Over 75% lung cancer patients are not diagnosed until at advanced or metastatic stage with <5% 5-year survival rate. A panel of microRNAs (miRNAs) in blood, urine and other body fluids were found to be lung cancer biomarkers. Thus, we propose to develop miRNA-based low-cost, untrasensitive (<1 ul serum needed) and fast responsive point-of-care (POC) chips using multiplex nanowell technology for early diagnosis, prognosis and response to therapy of lung cancer at clinics. During Phase I, label-free ultrasensitive lung cancer specific-nanowell arrays will be developed using ~10 miRNA standards for non-small cell lung cancer (NSCLC, ~80% of lung cancer cases), and utility will be explored using NSCLC and normal lung cell lines. Levels of the 10 miRNAs in sera from ~30 NSCLC patients and 30 matching healthy subjects will be determined using the arrays to verify NSCLC-specific miRNA signatures for clinical use. During Phase II, we will screen thousands of lung cancer patients' sera using the miRNA nanowell technology to confirm the lung cancer miRNA signatures and develop a finger prick test. We will also develop miRNA nanowell technologies for other cancers. We will apply for an FDA approval of the miRNA nanowell devices for cancer diagnosis at clinics.