CN1898566A - Optical nanowire biosensor based on energy transfer - Google Patents
Optical nanowire biosensor based on energy transfer Download PDFInfo
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- CN1898566A CN1898566A CN 200480038320 CN200480038320A CN1898566A CN 1898566 A CN1898566 A CN 1898566A CN 200480038320 CN200480038320 CN 200480038320 CN 200480038320 A CN200480038320 A CN 200480038320A CN 1898566 A CN1898566 A CN 1898566A
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Abstract
The present invention relates to the use of the optical properties of nanowires (1) for biomolecule (2) detection. The advantages of using nanowires (1) are a high specific surface area (1a) to bind receptor molecules (3) and size dependent optical properties because of strong quantum confinement of the carriers, i.e. nanowires (1) with different diameters show different colours. The proposed transduction mechanism is based on energy transfer between the biomolecule (2) and the nanowire (1) (or vice versa). Preferably, the target biomolecule (2) is a luminescent biomolecule (2), or said biomolecule (2) is labelled with a dye for quenching of the luminescence of the nanowire (1).
Description
The present invention relates to be used for the method and apparatus that the existence of detection of biological chemistry or biomolecule and/or amount and biochemistry or biological or chemical are analyzed.
The introducing of microarray or biochip makes the analysis generation great variety of DNA (DNA (deoxyribonucleic acid)), RNA (RNA (ribonucleic acid)) and protein.Application examples is human gene somatotype (for example in hospital or by solo practitioner or nurse), bacteria screening, biology and pharmacological research in this way.
Biochip is also referred to as biologic sensor chip, biological microchips, genetic chip or DNA chip, its the simplest form is to adhere to a large amount of different probe molecules on substrate, if mate fully, can be in the clear and definite localized area of chip in conjunction with (bind) molecule or molecule fragment to be analyzed.For example, the dna molecular fragment is in conjunction with a unique complementary DNA (c-DNA) molecule fragment.Can detect the generation of association reaction, for example by adopting the fluorescent marker that combines with molecule to be analyzed.This is provided at the ability of interior a spot of many different moleculars of parallel parsing of short time or molecule fragment.Biochip can hold 1000 or the chemical examination of more a plurality of different molecular fragments.Be expected on the horizon ten years, because the engineering of Human Genome Project and so on and for example, so by adopting the become serviceability of information available of biochip to increase rapidly the follow-up investigation of gene and protein function.
Yet for example can buy the first generation biochip that obtains at present from Affymetrix, substrate only has support function, in the regeneration product afterwards, the expection substrate comprises the electron device of implementing some or all detections and control function (for example measuring temperature and pH).This has the following advantages:
-it makes does not need to adopt costliness and big optical detection system,
-it provides the possibility of the surface density of further increase probe molecule,
-it has improved speed and precision,
-it has reduced required test volume amount, and
-it has reduced labour cost.
The inexpensive method that is provided for diagnosing when biochip and do not consider that the place is (not only in hospital, the place that can also have solo practitioner and/or nurse) time at other, and when the use of biochip causes the total cost of disease treatment to descend, biochip will become mass product.
Nano-sensor based on nano wire has recently been proposed, to be used for high sensitivity and optionally detection of biological and chemical species (species).Nano wire is as the chemical grid in field effect transistor (FET) structure.The surface that molecule is incorporated into nano wire can cause charge carrier (carrier) loss or accumulation in nano wire " volume ", and the change of the nano wire electric conductivity of being followed can be carried out electronic surveying.
At Yi Cui, Qingqiao Wei, " Nanowire nanosensors for highly sensitive and selective detection ofbiological and chemical species (be used for high sensitivity and optionally the nano wire nano-sensor of detection of biological and chemical species) " of Hongkun Park and Charles M.Lieber, Science 293, show that the silicon nanowires with boron-doping of functionalized surface can be used to detect pH, skin rub the protein streptavidin and the Ca of level in 1289 (2001)
2+In the described first aspect of the document, provide the surface that to bear protonation and deprotonation effect by modifying (modify) silicon oxide surface with 3-aminopropyl triethoxysilane (APTES), thereby solid-state FET is converted into the pH nano-sensor with silicon nanowires (SiNW), and wherein the variation of surface charge can be to SiNW gating chemically.On the other hand, by the SiNW functionalization being come the biomolecule sensor is studied with biotin.Utilize this biology sensor, might study the ligand-receptor combination of the biotin-streptavidin of well-characterized.Nano-sensor in the above-mentioned document can high sensitivity and is optionally detected protein in real time.And, in another example, by calmodulin being fixed on the SiNW device to be used to detect Ca
2+Ion has produced Ca
2+Sensor, Ca
2+Ion is important in the bioprocess that activates for example contraction of muscle, protein excretion, cell death and so on.
Aforesaid nano-sensor has some shortcomings when adopting nano wire as chemical grid material.These shortcomings relate to contacting of nano wire and assembly and the nano wire location with respect to contact structures.And CHEM-EFT (chemical sensitive field effect transistor) has some built in problems aspect sensitivity/specificity.The charged biomolecule that exists in analyte will influence the electriferous state of grid, thereby the sensitivity/specificity that can reach is limited.
The purpose of this invention is to provide a kind of the sensitive of detection of biological, biochemistry and/or chemical species and method and apparatus selectively of being used for.
Above-mentioned purpose realizes by the method according to this invention and device.On the one hand, the present invention relates to utilize the optical property of nano wire to come the detection of biological molecule.The transduction mechanism that is proposed shifts based on the energy between biomolecule and the nano wire.
The invention provides a kind of test example that is used for as device at the molecule of analyte, and according to described detection output signal.Described device comprises that at least one has the nano wire of a surface and optical property.The surface of described at least one nano wire has at least one optionally binding site of binding molecule (site).Described device further comprises photoelectric detector, is used on molecular selectivity ground detecting the optical property of nano wire in conjunction with from the teeth outwards the time and being used for output signal.
In one embodiment of the invention, described photoelectric detector can be a phototransistor.Yet described photoelectric detector can also be for example any suitable photoelectric detector, for example photodiode, photocathode or photoconductor.
The molecule of selective binding can be biological example molecule or biologic artifact.In an embodiment of the present invention, described biomolecule can be the luminous organism molecule with first luminescent spectrum.
According to an aspect of the present invention, described nano wire can have second luminescent spectrum.Nano wire can be such, and promptly first luminescent spectrum is different from second luminescent spectrum.And described at least one nano wire can comprise activating ion.
In an embodiment of the present invention, the molecule of described selective binding can be used dye marker.
And, can comprise nano-wire array according to device of the present invention.In one embodiment, at least the first nano wire can be modified with at least one first binding site, and at least the second nano wire can be modified with at least one second binding site.Described first and second binding sites can be in conjunction with different molecules.Like this, might detect more than one molecule simultaneously with identical sensor device.And described device can comprise at least two nano wires with different size.
In one embodiment of the invention, described at least one nano wire can be dispersed in the liquid to form suspending liquid.The suspending liquid of described at least one nano wire can drip deposition (drop-deposited) to the surface.
In another embodiment, described at least one nano wire can be grown from the teeth outwards.This surface for example can be a plane of crystal, and it is that epitaxial growth is needed.
And described at least one nano wire can be grown in the porous matrix.
The present invention provides a kind of method that is used for detection molecules in addition.This method is utilized the optical property of at least one nano wire.In the method according to the invention, between molecule and at least one nano wire or energy conversely shift and to have determined the existence of molecule at least, perhaps if desired, determine the amount of the molecule that exists.In one embodiment, the energy transfer can occur in the luminous organism molecule with first luminescent spectrum and have between at least one nano wire of second luminescent spectrum.According to the present invention, first luminescent spectrum can be different from second luminescent spectrum.Described biomolecule can excite with the light with suitable wavelength.In another embodiment, energy shifts and can occur between the dyestuff with at least one luminous nano wire and labeled molecule, and nano wire is luminous by cancellation thus.In another embodiment of the present invention, described dyestuff or label can be used to transfer the energy to nano wire.
In the Photoelectric Detection of biological and chemical species, adopt nano wire to have several advantages.The first, high specific surface area can be used for the bind receptor molecule, for example enzyme, antibody or fit (aptamere).Second advantage is the optical property that depends on size, and this is because the strong quantum confinement of charge carrier promptly has the different color of nano wire demonstration of different-diameter.The 3rd, optical detecting method has been avoided the contact problems of known nanowire sensor based on electricity.
And, to compare with for example quantum dot, nano wire is easy to handle relatively.In field of nanometer technology, developing a lot of low cost method have the nano-wire array of controlled way with preparation surface.
By the following detailed description also in conjunction with the accompanying drawings, these and other characteristic of the present invention, feature and advantage will become apparent, and described accompanying drawing has illustrated principle of the present invention by way of example.This description only provides for example, and does not limit the scope of the invention.The reference number of below quoting is meant accompanying drawing.
Fig. 1 is the synoptic diagram according to the detection method of first embodiment of the invention.
Fig. 2 is the synoptic diagram according to the detection method of second embodiment of the invention.
Fig. 3 is the synoptic diagram of an apparatus in accordance with one embodiment of the invention.
In different figure, identical reference number is meant same or analogous element.
To describe the present invention with respect to specific embodiment and with reference to some accompanying drawing, but the present invention is not limited to this, but only limits by claims.Described accompanying drawing only is schematically, and is nonrestrictive.In the accompanying drawings, for purposes of illustration, some size of component may have been exaggerated, and proportionally do not draw." comprise " that at term when being used for this instructions and claims, it does not get rid of other element or step.Use indefinite article or definite article for example when " a " or " an ", " the " when relating to singular noun, this also comprises the plural form of this noun, unless expressly stated otherwise.
The invention provides a kind of method and apparatus that is used for check and analysis thing biological example, biochemistry or chemical species.In this manual, described analyte will further be called as biomolecule, and it is as just the example that is used for suitable analyte of the present invention.Any biomolecule that can be bonded to matrix all may be used in this application.Example is:
-nucleic acid: DNA, RNA: the two strands or strand or DNA-RNA hybrid or the DNA-protein complex that have or do not have modification.Nucleic acid array is known.
-have or do not have the protein or the peptide of modification, for example antibody, DNA or rna binding protein matter, enzyme, acceptor, hormone, a signal-proteins.Recently, delivered form (grid) with complete Yeast protein group.
-oligosaccharides or polysaccharide or sugar.
-micromolecule for example itself is cross-linked to matrix or is connected to inhibitor, the part of matrix by spacer molecule.
Method of the present invention utilizes the optical property of nano wire to come the existence of check and analysis thing biological example molecule.The transduction mechanism that is proposed shifts based on the energy of (or conversely) between analyte biological example molecule and the nano wire in the method according to the invention.
Nanometer technology or be called the engineering science branch that the molecule manufacturing is research minimum Design of device and manufacturing sometimes, described minimum device for example is electronic circuit and the mechanical hook-up of setting up on the molecule of material or big molecular level.There is restriction for the number of components that can be manufactured on semiconductor wafer or the chip.Traditionally, circuit is promptly to make by the sequential aggradation and the etching of layer by so-called top-down method.Selectively, also might adopt so-called bottom-up method and self-assembling technique to construct the device of nano-scale scale, described bottom-up method is used the parts that resemble carbon nano-tube, nano wire etc.Like this, can make the have new function device of (being derived from the electron confinement effect).According to the present invention, focus is can be by the nano wire of conduction or semiconductor material manufacturing.The aspect ratio of these nano wires is usually 100 or the more order of magnitude (for example 10000), and the aspect ratio of bar and post (they are produced by top-down method) normally 10 to maximum 100 for example.In order to observe the electron confinement effect that depends on size, the radius of nano wire usually must be less than the Bohr radius of exciton, i.e. 20nm.
Can grow nano wire by for example so-called gas-liquid-solid (VLS) growing method, described method adopts for example has gold grain as the surface at catalytic growth center, referring to XiangfengDuan and Charles, M.Lieber is at the article of Advanced Materials 12,298 (2000).Can synthesize a large amount of binary and ternary III-V by this way, II-VI, IV-IV family element, GaAs for example, GaP, GaN, InP, GaAs/P, InAs/P, ZnS, ZnSe, CdS, CdSe, ZnO, SiGe etc.Can generally control the diameter of nano wire by the size of catalyzer gold grain.If desired, can carry out fine tuning to the diameter of nano wire, in etching process, determine the diameter of nano wire thus by the incident light wavelength by photochemical etching.With regard to regard to the sensor of nano wire, the sensing area is very big with respect to this volume, promptly can obtain a large amount of binding sites and realize that energy shifts on nano wire.Disclose one group of optional method with semiconductor nanowires of required linear diameter (d) of a kind of manufacturing in corresponding patented claim EP03104900.0, described patented claim is incorporated into this by reference.Described optional method may further comprise the steps:
-one group of previously prepared semiconductor nanowires (10 ') is provided, the linear diameter of at least one previously prepared semiconductor nanowires (d ') greater than required linear diameter (d), and
-reduce the diameter of described at least one previously prepared nano wire (10 ') by etching, this etching is brought out by electromagnetic radiation, described electromagnetic radiation is absorbed by described at least one previously prepared nano wire (10 '), select the minimum wavelength of described electromagnetic radiation, so that when described at least one previously prepared nano wire reached required linear diameter (d), the absorption of described at least one previously prepared nano wire significantly reduced.
To describe the optical property of utilizing nano wire 1 in the first embodiment of the present invention shown in Figure 1 comes first of check and analysis thing to select.The surperficial 1a of nano wire 1 utilizes at least one acceptor 3 to modify.Acceptor 3 can be the surface that is for example limited by biomolecule, and this surface is particularly discerned and in conjunction with analyte to be detected.This biomolecule can for example be polymkeric substance, enzyme, antibody or fit.
In first embodiment, at the target luminesceence analysis thing and the nano wire 1 of biological example molecule 2 or be present in energy between the activating ion (not shown in figure 1) in the nano wire 1 and shift a kind of detection means is provided.Described target luminous organism molecule 2 can excite with the light of appropriate first wavelength.When target luminous organism molecule 2 was combined in acceptor 3 on the surperficial 1a of nano wire 1, it can be transferred to its energy nano wire 1 or the activating ion in nano wire 1.Shift by this energy, so nano wire 1 sends radiation with second wavelength.According to shifting to the energy of nano wire 1, and, can detect the existence of target biomolecule thus according to the radiation of sending by nano wire 1 from target luminous organism molecule 2 to be detected.In addition, amount that can also quantitative measurment target biomolecule 2 is for example according to the amount of the light that is sent.Can select the diameter of activating ion or nano wire 1, occur so that the feature luminescent spectrum of nano wire 1 is compared with the emission wavelength of target biomolecule 2 with different wavelength, even it is different with second wavelength to win.Can realize high sensitivity like this.
Therefore the advantage of this embodiment of the present invention is, does not need analyte is carried out label or tag, can reach the skin (pM=10 that rubs
-12M) or even the more sensitivity of decimal magnitude.
The surperficial 1a of nano wire 1 can possess one or more acceptors 3, and all acceptors 3 on a nano wire are all identical, still acceptor 3 differences for different nano wire 1.Like this, can produce not nano wire 1-acceptor 3 on the same group, every group interrelates with particular target biomolecule 2 measuring abilities, and has a luminescent spectrum of specific little band, this luminescent spectrum is different on the same group nano wire 1-acceptor 3 not selectively, for example according to the diameter of relevant nanometer line 1.Utilize not on the same group nano wire 1-acceptor 3 to make might to use method of the present invention come simultaneously qualitative with detect different analytes quantitatively.
In the another embodiment of the present invention of not representing, can realize parallel detector in the accompanying drawings, it comprises the array of nano wire 1, and as mentioned above, at least two nano wires in this array possess different acceptor 3.In this case, on the same group nano wire 1 does not have the luminescent spectrum of different specific little bands.This nano-wire array can be for example by adopting the anodic oxidation aluminium substrate to make.Anodic oxidation produces multiaperture pellumina on the aluminium surface, it has systematized compact arranged hexagonal nano hole, referring to people such as Bandyopadhyay, and Nanotechnology7,360 (1996).Can grow nanowire in these holes, as by C.R.Martin for example at Chem.Mater.8, shown in 1739 (1996).After the depositing nano line, can come selectivity to remove described porous alumina formwork by wet chemical etching.
In this embodiment, might in same measuring process, detect different target biomolecule 2, because, can detect a series of biomolecule 2 simultaneously by measuring single luminescent spectrum based on the array of nano wire at different wavelength places.On measured spectrum, will be visible corresponding to a plurality of peaks of the analyte of a plurality of institute combination.The height at peak is measuring of each analyte amount, is measuring of concentration therefore.
In another embodiment of the present invention shown in Figure 2, the mode that adopts another kind of energy to shift is come detection of biological molecule 4.Herein, energy shifts the luminous cancellation that makes nano wire 1 based on target biomolecule 4.
As in first embodiment, the surperficial 1a of nano wire 1 is modified by at least one acceptor 3.Described acceptor 3 is particularly discerned target biomolecule to be detected 4.Acceptor 3 can be for example enzyme, antibody or fit.In this embodiment, biomolecule 4 can optionally be used dyestuff 5 marks, and described dyestuff 5 can be for example non-fluorescent quenching agent, and for example from the available QSY 7 of Molecular Probes, QSY 9, and QSY 21, and QSY 35.Nano wire 1 has the feature luminescent spectrum.When the biomolecule 6 of mark was bonded to acceptor 3 on specific site or the surperficial 1a at nano wire 1, it made the luminous cancellation of nano wire 1.As already mentioned, it only is optional biomolecule 4 being carried out mark.Yet when biomolecule 4 usefulness dyestuffs 5 marks, cancellation is the most effective.Under one situation of back, alms giver's's (nano wire) emission spectrum and be subjected between the absorption spectrum of main (dyestuff) preferred exist significantly overlapping, further details is referring to P.T.Tran, E.R.Goldman, G.P.Anderson, J.M.Mauro and H.Mattoussi, Phys.Stat.Sol.B 229,427 (2002).
Similar with first embodiment, also might modify, thereby produce not on the same group nano wire-acceptor combination with the surperficial 1a of isoacceptor not to different nano wires 1.Every group of nano wire-acceptor makes up with specific target biomolecule 2 measuring abilities and interrelates, and has the luminescent spectrum of specific little band alternatively, for example depends on the diameter of nano wire 1.Like this, can use method of the present invention to detect different analytes by using not on the same group nano wire-acceptor to make up.
Once more, can adopt the array of nano wire 1 in this embodiment.By modifying, for example when employing has diameter change and has the nano wire 1 of different photoluminescence spectras thus, can detect different target biomolecule 4 simultaneously with the surperficial 1a of different acceptors to nano wire 1.
The advantage of method and apparatus of the present invention is, by adopting nano wire and optical means for example luminous, no longer needs the complex appts structure that requires in the prior art and the contact of nano wire.Utilize method of the present invention, can avoid the sensitivity problem relevant with the biomolecule autoluminescence.
The embodiment of various other biology sensors based on nano wire is included in the scope of the present invention.For example, nano wire 1 can be used for homogeneous solution/suspending liquid.Have for example diameters and be coated with not the nano wire 1 of isoacceptor 3 and can be dispersed in the liquid to form suspending liquid of different sizes, with regard to type of solvent, pH, described liquid and analyte to be detected are compatible.In described suspending liquid, can add analyte and fully mixing.The existence that can draw different target biomolecules the analyte from the change of the luminescent spectrum of nano wire 1.
And, in another embodiment, nano wire 1 can direct growth from the teeth outwards.According to the crystal property of substrate, the growth of nano wire can be at random, promptly with respect to substrate surface, and the not preferred orientation of nano wire, perhaps under epitaxially grown situation, nano wire can be by directed especially.
In another embodiment, nano wire 1 can be grown in the Woelm Alumina matrix.After growth, can optionally remove host material by etching, stay the dense array of the nano wire of arranging perpendicular to substrate.
And nano wire 1 can be fixed on the substrate to form 2D type detecting device, perhaps is fixed on the substrate of shaping to form 3D type detecting device.Therefore, in one embodiment, the suspending liquid of nano wire 1 can drip deposition from the teeth outwards.Like this, form nanometer line network at random from the teeth outwards, it can be used as sensor.
In another embodiment of the present invention, provide the device 10 that comprises nano wire 1 to come detection molecules 2,4.Device 10 shown in Fig. 3 comprises photoelectric detector 11, light filter 12 and at least one nano wire 1, and described nano wire can be modified with at least one acceptor 3.Should be noted that Fig. 3 is only for the purpose that is easy to explain this embodiment, and it is not a limitation of the present invention.
On the semiconductor chip 13 that can comprise well (well) or groove 14, form photoelectric detector 11.In this embodiment, photoconductor 11 can for example be a phototransistor.Yet, also can adopt the photoelectric detector 11 of other type, for example photocathode, photodiode or photoconductor.Light filter 12 is placed at top at photoelectric detector 11.According to the present invention, can adopt specific light filter 12 to light with particular color or wavelength.Like this, the light that only has relevant wavelength just can pass through light filter 12, and all other stray lights all can be removed.
Top at light filter 12 can depositing nano line 1.Nano wire 1 can be for example drips from the suspending liquid of nano wire 1 and is deposited into light filter 12.Discuss as the above embodiments, nano wire 1 can be modified with acceptor 3.Once more, nano wire 1 can with same receptor 3 or not isoacceptor 3 modify.
In an embodiment shown in Figure 3, molecule to be detected can be a luminous organism molecule 2.Described luminous organism molecule 2 can excite with the light with appropriate first wavelength.When luminous organism molecule 2 was bonded to acceptor 3, it can be transferred to its energy the activating ion in nano wire 1 or the nano wire 1.Shift by described energy, so nano wire 1 sends radiation with second wavelength.Pass through light filter 12 with the radiation that second wavelength is sent, and can be detected by photoelectric detector 11 then.The signal output of photoelectric detector 11 can be the indication of the existence of luminous organism molecule 2.Can also come the amount of target biomolecule 2 is carried out quantitative measurment from the light quantity of for example sending.(not shown among Fig. 3) in another embodiment, molecule 4 to be detected can be used dyestuff 5 marks.Nano wire 1 can have the feature luminescent spectrum.When the biomolecule 6 of mark was bonded to acceptor 3 on specific site or the surperficial 1a at nano wire 1, it made the luminous cancellation of nano wire 1.The luminous of 1 cancellation of nano wire can be passed through specific light filter 12, and detected by photoelectric detector 11 then.Once more, the output of photoelectric detector 11 can be the indication of the existence of molecule 4.Also might carry out detection by quantitative to molecule 4.Nano wire 1 luminous cancellation degree can be measuring of molecule 4 amounts.
In another embodiment of the present invention, device 10 can comprise 2 photoelectric detectors 11, and their top all has a light filter 12, and described light filter can be same to each other or different to each other, and deposits nano wire 1 on light filter.By adopting different light filters, promptly to having the light activated light filter of other wavelength, described device 10 can be operated under two different frequencies, therefore can determine different molecule 2,4 simultaneously.
Although should be appreciated that for device according to the present invention preferred embodiment, ad hoc structure and structure and material have been discussed, under the situation that does not depart from scope and spirit of the present invention, can make various variations or modification in form and details.
Claims (21)
1. device comprises: the nano wire (1) that at least one has surface (1a) and has optical property, described surface (1a) possess the binding site (3) that at least one can selective binding molecule (2,4); And photoelectric detector (12), be used for when described molecule (2,4) binds selectively to surface (1a), detecting the optical property of nano wire (1) and being used for output signal.
2. device according to claim 1, wherein said photoelectric detector (12) is a phototransistor.
3. device according to claim 1 and 2, wherein said molecule (2,4) is a biomolecule.
4. device according to claim 3, wherein said biomolecule are the luminous organism molecules with first luminescent spectrum.
5. according to any one described device in the claim 1 to 4, wherein said at least one nano wire (1) has second luminescent spectrum.
6. device according to claim 5, wherein said nano wire (1) is such, promptly first luminescent spectrum is different from second luminescent spectrum.
7. according to any one described device in the claim 1 to 6, wherein said at least one nano wire (1) comprises activating ion in addition.
8. according to any one described device in the claim 1 to 3, wherein said molecule (2,4) comes mark with dyestuff (5).
9. according to any one described device in the claim of front, wherein said device comprises the array of nano wire (1).
10. according to any one described device in the claim of front, wherein at least the first nano wire (1) is modified with at least one first binding site (3), and at least the second nano wire (1) modify with at least one second binding site (3), described first and second binding sites (3) are in conjunction with the molecule (2,4) that differs from one another.
11. according to any one described device in the claim of front, wherein at least two nano wires (1) have different sizes.
12. according to any one described device in the claim of front, wherein said at least one nano wire (1) is dispersed in the liquid to form suspending liquid.
13. device according to claim 12, wherein the suspending liquid dropping with described at least one nano wire (1) deposits on the surface.
14. according to any one described device in the claim 1 to 11, wherein said at least one nano wire (1) is grown from the teeth outwards.
15. according to any one described device in the claim 1 to 11, wherein said at least one nano wire (1) is grown in the porous matrix.
16. according to any one described device in the claim 1 to 15, wherein said device is to be used for check and analysis thing (2,4) nanowire sensor, wherein said at least one binding site (3) can selective binding analyte (2,4), the optical property of wherein said nano wire (1) is used for the detection of analyte (2,4).
17. one kind is used for detection molecules (2,4) method, wherein said method has been utilized the optical property of at least one nano wire (1), and wherein at described molecule (2,4) and between described at least one nano wire (1) or energy conversely shift the existence of determining described molecule (2,4) at least.
18. method according to claim 17, wherein the energy transfer occurs in the luminous organism molecule (2) with first luminescent spectrum and has between described at least one nano wire (1) of second luminescent spectrum, and described first luminescent spectrum is different from described second luminescent spectrum.
19. method according to claim 18, wherein luminous organism molecule (2) utilizes the light with suitable wavelength to excite.
20. method according to claim 17, wherein energy shifts and to occur between the dyestuff (5) with luminous at least one nano wire (1) and described molecule of mark (2,4), described thus nano wire (1) luminous by cancellation.
21. according to any one described method in the claim 17 to 20, wherein said molecule (2,4) be analyte, and between described analyte and described at least one nano wire (1) or energy conversely shift to determine the existence and/or the amount of described analyte (2,4).
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|---|---|---|---|
| EP03104907 | 2003-12-22 | ||
| EP03104900.0 | 2003-12-22 | ||
| EP03104907.5 | 2003-12-22 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104152141A (en) * | 2014-08-27 | 2014-11-19 | 中国科学院理化技术研究所 | Preparation method of trypsin fluorescent chemical sensor |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104152141A (en) * | 2014-08-27 | 2014-11-19 | 中国科学院理化技术研究所 | Preparation method of trypsin fluorescent chemical sensor |
| CN104152141B (en) * | 2014-08-27 | 2016-06-01 | 中国科学院理化技术研究所 | The preparation method of trypsinase fluorescence chemical sensor |
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Application publication date: 20070117 |