Abstract
High-throughput partial wave spectroscopy (HTPWS) is introduced as a high-speed spectral nanocytology technique that utilizes the field effect of carcinogenesis to perform minimally invasive cancer screening on at-risk populations. HTPWS uses fully automated hardware and an acousto-optic tunable filter to scan slides at low magnification, to select cells, and to rapidly acquire spectra at each spatial pixel in a cell between 450 and 700 nm, completing measurements of 30 cells in 40 min. Statistical quantitative analysis on the size and density of intracellular nanostructures extracted from the spectra at each pixel in a cell yields the diagnostic biomarker, disorder strength (Ld). Linear correlation between Ld and the length scale of nanostructures was measured in phantoms with R2=0.93. Diagnostic sensitivity was demonstrated by measuring significantly higher Ld from a human colon cancer cell line (HT29 control vector) than a less aggressive variant (epidermal growth factor receptor knockdown). Clinical diagnostic performance for lung cancer screening was tested on 23 patients, yielding a significant difference in Ld between smokers and cancer patients, p=0.02 and effect size=1.00. The high-throughput performance, nanoscale sensitivity, and diagnostic sensitivity make HTPWS a potentially clinically relevant modality for risk stratification of the large populations at risk of developing cancer.
Highlights
In the United States, cancer continues to be a critical health care issue, ranking as the second leading cause of death behind cardiovascular disease.[1]
We have shown that via the field effect of carcinogenesis, nanoarchitectural changes associated with the development of different types of cancers are detectable in cells further away from the location of the actual tumor using partial wave spectroscopic (PWS) microscopy.[15,16,17]
We present a completed prototype for High-throughput partial wave spectroscopy (HTPWS) measurements that has the potential to become a tool for automated cancer nanocytology
Summary
In the United States, cancer continues to be a critical health care issue, ranking as the second leading cause of death behind cardiovascular disease.[1]. The current gold standard for detection of most major cancers remains performing imaging using techniques such as CT, MRI, X-ray, and positron emission tomography on symptomatic individuals followed by a diagnosis confirmed with tissue collection via biopsy or fine-needle aspiration. All of these techniques have proven to be either unrealistic due to cost and/or risk or ineffective as screening modalities for early detection in at-risk populations.[2] In particular, none of the aforementioned techniques can be feasibly implemented in a primary-care setting for the stratification of a large at-risk population. Development of minimally invasive screening techniques for cancer is critical in order to identify individuals with abnormalities requiring more invasive investigation and to help stratify the high-risk
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