Terahertz Spectroscopy Characterization with High Spectral and Spatial Resolution for Biological and Chemical Sensing and Method of Use

• US 20140070102A1
• Filed: 08/01/2013
• Published: 03/13/2014
• Est. Priority Date: 08/01/2012
• Status: Active Grant

• Current Assignee: Aaron Moyer, Boris Gelmont, Jerome Ferrance, Tatiana Globus
• Original Assignee: Aaron Moyer, Boris Gelmont, Jerome Ferrance, Tatiana Globus
• Inventors: Globus, Tatiana, Gelmont, Boris, Moyer, Aaron, Ferrance, Jerome
• Granted Patent: US 9,417,193 B2
• Time in Patent Office: Days
• US Class Current: 250/339.07
• CPC Class Codes: G01N 21/3586 by Terahertz time domain spectroscopy [THz-TDS]
• CPC Class Codes: G01N 22/00 Investigating or analysing materials by the use of microwaves or radio waves, i.e. electromagnetic waves with a wavelength of one millimetre or more G01N3/00 - G01N17/00, G01N24/00 take precedence

Abstract

Biological cells or spores are analyzed by using enhanced THz coupling to molecules by depositing a test material in a channel of a microfluidic chip using near field sensing of sub-THz radiation from the molecules. The THz radiation is enhanced by transmitting THz radiation through slots in the chip, illuminating molecules of the test material with the enhanced THz radiation transmitted through the slots. A spectroscopic signature of the test material is generated, and a database of signatures of materials is generated. The test material is identified by comparing the signature of the test material with signatures of materials in the database.

Claims

1. Method of analyzing biological or spores using enhanced THz coupling to molecules, comprising the steps of:

depositing a test material near a member selected from the group comprising doped semiconductors, metal films, and multilayer structures, said member being characterized by supporting modes that locally enhance EM fields, and near field sensing of THz radiation from said molecules,

enhancing said THz radiation by transmitting THz radiation through slots in said member,

illuminating molecules of said test material with said enhanced THz radiation transmitted through said slots,

generating a spectroscopic signature of said test material,

generating a database of signatures of materials,

identifying said test material by comparing the signature of said test material with signatures of materials in said database.

2. The method of claim 1, wherein generating a signature for said test material further comprises said enhanced THz radiation being an EM field of terahertz radiation in a submicron region and further comprising analyzing the THz vibration absorption by said test material and thereby generating said signature for said test material.

3. The method of claim 1, wherein said test material comprises a strain of E coli and said database comprises signatures of pathogenic and non-pathogenic strains of E coli, and further comprising the step of:

comparing the signature of aid test material with signatures of pathogenic and non-pathogenic strains of E coli, and

determining whether said test material is a pathogenic strain of E coli, or a non-pathogenic strain of E coli.

4. The method of claim 1, wherein said test material comprises a cancer cell and further comprising identifying a single cancer cell by interrogation of specific resonances caused by intra-molecular motions within the cell.

5. The method of claim 4, further comprising at least one of the steps of detection of signaling molecules circulating in blood and assessing therapeutic responses from cancer cells.

7. The method of claim 1, further comprising the step of near field scanning with a THz antenna, of transmitted radiation of a slotted member from sample material near discontinuity edges of said slotted member.

8. The method of claim 1 wherein said transmitting of THz radiation through said slots increases the degree of the coupling of EM radiation in the THz spectral range to materials of interest by transmitting THz radiation through an array of openings, transmitting said THz radiation from said array of openings through bio- or chemical material and sensing near field THz radiation that has been transmitted through said slots and said material, and further comprising detection of the spectroscopic signatures of said bio- or chemical material.

9. Method of increasing coupling of EM radiation in the THz spectral range to weak bonds in molecules using a spectroscopic instrument, said spectroscopic instrument having a chip, said chip having at least one micro/nano fluidic channel comprising the steps of:

depositing a material in a channel in a said chip,

positioning a non-contact probe within a distance of 2-10 μ

m of said chip,

and further comprising the steps of;

generating THz radiation;

transmitting THz radiation through said material, and illuminating said material with the transmitted THz radiation;

generating EM field enhancement at said microfluidic chip;

selectively detecting enhanced THz transmitted through said material;

monitoring said selectively detected enhanced THz radiation, and

determining the spectroscopic signature of said material.

10. The method of claim 9, wherein said material is a bio-material in a biophysical process,

monitoring at room temperature in at least near real-time changes of a dielectric property of the bio-material in a biophysical process in at least near real-time, wherein said process is selected from the group comprising denaturation of DNA, folding-unfolding of proteins, and structural conformational changes of biomolecules in interactions with drugs.

11. An all-optical, apertureless continuous-wave frequency-domain spectroscopic sensor instrument free of mechanical tips or probes to contact testing material, comprising:

microfluidic chip,

a source of sub-THz radiation,

an analyte material in a channel of said microfluidic chip,

means for illuminating said analyte material with said sub-THz radiation,

and means to sense near field sub-THz radiation in the sub-THz spectral region between 315 and 480 GHz, from said analyte material,

12. The spectroscopic sensor instrument of claim 11, wherein said analyte material is a nano-gram sample of a biological material.

13. The all-optical, apertureless continuous-wave frequency-domain spectroscopic sensor instrument of claim 11, further comprising:

a non-contact probe,

means for positioning said non-contact probe within a distance in the range from 2-10 μ

m of said chip,

means for monitoring said selectively detected enhanced THz radiation, and

means for determining the spectroscopic signature of said material.

14. The all-optical, apertureless continuous-wave frequency-domain spectroscopic sensor instrument of claim 13, wherein said analyte material is molecules in dilute solutions and wherein said molecules are selected from the group comprising monolayers of biological material and cancer cells.

15. The all-optical, apertureless continuous-wave frequency-domain spectroscopic sensor instrument of claim further comprising:

means for generating a spectroscopic signature of said test material,

means for generating a database of spectroscopic signatures of materials,

means for identifying said analyte material by comparing the spectroscopic signature of said analyte material with spectroscopic signatures of materials in said database.