CN107991263A - Cancer cell Spectrum Analysis device and method based on graphene THz source and detector - Google Patents

Cancer cell Spectrum Analysis device and method based on graphene THz source and detector Download PDF

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CN107991263A
CN107991263A CN201711454231.XA CN201711454231A CN107991263A CN 107991263 A CN107991263 A CN 107991263A CN 201711454231 A CN201711454231 A CN 201711454231A CN 107991263 A CN107991263 A CN 107991263A
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CN107991263B (en
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李向军
殷杰
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China Jiliang University
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/35Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
    • G01N21/3581Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light using far infrared light; using Terahertz radiation
    • G01N21/3586Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light using far infrared light; using Terahertz radiation by Terahertz time domain spectroscopy [THz-TDS]
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/255Details, e.g. use of specially adapted sources, lighting or optical systems

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Abstract

The invention discloses a kind of cancer cell Spectrum Analysis device and method based on graphene THz source and detector.The major part of this analytical equipment mainly has graphene THz wave generating unit, the metal medium metal waveguide for being loaded with cancer cell, graphene Terahertz field-effect tube probe unit and lock-in amplifier.Wide range THz wave is produced when the high-speed electron flow that graphene produces under applied voltage effect flows through covered duty cycle silica grating incremented by successively, the wide range Terahertz is received by being loaded with the metal medium metal waveguide of cancer cell by Terahertz field-effect tube probe unit, is eventually passed through lock-in amplifier and is obtained response signal of the cancer cell to wide Terahertz wave spectrum.The analytical equipment is highly integrated together by multiple unit components, can be combined with microfluidic system and efficiently carry out THz wave spectrum analysis to biological samples such as cancer cells, potentiality are had a wide range of applications in field of biological detection.

Description

Cancer cell Spectrum Analysis device and method based on graphene THz source and detector
Technical field
The invention belongs to THz wave technology field, is related to a kind of cancer cell based on graphene THz source and detector Spectrum Analysis device and method.
Background technology
Terahertz (Terahertz or THz) ripple typically refers to electromagnetic wave of the frequency in 0.1~10THz sections, its photon Energy be about 1~10meV, just the energy of transition is roughly the same between molecular vibration and rotational energy level.Most of polarity Molecule such as hydrone, amino molecule etc. have THz radiation strong absorption, the vibration of many organic macromolecules (DNA, protein etc.) Transition between energy level and rotational energy level is also just in THz wavelength bands.Therefore, the THz spectrum of material (including are launched, are reflected And transmitted spectrum) including abundant physics matter and chemical information, it is absorbed and dispersion characteristics can be used for doing explosive, medicine Deng the detection and identification of chemistry and biological sample, in physics, chemistry, biomedicine, astronomy, material science and environmental science Etc. there is important application value.
Graphene be it is a kind of only single layer of carbon atom thickness six side comb shapes two-dimensional material, from 2004 find with Come, increasingly paid attention to by people, have and be extremely widely applied prospect.Graphene is (200 times of the highest material of intensity in the world In steel), there are very high heat conduction and electric conductivity (5300W/mK) (50 Ω/cm), there is high 2 630m of specific surface area2/ g, there is height Elastic high rigidity (130GPa).The chemical reactivity of graphene is strong, easily forms compound with other chemical reactions, moreover it is possible to Ionising radiation is born, at the same it is very slim and graceful, there is the toughness similar to carbon fiber, and Joule effect is than carbon fiber smaller.Graphene Support surface plasmon is can be very good in THz wave bands, there are many potential applications in sensing, communication etc..
Spectrum Analysis is interacted as condition with material and light mainly based on optical theory, establishes material molecule Correlation between structure and electromagnetic radiation, so as to carry out material molecule geometrical isomerism, alloisomerism, conformational isomerism and molecule Structural analysis and the method for identification.Spectrum Analysis become the modern main method for carrying out material molecular structure analysis and identification it One.With the development of science and technology, the innovation and computer application of technology, Spectrum Analysis are also developed rapidly.Spectra Analysis has There is the features such as advantages, extensive use, be the indispensable instrument in many research and production fields.With development in science and technology and divide Analyse desired continuous improvement so that researcher is also constantly bringing forth new ideas Spectra Analysis.Spectra Analysis due to it is quick, It is sensitive, accurate, to playing an important role in terms of cell detection, it has also become cancer cell assay and identify common analysis tool and Important analysis method.
Cancer has become the 2nd big lethal factor of Present Global, and death caused by about more than 90% malignant tumour is by morning Caused by phase finds the three big reasons such as difficult, easy relapse and metastasis and antiradiation drug, wherein relapse and metastasis is to cause tumor patient dead The first cause died.The reason for relapse and metastasis be due in the presence of coming off from cancer original site, by blood vessel or lymphatic system into The cancer cell of human blood circulation, i.e. circulating tumor cell (CTC).CTC has been found to form a series of of transfer in malignant tumour During play key player, clinical stages, progression free survival phase, Overall survival with kinds of tumors and antitumor drug are treated Effect etc. is closely related, is acknowledged as a kind of potential, real-time " liquid biopsy ".CTC can reflect tumor load, predict cancer Disease is developed, co-treatment decision-making, its effect for diagnosing with predictive value and in translational medicine research is paid more and more attention, together When CTC be also possible to novel targets as cancer therapy drug newly developed, there is provided the new approaches for the treatment of of cancer.Develop highly sensitive, high special The detection method of property is urgent tasks of the current CTC from basic research to clinical practice.
Research known cancer cell metabolism is vigorous, and the content of the macromolecular such as nucleic acid is more compared with normal structure.On the other hand, The abnormality proliferation of cell carcinogenesis causes the change of water content and water state in cell sensitively to be captured by THz wave. 2002, Woodward etc. reported application of the terahertz light spectral imaging technology in cutaneum carcinoma detection first.Thereafter the technology The detection of colorectal cancer, breast cancer, liver cancer, cervical carcinoma, oral cavity and brain tumor tissue is attempted for, PRELIMINARY RESULTS is shown normally Tissue is woven with notable difference with tumor group.
The content of the invention
The present invention seeks to overcome existing relatively narrow, the equipment using detection device wave spectrum existing for THz wave detection cancer cell Volume is excessive, it is complicated the problems such as, there is provided a kind of compact cancer cell wave spectrum based on graphene THz source and detector Analytical equipment.The device can be connected with microfluidic system, become the important tool of cancer early screening and diagnosis.
In order to solve the above technical problems, the technical solution adopted in the present invention is:
A kind of cancer cell Spectrum Analysis device based on graphene THz source and detector, including:Graphene Terahertz Ripple generating unit, the metal-dielectric-metal waveguide for loading cancer cell, graphene Terahertz field-effect tube probe unit and Lock-in amplifier;
The graphene THz wave generating unit include first grid, the first silicon dioxide layer, the first graphene layer, First source electrode and the first drain electrode, the bottom of graphene THz wave generating unit is first grid, and first grid is followed successively by upwards First silicon dioxide layer and the first graphene layer, the side that first silicon dioxide layer is contacted with the first graphene layer are set There are some grooves arranged in parallel, the groove Y direction length is identical, and X-direction width increases successively, forms grating knot Structure, first source electrode and the first drain electrode are arranged at the first graphene layer top and respectively positioned at the two of the first graphene layer Side;
The metal-dielectric-metal waveguide includes two metal derbies and the dielectric cavity for placing cancer cell, two metals Block is respectively arranged at the first source electrode and the first drain electrode top, is dielectric cavity between two metal derbies;
The graphene Terahertz field-effect tube probe unit includes the second silicon dioxide layer, the second graphene layer, second Grid, second drain electrode and the second source electrode, second silicon dioxide layer as the supporter of the second graphene layer be located at metal- Above dielectric-metal waveguide, covered with the second graphene layer, second grid, the second drain electrode and second in the second silicon dioxide layer Source electrode is located above the second graphene layer;
The lock-in amplifier is connected with the first source electrode, the second drain electrode.
Preferably, the second grid of the graphene Terahertz field-effect tube probe unit is imitated with graphene THz electric field Alundum (Al2O3) layer should be additionally provided between second graphene layer of pipe probe unit, play limitation quantum tunneling effect, avoid The effect of drain leakage.
Preferably, first source electrode and the first drain electrode and the groove of optical grating construction are arranged in parallel.
Preferably, directly over the first drain electrode, the second source electrode is located at directly over the first source electrode for second drain electrode, the Two grids are located at directly over dielectric cavity.
Preferably, the depth of groove in first silicon dioxide layer is identical.
Preferably, first grid in above-mentioned analytical equipment, the first source electrode, the first drain electrode, second grid, the second drain electrode and the Two source electrode materials are the mixing material being made of titanium, palladium and copper;First silicon dioxide layer, the second silica layer material are low folding Penetrate the silica of rate;First graphene layer, the second graphene layer material are single-layer graphene;Alundum (Al2O3) layer material is height Purity alundum (Al2O3);Two metal derby materials are metallic aluminium.
Invention also provides a kind of cancer cell analysis method by use of spectrum based on graphene THz source and detector, tool Body includes the following steps:Cell to be measured is placed in dielectric cavity, " the source electrode-leakage to the first drain electrode, the additional setting of the first source electrode Pole " voltage, to the grid voltage of the additional setting of first grid, the first graphene layer in graphene THz wave generating unit exists The applied voltage effect lower high-speed electron flow produced produces when flowing through covered duty cycle silica grating incremented by successively The THz wave of bandwidth is set, and lock-in amplifier is sent to using control voltage signal as with reference to signal;THz wave penetrates Graphene Terahertz field-effect tube probe unit is reached after crossing cancer cell, " the source to the second drain electrode, the additional setting of the second source electrode Gate-drain " voltage, to the grid voltage of the additional setting of second grid, when THz wave is irradiated to graphene THz electric field effect During the second graphene layer in pipe probe unit, thus it is possible to vary the carrier mobility of the second graphene layer, so as to cause second Graphene-channel electric current changes between drain electrode, the second source electrode, which can be phase locked amplifier measurement by magnification;Coordinate scanning Change the one the first drain electrodes, " source drain " voltage of the first source electrode, can finally measure the Terahertz wave spectrum of cancer cell.
Compared with prior art, the invention has the advantages that:
1. due to convenient tunability and material flexibility possessed by graphene itself, thus this analytical equipment can provide it is dynamic The regulatory function of state, is easy to practical operation.
2. increased grating can produce wide ripple to the X-direction duty cycle in an analytical equipment THz source generating unit successively The THz wave of spectrum, is easy to the detection to cancer cell.
3. the analytical equipment is operated in terahertz wave band, and terahertz wave band is just at the sensitive band of biology, therefore Potentiality are had a wide range of applications in field of biological detection.
4. the equipment volume is smaller, it is easy to actually detected and carries.
Brief description of the drawings
Fig. 1 is the structural profile of the cancer cell Spectrum Analysis device of the invention based on graphene THz source and detector Figure;
Fig. 2 is the structural upright of the cancer cell Spectrum Analysis device of the invention based on graphene THz source and detector Figure.
Marked in figure:1- graphene THz wave generating units, 2- can be loaded with for load cancer cell metal-dielectric- Metal waveguide, 3- graphene Terahertz field-effect tube probe units, 4- lock-in amplifiers, 5- first grids, the first titanium dioxides of 6- Silicon layer, the first graphene layers of 7-, 8- first drain, 9- metal derbies, the second silicon dioxide layers of 10-, the second graphene layers of 11-, 12- Second drain electrode, 13- second grids, 14- alundum (Al2O3) layers, the second source electrodes of 15-, 16- cells to be measured, the first source electrodes of 17-, 18- Optical grating construction.
Embodiment
With reference to embodiment, the invention will be further described, and described embodiment is only one of the present invention Divide embodiment, be not whole embodiments.Based on the embodiments of the present invention, those of ordinary skill in the art are not doing Other embodiments used obtained on the premise of going out creative work, belong to protection scope of the present invention.
With reference to 1~attached drawing of attached drawing 2, the cancer cell Spectrum Analysis device of the invention based on graphene THz source and detector Including first grid 5, the first silicon dioxide layer 6, the first graphene layer 7, the first source electrode 17 and the first drain electrode 8, graphene terahertz Hereby the bottom of ripple generating unit 1 is first grid 5, and first grid 5 is followed successively by the first silicon dioxide layer 6 and the first graphene upwards Layer 7, first silicon dioxide layer 6 is provided with some grooves arranged in parallel, institute with the side that the first graphene layer 7 contacts The groove Y direction length stated is identical, and X-direction width increases successively, forms optical grating construction 18,17 He of the first source electrode First drain electrode 8 is arranged at 7 top of the first graphene layer and is located at the both sides of the first graphene layer 7 respectively;The metal-dielectric- Metal waveguide 2 includes two metal derbies 9 and the dielectric cavity for placing cancer cell, and two metal derbies 9 are respectively arranged at the first source It is dielectric cavity between two metal derbies 9 above the drain electrode of pole 17 and first 8;The graphene Terahertz field-effect tube probe unit 3 It is described including the second silicon dioxide layer 10, the second graphene layer 11, the drain electrode 12 of second grid 13, second and the second source electrode 15 Second silicon dioxide layer 10 is located above metal-dielectric-metal waveguide 2 as the supporter of the second graphene layer 11, and the two or two It is located at the second stone covered with the second graphene layer 11, the drain electrode 12 of second grid 13, second and the second source electrode 15 on silicon oxide layer 10 The black top of alkene layer 11;The lock-in amplifier 4 is connected with the first source electrode 17, second drain electrode 12.
In above-mentioned technical proposal, the first source electrode 17 and the first drain electrode 8 and the groove of optical grating construction 18 are arranged in parallel.
In above-mentioned technical proposal, second grid 13 and the graphene terahertz of graphene Terahertz field-effect tube probe unit 3 Alundum (Al2O3) layer 14 hereby is additionally provided between the second graphene layer 11 of field-effect tube probe unit 3, plays limitation quantum tunnel Effect is worn, avoids the effect of drain leakage.
In above-mentioned technical proposal, directly over the first drain electrode 8, the second source electrode 15 is located at the first source electrode 17 for the second drain electrode 12 Surface, second grid 13 are located at directly over dielectric cavity.
In above-mentioned technical proposal, the depth of groove in the first silicon dioxide layer (6) is identical.
Invention also provides a kind of cancer cell analysis method by use of spectrum based on graphene THz source and detector, tool Body includes the following steps:Cell 16 to be measured is placed in dielectric cavity, gives first the 8, first source electrode of drain electrode 17 additional certain " source Gate-drain " voltage, gives first grid 5 additional certain grid voltage, the first stone in graphene THz wave generating unit 1 The high-speed electron flow that black alkene layer 7 produces under applied voltage effect flows through covered duty cycle silica light incremented by successively The THz wave of certain bandwidth is produced during grid, and lock-in amplifier is sent to using control voltage signal as with reference to signal;Terahertz Hereby ripple reaches graphene Terahertz field-effect tube probe unit 3 after being perforated through cancer cell, drains to second outside the 12, second source electrode 15 Add certain " source drain " voltage, give second grid 13 additional certain grid voltage, when THz wave is irradiated to graphene During the second graphene layer 11 in Terahertz field-effect tube probe unit 3, thus it is possible to vary the carrier of the second graphene layer 11 moves Shifting rate, so as to cause graphene-channel electric current between the second drain electrode 12, the second source electrode 15 to change, which can be phase locked and put 4 measurement by magnification of big device;Coordinate scanning to change " source drain " voltage of first the 8, first source electrode 17 of drain electrode, can finally measure cancer The Terahertz wave spectrum of cell.
First grid 5, the first source electrode 17, first drain electrode 8,12 and of the drain electrode of second grid 13, second in above-mentioned analytical equipment Second source electrode, 15 material is the mixing material being made of titanium, palladium and copper;First silicon dioxide layer 6,10 material of the second silicon dioxide layer Expect the silica for low-refraction;First graphene layer 7,11 material of the second graphene layer are single-layer graphene;Three oxidations two 14 material of aluminium lamination is high-purity alundum (Al2O3);Two 9 materials of metal derby are metallic aluminium.

Claims (6)

  1. A kind of 1. cancer cell Spectrum Analysis device based on graphene THz source and detector, it is characterised in that including:Graphite Alkene THz wave generating unit (1), the metal-dielectric-metal waveguide (2) for loading cancer cell, graphene THz electric field effect Should pipe probe unit (3) and lock-in amplifier (4);
    The graphene THz wave generating unit (1) includes first grid (5), the first silicon dioxide layer (6), the first graphite Alkene layer (7), the first source electrode (17) and the first drain electrode (8), the bottom of graphene THz wave generating unit (1) is first grid (5), first grid (5) is followed successively by the first silicon dioxide layer (6) and the first graphene layer (7), first titanium dioxide upwards Silicon layer (6) is provided with some grooves arranged in parallel, the groove Y direction with the side that the first graphene layer (7) contacts Length is identical, and X-direction width increases successively, forms optical grating construction (18), first source electrode (17) and the first drain electrode (8) It is arranged at the first graphene layer (7) top and is located at the both sides of the first graphene layer (7) respectively;
    The metal-dielectric-metal waveguide (2) includes two metal derbies (9) and the dielectric cavity for placing cancer cell, two gold Belong to block (9) to be respectively arranged above the first source electrode (17) and the first drain electrode (8), be dielectric cavity between two metal derbies (9);
    The graphene Terahertz field-effect tube probe unit (3) includes the second silicon dioxide layer (10), the second graphene layer (11), second grid (13), the second drain electrode (12) and the second source electrode (15), second silicon dioxide layer (10) are used as second The supporter of graphene layer (11) is located above metal-dielectric-metal waveguide (2), in the second silicon dioxide layer (10) covered with Second graphene layer (11), second grid (13), the second drain electrode (12) and the second source electrode (15) are located at the second graphene layer (11) Top;
    The lock-in amplifier (4) is connected with the first source electrode (17), the second drain electrode (12).
  2. 2. a kind of cancer cell Spectrum Analysis device based on graphene THz source and detector according to claim 1, It is characterized in that:The second grid (13) of the graphene Terahertz field-effect tube probe unit (3) and graphene Terahertz Alundum (Al2O3) layer (14) is additionally provided between the second graphene layer (11) of field-effect tube probe unit (3).
  3. 3. a kind of cancer cell Spectrum Analysis device based on graphene THz source and detector according to claim 1, It is characterized in that:First source electrode (17) and the first drain electrode (8) and the groove of optical grating construction (18) are arranged in parallel.
  4. 4. a kind of cancer cell Spectrum Analysis device based on graphene THz source and detector according to claim 1, It is characterized in that:Directly over the first drain electrode (8), the second source electrode (15) is located at the first source electrode for second drain electrode (12) (17) directly over, second grid (13) is located at directly over dielectric cavity.
  5. 5. a kind of cancer cell Spectrum Analysis device based on graphene THz source and detector according to claim 1, It is characterized in that:Depth of groove on first silicon dioxide layer (6) is identical.
  6. A kind of 6. cancer cell Spectrum Analysis side based on graphene THz source and detector of device according to claim 1 Method, it is characterised in that include the following steps:Cell to be measured (16) is placed in dielectric cavity, to the first drain electrode (8), the first source electrode (17) " source drain " voltage of additional setting, to the grid voltage of first grid (5) additional setting, graphene THz wave The high-speed electron flow that the first graphene layer (7) in generating unit (1) produces under applied voltage effect flows through accounting for of being covered The THz wave of setting bandwidth is produced when sky is than silica grating incremented by successively, and using control voltage signal as with reference to letter Number it is sent to lock-in amplifier;THz wave reaches graphene Terahertz field-effect tube probe unit (3) after being perforated through cancer cell, To " source drain " voltage of the second drain electrode (12), the second source electrode (15) additional setting, to second grid (13) additional setting Grid voltage, the second graphene layer (11) being irradiated to when THz wave in graphene Terahertz field-effect tube probe unit (3) When, thus it is possible to vary the carrier mobility of the second graphene layer (11) so that cause the second drain electrode (12), the second source electrode (15) it Between graphene-channel electric current change, which can be phase locked amplifier (4) measurement by magnification;Scanning is coordinated to change the first drain electrode (8), " source drain " voltage of the first source electrode (17), can finally measure the Terahertz wave spectrum of cancer cell.
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CN109765178B (en) * 2018-05-30 2020-04-21 京东方科技集团股份有限公司 Microfluidic device, driving method and microfluidic detection system
US11383237B2 (en) 2018-05-30 2022-07-12 Boe Technology Group Co., Ltd. Microfluidic device, driving method and microfluidic detection system

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