Digital surface-enhanced Raman spectroscopy sensing platform

12140,547

17/587541

January 28, 2022

The present disclosure relates to a surface-enhanced Raman spectroscopy complex probe capable of effectively detecting a catecholamine compound even at extremely low concentrations. The complex probe includes a nanolaminate including a nanogap and metal nanoparticles. In this case, the nanolaminate and the metal nanoparticles are modified to a compound that may be bound to each functional group included in catecholamine, and thus, catecholamine included in an analyte is doubly recognized by the complex probe. In addition, since a hotspot emitting a strong SERS signal is formed by a nanogap included in a nanolaminate, it is possible to effectively detect a catecholamine compound even at extremely low concentrations.

KOREA RESEARCH INSTITUTE OF STANDARDS AND SCIENCE (Daejeon, KR); VIRGINIA TECH INTELLECTUAL PROPERTIES, INC. (Blacksburg, VA, US)

KOREA RESEARCH INSTITUTE OF STANDARDS AND SCIENCE (Daejeon, KR), VIRGINIA TECH INTELLECTUAL PROPERTIES, INC. (Blacksburg, VA, US)

1. A method of detecting catecholamine included in an analyte comprising: preparing a nano-laminate in which a plasmonic metal layer and an etching layer are alternately stacked, and a surface of the nanolaminate being modified with a compound that binds to a first functional group of catecholamine, and the nanolaminate comprises nanogap formed by etching the etching layer; preparing a metal nanoparticle whose surface is modified with a compound that binds to a second functional group of the catecholamine; incubating the nanolaminate, the metal nanoparticle, and catecholamine; detecting a signal through Surface-enhanced Raman spectroscopy (SERS); wherein the average diameter of the metal nanoparticles is smaller than the width of the nanogap, and the metal nanoparticles are attracted to the nanogap, thereby generating overlapping hot spots.

2. The method of claim 1 , wherein the first functional group and the second functional group are each selected from an amine group or a diol group.

3. The method of claim 1 , wherein the etching layer includes oxide or nitride.

4. The method of claim 1 , wherein the etching layer is etched using a buffered oxide etchant (BOE) solution.

5. The method of claim 1 , wherein the nanogap has a width of 1 nm to 20 nm.

6. The method of claim 1 , wherein the metal nanoparticle is at least one selected from gold (Au), silver (Ag), copper (Cu), aluminum (Al), platinum (Pt), or palladium (Pd).

7. The method of claim 1 , wherein the catecholamine binds to both the nanolaminate and the metal nanoparticle.

8. The method of claim 1 , wherein the catecholamine includes at least one selected from dopamine, polydopamine, alpha-methyldopamine, norepinephrine, epinephrine, methyldopa, droxidopa, or 5-hydroxydopamine.

9. A method of providing information necessary for analyzing a concentration of catecholamine of an analyte for a diagnosis of neurological diseases comprising: preparing a nano-laminate in which a plasmonic metal layer and an etching layer are alternately stacked, and a surface of the nanolaminate being modified with a compound that binds to a first functional group of catecholamine, and the nanolaminate comprises nanogap formed by etching the etching layer; preparing a metal nanoparticle whose surface is modified with a compound that binds to a second functional group of the catecholamine; incubating the nanolaminate, the metal nanoparticle, and catecholamine; detecting a signal through Surface-enhanced Raman spectroscopy (SERS); and analyzing the concentration of catecholamine of the analyte; wherein the average diameter of the metal nanoparticles is smaller than the width of the nanogap, and the metal nanoparticles are attracted to the nanogap, thereby generating overlapping hot spots.

10. The method of claim 9 , wherein the neurological disease is Parkinson's disease, schizophrenia, attention deficit hyperactivity disorder, Huntington's disease, Lou Gehrig's disease, stroke, dementia, or epilepsy.

7271896 September 2007 Chan
8821978 September 2014 Cheng
9052598 June 2015 Wu
20030138375 July 2003 Leyland-Jones
20140011691 January 2014 Sierks
101272316 June 2013
20130003843 June 2013
20170129633 November 2017
20180052101 May 2018
20210028988 March 2021

Zhang, K., et al. “Quantitative SERS detection of dopamine in cerebrospinal fluid by dual-recognition-induced hot spot generation.” ACS applied materials & interfaces 10.18 (2018): 15388-15394 (Year: 2018). cited by examiner
Tahir, M. A., et al. “Surface-enhanced Raman spectroscopy for bioanalysis and diagnosis.” Nanoscale 13.27 (2021): 11593-11634 (Year: 2021). cited by examiner
Song, J. et al. “Scalable high-performance nanolaminated SERS substrates based on multistack vertically oriented plasmonic nanogaps.” Advanced Materials Technologies 4.5 (2019): 1800689 (Year: 2019). cited by examiner
Zhang et al., “Quantitative SERS Detection of Dopamine in Cerebrospinal Fluid by Dual-Recognition Induced Hot Spot Generation,” ACS Applied Materials & Interfaces, 8 pages. cited by applicant
Tahir et al., “Surface-enhanced Raman spectroscopy for bioanalysis and diagnosis,” Royal Society of Chemistry, Nanoscale, 2021, 13, 11593-11634 pages. cited by applicant
Korean Office Action issued in corresponding Korean Patent Application No. 10-2021-0167646 on Aug. 10, 2022, pp. 1-8. cited by applicant
Korean Notice of Allowance issued in corresponding Korean Patent Application No. 10-2021-0167646 on Nov. 23, 2022, pp. 1-7. cited by applicant
[Supportive materials for Exception to Loss of Novelty] Wonil Nam et al., “A digital SERS sensing platform using 3D nanolaminate plasmonic crystals coupled with Au nanoparticles for accurate quantitative detection of dopamine”, The Royal Society of Chemistry, Sep. 7, 2021, 10 pages. cited by applicant
[Supportive materials for Exception to Loss of Novelty] Eun-Ah You et al., “Accurately measure dopamine concentration with digital signal technique”, Korea Research Institute of Standards and Science, Nov. 17, 2021, 7 pages. Machine translated English Abstract. cited by applicant
Shilpi Verma et al., “ZnO-rGO nanocomposite based bioelectrode for sensitive and ultrafast detection of dopamine in human serum”, Biosensors and Bioelectronics, Jun. 5, 2020, 8 pages, cited in the Specification. cited by applicant

edspgr.12140547