Abstract
Accurate early diagnosis is critical to patient survival, management and quality of life. Biofluids are key to early diagnosis due to their ease of collection and intimate involvement in human function. Large-scale mid-IR imaging of dried fluid deposits offers a high-throughput molecular analysis paradigm for the biomedical laboratory. The exciting advent of tuneable quantum cascade lasers allows for the collection of discrete frequency infrared data enabling clinically relevant timescales. By scanning targeted frequencies spectral quality, reproducibility and diagnostic potential can be maintained while significantly reducing acquisition time and processing requirements, sampling 16 serum spots with 0.6, 5.1 and 15% relative standard deviation (RSD) for 199, 14 and 9 discrete frequencies respectively. We use this reproducible methodology to show proof of concept rapid diagnostics; 40 unique dried liquid biopsies from brain, breast, lung and skin cancer patients were classified in 2.4 cumulative seconds against 10 non-cancer controls with accuracies of up to 90%.
Highlights
Key objectives for new diagnostic systems for diseases such as cancer include improving patient outcome through the identification of earlier stages, monitoring drug resistance and identifying high-risk populations for tumour progression
Biomedical applications of FTIRM have been proved in research laboratories but despite a surge in technological advance and theoretical understanding[10], FTIRM has yet to be fully integrated into large-scale clinical application
Several studies have proven manual spotting of serum samples to be an adequate method of preparation for disease-state IR diagnostics[2,13,14]
Summary
Key objectives for new diagnostic systems for diseases such as cancer include improving patient outcome through the identification of earlier stages, monitoring drug resistance and identifying high-risk populations for tumour progression. While the method has been proven to provide cancer discrimination using blood serum[2], it does not offer high-throughput utility as it requires a liquid biopsy to be spotted and dried on the ATR crystal surface before the spectrum is recorded. FTIRM is fast proving to be a reliable research tool with clinical utility for disease-state diagnostics[4,5,6,7,8]. By using an infrared imaging approach, a high-throughput screening application can be realised for the biomedical laboratory; liquid biopsies that are dispensed and dried to create multi-patient micro-arrays to deliver rapid data collection, quality control and classification processes[3]. One of the technological caveats of the imaging technique is the requirement to scan the entire IR spectrum; a redundant approach as clinically relevant diagnostic markers are found at very specific frequencies. FTIRM in its current state of development is not considered to be an efficiently rapid and high-throughput technique per se
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