurate.
Therefore, current biosensor is needed when detecting the marker of cell interior using first will be after cell cracking
The sample after cracking, then the mode being detected and analyzed just are collected, there are sample consumptions, and big, Partial key marker is lost
It loses, so that marker can not be detected, so that the problem of testing result inaccuracy.
Summary of the invention
In order to solve current biosensor when detecting the marker of cell interior, need using first by cell cracking
The sample after cracking, then the mode being detected and analyzed just are collected afterwards, and there are sample consumptions, and big, Partial key marker is lost
It loses, so that marker can not be detected, so that the problem of testing result inaccuracy, the embodiment of the present invention provide a kind of cell cracking
Optical sensing detection chip and its preparation and application in situ.
In a first aspect, the embodiment of the present invention provides a kind of cell cracking original position optical sensing detection chip, which includes:
Piezoelectric substrate, and the micro-elasticity band set on piezoelectric substrate upper surface, nanostructure sensor array and interdigital transducer；Wherein:
Micro-elasticity band and interdigital transducer both sides opposite respectively close to piezoelectric substrate, and micro-elasticity band is opposite with interdigital transducer, it is micro-
Elastic webbing is parallel with the interdigital electrode of interdigital transducer；Nanostructure sensor array be located at micro-elasticity band and interdigital transducer it
Between；Interdigital transducer is used to crack the cell on nanostructure sensor array surface.
Preferably, chip further include: the polydimethylsiloxane cover plate with microfluidic channel, PDMS cover plate key
On nanostructure sensor array, and microfluidic channel is parallel with interdigital electrode；PDMS cover plate is used to pass in nanostructure
Feel array surface and carries out antibody conjugate.
Preferably, the length of the length and interdigital electrode of micro-elasticity band, respectively greater than nanostructure sensor array with
Micro-elasticity band or interdigital electrode it is parallel side distribution length.
Preferably, nanostructure sensor array is metal Nano structure sensor array, and metal includes one in gold, silver or copper
Kind is a variety of.
Preferably, the array of nanostructure sensor array is dot matrix, Kong Zhen or grating array, dot matrix, Kong Zhen or grating battle array
The characteristic size of column is 30nm~100nm.
Second aspect, the embodiment of the present invention provide a kind of preparation method of cell cracking original position optical sensing detection chip,
The preparation method includes: S1, using the double-deck glue self-priming nanometer embossing or electron beam evaporation technique, in the upper table of piezoelectric substrate
Wheat flour is for nanostructure sensor array；S2, using photoetching, electron beam evaporation technique and ultrasonic lift-off technology, in piezoelectric substrate
On one side between nanostructure sensor array, interdigital transducer is prepared；S3, it is sensed in the another side of piezoelectric substrate and nanostructure
Between array, the micro-elasticity band opposite with interdigital transducer is pasted.
Preferably, after step S3, further includes: in the upper surface of nanostructure sensor array, bonding has microfluidic channel
PDMS cover plate, by PDMS cover plate nanostructure sensor array surface carry out antibody conjugate；Remove PDMS cover plate.
Preferably, step S1 is specifically included: after cleaning to the upper surface of piezoelectric substrate, in the upper surface of piezoelectric substrate
Spin coating lower layer glue is simultaneously heating and curing；In lower layer's glue surface spin coating upper layer glue；It is covered in the PDMS soft template with nanostructure
Upper layer glue surface, and the upper layer glue that is heating and curing form nanostructure on the lower layer's glue and upper layer glue of PDMS covering；Remove PDMS
Soft template with developing liquid developing and makes the inside undercutting formation of lower layer's glue fall from power at nanostructure；Utilize electron beam evaporation metal
In the surface shape metal film fallen from power；It is removed with acetone ultrasound and removes lower layer's glue and upper layer glue, in the upper surface system of piezoelectric substrate
Standby nanostructure sensor array out.
Preferably, step S2 is specifically included: being carried out to the upper surface for the piezoelectric substrate for having prepared nanostructure sensor array
After cleaning, the negative photoresist in the upper surface spin coating of piezoelectric substrate；After front baking and exposure, by negative photoresist aobvious
Develop in shadow liquid, forms the shape of patterning interdigital transducer；Using electron beam evaporation metal film, is removed and gone with acetone ultrasound
Except negative photoresist, the area of metal interdigital transducers and nanostructure sensor array is prepared in the upper surface of piezoelectric substrate
Domain limits label.
The third aspect, the embodiment of the present invention provide a kind of application method of cell cracking original position optical sensing detection chip,
The application method includes: to sense battle array in the nanostructure being bonded with PDMS cover plate by the PDMS cover plate with microfluidic channel
After the surface of column carries out antibody conjugate, PDMS cover plate is removed；If the surface of nanostructure sensor array drip upper stem cell and
Microballoon sample mixing liquid for lytic cell；Pass through interdigital transducer lytic cell and obtain marker to be measured, makes marker to be measured
Specific reaction occurs with antibody, and obtains specific reaction substance；Specific reaction substance is carried out by optical tester
The test of metallic particles fluorescence enhancement, local surface plasma resonance LSPR spectrum test or surface-enhanced Raman SERS spectra are surveyed
Examination.
The embodiment of the present invention provides a kind of cell cracking original position optical sensing detection chip and its preparation and application, leads to
It crosses the both sides opposite in piezoelectric substrate upper surface and interdigital transducer and micro-elasticity band is respectively set, and in interdigital transducer and micro- bullet
Property band between be arranged nanostructure sensor array, thus make nanostructure sensor array as cell cracking and be directed to cell cracking
Marker afterwards carries out the region of optical detection.The chip is in application, carry out antibody on nanostructure sensor array surface first
Then coupling makes piezoelectric substrate generate surface acoustic wave by interdigital transducer, the generation sound of piezoelectric substrate is made to cause miniflow effect, from
And cell of the drop in nanostructure sensor array surface and the drop high-speed motion for lytic cell are driven, after cell cracking
Marker to be measured and the antibody on nanostructure sensor array surface occur specific reaction and form specific reaction substance, Jin Erli
Local with nanostructure sensor array etc. carries out metal to specific reaction substance from resonance effects, by optical detector
The test of grain fluorescence enhancement, LSPR spectrum test or SERS spectra test.The embodiment of the present invention can to after cell cracking to mark
Remember that object carries out optical detection in situ, without being detected again after the sample after cell cracking is collected and is shifted, makes
Detection process fast and easy is obtained, and testing result is accurate, reduces sample preparation transfer bring sample loss and pollution.
Detailed description of the invention
In order to more clearly explain the embodiment of the invention or the technical proposal in the existing technology, to embodiment or will show below
There is attached drawing needed in technical description to be briefly described, it should be apparent that, the accompanying drawings in the following description is this hair
Bright some embodiments for those of ordinary skill in the art without creative efforts, can be with root
Other attached drawings are obtained according to these attached drawings.
Fig. 1 is the structural schematic diagram of the cell cracking original position optical sensing detection chip of the embodiment of the present invention；
Fig. 2 is that the cell cracking original position optical sensing detection chip encapsulation of the embodiment of the present invention has microfluidic channel
The structural schematic diagram of PDMS cover plate；
Fig. 3 is the structural representation that drop has drop in the cell cracking original position optical sensing detection chip of the embodiment of the present invention
Figure；
Fig. 4 is that the step process of the preparation method of the cell cracking original position optical sensing detection chip of the embodiment of the present invention is shown
It is intended to；
Fig. 5 is that the pattern process of the preparation method of the cell cracking original position optical sensing detection chip of the embodiment of the present invention is shown
It is intended to；
Fig. 6 is the process signal of the preparation process of the cell cracking original position optical sensing detection chip of the embodiment of the present invention
Figure；
Fig. 7 is that the overall procedure of the application method of the cell cracking original position optical sensing detection chip of the embodiment of the present invention shows
It is intended to；
Fig. 8 is that the detailed process of the application method of the cell cracking original position optical sensing detection chip of the embodiment of the present invention is shown
It is intended to；
Wherein:
1, piezoelectric substrate 2, interdigital transducer 3, micro-elasticity band
4, nanostructure sensor array 5, PDMS cover plate 51, sample inlet
52, sample export 6, cell and microballoon sample mixing liquid.
Specific embodiment
In order to make the object, technical scheme and advantages of the embodiment of the invention clearer, below in conjunction with the embodiment of the present invention
In attached drawing, technical scheme in the embodiment of the invention is clearly and completely described, it is clear that described embodiment is
A part of the embodiment of the present invention, instead of all the embodiments.Based on the embodiments of the present invention, those of ordinary skill in the art
Every other embodiment obtained without making creative work, shall fall within the protection scope of the present invention.
When being detected at present to the marker to be measured after cell cracking, need by the marker to be measured after cell cracking into
Row is collected and transfer, sample consumption is big, Partial key marker is lost, so that marker can not be detected, so that detection
As a result inaccurate problem.
Fig. 1 is the structural schematic diagram of the cell cracking original position optical sensing detection chip of the embodiment of the present invention, such as Fig. 1 institute
To show, the embodiment of the present invention provides a kind of cell cracking original position optical sensing detection chip, which includes: piezoelectric substrate 1, and
Set on the micro-elasticity band 3 of 1 upper surface of piezoelectric substrate, nanostructure sensor array 4 and interdigital transducer 2；Wherein: micro-elasticity band 3
The both sides opposite respectively close to piezoelectric substrate 1 with interdigital transducer 2, and micro-elasticity band 3 and interdigital transducer 2 are opposite, micro-elasticity
It is parallel with the interdigital electrode of interdigital transducer 2 with 3；Nanostructure sensor array 4 be located at micro-elasticity band 3 and interdigital transducer 2 it
Between；Interdigital transducer 2 is used to crack the cell on 4 surface of nanostructure sensor array.
Specifically, interdigital transducer 2 is set in piezoelectric substrate 1, is equivalent to and constitutes surface acoustic wave generator, interdigital
Load tool high frequency ac signal, can make piezoelectric substrate 1 generate surface acoustic wave on energy converter 2, make piezoelectric substrate 1 that there is sound to cause micro-
Flow effect.Meanwhile micro-elasticity band 3 and the both sides opposite respectively close to piezoelectric substrate 1 of interdigital transducer 2, nanostructure sense battle array
Column 4 be set between micro-elasticity band 3 and interdigital transducer 2, and micro-elasticity band 3 in length sides to the interdigital electricity with interdigital transducer 2
It is extremely parallel, so that micro-elasticity band 3 and interdigital transducer 2 are used for the area size of limits nano-structure sensor array 4, the core
In actual use, by interdigital transducer 2, generation sound causes miniflow benefit to piece in piezoelectric substrate 1, passes for cracking nanostructure
The cell on 4 surface of array is felt to obtain marker to be measured, so as in situ in 4 surfaces of nanostructure sensor array, that is, cell cracking
Survey marker is treated to be detected.
The embodiment of the invention provides a kind of cell cracking original position optical sensing detection chips, pass through the table in piezoelectric substrate
Interdigital transducer and micro-elasticity band is respectively set in the opposite both sides in face, and nanometer is arranged between interdigital transducer and micro-elasticity band
Structure sensor array, thus make nanostructure sensor array as cell cracking and for the marker to be measured after cell cracking into
The region of row optical detection.The embodiment of the present invention can marker to be measured after the cell cracking to nanostructure sensor array surface
Optical detection in situ is carried out, without detecting again after the sample after cell cracking is collected and is shifted, so that inspection
Survey process fast and easy, and testing result is accurate, reduces sample preparation transfer bring sample loss and pollution.
It should be noted that the length and width of entire chip is 3 centimetres in the embodiment of the present invention.Piezoelectric substrate 1
Material is lithium columbate crystal material or Zinc oxide film material.Micro-elasticity band 3 is apart from its inter-digital electrode edges
1.3cm, the height of micro-elasticity band 3 are 0.5 to 1mm, length 2cm, width 0.6cm；Micro-elasticity band 3 can be flexible
Adhesive tape is also possible to PDMS (dimethyl silicone polymer).
Further, interdigital transducer 2 is prepared by semiconductor technology using metal, for example, consist of 5nm chromium and
200nm gold；The interdigital electrode logarithm of interdigital transducer 2 is 40 to 50 pairs, and the width of every interdigital electrode is 50 microns, interdigital electricity
Gap between pole is 50 microns, and the length of every interdigital electrode is 2 centimetres；Interdigital transducer 2 can be by changing its interdigital electricity
For the finger period of pole to adjust its frequency, the period of interdigital electrode is 200 to 260 microns；Interdigital transducer 2 is in piezoelectric substrate
The surface acoustic wave generated on 1 is R wave.
Further, nanostructure sensor array 4 is metal Nano structure sensor array, and metal includes in gold, silver or copper
It is one or more, in the embodiment of the present invention use chromium and gold.The array of nanostructure sensor array 4 is dot matrix, Kong Zhen or light
Grid array, the characteristic size of dot matrix, Kong Zhen or grating array are 30nm~100nm；If nanostructure sensor array 4 be dot matrix or
Kong Zhen, then dot matrix or hole battle array period are 80-100nm, duty ratio 1:1；If nanostructure sensor array 4 is grating, grating
Duty ratio be 1:2.The uniformity of nanostructure sensor array 4 will be got well, and relative error is less than 5%.
It should also be noted that, the length of micro-elasticity band 3 and the length of interdigital electrode, respectively greater than nanostructure is sensed
The length that array 4 is distributed in the side parallel with micro-elasticity band 3 or interdigital electrode.Wherein, the length of micro-elasticity band 3 is greater than nanometer
Structure sensor array 4 is for the area of limits nano-structure sensor array 4 in the length of the parallel side distribution of micro-elasticity band 3
Domain size, to prevent the drop on 4 surface of nanostructure sensor array from flowing out the upper surface of chip；And interdigital transducer 2 is interdigital
The length of electrode be greater than nanostructure sensor array 4 interdigital electrode it is parallel side distribution length, on the one hand also for
On the other hand the area size of limits nano-structure sensor array 4 is the cell energy in order to enable in nanostructure sensor array 4
It maximally utilizes the surface acoustic wave that interdigital transducer 2 generates in piezoelectric substrate 1 and sufficiently cracks, so that cell cracking to the greatest extent may be used
Can be abundant, in order to which the subsequent marker to be measured to after cell cracking detects.
Fig. 2 is that the cell cracking original position optical sensing detection chip encapsulation of the embodiment of the present invention has microfluidic channel
The structural schematic diagram of PDMS cover plate, as shown in Fig. 2, the chip further include: the PDMS cover plate 5 with microfluidic channel, PDMS lid
Piece 5 is bonded on nanostructure sensor array 4, and microfluidic channel is parallel with interdigital electrode；PDMS cover plate 5 is used in nanometer
The surface of structure sensor array 4 carries out antibody conjugate.
Specifically, the chip is in application, first have to carry out antibody conjugate, the present invention on 4 surface of nanostructure sensor array
Embodiment carries out antibody conjugate on the surface of nanostructure sensor array 4 using the PDMS cover plate 5 with microfluidic channel.It will
PDMS cover plate 5 is bonded to the surface of nanostructure sensor array 4, and the microfluidic channel of PDMS cover plate 5 and interdigital transducer 2
Interdigital electrode is parallel, wherein microfluidic channel includes sample inlet 51 and sample export 52.The antibody that couples will be needed from sample
Entrance 51 is passed through microfluidic channel, couples it with nanostructure sensor array 4, and extra does not couple antibody from sample export 52
Outflow, so that antibody conjugate is on the surface of nanostructure sensor array 4.
It should be noted that the microfluidic channel of PDMS cover plate 5 can process on silicon wafer, mold duplication also can use
Mode process on polymeric materials；The capping of PDMS cover plate 5 and shell can be polymer material or glass material.
The embodiment of the present invention is resisted by the PDMS cover plate with microfluidic channel on nanostructure sensor array surface
Body coupling, so that used antibody samples are few, reaction speed is fast, and can be carried out fine antibody samples coupling.
Fig. 4 is that the step process of the preparation method of the cell cracking original position optical sensing detection chip of the embodiment of the present invention is shown
It is intended to, Fig. 5 is the pattern process signal of the preparation method of the cell cracking original position optical sensing detection chip of the embodiment of the present invention
Figure, as shown in Figure 4 and Figure 5, the embodiment of the present invention provides a kind of preparation method of cell cracking original position optical sensing detection chip,
The preparation method includes: S1, using the double-deck glue self-priming nanometer embossing or electron beam evaporation technique, in the upper table of piezoelectric substrate
Wheat flour is for nanostructure sensor array；S2, using photoetching, electron beam evaporation technique and ultrasonic lift-off technology, in piezoelectric substrate
On one side between nanostructure sensor array, interdigital transducer is prepared；S3, it is sensed in the another side of piezoelectric substrate and nanostructure
Between array, the micro-elasticity band opposite with interdigital transducer is pasted.
Specifically, the embodiment of the present invention first uses the double-deck glue self-priming nanometer embossing or electron beam evaporation technique, is pressing
Prepare nanostructure sensor array in the upper surface of electric substrate；Then using photoetching, electron beam evaporation technique and ultrasound removing skill
Art prepares interdigital transducer between one side and nanostructure sensor array of piezoelectric substrate；Finally in the another of piezoelectric substrate
On one side between nanostructure sensor array, the micro-elasticity band opposite with interdigital transducer is pasted.
Fig. 6 is the process signal of the preparation process of the cell cracking original position optical sensing detection chip of the embodiment of the present invention
Figure, as shown in fig. 6, step S1 is specifically included:
(a) after being cleaned to the upper surface of piezoelectric substrate, piezoelectric substrate upper surface spin coating lower layer glue and heat solid
Change；In lower layer's glue surface spin coating upper layer glue；
(b) upper layer glue table is covered in using self-priming mode with the polydimethylsiloxane soft template with nanostructure
Face, and the upper layer glue that is heating and curing form nanostructure on the lower layer's glue and upper layer glue of PDMS covering；
(c) PDMS soft template is removed, at nanostructure, with developing liquid developing and the inside undercutting of lower layer's glue is made to be formed
Platform；
(d) it is formed using electron beam evaporation metal (successively evaporate chromium 5nm and gold 30nm) on the surface of (T-type structure) of falling from power
Metal film；
(e) ultrasound removing in acetone, prepares nanostructure sensor array in the upper surface of piezoelectric substrate.
Further, step S2 is specifically included:
(f) after being cleaned to the upper surface for the piezoelectric substrate for having prepared nanostructure sensor array, in piezoelectric substrate
Upper surface spin coating on negative photoresist, make negative photoresist thickness in 1 microns；
(g) after front baking and exposure, negative photoresist is developed in developer solution, forms patterning interdigital transducer
Shape；Metal is formed in the shape face of interdigital transducer using electron beam evaporation metal (successively evaporating chromium 5nm and gold 200nm)
Film, ultrasound removing negative photoresist, prepares interdigital transducer and nanostructure in the upper surface of piezoelectric substrate in acetone
The region of sensor array limits label.
Further, as shown in Fig. 2, after step S3, further includes: be bonded tool in the upper surface of nanostructure sensor array
There is the PDMS cover plate of microfluidic channel, is resisted by surface of the microchannel in PDMS cover plate to nanostructure sensor array
Body modification；Remove PDMS cover plate.The detailed process includes:
(h) silicon mould is prepared using semiconductor technology, which is used to prepare the PDMS cover plate with microfluidic channel；
(i) silicon mould surface is subjected to silanization treatment, with PDMS casting, solidification；
(j) the PDMS cover plate with microfluidic channel is separated, is punched on PDMS cover plate, sample inlet 51 and sample are formed
Product outlet 52 is simultaneously clean by the processing of PDMS coverslip surface；
(k) oxygen plasma treatment PDMS coverslip surface is used, the PDMS cover plate with microfluidic channel is bonded to preparation
Then the surface of nanostructure sensor array in nanostructure sensor array and the piezoelectric substrate of interdigital transducer out will have viscous
Property micro-elasticity band be close to PDMS cover plate on the outside of be pasted in piezoelectric substrate.
Fig. 7 is that the overall procedure of the application method of the cell cracking original position optical sensing detection chip of the embodiment of the present invention shows
It is intended to, as shown in fig. 7, the embodiment of the present invention provides a kind of application method of cell cracking original position optical sensing detection chip, it should
The overall process of application method includes: A1, using Micropump various samples is entered metal by microfluidic channel on PDMS cover plate
In the corresponding microcavity of nano-structure array, after the surface of various samples and metal Nano structure sensor array is combined, removal
PDMS cover plate；If A2, dripping upper stem cell on the surface of nanostructure sensor array and for the microballoon sample mixing liquid of lytic cell；
A3, pass through interdigital transducer lytic cell and obtain marker to be measured, make marker to be measured and antibody that specific reaction occur, and
Obtain specific reaction substance；A4, by optical tester to specific reaction substance carry out the test of metallic particles fluorescence enhancement,
LSPR spectrum test or SERS spectra test.
Specifically, the PDMS cover plate with microfluidic channel is first bonded to nanostructure sensor array by the embodiment of the present invention
Surface, using PDMS cover plate make antibody conjugate in the surface of nanostructure sensor array and then removal PDMS cover plate；Then
If cracking cell sufficiently on the surface of nanostructure sensor array stem cell and the microballoon sample mixing drop for being used for lytic cell
And marker to be measured is obtained, make marker to be measured and antibody that specific reaction occur, and obtain specific reaction substance；Last benefit
Local surface with nanostructure sensor array etc. carries out gold to specific reaction substance from resonance effects, by optical tester
The test of metal particles fluorescence enhancement, LSPR spectrum test or SERS spectra test.
Fig. 8 is that the detailed process of the application method of the cell cracking original position optical sensing detection chip of the embodiment of the present invention is shown
It is intended to, as shown in figure 8, the embodiment of the present invention provides the specifically used process of the cell cracking original position optical sensing detection chip:
(1) chip surface is handled 2 minutes with oxygen plasma, keep chip surface clean and there is hydrophily；
(2) the PDMS cover plate with microfluidic channel is bonded to the surface of nanostructure sensor array；
(3) biological functional processing, needle in nanostructure sensor array surface modification are carried out to nanostructure sensor array
Treat the antibody for surveying marker；
(4) 2mM dithiodiglycollic acid solution is passed into the LSPR sensitive zones (nanostructure with microfluidic channel
Sensor array and PDMS cover plate microcavity corresponding with nanostructure are referred to as the LSPR sensitive zones with microfluidic channel) it is inner,
And it is reacted；
(5) (1-ethyl-3- (3-dimethylaminopropyl) carbodiimide-HCI) of same volume proportion
EDC (0.4M) and (sulfo-nhydroxysuccinimide) S-NHS (0.1M) mixed liquor are and anti-into LSPR sensitive zones
It answers 30 minutes, activates the carboxyl in sub- two mercaptan dihydroxy acetic acids；
(6) nanostructure sensor array is rinsed with phosphate buffered saline solution (PBS) buffer of 0.01M；
(7) antibody-solutions are passed through into the region LSPR, make the basic amine group phenol of active carboxyl and immunoglobulin
The amino of (alkaline aminophenol (Arg and Lys)) is chemically reacted, so that antibody is coupled to nano junction
The surface of structure sensor array；
(8) it is passed through PBS buffer solution, removes extra antibody；
(9) it is passed through ethanol amine (ethanolamine) solution of 1M, is inactivated；
(10) PBS buffer solution for being passed through 0.01M rinses extra ethanol amine (ethanolamine) solution；
(11) Fig. 3 is that drop has the structure of drop to show in the cell cracking original position optical sensing detection chip of the embodiment of the present invention
It is intended to, as shown in figure 3, removal has the PDMS cover plate of microfluidic channel, upper cell and micro- is dripped in nanostructure sensor array
Ball sample mixing liquid 6；
(12) the load tool high frequency ac signal on interdigital transducer, makes piezoelectric substrate generate surface acoustic wave, makes piezoelectricity base
There is sound to cause miniflow effect at bottom, drives cell and 6 high-speed motion of microballoon sample mixing liquid, keeps volume in cell and microballoon sample mixing liquid 6 big
Cell and microballoon small in size generate mutually collision since speed is different, so that cell cracking be made to go out marker to be measured, to
The antibody for surveying marker and nanostructure sensor array surface generates specific reaction, generates specific reaction substance.
(13) since nanostructure sensor array has local etc. from resonance effects, nanometer can be realized using the effect
Structure sensor array treats the fluorescence intensity enhancing for surveying marker, for directly observation and charge coupled cell (CCD) record, root
Reflect that the concentration of marker to be measured, i.e. metallic particles fluorescence enhancement are tested indirectly according to fluorescence intensity；Meanwhile utilizing local surface
Plasma resonance system, the formant movement by observing white-light spectrum can reflect the concentration of also marker to be measured indirectly,
That is LSPR spectrum test；In addition, being detected using Raman spectrometer, the characteristic peak by treating survey marker is identified, is adsorbed
Sample to be tested concentration is different, and the height of characteristic peak is different, can reflect the concentration of also marker to be measured indirectly, i.e. SERS spectra is surveyed
Examination.
It should be noted that being to the same chip, with primary modification when treating survey marker progress optical sensing detection
It is carried out on surface for the antibody of marker to be measured and same site；Meanwhile the test of metallic particles fluorescence enhancement, LSPR
Spectrum test or SERS spectra test three kinds of detection methods mutually it is auxiliary just, for should mutually verify, avoid the occurrence of the test of mistake
As a result, improving the accuracy of test result mutually.
The embodiment of the present invention provides a kind of cell cracking original position optical sensing detection chip and its preparation and application, energy
Optical detection in situ is carried out to the marker to be measured after cell cracking, it is not necessary that the sample after cell cracking to be collected and turn
It is detected again after moving, so that detection process fast and easy, and testing result is accurate, reduces sample preparation transfer bring
Sample loss and pollution.Meanwhile the embodiment of the present invention is being received before lytic cell by the PDMS cover plate with microfluidic channel
Rice structure sensor array surface carries out antibody conjugate, so that used antibody samples are few, reaction speed is fast, and can be carried out spy
Anisotropic antibody samples coupling.
Optical sensing detection chip structure in cell cracking original position provided in an embodiment of the present invention is simple, small in size, convenient for collection
Preparation process and detection are carried out at cells in situ cracking and multifunctional optical sensing detection chip, and using micro-nano processing technology
Process is treated survey marker (Trinity inhereditary material, including protein, vesica and thin in situ while cell cracking
Born of the same parents' device) realize a variety of optical sensing detections, reduce detection time, improves detection efficiency.This needs micro-example
Multifunctional optical sensing detection chip technology in situ is with a wide range of applications in clinical major disease sensing detection method,
With huge potential economic results in society.
Finally, it should be noted that the above embodiments are merely illustrative of the technical solutions of the present invention, rather than its limitations；Although
Present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that: it still may be used
To modify the technical solutions described in the foregoing embodiments or equivalent replacement of some of the technical features；
And these are modified or replaceed, technical solution of various embodiments of the present invention that it does not separate the essence of the corresponding technical solution spirit and
Range.
Claims (10)
1. a kind of cell cracking original position optical sensing detection chip characterized by comprising piezoelectric substrate, and be set to described
Micro-elasticity band, nanostructure sensor array and the interdigital transducer of piezoelectric substrate upper surface；Wherein:
The micro-elasticity band and interdigital transducer both sides opposite respectively close to the piezoelectric substrate, and the micro-elasticity band
Opposite with the interdigital transducer, the micro-elasticity band is parallel with the interdigital electrode of the interdigital transducer；The nanostructure
Sensor array is between the micro-elasticity band and the interdigital transducer；
The interdigital transducer is used to crack the cell on nanostructure sensor array surface.
2. cell cracking original position optical sensing detection chip according to claim 1, which is characterized in that further include: have
The PDMS cover plate of microfluidic channel, the PDMS cover plate is bonded on the nanostructure sensor array, and the microfluid
Channel is parallel with the interdigital electrode；The PDMS cover plate is used to carry out antibody coupling on nanostructure sensor array surface
It closes.
3. cell cracking original position optical sensing detection chip according to claim 1, which is characterized in that the micro-elasticity band
Length and the interdigital electrode length, the respectively greater than described nanostructure sensor array with the micro-elasticity band or institute
State the length of the parallel side distribution of interdigital electrode.
4. cell cracking original position optical sensing detection chip according to claim 1, which is characterized in that the nanostructure
Sensor array is metal Nano structure sensor array, and the metal includes one of gold, silver or copper or a variety of.
5. cell cracking original position optical sensing detection chip according to claim 1, which is characterized in that the nanostructure
The array of sensor array is dot matrix, Kong Zhen or grating array, the characteristic size of the dot matrix, Kong Zhen or grating array be 30nm~
100nm。
6. a kind of preparation method of cell cracking original position optical sensing detection chip characterized by comprising
S1, using the double-deck glue self-priming nanometer embossing or electron beam evaporation technique, prepare nanometer in the upper surface of piezoelectric substrate
Structure sensor array；
S2, using photoetching, electron beam evaporation technique and ultrasonic lift-off technology, in one side and the nano junction of the piezoelectric substrate
Between structure sensor array, interdigital transducer is prepared；
S3, between the another side and the nanostructure sensor array of the piezoelectric substrate, paste with the interdigital transducer
Opposite micro-elasticity band.
7. the preparation method of cell cracking original position optical sensing detection chip according to claim 6, which is characterized in that step
After rapid S3, further includes:
In the upper surface of the nanostructure sensor array, bonding has the PDMS cover plate of microfluidic channel, is covered by the PDMS
Piece carries out antibody conjugate on the surface of the nanostructure sensor array；
Remove the PDMS cover plate.
8. the preparation method of cell cracking original position optical sensing detection chip according to claim 6, which is characterized in that step
Rapid S1 is specifically included:
After being cleaned to the upper surface of the piezoelectric substrate, the piezoelectric substrate upper surface spin coating lower layer glue and heat solid
Change；In lower layer's glue surface spin coating upper layer glue；
Upper layer glue surface is covered in using self-priming mode with the PDMS soft template with nanostructure, and it is described to be heating and curing
Upper layer glue forms nanostructure on the lower layer's glue and the upper layer glue of PDMS covering；
The PDMS soft template is removed, at the nanostructure, with developing liquid developing and makes the inside undercutting shape of lower layer's glue
At falling from power；
Metal film is formed on the surface fallen from power using electron beam evaporation metal；
Lower layer's glue and the upper layer glue are removed and removed, prepares the nanostructure in the upper surface of the piezoelectric substrate
Sensor array.
9. the preparation method of cell cracking original position optical sensing detection chip according to claim 8, which is characterized in that step
Rapid S2 is specifically included:
After being cleaned to the upper surface for the piezoelectric substrate for having prepared the nanostructure sensor array, in the piezoelectricity
Negative photoresist in the upper surface spin coating of substrate；
After front baking and exposure, the negative photoresist is developed in developer solution, forms the shape of patterning interdigital transducer
Shape；
Shape face using electron beam evaporation metal in the interdigital transducer forms metal film, and ultrasound is removed simultaneously in acetone
The negative photoresist is removed, prepares the interdigital transducer and the nano junction in the upper surface of the piezoelectric substrate
The region of structure sensor array limits label.
10. a kind of application method of cell cracking original position optical sensing detection chip characterized by comprising
By the PDMS cover plate with microfluidic channel, on the surface for the nanostructure sensor array being bonded with the PDMS cover plate
After carrying out antibody conjugate, the PDMS cover plate is removed；
If dripping upper stem cell on the surface of the nanostructure sensor array and the microballoon sample mixing liquid for cracking the cell；
The cell is cracked by interdigital transducer and obtains marker to be measured, and the marker to be measured and the antibody occurs
Specific reaction, and obtain specific reaction substance；
By optical tester to the specific reaction substance carry out the test of metallic particles fluorescence enhancement, LSPR spectrum test or
SERS spectra test.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112011446A (en) * | 2020-08-31 | 2020-12-01 | 吉林大学 | Micro-fluidic chip for bacterial lysis, bacterial lysis device and application thereof |
| CN113000079A (en) * | 2020-06-02 | 2021-06-22 | 山东大学 | Electrochemical micro-fluidic sensing chip for heavy metal ion detection and preparation method thereof |
| WO2022120769A1 (en) * | 2020-12-10 | 2022-06-16 | 深圳先进技术研究院 | High-throughput lysis system based on resonant micro-bubble array |
Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102507733A (en) * | 2011-11-01 | 2012-06-20 | 中国科学院微电子研究所 | Surface acoustic wave gas sensor and manufacturing method thereof |
| CN102680452A (en) * | 2012-05-14 | 2012-09-19 | 中央民族大学 | Dual-detection biochemical sensing detector integrated with optofluidics |
| CN102706835A (en) * | 2012-05-14 | 2012-10-03 | 中央民族大学 | Sensing chip of dual-detecting biochemical sensing detector and preparation method thereof |
| CN103105423A (en) * | 2013-01-25 | 2013-05-15 | 中国人民解放军国防科学技术大学 | Interdigital electrode with nano-dot array, and preparation method and application thereof |
| CN104056708A (en) * | 2014-05-30 | 2014-09-24 | 浙江大学 | Surface acoustic wave-based cell crusher |
| WO2015028811A2 (en) * | 2013-08-30 | 2015-03-05 | The University Court Of The University Of Glasgow | Methods for detecting proteins |
| CN108414303A (en) * | 2018-01-23 | 2018-08-17 | 中央民族大学 | A kind of particles collision cell cracking device based on surface acoustic wave |
| CN108477675A (en) * | 2018-02-28 | 2018-09-04 | 云南中烟工业有限责任公司 | A kind of preparation method of electronic cigarette atomizing chip |
| CN109103328A (en) * | 2018-03-23 | 2018-12-28 | 北京航天微电科技有限公司 | A kind of surface acoustic wave chip and preparation method thereof |
| CN109482121A (en) * | 2018-12-27 | 2019-03-19 | 苏州纳葛诺斯生物科技有限公司 | Micro-and nano-particles highly effective reaction micro-fluidic chip based on surface acoustic wave |
-
2019
- 2019-06-11 CN CN201910500962.6A patent/CN110244050B/en active Active
Patent Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102507733A (en) * | 2011-11-01 | 2012-06-20 | 中国科学院微电子研究所 | Surface acoustic wave gas sensor and manufacturing method thereof |
| CN102680452A (en) * | 2012-05-14 | 2012-09-19 | 中央民族大学 | Dual-detection biochemical sensing detector integrated with optofluidics |
| CN102706835A (en) * | 2012-05-14 | 2012-10-03 | 中央民族大学 | Sensing chip of dual-detecting biochemical sensing detector and preparation method thereof |
| CN103105423A (en) * | 2013-01-25 | 2013-05-15 | 中国人民解放军国防科学技术大学 | Interdigital electrode with nano-dot array, and preparation method and application thereof |
| WO2015028811A2 (en) * | 2013-08-30 | 2015-03-05 | The University Court Of The University Of Glasgow | Methods for detecting proteins |
| CN104056708A (en) * | 2014-05-30 | 2014-09-24 | 浙江大学 | Surface acoustic wave-based cell crusher |
| CN108414303A (en) * | 2018-01-23 | 2018-08-17 | 中央民族大学 | A kind of particles collision cell cracking device based on surface acoustic wave |
| CN108477675A (en) * | 2018-02-28 | 2018-09-04 | 云南中烟工业有限责任公司 | A kind of preparation method of electronic cigarette atomizing chip |
| CN109103328A (en) * | 2018-03-23 | 2018-12-28 | 北京航天微电科技有限公司 | A kind of surface acoustic wave chip and preparation method thereof |
| CN109482121A (en) * | 2018-12-27 | 2019-03-19 | 苏州纳葛诺斯生物科技有限公司 | Micro-and nano-particles highly effective reaction micro-fluidic chip based on surface acoustic wave |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113000079A (en) * | 2020-06-02 | 2021-06-22 | 山东大学 | Electrochemical micro-fluidic sensing chip for heavy metal ion detection and preparation method thereof |
| CN113000079B (en) * | 2020-06-02 | 2023-09-22 | 山东大学 | Electrochemical microfluidic sensing chip for heavy metal ion detection and preparation method thereof |
| CN112011446A (en) * | 2020-08-31 | 2020-12-01 | 吉林大学 | Micro-fluidic chip for bacterial lysis, bacterial lysis device and application thereof |
| WO2022120769A1 (en) * | 2020-12-10 | 2022-06-16 | 深圳先进技术研究院 | High-throughput lysis system based on resonant micro-bubble array |
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| Publication number | Publication date |
|---|---|
| CN110244050B (en) | 2022-12-23 |
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