Toward Point-of-Care Drug Testing: A New Paradigm for On-Chip Chromatography Coupled with Surface-Enhanced Raman Scattering PROJECT SUMMARY In principle, surface enhanced Raman spectroscopy (SERS) can provide unique identification to a target analyte, especially small molecules such as illicit drugs. In practice, however, this is not always true for real- world samples due to various forms of interference such as nonspecific binding from large biomolecules (proteins, DNAs, etc.) in complex biological samples to the surface of metallic nanoparticles (NPs). Therefore, a selective (e.g., assay) or separation (e.g., chromatography) process with certain specificity is needed to transform existing SERS technique from a lab analysis tool into clinical usage. One urgent need for such on- chip sensing technology is point-of-care (POC) drug testing due to the alarming spread in drug abuse, fuelled by the production of inexpensive, easy-to-manufacture drug variants. Existing testing methods, including gas chromatography with mass spectrometry (GC/MS) and high-performance liquid chromatography (HPLC), demand tedious sample preparation with expensive reagents and substantive operator expertise, and are ill- suited to clinical and law enforcement settings for POC testing. Diatomaceous earth, also known as diatomite, consists of fossilized remains of diatoms, a type of hard-shelled algae. As a type of abundant and cost-effective natural photonic biosilica from geological deposits, it has a variety of unique properties including highly porous micro- and nano-structures, excellent adsorption capacity, rich surface chemistry, and unique micro-fluidic properties. The objective of this R21 project is to develop a new on-chip chromatography technology coupled with SERS sensing using diatomaceous earth thin film, which can provide a portable, cost-effective solution to detect various illicit drugs in complex biological fluidic samples. Particularly in this project, we will apply this lab-on-chip technology for POC testing of cocaine and Marijuana. Briefly, we will spin coat ultra-thin (eventually down to monolayer around 5?m) diatomaceous earth on regular glass substrates, and integrate high-density plasmonic NPs through in-situ synthesis. This hybrid photonic-plasmonic nanostructured thin film will act simultaneously as a thin layer chromatography (TLC) to separate drug molecules from the complex biofluid and ultra-sensitive SERS substrates to probe the signature Raman peaks. Through the combination with commercially available portable Raman spectrometers, our diatomite TLC-SERS technology will enable rapid, multiplex POC sensing with high specificity. Compared with existing TLC-SERS methods based on silica gel plates, we expect our technology to achieve >100 enhanced sensitivity (down to <1ppm) due to the photonic crystal effect from diatom frustules and the ultra-small thickness of the multi-scale porous structure. Last but not the least, the wide availability and low cost (<$1/chip) of the multifunctional TLC-SERS substrates are perfectly suitable for POC drug testing of cocaine, marijuana, and other illicit drugs from urine, saliva and blood. We must point out that such TLC-SERS sensors can be readily applied for label-free sensing for many other applications such as food safety, water quality monitoring, and allergic biomarker detection.
(RELEVANCE) This project aims at developing a new on-chip chromatography technology coupled with surface-enhanced Raman scattering (SERS) sensing. Particularly, this project will focus on the detection of sub-ppm level cocaine and other illicit drugs from urine, plasma and saliva using diatomite thin film with high density plasmonic nanoparticles (NPs), which can separate drug molecules from complex biofluid and probe the signature Raman peaks with high specificity. The success of this project will enable a portable, sensitive, cost- effective solution for point-of-care drug testing.
|Kong, Xianming; Chong, Xinyuan; Squire, Kenny et al. (2018) Microfluidic Diatomite Analytical Devices for Illicit Drug Sensing with ppb-Level Sensitivity. Sens Actuators B Chem 259:587-595|
|Kong, Xianming; Li, Erwen; Squire, Kenny et al. (2017) Plasmonic nanoparticles-decorated diatomite biosilica: extending the horizon of on-chip chromatography and label-free biosensing. J Biophotonics 10:1473-1484|