Cellphone enabled point-of-care assessment of breast tumor cytology and molecular HER2 expression from fine-needle aspirates

Abstract

Management of breast cancer in limited-resource settings is hindered by a lack of low-cost, logistically sustainable approaches toward molecular and cellular diagnostic pathology services that are needed to guide therapy. To address these limitations, we have developed a multimodal cellphone-based platform—the EpiView-D4—that can evaluate both cellular morphology and molecular expression of clinically relevant biomarkers directly from fine-needle aspiration (FNA) of breast tissue specimens within 1 h. The EpiView-D4 is comprised of two components: (1) an immunodiagnostic chip built upon a “non-fouling” polymer brush-coating (the “D4”) which quantifies expression of protein biomarkers directly from crude cell lysates, and (2) a custom cellphone-based optical microscope (“EpiView”) designed for imaging cytology preparations and D4 assay readout. As a proof-of-concept, we used the EpiView-D4 for assessment of human epidermal growth factor receptor-2 (HER2) expression and validated the performance using cancer cell lines, animal models, and human tissue specimens. We found that FNA cytology specimens (prepared in less than 5 min with rapid staining kits) imaged by the EpiView-D4 were adequate for assessment of lesional cellularity and tumor content. We also found our device could reliably distinguish between HER2 expression levels across multiple different cell lines and animal xenografts. In a pilot study with human tissue (n = 19), we were able to accurately categorize HER2-negative and HER2-positve tumors from FNA specimens. Taken together, the EpiView-D4 offers a promising alternative to invasive—and often unavailable—pathology services and may enable the democratization of effective breast cancer management in limited-resource settings.

Environmentally Resilient Microfluidic Point-of-Care Immunoassay Enables Rapid Diagnosis of Talaromycosis

“…The D4 is a fluorescence-based POC immunoassay platform developed in our laboratory for diverse applications including breast cancer detection, Ebola virus diagnostics, and most recently for the serological profiling of SARS-CoV-2 and its variants . The D4 is a completely “self-contained” immunoassay built on a nonfouling poly­(oligoethylene glycol methyl ether methacrylate) (POEGMA) brush grafted from silica glass, as described in more detail elsewhere. , All antibodies are printed directly onto the POEGMA brush by inkjet printing.…”

Smartphone-based platforms implementing microfluidic detection with image-based artificial intelligence

“…The binding reaction between antibody and antigen can be directly used for protein detection. For example, Joh et al developed a mHealth platform that was comprised of a custom cellphone-based optical microscope and an immunodiagnostic chip built upon a non-fouling polymer brush-coating that could quantify the expression of protein biomarkers directly from crude cell lysates 114 (Fig. 8b).…”

Point‐of‐care optical devices in clinical imaging and screening: A review on the state of the art

“…An integrated immunofluorescence‐based single‐cell analyzer (i2SCAN) for comprehensive profiling of fine‐needle aspirates or core tissue samples from breast cancer has recently been reported [64]. The device uses a multiplex imaging system and a cyclic antibody panel to enable the detection of multiple biomarkers.…”