CN108089061A - Suitable for the Terahertz markless detection method and apparatus of biochemistry fluid sample - Google Patents
Suitable for the Terahertz markless detection method and apparatus of biochemistry fluid sample Download PDFInfo
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- CN108089061A CN108089061A CN201711345667.5A CN201711345667A CN108089061A CN 108089061 A CN108089061 A CN 108089061A CN 201711345667 A CN201711345667 A CN 201711345667A CN 108089061 A CN108089061 A CN 108089061A
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
- G01R27/00—Arrangements for measuring resistance, reactance, impedance, or electric characteristics derived therefrom
- G01R27/02—Measuring real or complex resistance, reactance, impedance, or other two-pole characteristics derived therefrom, e.g. time constant
- G01R27/26—Measuring inductance or capacitance; Measuring quality factor, e.g. by using the resonance method; Measuring loss factor; Measuring dielectric constants ; Measuring impedance or related variables
- G01R27/2617—Measuring dielectric properties, e.g. constants
- G01R27/2623—Measuring-systems or electronic circuits
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
- G01R27/00—Arrangements for measuring resistance, reactance, impedance, or electric characteristics derived therefrom
- G01R27/02—Measuring real or complex resistance, reactance, impedance, or other two-pole characteristics derived therefrom, e.g. time constant
- G01R27/26—Measuring inductance or capacitance; Measuring quality factor, e.g. by using the resonance method; Measuring loss factor; Measuring dielectric constants ; Measuring impedance or related variables
- G01R27/2617—Measuring dielectric properties, e.g. constants
- G01R27/2682—Measuring dielectric properties, e.g. constants using optical methods or electron beams
Abstract
The invention discloses a kind of Terahertz markless detection methods suitable for biochemistry fluid sample, and provide detection device and its manufacture craft, the detection device includes Terahertz rectangular-wave resonant cavity, microchannel and detector slot, microflow channels are inserted in microchannel, terahertz detector is inserted in detector slot；Emit THz wave in the one side of waveguide resonant cavity；Sample to be tested is introduced in microchannel, at this moment the electromagnetic field in waveguide resonant cavity generates disturbance, and the resonant frequency and quality factor for causing resonator change；The variation of the resonant frequency and quality factor of waveguide resonant cavity before and after being added in by detector measurement sample draws the complex dielectric permittivity of sample to be tested.The present invention detects biochemistry fluid sample using Terahertz Technology, has the characteristics that detection sensitivity is high, accuracy of detection is high, sample requirements are small, while the detection device has the advantages that high integration, miniaturization and portable, has a extensive future.
Description
Technical field
The present invention relates to the detection technique of biochemical samples, especially a kind of Terahertz markless detection method and dress
It puts.
Background technology
Up to now, the detection method for being widely used in biochemical samples is with labels such as fluorescence or isotopes mostly
Based on have mark detection method, pass through the detection for object of externally labelling so as to indirectly infer property and the spy of original target molecule
Point.Although it is this have the advantages that mark detection method have it is simple and convenient, easily operated, image taking speed is fast, spatial resolution is high,
It is since the introducing of mark molecule inevitably destroys the structure and activity of target source molecule, and the efficiency of transmitting fluorescence
With the different and different of reactant, additionally there are the problems such as photobleaching.Therefore Yi Shang bottleneck has limited mark detection method
In the further development of biochemical samples detection field.
In recent years, Terahertz Technology is increasingly becoming a kind of important solutions of biochemical samples markless detection, this
It is the following distinctive performance advantages having due to its own：(1) terahertz emission is completely non-ionized, and photon energy is extremely low,
Ionization injury will not be generated to most large biological molecules, biological cell and tissue, is particularly suitable for nondestructive inspection (NDI)；(2) nucleic acid
With the weak interaction of protein and other (such as：Hydrogen bond, Van der Waals force etc.), skeletal vibration and dipole rotation etc. just
Benefit is in Terahertz spectral range, therefore terahertz wave band can disclose the large biological molecule that other electromagnetic wave bands can not detect
It is internal and between important information；(3) terahertz detection is a kind of pure physical process, without any indicia means.Therefore, utilize
Terahertz Technology is detected biochemical samples, can detect the spectral information of substance in real time, realizes unmarked, not damaged
And non-ionized sensing.At present, it is to pass through terahertz mostly to carry out markless detection to biochemical samples using Terahertz Technology
Hereby time-domain spectroscopy system is realized, but this method is mainly for solid sample, it usually needs substantial amounts of sample, while spectrum point
Resolution and spatial resolution are relatively low, and accuracy in detection and accuracy be not high, and in addition experimental provision is bulky, integrated level and portable
Property is poor, and practicability is not high in many actual field diagnostic applications.
In conclusion detection method or profit are marked in either traditional having in biochemical samples detection field at present
With the markless detection technology of terahertz time-domain spectroscopy system, some problems are all individually present.
The content of the invention
The present invention provides a kind of real-time, the markless detection of the new biochemistry fluid sample based on Terahertz Technology
Method, this method have the characteristics that detection sensitivity is high, accuracy of detection is high, sample requirements are small.
To achieve the above object, technical scheme is as follows：
A kind of Terahertz markless detection method suitable for biochemistry fluid sample, including：
Detection device is provided, the detection device includes Terahertz rectangular-wave resonant cavity, microchannel and detector slot,
Microflow channels are inserted in microchannel, terahertz waveguide detector is inserted in detector slot；
Emit THz wave in one side of the waveguide resonant cavity away from detector；
Sample to be tested is introduced in microchannel, at this moment the electromagnetic field in waveguide resonant cavity generates disturbance, causes resonator
Resonant frequency and quality factor change；
The variation of the resonant frequency and quality factor of waveguide resonant cavity, draws and treats before and after being added in by detector measurement sample
The complex dielectric permittivity of sample.
In a wherein embodiment, if the resonant frequency of waveguide resonant cavity is respectively f before and after sample addition0、fS, quality because
Son is respectively Q0、QS, then the real part ∈ ' of sample to be tested complex dielectric permittivity and imaginary part ∈ " are acquired respectively by following equation：
Wherein VCFor the volume of resonator, VSFor the volume of sample to be tested.
The present invention also provides a kind of Terahertz markless detection device suitable for biochemistry fluid sample, including first
Part and second portion are relatively fixed the apparatus main body cooperatively formed, microflow channels and terahertz waveguide detector, first portion with
Second portion is equipped with silicon base, and the silicon base horizontal direction centre position is equipped with both sides conduit and intermediate channel, Vertical Square
The miniflow hemichannel of perforation is equipped with to centre position, lateral location is equipped with vertically through the detector to wherein one side conduit half
Slot；It is respectively equipped between the both sides conduit and intermediate channel and couples half bore；The first portion and second portion are relatively fixed
After cooperation, the intermediate channel in intermediate channel and second portion in first portion is connected to each other to form Terahertz rectangular waveguide resonance
Chamber, the both sides conduit in first portion is connected to each other to form waveguiding structure with the both sides conduit on second portion, in first portion
Miniflow hemichannel on miniflow hemichannel and second portion is connected to each other to form microchannel, half slot of detector in first portion with
Half slot of detector on second portion is connected to each other to form detector slot；Microflow channels are located in microchannel, and detector is located at detection
In tank.
In a wherein embodiment, the coupling half bore, miniflow hemichannel and half slot of detector have same depth.
In a wherein embodiment, the inner wall of the waveguide resonant cavity, coupling aperture and waveguiding structure is plated equipped with gold plate.
In a wherein embodiment, the first portion and second portion are relatively fixed cooperation by bonding pattern.
In a wherein embodiment, the detection device making step includes：
The thin metal film of last layer is plated on a silicon substrate, photoresist is then got rid of above, with being printed on waveguiding structure and waveguide
The photomask board I of resonator figure exposes under ultraviolet light, forms figure to photoresist, photoresist is cleaned with developer solution, expose
The waveguiding structure etched and waveguide resonant cavity position are needed, is then etched and provided on a silicon substrate with deep reaction ion etching method
There are the waveguiding structure and waveguide resonant cavity of certain depth；
Photoresist is filled up in the waveguiding structure and waveguide resonant cavity that are first formed in the first round, then, face is got rid of on the metal layer
The thin photoresist of the second layer, and form figure with the photomask board II for the figure for being printed on coupling aperture, microchannel and detector slot
Shape etches the coupling half bore with slight depth, miniflow half with deep reaction ion etching method again afterwards and leads on a silicon substrate
Half slot of road and detector disposes extra photoresist and carries out wafer coupons afterwards；
Microflow channels are inserted at miniflow hemichannel, terahertz waveguide detector is inserted at half slot of detector, and completes two
The production process for being relatively fixed cooperation, completing whole device of part-structure.
In a wherein embodiment, the making step of the detection device further includes：In the waveguide resonant cavity, coupling aperture
It is gold-plated with the inner wall of waveguiding structure.
The beneficial effects of the invention are as follows：
The present invention detects biochemistry fluid sample using Terahertz Technology, has detection sensitivity height, accuracy of detection
High, the features such as sample requirements are small, while the detection device has the advantages that high integration, miniaturization and portable, before
Scape is wide.
Description of the drawings
Fig. 1 is that detection device of embodiment of the present invention first portion or second portion are inserted into the schematic diagram after microflow channels.
Fig. 2 is the schematic diagram of the first making step of detection device of embodiment of the present invention first portion or second portion.
Fig. 3 is the schematic diagram of the second making step of detection device of embodiment of the present invention first portion or second portion.
Specific embodiment
Below in conjunction with the accompanying drawings and example, the present invention will be further described.
In the present embodiment, as shown in Figure 1 to Figure 3, filled suitable for the Terahertz markless detection of biochemistry fluid sample
It puts including Terahertz rectangular-wave resonant cavity, microchannel and detector slot.Wherein, microchannel is located at along direction shown in figure
The broadside midline (i.e. resonator internal electric field most strength) of rectangular-wave resonant cavity.
During specific implementation, detection device includes first portion and second portion is relatively fixed the apparatus main body cooperatively formed
(Fig. 1 only shows first portion and one in second portion), microflow channels 9 and terahertz waveguide detector (not shown).First
Part is equipped with silicon base 1 with second portion, and the 1 horizontal direction centre position of silicon base is equipped with both sides conduit and medial launder
Road makes silicon base 1 form the first transverse part 2, the second transverse part 3 positioned at lower half, vertical connection first positioned at the first half
The first longitudinal direction portion 4 of 2 and second transverse part 3 of transverse part and second longitudinal direction portion 5.The 1 vertical direction interposition of silicon base installs
There is the miniflow hemichannel 6 of perforation, lateral location is equipped with vertically through half slot 7 of detector to wherein one side conduit；The both sides
It is respectively equipped between conduit and intermediate channel and couples half bore 8.
After the first portion and second portion are relatively fixed cooperation, in the intermediate channel and second portion in first portion
Intermediate channel be connected to each other to form Terahertz rectangular-wave resonant cavity, two on the both sides conduit in first portion and second portion
Side channel road is connected to each other to form waveguiding structure, and the miniflow hemichannel 6 in first portion is opposite with the miniflow hemichannel 6 on second portion
It connects to form microchannel, half slot 7 of detector in first portion is connected to each other to form detection with half slot 7 of detector on second portion
Tank；Microflow channels 9 are located in microchannel, and detector is located in detector slot.
In a wherein embodiment, the coupling half bore 8, miniflow hemichannel 6 and half slot 7 of detector have same depth.
In a wherein embodiment, the inner wall of the waveguide resonant cavity, coupling aperture and waveguiding structure is plated equipped with gold plate.
In a wherein embodiment, the first portion and second portion are relatively fixed cooperation by bonding pattern.
The operation principle of the present embodiment is described as follows.
Emit THz wave in one side (i.e. left side in Fig. 1) of the waveguide resonant cavity away from detector, work as microchannel
During middle introducing liquid sample, the electromagnetic field in waveguide resonant cavity generates disturbance, causes the resonant frequency f of resonator0And product
The parameters such as prime factor Q change, thus by measure sample add in before and after waveguide resonant cavity resonant frequency and quality factor
Variation, you can be finally inversed by the dielectric constant of sample to be tested.Since microchannel is small-sized (micron order), resonance is introduced
Fluid sample amount very little (picoliters grade) in chamber, can be analyzed according to perturbation theory.The offset of usual resonant frequency is with answering
The real part (dielectric constant) of dielectric constant is related, the knots modification of quality factor q and imaginary part (loss tangent) phase of complex dielectric permittivity
It closes.
Rectangular waveguide broadside size is made as a, narrow side size is b, cavity length d.According to boundary condition, in resonance frequency
At rate, the length d of resonator must be the integral multiple (δ) of half waveguide wavelength.The resonant frequency of resonator is：
Wherein c is the light velocity, μrAnd ∈rIt is the magnetic conductivity and dielectric constant of packing material in resonator.M, n and δ are y respectively,
The standing wave graphic change number of x and z directions.Fundamental resonance pattern is TE10δMould, the natural quality factor Q of resonator is by cavity
The dielectric loss of packing material and the conductance loss of cavity wall determine.Assuming that it is vacuum in resonator, quality factor is：
Wherein η is intrinsic impedance, RSIt is the surface resistivity of cavity wall.
When complex dielectric permittivity is ∈rDuring the sample to be tested insertion resonator of=∈ '-j ∈ ", the electromagnetic property of resonator is (humorous
Vibration frequency f0And quality factor q0) will change (fSAnd QS).Since sample size is very small (picoliters grade), according to perturbation theory,
The complex dielectric permittivity of sample can be derived by more than parameter change amount：
Wherein VCFor the volume of resonator, VSFor the volume of sample to be tested.
From above formula, the variation of resonant frequency and quality factor in resonator before and after sample to be tested is added in by measuring,
It can obtain the complex dielectric permittivity of sample.
The production process and technique of the present embodiment detection device are described as follows.
Detection device of the present invention is divided into identical two parts (per part all as schemed along waveguiding structure broadside midline
Shown in 1), two parts are made in two silicon bases using micro fabrication respectively, then in waveguiding structure, resonator
With it is gold-plated on the inner wall of coupling aperture, finally again by two part bonding get up forming apparatus agent structure.
Specific micro fabrication flow is as shown in Figures 2 and 3.Due to waveguiding structure, resonator and miniflow in the device
Hemichannel has different depth, therefore the etching of silicon base divides two-wheeled to carry out, and is utilized respectively two photomask boards (I and II),
Mask plate I is printed on the figure of waveguide resonant cavity and waveguiding structure, and mask plate II is printed on microchannel, coupling aperture and detector slot
Figure.
First round etching process：The thin metal film (Ni or Al) of last layer is plated on a silicon substrate, and photoetching is then got rid of above
Glue is exposed under ultraviolet light with photomask board I, and figure is formed to photoresist, cleans photoresist with developer solution, exposing needs to etch
Waveguiding structure and resonator position, then etched on a silicon substrate with certain depth with deep reaction ion etching method
Waveguiding structure and resonator, as shown in Figure 2.
Second wheel etching process：AZ4620 photoresists are filled up in the waveguiding structure and resonator that are first formed in the first round.So
Afterwards, the thin photoresist of the second layer is got rid of in face on the metal layer, and forms figure with mask plate II.It is carved again with deep reactive ion afterwards
Etching method etches half slot of the coupling half bore with slight depth, miniflow hemichannel and detector on a silicon substrate.It removes afterwards
Fall extra photoresist and complete wafer coupons.As shown in Figure 3.
After the completion of produced by micro processing, by the inner wall of waveguiding structure, coupling aperture resonant cavity, gold-plated (thickness should be greater than 5-6 times
Terahertz skin depth), microflow channels and terahertz waveguide detector are inserted into respectively at half slot of miniflow hemichannel and detector, and
The back bonding of two-part structure is completed, as shown in Figure 1, completing the production process of whole device.
In simple terms, the detection device production process that the present embodiment proposes：(a) formed after first round etching process deeper
Apparatus main body；(b) half slot of coupling aperture, miniflow hemichannel and detector is formed after the second wheel etching process；(c) waveguide inner wall plates
Gold is inserted into microflow channels and terahertz waveguide detector at half slot of miniflow hemichannel and detector, and completes two parts knot respectively
The back bonding of structure.
The present embodiment has the following advantages due to taking above technical scheme：
1) sample consumption is significantly reduced, it can be achieved that the detection of skin upgrading sample；
2) detection sensitivity and accuracy are high；
3) minimize, integrated level is high, good portability, whole device size only one laptop size.
Claims (8)
- A kind of 1. Terahertz markless detection method suitable for biochemistry fluid sample, which is characterized in that including：Detection device is provided, the detection device includes Terahertz rectangular-wave resonant cavity, microchannel and detector slot, will be micro- Flow tube is inserted in microchannel, and terahertz waveguide detector is inserted in detector slot；Emit THz wave in one side of the waveguide resonant cavity away from detector；Sample to be tested is introduced in microchannel, at this moment the electromagnetic field in waveguide resonant cavity generates disturbance, causes the resonance of resonator Frequency and quality factor change；The variation of the resonant frequency and quality factor of waveguide resonant cavity, draws and treats test sample before and after being added in by detector measurement sample The complex dielectric permittivity of product.
- 2. detection method according to claim 1, which is characterized in that set the resonance frequency of waveguide resonant cavity before and after sample adds in Rate is respectively f0、fS, quality factor is respectively Q0、QS, then the real part ∈ ' of sample to be tested complex dielectric permittivity and imaginary part ∈ " respectively by Following equation acquires：Wherein VCFor the volume of resonator, VSFor the volume of sample to be tested.
- 3. a kind of Terahertz markless detection device suitable for biochemistry fluid sample, which is characterized in that including first Divide and second portion is relatively fixed the apparatus main body cooperatively formed, microflow channels (9) and terahertz waveguide detector；First portion with Second portion is equipped with silicon base (1), and silicon base (1) the horizontal direction centre position is equipped with both sides conduit and intermediate channel, Vertical direction centre position is equipped with the miniflow hemichannel (6) of perforation, and lateral location is equipped with vertically through to wherein one side conduit Half slot of detector (7)；It is respectively equipped between the both sides conduit and intermediate channel and couples half bore (8)；The first portion and After two parts are relatively fixed cooperation, the intermediate channel in intermediate channel and second portion in first portion is connected to each other to form terahertz Hereby rectangular-wave resonant cavity, the both sides conduit in first portion are connected to each other to form waveguide junction with the both sides conduit on second portion Structure, the miniflow hemichannel (6) in first portion are connected to each other to form microchannel with the miniflow hemichannel (6) on second portion, the Half slot of detector (7) in a part is connected to each other to form detector slot with half slot of detector (7) on second portion；Microflow channels (9) it is located in microchannel, detector is located in detector slot.
- 4. detection device according to claim 3, which is characterized in that it is described coupling half bore (8), miniflow hemichannel (6) and Half slot of detector (7) has same depth.
- 5. detection device according to claim 3, which is characterized in that the waveguide resonant cavity, coupling aperture and waveguiding structure Inner wall plate equipped with gold plate.
- 6. detection device according to claim 3, which is characterized in that the first portion and second portion pass through bonding side Formula is relatively fixed cooperation.
- 7. detection device according to claim 3, which is characterized in that the detection device making step includes：The thin metal film of last layer is plated on a silicon substrate, photoresist is then got rid of above, with being printed on waveguiding structure and wave guide resonance The photomask board I of chamber figure exposes under ultraviolet light, and figure is formed to photoresist, cleans photoresist with developer solution, exposing needs The waveguiding structure of etching and waveguide resonant cavity position, are then etched on a silicon substrate with deep reaction ion etching method with one The conduit of depthkeeping degree；Photoresist is filled up in the conduit first formed in the first round, then, the thin photoresist of the second layer is got rid of in face on the metal layer, is used in combination The photomask board II of the figure of coupling aperture, microchannel and detector slot is printed on to form figure, uses deep reactive ion again afterwards Lithographic method etches half slot of the coupling half bore with slight depth, miniflow hemichannel and detector, Zhi Houqing on a silicon substrate It removes extra photoresist and carries out wafer coupons；Microflow channels are inserted at miniflow hemichannel, terahertz waveguide detector is inserted at half slot of detector, and completes two parts The production process for being relatively fixed cooperation, completing whole device of structure.
- 8. detection device according to claim 7, which is characterized in that the making step of the detection device further includes： The inner wall of the waveguide resonant cavity, coupling aperture and waveguiding structure is gold-plated.
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| CN109490245A (en) * | 2019-01-04 | 2019-03-19 | 上海理工大学 | Acetone liquid concentration detection method based on terahertz time-domain spectroscopic technology |
| CN109765516A (en) * | 2019-01-04 | 2019-05-17 | 西安交通大学 | A kind of microwave cavity measurement sheet resistance/conductivity calibration method |
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