A Microfabricated Sandwiching Assay for Nanoliter and High‐Throughput Biomarker Screening

• Published in: Small (Weinheim an der Bergstrasse, Germany) Germany), 2019-04, Vol.15 (15), p.e1900300-n/a
• Main Authors: Bandaru, Praveen, Chu, Dafeng, Sun, Wujin, Lasli, Soufian, Zhao, Chuanzhen, Hou, Shuang, Zhang, Shiming, Ni, Jiahua, Cefaloni, Giorgia, Ahadian, Samad, Dokmeci, Mehmet Remzi, Sengupta, Shiladitya, Lee, Junmin, Khademhosseini, Ali
• Format: Article
• Language: English
• Subjects: Arrays; Assaying; Biomarkers; Biomolecules; Drug delivery systems; drug screening; high‐throughput screening; Immunology; Interleukins; Microfluidics; micropillars; microwells; Nanotechnology; Screening; Secretions
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.201900300

Cells secrete substances that are essential to the understanding of numerous immunological phenomena and are extensively used in clinical diagnoses. Countless techniques for screening of biomarker secretion in living cells have generated valuable information on cell function and physiology, but low volume and real‐time analysis is a bottleneck for a range of approaches. Here, a simple, highly sensitive assay using a high‐throughput micropillar and microwell array chip (MIMIC) platform is presented for monitoring of biomarkers secreted by cancer cells. The sensing element is a micropillar array that uses the enzyme‐linked immunosorbent assay (ELISA) mechanism to detect captured biomolecules. When integrated with a microwell array where few cells are localized, interleukin 8 (IL‐8) secretion can be monitored with nanoliter volume using multiple micropillar arrays. The trend of cell secretions measured using MIMICs matches the results from conventional ELISA well while it requires orders of magnitude less cells and volumes. Moreover, the proposed MIMIC is examined to be used as a drug screening platform by delivering drugs using micropillar arrays in combination with a microfluidic system and then detecting biomolecules from cells as exposed to drugs. In this work, a simple and low‐cost but sensitive, low‐volume, and scalable bioassay for monitoring of biomarkers with orders of magnitude less cells and sample volume is developed. The combination of microwell arrays as a cell culture substrate and micropillar arrays for drug delivery or biomolecular detection in response to drugs enables drug screening in one platform.