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

Praveen Bandaru; Dafeng Chu; Wujin Sun; Soufian Lasli; Chuanzhen Zhao; Shuang Hou; Shiming Zhang; Jiahua Ni; Giorgia Cefaloni; Samad Ahadian; Mehmet Remzi Dokmeci; Shiladitya Sengupta; Junmin Lee; Ali Khademhosseini

doi:10.1002/smll.201900300

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

Small. 2019 Apr;15(15):e1900300. doi: 10.1002/smll.201900300. Epub 2019 Mar 18.

Authors

Praveen Bandaru^{1

2}, Dafeng Chu^{1

2}, Wujin Sun^{1

2}, Soufian Lasli^{1

2}, Chuanzhen Zhao³, Shuang Hou⁴, Shiming Zhang^{1

2}, Jiahua Ni^{1

2}, Giorgia Cefaloni^{1

2}, Samad Ahadian^{1

2}, Mehmet Remzi Dokmeci^{2

5}, Shiladitya Sengupta^{6

7}, Junmin Lee^{1

2}, Ali Khademhosseini^{1

2

5

8}

Affiliations

¹ Department of Bioengineering, Henry Samueli School of Engineering and Applied Sciences, University of California-Los Angeles, Los Angeles, CA, 90095, USA.
² Center for Minimally Invasive Therapeutics (C-MIT), University of California-Los Angeles, Los Angeles, CA, 90095, USA.
³ Department of Chemistry and Biochemistry, University of California-Los Angeles, Los Angeles, CA, 90095, USA.
⁴ Department of Molecular and Medical Pharmacology, University of California-Los Angeles, Los Angeles, CA, 90095, USA.
⁵ Department of Radiology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, 90095, USA.
⁶ Department of Medicine, Division of Engineering in Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, 02139, USA.
⁷ Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
⁸ Department of Chemical and Biomolecular Engineering, Henry Samueli School of Engineering and Applied Sciences, University of California-Los Angeles, Los Angeles, CA, 90095, USA.

PMID: 30884183
DOI: 10.1002/smll.201900300

Abstract

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.

Keywords: drug screening; high-throughput screening; micropillars; microwells.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Antibodies / analysis
Biomarkers / analysis*
Cell Count
Cell Line, Tumor
Cell Proliferation
Cell Survival
Drug Delivery Systems
Drug Evaluation, Preclinical
High-Throughput Screening Assays / methods*
Humans
Mice
Microtechnology / methods*

Substances

Antibodies
Biomarkers

Abstract

Publication types

MeSH terms

Substances

Grants and funding