CN108828014A - Sensor chip, marker detection device and detection method - Google Patents
Sensor chip, marker detection device and detection method Download PDFInfo
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- CN108828014A CN108828014A CN201810438206.0A CN201810438206A CN108828014A CN 108828014 A CN108828014 A CN 108828014A CN 201810438206 A CN201810438206 A CN 201810438206A CN 108828014 A CN108828014 A CN 108828014A
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- G—PHYSICS
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N22/00—Investigating or analysing materials by the use of microwaves or radio waves, i.e. electromagnetic waves with a wavelength of one millimetre or more
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- G—PHYSICS
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/02—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/02—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance
- G01N27/22—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance by investigating capacitance
- G01N27/221—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance by investigating capacitance by investigating the dielectric properties
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Abstract
Present invention discloses a kind of sensor chip, marker detection device and detection method, sensor chips to include：Nested type open-loop resonator and microstrip transmission line, the nested type open-loop resonator includes the nesting of multiple split rings, the opening of the multiple split ring is sequentially arranged at intervals and orientation and perpendicular to opening edge, and the nested type open-loop resonator and the microstrip transmission line constitute LC resonance device.The marker detection device and detection method obtained based on this, has the advantages that easy to detect, high sensitivity, accurate, fireballing.
Description
Technical field
The present invention relates to detection field more particularly to a kind of sensor chips based on wireless radiofrequency detection technique, mark
Analyte detection device and detection method.
Background technique
In the several years in past, the progress based on Meta Materials, the application that people have carried out numerous associated fields is ground
Study carefully.Meta Materials are all widely used in many ambits, such as optics, electromagnetism and microwave engineering.Half-wave resonator
Have the characteristics that size is small, electrical characteristics are stable, the structure of Meta Materials transmission line is compact to design, these performances make people are integrated to have spy
The microwave device of different property is possibly realized.In small size microwave device research field, the microwave component of Meta Materials transmission line has weight
It influences.Therefore, Meta Materials become a hot research topic in the application study of microwave band, and Recent study personnel deliver
Many related research results.
There is no a completely specified definition for Meta Materials, need to consider different situations.Periodical and abnormal electromagnetic property
It is the necessary factor that a structure is defined as to metamaterial structure.Meta Materials are thought of as period or quasi-periodic structure herein,
By designing metamaterial structure, material is made to show controllable electromagnetic property.
The unit size structure cell of metamaterial structure is referred to alternatively as electromagnetism structure cell (or electro-magnetic bandgap electromagnetic
Band-gaps-EBGs), alternatively referred to as Effective medium.When its period size and wavelength are a magnitude, it is considered as electromagnetism
Structure cell, by reaction between the cells, frequency band gap becomes larger, and is called Prague dispersion (Bragg dispersion).On the contrary,
It is much smaller than when the period of structure cell than wavelength, is defined as Effective medium, which seems identical as electromagnetic field, therefore, has shown
Imitate electromagnetic property.It is worth noting that, effective electromagnetic property of all Effective mediums is not necessarily identical, Meta Materials are presented in this
The characteristic that can not have in nature out.
Left-handed medium (Left-Handed media or LHM) in Effective medium is used to characterize electromagnetic wave in Meta Materials
The dielectric constant (dielectric permittivity, ε) and magnetic conductivity (magnetic propagated in the medium
Permeability, μ) simultaneously be negative the case where.Dielectric constant and conductivity are negative (double negative, DNG)
Medium occur, make it possible a variety of new applications.
In microwave spectrum frequency range, the radio frequency bio-sensing based on resonance structure is studied to obtain extensive concern.The research is in nothing
Simple, quick biomacromolecule detection is realized on line sensing platform.Before this, most of conventional radio frequencies and optical bio
Sensing technology, it usually needs use specific label, such as fluorescent molecule, magnetic or metallic or other in antibody contact
Surface is handled to improve the label substance of signal distinguishing.Although these technologies can be effectively detected and analyze biomolecule
And its cohesive process, but there are still some disadvantages, for example need complicated equipment, cumbersome sample preparation procedure, and cannot show
Field is verified, excessive material consumption.In microwave and Terahertz frequency range, people constantly propose simple and straight to cope with these problems
The resonant biosensor scheme detected using label technique is exempted from connect.
As shown in Figure 1, biosensor is defined as biological sensing element, consist of three parts substantially：Detector 3 passes
Sensor 5 and signal controller 7, detector 3 are connect by bilayer 4 with sensor.Detector 3 works in sensitive biological elements
In environment, such as enzyme, antibody, nucleic acid, cell receptor or micro-assembly robot, wherein substance to be detected includes impurity 1 and object 2, mesh
Mark object 2 can be matched with detector 3, physically or chemically be measured so that the signal measured is converted to by sensor 5, with the transmitting of electric signal 6
It to signal controller 7 and exports, 6 amplitude of electric signal that normally result is shown can be proportional to concentration and the electricity spy of a certain predetermined substance
Property.
However, these schemes still remain distinct disadvantage, such as complex manufacturing process, production funds are expensive, elapsed time mistake
It is long.
Summary of the invention
The object of the present invention is to provide a kind of sensor chip, marker detection device and detection methods, realize to be measured
Quick, the sensitive and accurate detection of marker in solution.
The object of the present invention is to provide a kind of sensor chip, marker detection device and detection methods, realize to be measured
Quick, the sensitive and accurate detection of the dielectric property of solution.
In order to solve the above technical problems, the present invention provides a kind of sensor chip, including：Nested type open-loop resonator and micro-
Band transmission line, the nested type open-loop resonator includes the nesting of multiple split rings, the opening of the multiple split ring successively between
LC resonance is constituted every arrangement and orientation and perpendicular to opening edge, the nested type open-loop resonator and the microstrip transmission line
Device.
Optionally, for the sensor chip, the split ring is in lack the rectangular-shaped of one side.
Optionally, for the sensor chip, in the multiple split ring, it is opposite with the opening edge on one side altogether
With the opposing edge portions of the opening edge two sides share.
Optionally, for the sensor chip, the width of each opening edge is 0.05~0.1mm, adjacent institute
Stating the spacing between opening edge is 0.05~0.1mm, and the longest edge lengths of the opening edge two sides are 1.5~2mm.
Optionally, for the sensor chip, the resonance frequency of the sensor chip is 5~20GHz.
The present invention also provides a kind of marker detection device, including sensor chip as described above, solution fixing layer and
The sensor chip and the solution fixing layer, institute is isolated in the sensor core on piece in hydrophobic layer, the hydrophobic layer setting
It states solution fixing layer and is provided with the cavity towards the sensor chip to accommodate solution to be measured.
Optionally, for the marker detection device, the hydrophobic layer with a thickness of 2.5 μm~10 μm.
Optionally, for the marker detection device, the material of the hydrophobic layer includes benzocyclobutene.
Optionally, for the marker detection device, the material of the solution fixing layer includes polydimethylsiloxanes
Alkane.
The present invention also provides a kind of marker detection methods, using marker detection device as described above, this method packet
It includes：
Solution to be measured is provided, resonance characteristic when being arranged in the cavity, and measuring with the solution to be measured；And
Resonance characteristic is corresponding with resonant network-marker sample database when will have the solution to be measured, described in acquisition
The concentration of solution to be measured.
Optionally, for the marker detection method, the resonance characteristic includes impedance real part bandwidth, centre frequency
And resonance peak.
The present invention also provides a kind of marker detection methods, using marker detection device as described above, this method packet
It includes：
Solution to be measured is provided, resonance characteristic when being arranged in the cavity, and measuring with the solution to be measured；And
It makes comparisons, obtains described to be measured with the resonance characteristic of marker detection device described when not having the solution to be measured
The dielectric property of solution.
It optionally, include obtaining frequency shift (FS) when the resonance characteristic is made comparisons for the marker detection method
F is measured, is expressed as：
Wherein, L=L0+△L(L0>>△ L), C=C0+△C(C0>>△ C), f0、L0And C0The resonance frequency of marker detection device when respectively without the solution to be measured
Rate, inductance and capacitor, Δ L are inductance knots modification, and Δ C is capacitance change.
Sensor chip in the present invention, including：Nested type open-loop resonator and microstrip transmission line, the nested type are opened
Ring resonator includes the nesting of multiple split rings, and the opening of the multiple split ring is sequentially arranged at intervals and orientation and vertical
In opening edge, the nested type open-loop resonator and the microstrip transmission line constitute LC resonance device.The marker obtained based on this
Detection device and detection method have the advantages that easy to detect, high sensitivity, accurate, fireballing, and its advantages are specifically wrapped
It includes：
(1) less radio-frequency detection technique, accurate, the quick and highly sensitive realization marker detection of energy are used.Using RLC net
The variation of network resonance characteristic can significantly reflect the small-signal applied before and after solution to be measured, and customary DC resistance is avoided to survey
Impedance signal variation is flooded by the impedance greatly of system background when examination, while radiofrequency signal also has stronger anti-interference ability.
(2) when being detected using the device of the invention, have the advantages that convenient, quick detection and other conventional methods
It compares, detection process is simpler, conveniently, and detection speed is also very fast, once capture, can directly measure result.
(3) the device of the invention precision is high, at low cost, and detection program is few, simply, conveniently, is suitable for large sample, extensive
It promotes the use of, there is important application value.
Detailed description of the invention
Fig. 1 is a kind of schematic diagram of biosensor of the present invention；
Fig. 2 is the schematic diagram of the nested type open-loop resonator of sensor chip in one embodiment of the invention；
Fig. 3-Fig. 6 is the schematic diagram of marker detection device in one embodiment of the invention；
Fig. 7 is the connection schematic diagram of marker detection device in one embodiment of the invention.
Specific embodiment
Sensor of the invention chip, marker detection device and detection method are carried out below in conjunction with schematic diagram more detailed
Thin description, which show the preferred embodiment of the present invention, it should be appreciated that those skilled in the art can modify and be described herein
The present invention, and still realize advantageous effects of the invention.Therefore, following description should be understood as those skilled in the art
Member's is widely known, and is not intended as limitation of the present invention.
The present invention is more specifically described by way of example referring to attached drawing in the following passage.It is wanted according to following explanation and right
Book is sought, advantages and features of the invention will become apparent from.It should be noted that attached drawing is all made of very simplified form and using non-
Accurately ratio, only for the purpose of facilitating and clarifying the purpose of the embodiments of the invention.
The present invention proposes a kind of sensor chip, marker detection device and method, realizes marker in solution to be measured
Quickly, sensitive and accurate detection.
Fig. 2 and Fig. 3 are please referred to, the sensor chip includes：Nested type open-loop resonator (nested split-ring
Resonator, nSRR) 10 and microstrip transmission line 30, the nested type open-loop resonator 10 includes the embedding of multiple split rings 101
Set, the opening of the multiple split ring 101 is sequentially arranged at intervals and orientation and perpendicular to opening edge 102, the nested type
Open-loop resonator 10 and the microstrip transmission line 30 constitute LC resonance device.
As shown in Figure 2, the split ring 101 is in lack the rectangular-shaped of one side.It is and described in the multiple split ring 101
The opposite one side 103 of opening edge 102 shares, and the opposing edge portions of 102 two sides of opening edge share.
In the present invention, capacitor is formed between adjacent apertures side 102, and the opposite one side 103 of opening edge is then used as inductance.
In one embodiment, the width w1 of each opening edge 102 is 0.05~0.1mm, the adjacent opening edge
Spacing w2 between 102 is 0.05~0.1mm, and the longest length x1 in side of 102 two sides of opening edge is 1.5~2mm.
The resonance frequency of the sensor chip with above-mentioned specification is 5~20GHz.
It is understood that the size of the split ring 101 can also be other numerical value, the example above is not intended as especially
Limitation.
As shown in figure 3, the sensor chip can be set on a substrate 20, the substrate 20 is, for example, quartzy glass
Glass substrate etc..
Wherein, in order to obtain preferable LC resonance device, the corresponding nested type of the microstrip transmission line 30 can be made to open
It is a narrow portion 301 at ring resonator 10, that is, the reduction microstrip transmission line 30 at the nested type open-loop resonator 10 is being set
Width, formed recess, by the nested type open-loop resonator 10 be arranged in the recess, and the microstrip transmission line 30 its
His part then can be relatively wide, and both ends are to outer signal line.
In one embodiment, the spacing between the nested type open-loop resonator 10 and the microstrip transmission line 30 is
0.1mm~1mm, such as 0.2mm, 0.3mm etc..
Marker detection device of the invention is illustrated below.As shown in fig. 4-5, including the sensor core
The sensor core is isolated in the sensor core on piece in piece, solution fixing layer 50 and hydrophobic layer 40, the setting of hydrophobic layer 40
Piece and the solution fixing layer 50, the solution fixing layer 50 are provided with the cavity 501 towards the sensor chip to accommodate
Solution to be measured.
Further, the marker detection device can be set on the substrate 20.
In one embodiment, the hydrophobic layer 40 with a thickness of 2.5 μm~10 μm.For example, the hydrophobic layer 40 covers
The thickness of sensor chip can be at 3 μm, 3.1 μm, 3.2 μm etc., and the thickness on 20 surface of substrate in addition to this can be 5
μm, 6 μm, 7 μm, 8 μm etc..
For example, the material of the hydrophobic layer 40 includes benzocyclobutene (Benzocyclobutene, BCB).It is understood that
, other materials with hydrophobic effect can also be used for this invention, herein without enumerating.
In one embodiment, the material of the solution fixing layer 50 includes dimethyl silicone polymer
(Polydimethysiloxane, PDMS).Likewise, the citing is not intended as limitation of the present invention, for example, can choose
Other substances not reacted under normal conditions with water of dielectric constant in 2 to 3 ranges.
It in one embodiment, can be in the substrate 20 as shown in fig. 6, for the ease of being connected and fixed with other component
The upper multiple apertures 60 of setting.As Fig. 6 is shown as that the two sides at 30 both ends of microstrip transmission line are arranged in.
A kind of preparation process of marker detection device of the invention is given below：
Such as can be handled by printed circuit board technology (printed circuit board, PCB), it has been produced on double
On the substrate 20 of face metallic film.Substrate 20 selects the quartz glass of 0.5~1.0mm thickness, and metallic film material is gold, titanium
Deng.
Quartz glass plate is cleaned repeatedly first, carries out electron beam evaporation Ti/Au seed layer to it after cleaning.Then,
In quartz glass plate surface coating photoetching, the metallic gold or titanium of upper 3~5 micron thickness is electroplated, is removed photoresist and etched later kind
Sublayer, thus the sensor chip needed for being formed.
The preparation process of solution fixing layer can be:Graphics chip is drawn using graphics software, is shone with high resolution laser
Photo etched mask is made in row's machine on photographic negative, plates chromium film using the sensor chip of magnetron sputtering coater after cleaning,
Then in the even upper positive photoresist in its surface, such as the photoresist of model RZJ-340.It, will after front baking, exposure, development
Sheet glass, which immerses in the etching liquid of chromium, performs etching and improves by post bake technique photoresist and substrate (such as quartz glass
Piece) adhesive force, then treated sensor chip is immersed and contains HF and HNO3Etching liquid in carry out wet etching.Pre-polymerization
Body (such as Sylgard184) and curing agent in mass ratio 10:After 1 uniformly mixes and removes bubble removing, solidify at 50~100 DEG C
PDMS cover plate can be obtained as the solution fixing layer.
The preparation of hydrophobic layer carries out after completing sensor chip preparation.Hydrophobic layer covers in certain area except metal
The substrate surface of structure (i.e. sensor chip), thickness is between 2.5 μm~10 μm, including hydrophobic layer covers nonmetal structure portion
Divide with a thickness of 5~10 μm, such as 5 μm, 6 μm, 7 μm, 8 μm etc., covers the thickness of metal structure at 3 μm or so, such as 3 μm, 3.1
μm, 3.2 μm etc..It can be by coating one layer of benzocyclobutene (Benzocyclobutene, BCB) glue, which has hydrophobic function
Energy.Then, to its photoetching development, solidify in the environment of temperature is 200 DEG C~300 DEG C (such as 250 DEG C), obtain described hydrophobic
Layer.
Include using the marker detection method that above-mentioned marker detection device carries out：
Solution to be measured is provided, resonance characteristic when being arranged in the cavity, and measuring with the solution to be measured；And
Resonance characteristic is corresponding with resonant network-marker sample database when will have the solution to be measured, described in acquisition
The concentration of solution to be measured.
In view of variety classes and the marker (such as large biological molecule) of quantity influence the resonance characteristic of resonant network
It is very sensitive, therefore, can be by resonant network-marker sample database foundation of optimization design, it can be very sensitive
Ground detects the concentration of solution marker to be measured.Solution mark to be measured is detected using this wireless radiofrequency coupled modes sense analysis
The method of object signal can also avoid weak signal amplifier when directlying adopt DC impedance measurement easily by biggish circuit simultaneously
The problem of big resistance is flooded and is interfered.
When being detected, as shown in fig. 7, the both ends of the microstrip transmission line 30 can be connected by fixture 70, and clamp
On the substrate 20, while the fixture 70 can connect to such as vector network analyzer (Vector Network
Analyzer, VNA), e.g. connected by a port of SMA interface and vector network analyzer.VNA issues excitation letter
Number, sensor chip obtains the resonance characteristic of entire resonant network, and feeds back and arrive vector network analyzer.In this way from vector network
The resonance characteristic that resonant network can be obtained on analyzer changes, the variation including resonance frequency, impedance real part, imaginary part etc.,
Impedance real part bandwidth is obtained, centre frequency and resonance peak etc. e.g. finally calculate the impedance real part band of RLC resonant network
Wide variation, so that comparison obtains the concentration of the marker of the solution to be measured captured in detection chip.
Correspondingly, the marker detection device can be applied in following marker detection method, including：
Solution to be measured is provided, resonance characteristic when being arranged in the cavity, and measuring with the solution to be measured；And
It makes comparisons, obtains described to be measured with the resonance characteristic of marker detection device described when not having the solution to be measured
The dielectric property of solution.
The equipment connection of this method can refer to a upper method, herein without repeating.
Include obtaining frequency offset f when the resonance characteristic is made comparisons, is expressed as：Wherein, L=L0+△L(L0>>△ L), C=C0+△C(C0>
>△ C),f0、L0And C0Described in when respectively without the solution to be measured
Resonance frequency, inductance and the capacitor of marker detection device, Δ L are inductance knots modification, and Δ C is capacitance change.
From the offset of sensor resonant volume frequency before and after the placement solution to be measured measured, the dielectric for extrapolating the solution is special
Property, it can be studied for further large biological molecule and help is provided.
In conclusion the sensor chip in the present invention, including：Nested type open-loop resonator and microstrip transmission line, it is described
Nested type open-loop resonator includes the nesting of multiple split rings, and the opening of the multiple split ring is sequentially arranged at intervals and arrangement side
To and perpendicular to opening edge, the nested type open-loop resonator and the microstrip transmission line constitute LC resonance device.Based on this acquisition
Marker detection device and detection method, have the advantages that easy to detect, high sensitivity, accurate, fireballing, its advantages
It specifically includes：
(1) less radio-frequency detection technique, accurate, the quick and highly sensitive realization marker detection of energy are used.Using RLC net
The variation of network resonance characteristic can significantly reflect the small-signal applied before and after solution to be measured, and customary DC resistance is avoided to survey
Impedance signal variation is flooded by the impedance greatly of system background when examination, while radiofrequency signal also has stronger anti-interference ability.
(2) when being detected using the device of the invention, have the advantages that convenient, quick detection and other conventional methods
It compares, detection process is simpler, conveniently, and detection speed is also very fast, once capture, can directly measure result.
(3) the device of the invention precision is high, at low cost, and detection program is few, simply, conveniently, is suitable for large sample, extensive
It promotes the use of, there is important application value.
Obviously, various changes and modifications can be made to the invention without departing from essence of the invention by those skilled in the art
Mind and range.In this way, if these modifications and changes of the present invention belongs to the range of the claims in the present invention and its equivalent technologies
Within, then the present invention is also intended to include these modifications and variations.
Claims (13)
1. a kind of sensor chip, which is characterized in that including：Nested type open-loop resonator and microstrip transmission line, the nested type
Open-loop resonator includes the nesting of multiple split rings, and the opening of the multiple split ring is sequentially arranged at intervals and orientation and hangs down
Directly LC resonance device is constituted in opening edge, the nested type open-loop resonator and the microstrip transmission line.
2. sensor chip as described in claim 1, which is characterized in that the split ring is in lack the rectangular-shaped of one side.
3. sensor chip as claimed in claim 2, which is characterized in that in the multiple split ring, with the opening edge phase
Pair share on one side, the opposing edge portions of the opening edge two sides share.
4. sensor chip as claimed in claim 3, which is characterized in that the width of each opening edge be 0.05~
0.1mm, the spacing between the adjacent opening edge are 0.05~0.1mm, and the longest edge lengths of the opening edge two sides are 1.5
~2mm.
5. sensor chip as described in claim 1, which is characterized in that the resonance frequency of the sensor chip be 5~
20GHz。
6. a kind of marker detection device, including the sensor chip as described in any one of claim 1 to 5, solution is solid
Given layer and hydrophobic layer, the sensor chip is isolated in the sensor core on piece for the hydrophobic layer setting and the solution is fixed
Layer, the solution fixing layer are provided with the cavity towards the sensor chip to accommodate solution to be measured.
7. marker detection device as claimed in claim 6, which is characterized in that the hydrophobic layer with a thickness of 2.5 μm~10 μ
m。
8. marker detection device as claimed in claim 6, which is characterized in that the material of the hydrophobic layer includes benzocyclobutane
Alkene.
9. marker detection device as claimed in claim 6, which is characterized in that the material of the solution fixing layer includes poly- two
Methylsiloxane.
10. a kind of marker detection method, which is characterized in that using the marker as described in any one of claim 6-9
Detection device, this method include：
Solution to be measured is provided, resonance characteristic when being arranged in the cavity, and measuring with the solution to be measured；And
Resonance characteristic is corresponding with resonant network-marker sample database when will have the solution to be measured, obtains described to be measured
The concentration of solution.
11. marker detection method as claimed in claim 10, which is characterized in that the resonance characteristic includes impedance real part band
Width, centre frequency and resonance peak.
12. a kind of marker detection method, which is characterized in that using the marker as described in any one of claim 6-9
Detection device, this method include：
Solution to be measured is provided, resonance characteristic when being arranged in the cavity, and measuring with the solution to be measured；And
It makes comparisons with the resonance characteristic of marker detection device described when not having the solution to be measured, obtains the solution to be measured
Dielectric property.
13. marker detection method as claimed in claim 12, which is characterized in that include obtaining when the resonance characteristic is made comparisons
Frequency offset f is obtained, is expressed as：
Wherein, L=L0+ΔL(L0> > Δ L), C=C0+ΔC(C0> > Δ C),
f0、L0And C0Resonance frequency, inductance and the capacitor of the marker detection device, Δ L when respectively without the solution to be measured
For inductance knots modification, Δ C is capacitance change.
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