Exploring the Clinical Utility of Raman Spectroscopy for Point-of-Care Cardiovascular Disease Biomarker Detection

Abstract

A variety of innovative point-of-care (POC) solutions using Raman systems have been explored. However, the vast effort is in assay development, while studies of the characteristics required for Raman spectrometers to function in POC applications are lacking. In this study, we tested and compared the performance of eight commercial Raman spectrometers ranging in size from benchtop Raman microscopes to portable and handheld Raman spectrometers using paper fluidic cartridges, including their ability to detect cardiac troponin I and heart fatty acid binding protein, both of which are well-established biomarkers for evaluating cardiovascular health. Each spectrometer was evaluated in terms of excitation wavelength, laser characteristics, and ease of use to investigate POC utility. We found that the Raman spectrometers equipped with 780 and 785 nm laser sources exhibited a reduced background signal and provided higher sensitivity compared to those with 633 and 638 nm laser sources. Furthermore, the spectrometer equipped with the single acquisition line readout functionality showed improved performance when compared to the point scan spectrometers and allowed measurements to be made faster and easier. The portable and handheld spectrometers also showed similar detection sensitivity to the gold standard instrument. Lastly, we reduced the laser power for the spectrometer with single acquisition line readout capability to explore the system performance at a laser power that change the classification from a Class 3B laser device to a Class 3R device and found that it showed comparable performance. Overall, these findings show that portable Raman spectrometers have the potential to be used in POC settings with accuracy comparable to laboratory-grade instruments, are relatively low-cost, provide fast signal readout, are easy to use, and can facilitate access for underserved communities.

Improved point-of-care detection of P. gingivalis using optimized surface-enhanced Raman scattering in lateral flow assays

“…This type of system has been previously tested with SERS–LFA showing clinically significant results. 32,33 Herein, we tested a ‘hand-held’ SERS–LFA scanner prototype from Wasatch Photonics designed for LFA-based POC applications. This system is battery operated, portable (85 × 55 × 30 mm) and the laser excitation has been designed to form a line shape, to maximize signal from typical LFA strips.…”

“…More recently, to improve user accessibility, portable Raman systems have been demonstrated for measurement of SERS–LFAs. 28,32,33 This affordable and easy-to-use portable system enables SERS–LFAs to be used for POC applications.…”

Biosensing Platforms for Cardiac Biomarker Detection

“…171 SERS methods utilize the significant Raman scattering amplification afforded by the close association of Raman-active dyes or biomarkers with plasmonic metal nanostructures to detect targets of interest sensitively and specifically. 172 Wang et al developed a microcavity-based SERS biosensor for CK-MB and cTnI detection. Anti CK-MB and anti-cTnI monoclonal antibodies were immobilized on the microcavity-based SERS biosensor together with gold nanoparticles to form an immune chip on the Au−PS-PDA microcavity substrate.…”

“…SERS methods utilize the significant Raman scattering amplification afforded by the close association of Raman-active dyes or biomarkers with plasmonic metal nanostructures to detect targets of interest sensitively and specifically. 172 Wang et al. developed a microcavity-based SERS biosensor for CK-MB and cTnI detection.…”

Biomarkers and optical based biosensors in cardiac disease detection: early and accurate diagnosis

“…Using Raman spectroscopy not only can we develop noninvasive and label-free vibrational optical-based biosensors but also innovative pointof-care (POC) devices can be designed for clinical diagnosis of cardiovascular diseases. 123 Numerous works have been conducted to detect the cTnI cardiac biomarker in MI-related patients. To achieve low LOD, researchers prepared optical microspheres using silver nanoparticles.…”