Rapid analysis of disease state in liquid human serum combining infrared spectroscopy and “digital drying”

Abstract

In recent years, the diagnosis of brain tumors has been investigated with attenuated total reflection‐Fourier transform infrared (ATR‐FTIR) spectroscopy on dried human serum samples to eliminate spectral interferences of the water component, with promising results. This research evaluates ATR‐FTIR on both liquid and air‐dried samples to investigate “digital drying” as an alternative approach for the analysis of spectra obtained from liquid samples. Digital drying approaches, consisting of water subtraction and least‐squares method, have demonstrated a greater random forest (RF) classification performance than the air‐dried spectra approach when discriminating cancer vs control samples, reaching sensitivity values higher than 93.0% and specificity values higher than 83.0%. Moreover, quantum cascade laser infrared (QCL‐IR) based spectroscopic imaging is utilized on liquid samples to assess the implications of a deep‐penetration light source on disease classification. The RF classification of QCL‐IR data has provided sensitivity and specificity amounting to 85.1% and 75.3% respectively.

Biofluid analysis and classification using IR and 2D-IR spectroscopy

“…A 5-fold cross validation procedure was performed where 80% of the 2nd derivative spectra of patient samples were used to train the RF algorithm and the remaining 20% were used to test the model, yielding a sensitivity and specificity up to 92.8% and 91.5%, respectively. RF analysis applied to digitally dried serum spectra from 150 patients has been shown to classify brain cancer and non-cancer with a sensitivity of 93.7% and specificity of 84.0% [46]. This study demonstrates an increase in sensitivity and specificity compared to the values obtained from the analysis of the same serum samples in liquid form or air dried, providing greater accuracy in a much quicker timeframe when compared to the analysis of dried samples.…”

“…The impact of water absorptions in biological spectra is a common topic of discussion and as such different methods have been applied to remove the water contribution from the signal [1,11,46,47]. For example, methodologies using liquid samples may require the subtraction of a background water spectrum after acquisition [46], although this is often a subjective process and difficulties in producing optical pathlengths less than 10 μm have been documented [48].…”

“…The impact of water absorptions in biological spectra is a common topic of discussion and as such different methods have been applied to remove the water contribution from the signal [1,11,46,47]. For example, methodologies using liquid samples may require the subtraction of a background water spectrum after acquisition [46], although this is often a subjective process and difficulties in producing optical pathlengths less than 10 μm have been documented [48]. Some methodologies may involve dried droplets of biofluids whereby the water content of the fluid is decreased removing the need for water subtractions [49][50][51], however drying patterns are observed which has been noted to introduce experimental difficulties.…”

“…Random forest (RF) is a classifier based on a collective of decision trees and has shown promise in its analysis of data from biofluids [46,68,71]. A single tree represents a sequence of binary steps on single variables whereby in this scenario each variable is a wavenumber (Fig.…”

Grade Diagnosis of Human Glioma Based on Fingerprint and Artificial Neural Network

“…Therefore, a complementary approach based on a rapid, accurate, objective and quantitative analysis tool could provide classification advice for aggressive diseases for clinicians. Spectroscopy including FTIR, Raman and Terahertz are valuable instruments that have been used for studying molecular component changes in lipids, proteins and nucleic acids in biological samples, such as biological fluids, tissues, and cancer cell lines [4][5][6][7][8][9][10][11][12]. The commonly method of FTIR mainly relies on the resonant frequencies of the molecular bonds, which result 6 in some absorption peaks when the transmission electromagnetic waves are collected by a detector of the interferometer [13].…”