Peptide-based slides for improving the diagnostic quality of sputum specimens

SUMMARY ABSTRACT Lung cancer is the leading cause of cancer related mortality in both men and women in United States with a dismal year survival rate of While surgery is the only curative option of the patients are diagnosed with inoperable advanced disease thus highlighting a lack of effective early screening methods Typically low dose computed tomography LDCT is used as the primary screening modality however of suspicious lung lesions identified by LDCT eventually are found to be benign As a result such patients undergo medically unnecessary procedures and treatments resulting in increased cost time and morbidity Hence there is an urgent need to develop a non invasive complementary screening technique which can identify the high risk population for lung cancer and thus enable detection of lung lesions at an early and potentially curable stage To this end cytological and molecular aberrations found in exfoliated bronchial epithelial cells in sputum of smokers have shown a strong correlation to lung cancer incidence However these diagnostically important cells represent less than of the cellular composition of sputum thus making their detection extremely challenging Hence it is essential to develop a method which can isolate and capture these scant yet important cells while removing the other obscuring cells from sputum and thereby improve the clinical utility of these vital biospecimens The goal of this Phase I application is to develop a novel peptide coated glass slide which can selectively capture and retain the epithelial cells of interest in a peptide modified region while moving the obscuring cells to a separate region of the slide Epithelial cell capture on the peptide modified slides will be first optimized to identify lead peptides for subsequent clinical testing Thereafter compatibility of the peptide modified slides with commonly employed clinical staining techniques will be established Finally the feasibility of using these peptide modified slides for capturing cells from human sputum specimens will be validated Successful completion of this project will not only allow for better visualization of the captured epithelial cells to the clinicians but also enable further downstream processing of these cells to identify molecular and or genetic atypia present because of the non destructive nature of this technology PROJECT NARRATIVE An overabundance of blood cells dilute the already scant epithelial cells of interest in sputum making diagnosis of lung malignancies extremely challenging and eventually resulting in additional invasive testing In this application we propose to develop a novel method for preparing optimal sputum smears and thereby maximize the clinical utility of these vital biospecimens for enabling downstream molecular analysis and ultimately preventing medically unnecessary procedures surgeries