Evaluation of a Peak-Free Chemometric Laser-Induced Breakdown Spectroscopy Method for Direct Rapid Cancer Detection via Trace Metal Biomarkers in Tissue

Abstract

The ability to perform direct rapid analysis in air and at atmospheric pressure is a remarkable attraction of laser-induced breakdown spectroscopy (LIBS) for the diagnostic quantification of disease biomarker metals in body tissue. However, accurate trace analysis is limited by matrix effects and a pronounced background that masks the subtle (peak-free) analyte signals because tissue plasma is dense and most lines are optically thick. In this work, a peak-free chemometric LIBS method based on a single-shot (for rapidity and nondestructiveness) and an artificial neural network multivariate calibration strategy with spectral feature selection was evaluated for its utility for direct trace quantitative analysis of copper (Cu), iron (Fe), manganese (Mg), magnesium (Mg), and zinc (Zn) in model soft body tissue. The spectral signatures corresponding to the biometals (so-called because the metals are intrinsic to tissue biochemistry) were generated by spiking their known human-body-representative concentrations in molten paraffin wax. The developed multivariate analytical model achieved ≥95% accuracy as determined from the analysis of oyster tissue-certified reference material. The analytical models were tested on the liver, breast, and abdominal tissue biopsies. The results of applying the model to the clinical tissues indicated the absence or presence (including severity) of cancer as either malignant or benign, in agreement with the pathological examination report.

Laser-Induced Breakdown Spectroscopy in Biological Samples: A Review of Experiments with Soft Tissues

“…Although the area of knowledge is broad, the main emphasis is on research relevant to human tissues. In [49], the authors trained the ANN with a set of samples prepared as a human tissue model, together with a NIST standard reference sample. As a consequence, concentrations of Cu, Fe, Mn, Mg, and Zn were successfully predicted in human cancer tissue samples.…”

“…To obtain this, they immersed thyroids from untreated subjects into lithium solutions with 0, 0.28, 0.37, 0.55, and 1.10 ppm. In [49], a multivariate calibration strategy was employed by using a model tissue. This was prepared with a set of samples containing Fe, Mg, Zn, Cu, and Mn, with concentrations in the range in which they occur in human body tissues.…”

“…that plasma temperature and electron density were also higher for cancerous tissues. In 2022, [49] successfully differentiated malign and benign liver tissues by detecting trace amounts of biometals by LIBS on a single shot. Previously, a model of calibration was developed by using samples prepared with concentrations selected in the ranges in which they occur in the human soft body tissues.…”