CN101373175A - Method and apparatus for monitoring macromolecule conformation transformation and biochemical reaction of target and probe - Google Patents
Method and apparatus for monitoring macromolecule conformation transformation and biochemical reaction of target and probe Download PDFInfo
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- CN101373175A CN101373175A CNA2008100223790A CN200810022379A CN101373175A CN 101373175 A CN101373175 A CN 101373175A CN A2008100223790 A CNA2008100223790 A CN A2008100223790A CN 200810022379 A CN200810022379 A CN 200810022379A CN 101373175 A CN101373175 A CN 101373175A
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Abstract
The invention discloses a method and a device for observing the conformation transition of macromolecules and the biochemical reaction between target molecules and probe molecules. The method comprises the steps as follows: the macromolecules and one or more of the probe molecules which are different or identical are arranged on single side surfaces of various micro-cantilevers in a micro-cantilever array; the incident parallel rays emitted from a light source reach the micro-cantilevers, and the reflection rays are received by an optical receiver assembly to form an array of reflection ray spots corresponding to the micro-cantilevers one by one; when the conformation transition of macromolecules occurs or the combination of the probe molecules and the target molecules present in a solution to be tested occurs, the micro-cantilevers bend and deform with the deflection of the reflection rays, and accordingly, the positions of the corresponding reflection ray spots change; and according to the position change and the displacement of the reflection ray spots corresponding to each micro-cantilever, the conformation transition of the macromolecules can be learned, whether the target molecules corresponding to the probe molecules are present or absent in the solution to be tested can be determined, and the concentration of the target molecules present in the solution can be obtained. The invention can realize the simultaneous observation of the displacement signals of a plurality of micro-cantilevers, and at the same time eliminate the noise signals due to the variation of the refraction index and the change of the intensity of a light source. The invention has the advantages that the effects of vagabond rays can be greatly reduced by controlling the measurement of the light beam polarization state, and the measurement precision is improved.
Description
Technical field
The present invention relates to a kind of method and device of monitoring macromolecular conformation transformation and biochemical reaction, particularly a kind of method and device that adopts micro-cantilever array monitoring macromolecular conformation transformation and target molecule and probe molecule biochemical reaction.
Background technology
Through having modified the micro-cantilever of big molecule or probe molecule after the chemical conversion treatment, when environment change (as temperature, PH etc.) causes macromolecular conformation to change or when biochemical reaction takes place on its surface (as target molecule in the detected sample and the probe molecule generation biochemical reaction on the micro-cantilever time), the surface stress of micro-cantilever (surface energy just) thereby can change causes micro-cantilever to produce flexural deformation, just can know that by detecting this distortion whole molecule conformation transition or biochemical reaction carry out the information of process.Compare with isotope labeling with traditional fluorescence labeling, have the characteristics such as real-time monitoring, sensitivity height of non-marked, entire reaction course.
200510134675.6) and a kind of method and device (application number: proposed to utilize optical lever principle detection molecules conformation transition or biochemical reaction to cause the flexural deformation of micro-cantilever 200410103903.9) respectively that utilizes micro-cantilever to carry out biochemistry detection at the method for a kind of monitoring molecule conformation transition of patent of invention (application number:.Laser beam focuses on the free end of micro-cantilever, folded light beam is received and forms visible flare by photoelectric position sensor (PSD), when micro-cantilever flexural deformation, folded light beam deflects, the position that corresponding PSD goes up hot spot can be subjected to displacement, and this displacement is with regard to the flexural deformation of corresponding micro-cantilever.But following shortcoming is being arranged under the light path of this invention: when the buffer solution in the reaction vessel is caused the environment solution of molecule conformation transition or solution to be measured displacement, because the subtle change of solution refractive index, can cause folded light beam to deflect, promptly be coupled with noise signal (the Bumbu G G that the solution refraction index changing causes in the signal of Jian Ceing, Wolkenhauer M, etal.Micromechanical cantilever technique:A tool for investigating theswelling of polymer brushes[J] .Langmuir 2007,23:2203-2207); And only be applicable to single micro-cantilever, promptly once test the deformation signal that can only detect a micro-cantilever.
A kind of micro-cantilever array bio-chip of patent of invention (application number: 200610078269.7) method that has proposed to utilize optically filtering to micro-cantilever array in the displacement of micro-cantilever detect.Parallel beam is radiated at micro-cantilever array, folded light beam is through being received and form visible flare array by charge-coupled device (CCD) behind the 4f filtering system, when micro-cantilever flexural deformation, the light intensity of the last hot spot of CCD can change, this changes the flexural deformation with regard to corresponding micro-cantilever, thereby determines the situation of biochemical reaction on the micro-cantilever.But this detection method is subjected to influence that parasitic light and light source intensity change greatly.
Summary of the invention
The present invention is for avoiding above-mentioned existing weak point, provide a kind of and monitor the method and the device of macromolecular conformation transformation and target molecule and probe molecule biochemical reaction, detect be not coupled refraction index changing and light source intensity of the signal obtain and change the noise signal that causes by detecting many micro-cantilever deformation signals simultaneously; By line polarizing illumination technology, greatly reduce the influence of parasitic light.
The technical scheme that technical solution problem of the present invention is adopted is:
A kind of method of monitoring macromolecular conformation transformation and target molecule and probe molecule biochemical reaction is characterized in that in big molecule, the similar and different probe molecule any one or more is modified at the single side surface of different micro-cantilevers in the micro-cantilever array; Occurred conformation does not change, probe molecule is under the situation of binding target molecule at big molecule, the directional light that light source sends incides on the described micro-cantilever, after its directional light perpendicular to sensitive surface on the micro-cantilever is reflected, received formation flare array by optical receiver assembly, each flare is corresponding one by one with the sensitive surface of each micro-cantilever; When environmental baseline change that the macromolecular conformation cause the micro-cantilever single side surface changes or certain probe molecule of micro-cantilever single side surface when target molecule in the solution to be measured combines, this micro-cantilever occurs bending and deformation, corner changes, reflected light can deflect thereupon, and the position of corresponding flare also can be subjected to displacement thereupon; Causing under the environmental baseline of molecule conformation transition, detecting the poor of the displacement modified macromolecular micro-cantilever and the described macromolecular micro-cantilever displacement of unmodified, judging macromolecular conformation transition situation; According to probe molecule under the same background condition not during binding target molecule and behind the binding target molecule, the change in location of the flare of each micro-cantilever correspondence and displacement size are judged having or not or the size of concentration of target molecule corresponding with probe molecule in the solution to be measured.
The method of transformation of described monitoring macromolecular conformation and target molecule and probe molecule biochemical reaction, its feature is being: the described environmental baseline that causes molecule conformation transition comprises temperature, pressure, irradiate light, adds the physical factors such as change of electromagnetic field; And comprise chemical factors such as organic solvent, urea, guanidine, pH value, ion concentration.
The method of transformation of described monitoring macromolecular conformation and target molecule and probe molecule biochemical reaction is characterized in that: described same background condition comprises temperature, pH value, ion concentration etc.
The method of transformation of described monitoring macromolecular conformation and target molecule and probe molecule biochemical reaction is characterized in that: described big molecule comprises various synthetic macromolecules and natural macromolecular; Described probe molecule comprises antigen, antibody, agglutinin, sugar, Avidin, biotin, acceptor, ligand and DNA etc.
Described synthetic macromolecule such as poly-N-isopropyl acrylamide and natural macromolecular such as protein.
The method of transformation of described monitoring macromolecular conformation and target molecule and probe molecule biochemical reaction, it is characterized in that: in order to improve detection sensitivity, described micro-cantilever has certain initial corner, after being reflected perpendicular to the directional light of sensitive surface on the micro-cantilever, is received by optical receiver assembly.
The method of transformation of described monitoring macromolecular conformation and target molecule and probe molecule biochemical reaction is characterized in that described sensitive surface is the reflector that is positioned on the micro-cantilever, and reflector is positioned at the free end of micro-cantilever.
The method of transformation of described monitoring macromolecular conformation and target molecule and probe molecule biochemical reaction is characterized in that: described micro-cantilever thickness can be 0.1-2 μ m, and length can be 40-1000 μ m, and width is more than or equal to 20 μ m.
The method of transformation of described monitoring macromolecular conformation and target molecule and probe molecule biochemical reaction is characterized in that: described micro-cantilever array can be gone up with SiNx, SiO at silicon chip or glass sheet substrate (thickness can be 200-1000 μ m) according to a conventional method
2, membraneous material etching such as Si is made, as making of MEMS technology.
The method of transformation of described monitoring macromolecular conformation and target molecule and probe molecule biochemical reaction, it is characterized in that: behind the light process filtering pin hole that light source sends, become directional light through collimation lens again, directional light obtains linearly polarized light beam through behind the polarizer, linearly polarized light beam projects on the polarization spectroscope, after the polarization spectro mirror reflection, through quarter wave plate, arrive described micro-cantilever sensitive surface and be reflected and return, pass through aforesaid quarter wave plate once more, pass through quarter wave plate twice totally, change of polarized direction л/2 through behind the described polarization spectroscope, are received by optical receiver assembly then, form the flare array, the veiling glare of other polarization states is suppressed simultaneously.
The method of transformation of described monitoring macromolecular conformation and target molecule and probe molecule biochemical reaction is characterized in that: described optical receiver assembly is a charge-coupled device (CCD).
The method of transformation of described monitoring macromolecular conformation and target molecule and probe molecule biochemical reaction is characterized in that: described light source is the monochromatic source in the 400nm-700nm scope.
A kind of device of monitoring macromolecular conformation transformation and target molecule and probe molecule biochemical reaction, it is characterized in that: include light source, the filtering pin hole is arranged in the light path behind the light source successively, collimation lens, the polarizer, polarization spectroscope, in the reflected light path behind the polarization spectroscope reaction vessel is installed, quarter wave plate is stamped at the reaction vessel top, micro-cantilever array is installed in the reaction vessel, with big molecule, in the similar and different probe molecule any one or more is modified at the single side surface of the different micro-cantilevers in the micro-cantilever array, in the transmitted light path behind the described polarization spectroscope optical receiver assembly is installed.
The device of transformation of described monitoring macromolecular conformation and target molecule and probe molecule biochemical reaction, it is characterized in that: have lens to be positioned at before the optical receiver assembly in the transmitted light path behind the described polarization spectroscope, the target surface of optical receiver assembly is positioned at outside the picture plane of reflector.
In the prior art, micro-cantilever is made up of double layer material usually, and one deck is silicon nitride or silicon, and another layer is a gold, generally is to modify big molecule or probe molecule in gold surface.
The present invention adopts the micro-cantilever array of being made up of a plurality of micro-cantilevers, in big molecule, the similar and different probe molecule one or more are modified at the single side surface of different micro-cantilevers in the micro-cantilever array, that is to say single side surface big molecular modification one or more micro-cantilevers in micro-cantilever array; Perhaps one or more (not of the same race) probe molecules are modified at the single side surface of one or more micro-cantilevers in the micro-cantilever array respectively.
Among the present invention, under the environmental baseline that causes molecule conformation transition, detect the poor of the displacement modified macromolecular micro-cantilever and the described macromolecular micro-cantilever displacement of unmodified, judge macromolecular conformation transition situation; According to probe molecule under the same background condition not during binding target molecule and behind the binding target molecule, the change in location of the flare of each micro-cantilever correspondence and displacement size are judged having or not or the size of concentration of the target molecule corresponding with probe molecule in the solution to be measured; Need in advance under a certain environmental baseline that causes molecule conformation transition, the relation between the displacement of molecule conformation transition and flare to be demarcated or under a certain background condition relation between the displacement of concentration of target molecules and flare to be demarcated.Behind the database that obtains demarcating, the data that obtain according to experiment compare judgement again.
Innovative point of the present invention is:
1, realized detecting the distortion of every micro-cantilever the time in the micro-cantilever array, thereby realized monitoring biochemical reaction on the every micro-cantilever.Utilize the method for pointwise spraying to modify on the single side surface of different micro-cantilevers different molecular detections, can survey multiple corresponding target molecule, promptly realize the monitoring of multiple biochemical reaction.
2, with the single side surface of big molecular modification at the part micro-cantilever, all the other micro-cantilevers are not modified, can obtain simultaneously causing under the same environmental conditions of molecule conformation transition, modify the displacement and the described macromolecular micro-cantilever displacement of unmodified of described macromolecular micro-cantilever.
3, impinge perpendicularly on sensitive surface by parallel beam, eliminated the noise signal that the solution change of refractive produces.
4, by line polarizing illumination technology, reduced the influence of parasitic light greatly.
5, be change in displacement owing to what detect, the influence that detection sensitivity is not changed by light intensity.
6, because micro-cantilever has initial corner, the visible flare on the optics receiving device mainly is to be obtained by sensitive surface (reflector) reflection, has improved accuracy of detection.
Description of drawings
Fig. 1 is one of a inventive method optical detection embodiment structural representation.
Fig. 2 is the spot displacement synoptic diagram of one of embodiment.
Fig. 3 is two structural representations of the inventive method optical detection embodiment.
Fig. 4 is two a spot displacement synoptic diagram of embodiment.
Fig. 5 is the variation synoptic diagram of light beam through polarization spectroscope 5 and quarter wave plate 6 rear polarizer attitudes.
Fig. 6 is micro-cantilever array and enlarged drawing thereof.
Fig. 7 is that target molecule and probe molecule generation biochemical reaction cause micro-cantilever flexural deformation synoptic diagram.
Fig. 8 is that big molecule occurred conformation changes, and causes the synoptic diagram of micro-cantilever distortion.
Fig. 9 is that directional light is radiated at the reflection synoptic diagram on the micro-cantilever with initial corner.
Figure 10 is the visible flare figure that obtains on two times CCD of embodiment.
Figure 11 is the displacement diagram of visible flare on CCD.
Number in the figure: 1, light source, 2, the filtering pin hole, 3, collimation lens, 4, the polarizer, 5, polarization spectroscope, 6, quarter wave plate, 7, reaction vessel, 8, micro-cantilever array, 9, peristaltic pump, 10, constant temperature system, 11, lens, 12, the optics receiving device, 13, micro-cantilever, 14, reflector.
Below pass through embodiment, and in conjunction with the accompanying drawings the present invention is further described.
Embodiment
What Fig. 2 showed is the spot displacement synoptic diagram of one of embodiment, and solid line is the path of folded light beam under the original state, and dotted line is the occur bending and deformation path of back reflection light beam of micro-cantilever, and corresponding hot spot is subjected to displacement on the CCD target surface.
Fig. 4 shows is two spot displacement synoptic diagram of embodiment, and solid line is the path of folded light beam under the original state, and dotted line is the occur bending and deformation path of back reflection light beam of micro-cantilever, and corresponding hot spot is subjected to displacement on the CCD target surface.
What Fig. 5 showed is the variation synoptic diagram of light beam through polarization spectroscope 5 and quarter wave plate 6 rear polarizer attitudes, after the linear polarization illumination light projects polarization spectroscope 5, P polarized light generation transmission, the S polarized light is reflected, reflected light is through quarter wave plate 6, the polarization direction of the quick shaft direction of quarter wave plate 6 and S polarized light is at 45, therefore the S polarized light becomes rotatory polarization and incides on the micro-cantilever array 8 and reflection is returned, pass through aforesaid quarter wave plate 6 once more, change of polarized direction л/2 become the P polarized light, just be polarized spectroscope 5 transmissions, the veiling glare of other polarization states is suppressed simultaneously.
What Fig. 6 showed is micro-cantilever array and enlarged drawing thereof, and micro-cantilever 13 can be the rectangular beam that single leg supports, and also can be three cantilevered corner beams that both legs support, and is connected with reflector 14 at the free end of micro-cantilever 13.
What Fig. 7 showed is the probe molecule of micro-cantilever single side surface modification and the target molecule generation biochemical reaction in the solution to be measured, causes the synoptic diagram of micro-cantilever distortion.
What Fig. 8 showed is that the big molecule occurred conformation that the micro-cantilever single side surface is modified changes, and causes the synoptic diagram of micro-cantilever distortion.
What Fig. 9 showed is that directional light is radiated at the reflection synoptic diagram on the micro-cantilever with initial corner, parallel incident light is perpendicular to the surface of reflector, be radiated at the light generation scattering on the micro-cantilever, the light that only is radiated at reflector could be received by the CCD target surface by vertical reflection.
That Figure 10 shows is the visible flare figure that obtains on two times CCD of embodiment, and each hot spot all sensitive surface with micro-cantilever is corresponding one by one.
What Figure 11 showed is the displacement diagram of visible flare on CCD.The solid line hot spot is represented the position of the preceding hot spot of micro-cantilever distortion, and the dotted line hot spot is represented the position of micro-cantilever distortion back hot spot.It is corresponding with the upper and lower flexural deformation of micro-cantilever respectively that hot spot left and right moved, and on behalf of micro-cantilever, hot spot moves do not occur bending and deformation.
Monitoring target molecule and probe molecule biochemical reaction:
It is the reaction vessel 7 of quarter wave plate 6 that micro-cantilever array 8 places the top, modify probe molecule on the single side surface of micro-cantilever, control the temperature of reaction vessels by the constant temperature system 10 that contacts with container bottom, its temperature stability is ± 0.01K that solution to be measured is by peristaltic pump 9 turnover reaction vessels 7.When the solution that contains target molecule entered reaction vessel 7, probe molecule and target molecule generation biochemical reaction caused the flexural deformation of micro-cantilever, and this distortion can be detected by optical detection apparatus.
Monitoring molecule conformation transition:
Example 1:
It is the reaction vessel 7 of quarter wave plate 6 that micro-cantilever array 8 places the top, modify poly-N-isopropyl acrylamide on the single side surface of part micro-cantilever, by the temperature of the constant temperature system that contacts with container bottom 10 control reaction vessels, its temperature stability is ± 0.01K.When changing the temperature of reaction vessel by constant temperature system 10, the conformation of poly-N-isopropyl acrylamide molecule can change, thereby causes the flexural deformation of micro-cantilever, and this distortion can be detected by optical detection apparatus.
Example 2:
It is the reaction vessel 7 of quarter wave plate 6 that micro-cantilever array 8 places the top, modify trypsase on the single side surface of part micro-cantilever, be full of PBS solution in the reaction vessel 7, by the temperature of the constant temperature system that contacts with container bottom 10 control reaction vessels, its temperature stability is ± 0.01K.When by peristaltic pump 9 PBS solution being replaced into guanidine hydrochloride solution, the conformation of trypsase molecule can change, thereby causes the flexural deformation of micro-cantilever, and this distortion can be detected by optical detection apparatus.
One of optical detection embodiment:
Referring to Fig. 1, Fig. 2 and Fig. 5, filtering pin hole 2 is placed on the rear of light source 1, filtering pin hole 2 just in time is positioned at the front focus of collimation lens 3, and collimated lens 3 collimations of light are parallel illuminating bundle, obtain the linear polarization illumination light behind the adding polarizer 4 in the parallel illuminating bundle that forms.After the linear polarization illumination light projects polarization spectroscope 5, P polarized light generation transmission, the S polarized light is reflected, reflected light is through quarter wave plate 6, and the polarization direction of the quick shaft direction of quarter wave plate 6 and S polarized light is at 45, therefore the S polarized light becomes rotatory polarization and incides on the micro-cantilever array 8, parallel incident light perpendicular to reflector 14 on the micro-cantilever 13 is returned by vertical reflection, pass through aforesaid quarter wave plate 6 once more, pass through quarter wave plate 6 twice totally, change of polarized direction л/2 become the P polarized light, just are polarized spectroscope 5 transmissions, and the veiling glare of other polarization states is suppressed simultaneously.The measuring light that sees through polarization spectroscope 5 is received by optics receiving device 12, and it is corresponding one by one with the sensitive surface of micro-cantilever to form visible flare array and hot spot.Judge the flexural deformation of corresponding micro-cantilever according to the displacement of spot array, the displacement of hot spot can obtain by related algorithm.Because micro-cantilever has initial corner, scattering can take place in the light beam that is radiated on the micro-cantilever 13, and the visible flare on the optics receiving device 12 mainly is to be obtained by reflector 14 reflections.
Two of optical detection embodiment:
Referring to Fig. 3, Fig. 4 and Fig. 5, compare with two of optical detection embodiment, place lens 11 between polarization spectroscope 5 and optics receiving device 12, the measuring light of promptly carrying the micro-cantilever deformation information is through being received by optics receiving device 12 through lens 11 behind the polarization spectroscope 5 again.And optics receiving device target surface does not overlap with the picture plane, and certain defocusing arranged.Only in this way, when micro-cantilever occured bending and deformation, the visible flare that optics receiving device 12 is accepted just can produce displacement.
The end corner of supposing micro-cantilever changes θ, and the displacement of hot spot is Δ s on the corresponding CCD target surface, then:
One of embodiment: Δ s ≈ 2 θ L, L are the distance of reflector to the CCD target surface;
Two of embodiment:
U, f and d are respectively reflector to the distance of lens 11, the focal length and the defocus distance of lens 11.
At typical light path parameter L=50mm, f=100mm, u=2f, under the d=0.5f, the detection sensitivity of two kinds of embodiments is identical.Because the existence of diffraction, the hot spot that one of embodiment obtains is than two big several times of embodiment, and in order on the CCD target surface each hot spot to be separated, the distance in the micro-cantilever array that one of embodiment uses down between the micro-cantilever is wanted enough greatly.
Claims (9)
1. method of monitoring macromolecular conformation transformation and target molecule and probe molecule biochemical reaction is characterized in that in big molecule, the similar and different probe molecule any one or more is modified at the single side surface of different micro-cantilevers in the micro-cantilever array; Occurred conformation does not change, probe molecule is under the situation of binding target molecule at big molecule, the directional light that light source sends incides on the described micro-cantilever, after its directional light perpendicular to sensitive surface on the micro-cantilever is reflected, received formation flare array by optical receiver assembly, each flare is corresponding one by one with the sensitive surface of each micro-cantilever; When environmental baseline change that the macromolecular conformation cause the micro-cantilever single side surface changes or certain probe molecule of micro-cantilever single side surface when target molecule in the solution to be measured combines, this micro-cantilever occurs bending and deformation, corner changes, reflected light can deflect thereupon, and the position of corresponding flare also can be subjected to displacement thereupon; Causing under the environmental baseline of molecule conformation transition, detecting the poor of the displacement modified macromolecular micro-cantilever and the described macromolecular micro-cantilever displacement of unmodified, judging macromolecular conformation transition situation; According to probe molecule under the same background condition not during binding target molecule and behind the binding target molecule, the change in location of the flare of each micro-cantilever correspondence and displacement size are judged having or not or the size of concentration of target molecule corresponding with probe molecule in the solution to be measured.
2. the method for monitoring macromolecular conformation according to claim 1 transformation and target molecule and probe molecule biochemical reaction, its feature is being: the described environmental baseline that causes molecule conformation transition comprises temperature, pressure, irradiate light, adds the physical factors such as change of electromagnetic field; And comprise chemical factors such as organic solvent, urea, guanidine, pH value, ion concentration; Described same background condition comprises temperature, pH value, ion concentration etc.
3. the method for monitoring macromolecular conformation according to claim 1 transformation and target molecule and probe molecule biochemical reaction is characterized in that: described big molecule comprises various synthetic macromolecules and natural macromolecular; Described probe molecule comprises antigen, antibody, agglutinin, sugar, Avidin, biotin, acceptor, ligand and DNA etc.
4. the method for monitoring macromolecular conformation according to claim 3 transformation and target molecule and probe molecule biochemical reaction is characterized in that: described synthetic macromolecule such as poly-N-isopropyl acrylamide and natural macromolecular such as protein.
5. the method for monitoring macromolecular conformation according to claim 1 transformation and target molecule and probe molecule biochemical reaction, it is characterized in that described micro-cantilever has certain initial corner, after being reflected perpendicular to the directional light of sensitive surface on the micro-cantilever, received by optical receiver assembly.
6. monitor the method for macromolecular conformation transformation and target molecule and probe molecule biochemical reaction according to claim 1 or 5, it is characterized in that described sensitive surface is the reflector that is positioned on the micro-cantilever, reflector is positioned at the free end of micro-cantilever.
7. the method for monitoring macromolecular conformation according to claim 1 transformation and target molecule and probe molecule biochemical reaction, it is characterized in that: behind the light process filtering pin hole that light source sends, become directional light through collimation lens again, directional light obtains linearly polarized light beam through behind the polarizer, linearly polarized light beam projects on the polarization spectroscope, after the polarization spectro mirror reflection, through quarter wave plate, arriving described micro-cantilever sensitive surface is reflected and returns, pass through aforesaid quarter wave plate once more, pass through quarter wave plate twice totally, change of polarized direction л/2 through behind the described polarization spectroscope, are received by optical receiver assembly then, form the flare array, the veiling glare of other polarization states is suppressed simultaneously.
8. device of monitoring macromolecular conformation transformation and target molecule and probe molecule biochemical reaction, it is characterized in that: include light source, the filtering pin hole is arranged in the light path behind the light source successively, collimation lens, the polarizer, polarization spectroscope, in the reflected light path behind the polarization spectroscope reaction vessel is installed, quarter wave plate is stamped at the reaction vessel top, micro-cantilever array is installed in the reaction vessel, with big molecule, in the similar and different probe molecule any one or more is modified at the single side surface of the different micro-cantilevers in the micro-cantilever array, in the transmitted light path behind the described polarization spectroscope optical receiver assembly is installed.
9. the device of monitoring macromolecular conformation according to claim 9 transformation and target molecule and probe molecule biochemical reaction, it is characterized in that: have lens to be positioned at before the optical receiver assembly in the transmitted light path behind the described polarization spectroscope, the target surface of optical receiver assembly is positioned at outside the picture plane of reflector.
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103430018A (en) * | 2010-11-01 | 2013-12-04 | Koc大学 | Miniaturized integrated micro electo-mechanical systems (MEMS) optical sensor array |
| CN103675295A (en) * | 2013-12-04 | 2014-03-26 | 上海纳米技术及应用国家工程研究中心有限公司 | Protein pattern identification method based on microcantilever platform |
| TWI642939B (en) * | 2017-09-13 | 2018-12-01 | 誠希科技有限公司 | Optical system for detecting cantilever deformation and applications thereof |
| CN108956587A (en) * | 2018-07-11 | 2018-12-07 | 安徽理工大学 | A method of ionic adsorption is monitored based on micro-cantilever sensing technology |
| CN109142657A (en) * | 2017-06-28 | 2019-01-04 | 中国科学院宁波工业技术研究院慈溪生物医学工程研究所 | A kind of detection analysis instrument |
| CN112113932A (en) * | 2019-06-04 | 2020-12-22 | 易尚明天科技有限公司 | Two-dimensional biological signal quantitative detector |
| US11333661B2 (en) | 2017-06-28 | 2022-05-17 | Cixi Institute Of Biomedical Engineering Ningbo Institute Of Industrial Technology, Chinese Academy Of Sciences | Detection analyzer |
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- 2008-06-28 CN CNA2008100223790A patent/CN101373175A/en active Pending
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103430018A (en) * | 2010-11-01 | 2013-12-04 | Koc大学 | Miniaturized integrated micro electo-mechanical systems (MEMS) optical sensor array |
| CN103430018B (en) * | 2010-11-01 | 2016-05-04 | Koc大学 | Microminiaturized integrated micro-mechano electric system (MEMS) optic sensor array |
| CN103675295A (en) * | 2013-12-04 | 2014-03-26 | 上海纳米技术及应用国家工程研究中心有限公司 | Protein pattern identification method based on microcantilever platform |
| CN103675295B (en) * | 2013-12-04 | 2015-10-28 | 上海纳米技术及应用国家工程研究中心有限公司 | Based on the protein pattern recognition methods of micro-cantilever platform |
| CN109142657A (en) * | 2017-06-28 | 2019-01-04 | 中国科学院宁波工业技术研究院慈溪生物医学工程研究所 | A kind of detection analysis instrument |
| US11333661B2 (en) | 2017-06-28 | 2022-05-17 | Cixi Institute Of Biomedical Engineering Ningbo Institute Of Industrial Technology, Chinese Academy Of Sciences | Detection analyzer |
| TWI642939B (en) * | 2017-09-13 | 2018-12-01 | 誠希科技有限公司 | Optical system for detecting cantilever deformation and applications thereof |
| CN108956587A (en) * | 2018-07-11 | 2018-12-07 | 安徽理工大学 | A method of ionic adsorption is monitored based on micro-cantilever sensing technology |
| CN112113932A (en) * | 2019-06-04 | 2020-12-22 | 易尚明天科技有限公司 | Two-dimensional biological signal quantitative detector |
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