A cost-effective fluorescence mini-microscope for biomedical applications

Yu Shrike Zhang; João Ribas; Akhtar Nadhman; Julio Aleman; Šeila Selimović; Sasha Cai Lesher-Perez; Ting Wang; Vijayan Manoharan; Su-Ryon Shin; Alessia Damilano; Nasim Annabi; Mehmet Remzi Dokmeci; Shuichi Takayama; Ali Khademhosseini

doi:10.1039/C5LC00666J

A cost-effective fluorescence mini-microscope for biomedical applications†‡

Yu Shrike Zhang,

^ab João Ribas,^abcd Akhtar Nadhman,^abe Julio Aleman,§^ab Šeila Selimović,§^ab Sasha Cai Lesher-Perez,^f Ting Wang,^abg Vijayan Manoharan,^ab Su-Ryon Shin,^abh Alessia Damilano,^ab Nasim Annabi,^abi Mehmet Remzi Dokmeci,^abh Shuichi Takayama^fjk and Ali Khademhosseini*^abhl

Author affiliations

* Corresponding authors

^a Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA
E-mail: alik@rics.bwh.harvard.edu

^b Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA

^c Doctoral Programme in Experimental Biology and Biomedicine, Center for Neuroscience and Cell Biology, Institute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal

^d Biocant — Biotechnology Innovation Center, 3060-197 Cantanhede, Portugal

^e Biotechnology Department, Quaid-i-Azam University, Islamabad 45320, Pakistan

^f Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109 USA

^g Department of Optical Engineering, Zhejiang University, Hangzhou 310027, China

^h Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02139, USA

ⁱ Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA

^j Department of Macromolecular Science and Engineering, University of Michigan, Ann Arbor, MI 48109, USA

^k Division of Nano-Bio and Chemical Engineering WCU Project, UNIST, Ulsan, Republic of Korea

^l Department of Physics, King Abdulaziz University, Jeddah 21569, Saudi Arabia

Abstract

We have designed and fabricated a miniature microscope from off-the-shelf components and a webcam, with built-in fluorescence capability for biomedical applications. The mini-microscope was able to detect both biochemical parameters, such as cell/tissue viability (e.g. live/dead assay), and biophysical properties of the microenvironment such as oxygen levels in microfabricated tissues based on an oxygen-sensitive fluorescent dye. This mini-microscope has adjustable magnifications from 8–60×, achieves a resolution as high as <2 μm, and possesses a long working distance of 4.5 mm (at a magnification of 8×). The mini-microscope was able to chronologically monitor cell migration and analyze beating of microfluidic liver and cardiac bioreactors in real time, respectively. The mini-microscope system is cheap, and its modularity allows convenient integration with a wide variety of pre-existing platforms including, but not limited to, cell culture plates, microfluidic devices, and organs-on-a-chip systems. Therefore, we envision its widespread application in cell biology, tissue engineering, biosensing, microfluidics, and organs-on-chips, which can potentially replace conventional bench-top microscopy where long-term in situ and large-scale imaging/analysis is required.

This article is part of the themed collection: Lab on a Chip Pioneers of Miniaturization Lectureship winners

Lab on a Chip

A cost-effective fluorescence mini-microscope for biomedical applications†‡

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A cost-effective fluorescence mini-microscope for biomedical applications

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