Microbioreactors

Project Description

Micronit has been involved in several projects for developing microbioreactors based on microfluidics. Microbioreactors for culturing cells, tissue or microorganisms are of interest for several (bio)medical and pharmaceutical applications like tissue engineering, organ-on-chip and high-throughput drug screening. The integration of complex microfluidic flow networks with culture chambers/microwells into a biochip is one of Micronit’s core competences.

One example of using this microbioreactor technology in a potential (high-throughput) pharmaceutical application is the development of a zebrafish embryo microfluidic flow-through system. This project has been carried out together with the Institute of Biology at Leiden University. A summary of the published paper [1] is given below.

ZEBRAFISH EMBRYO DEVELOPMENT IN A MICROFLUIDIC FLOW-THROUGH SYSTEM

(Adapted from Ref. 1 with permission from The Royal Society of Chemistry)

Zebrafish embryos are commonly cultured in microtitre plates using cell culture protocols with static buffer replacement. Such protocols are highly invasive, consume large quantities of reagents and do not readily permit high-quality imaging. Zebrafish embryos have previously been cultured in static microfluidic drops and have also been raised in a prototype PDMS setup in a Petri dish. Other than this, no animal embryo has ever been shown to undergo embryonic development in a microfluidic flow-through system. A specialized lab-on-a-chip has been developed and prototyped, made from bonded layers of borosilicate glass.

The zebrafish embryos can develop in the chip for 5 days, with continuous buffer flow at pressures of 0.005–0.04 MPa. Survival rates of 100% could be reached with buffer flows of 2 ml per well per min. High quality imaging was possible. More than 100 embryos could be cultured in an area, excluding infrastructure, smaller than a credit card. This paper discusses how biochip technology, coupled with zebrafish embryos, could allow biological research to be conducted in massive, parallel experiments, at high speed and low cost.

zebrafishbiochip2

An example of a 32-microwell biochip (microbioreactor) used for zebrafish embryo development. [Lab Chip, 2011, 11, 1815-1824] – Reproduced by permission of The Royal Society of Chemistry.

zebrafishdevelopmentmicrowell2

zebrafishdevelopmentmicrowell2:

Zebrafish embryo cultured in one microwell of a biochip (microbioreactor) from 8 hours post-fertilisation (8hpf) up to 4 days post-fertilisation (4dpf). [Lab Chip, 2011, 11, 1815-1824] – Reproduced by permission of The Royal Society of Chemistry.

zebrafishbiochip2

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