Translating Clinical Chemistry to the Point-of-Care Using Surface-Enhanced Raman Spectroscopy
Abstract
Disease-identifying proteins, toxins and carcinogens, bacteria, viruses, cancerous cells, and many other biomarkers can all be found in the circulatory system, making the blood and other bodily fluids a diagnostic goldmine. Clinical chemistry: the analysis of bodily fluid components by pathologists, remains the most commonly used diagnostic tool, with the CDC estimating 6.8 billion various in-vitro laboratory tests performed per year by clinical pathologists. Conversely a staggering 87% of patient samples are sent to centralized laboratories. Lab-on-a-chip devices allow for low sample/reagent volumes, portability, and disposability, thereby automating sample preparation and analysis. Utilizing surface enhanced Raman spectroscopy (SERS) as the signal transduction method, ultra-low limits of detection can be achieved while also providing opportunities for high-throughput multiplexed assays.
Several SERS-on-a-chip sensor platforms were investigated, initially looking at both direct and indirect analysis of various biomarkers ranging from small molecules and single nucleotides, to labeled and unlabeled proteins. Finally, investigating deeply into the detection and isolation of non-immunogenic small molecule biomarkers from complex media, a competitive binding assay for detection of the small endocrine-disrupting toxin bisphenol-A (BPA) was developed. This assay has the potential to be translated to virtually any biomarker by utilizing aptamers: short synthetic ssDNA strands capable of binding to non-DNA targets. Specifically, this “turn off” competitive binding assay relies on aptamer-mediated assembly of SERRS active plasmonic and magnetic nanoparticles. Additionally, a magneto-fluidic SERS analysis chip for automated sample processing and quantification of BPA (0.2 pg/mL - 0.2 μg/mL) was developed. Last, this magnetic chip was attached to a blood filtration chip and the feasibility of the assay’s resilience in whole blood was analyzed.
This technology can potentially be made sensitive to other analytes by simply exchanging the aptamer - making the platform “programmable” The enablement of technologies like this help push medicine to become increasingly personalized, predictive, and preventative by moving away from initial symptom based diagnostics and towards fast, quantifiable monitoring.
Subject
Nanotechnologybiophotonics
colloidal nanoparticles
Raman scattering
point-of-care diagnostics
analytical biosensors
DNA aptamers
microfluidics
lab-on-a-chip technologies
Citation
Marks, Haley Lynn (2016). Translating Clinical Chemistry to the Point-of-Care Using Surface-Enhanced Raman Spectroscopy. Doctoral dissertation, Texas A&M University. Available electronically from https : / /hdl .handle .net /1969 .1 /187311.