Title: Towards microfluidic reactors for cell-free protein synthesis at the point-of-care

Abstract

Cell-free protein synthesis (CFPS) is a powerful technology that allows for optimization of protein production without maintenance of a living system. Integrated within micro- and nano-fluidic architectures, CFPS can be optimized for point-of care use. Here, we describe the development of a microfluidic bioreactor designed to facilitate the production of a single-dose of a therapeutic protein, in a small footprint device at the point-of-care. This new design builds on the use of a long, serpentine channel bioreactor and is enhanced by integrating a nanofabricated membrane to allow exchange of materials between parallel reactor and feeder channels. This engineered membrane facilitates the exchange of metabolites, energy, and inhibitory species, prolonging the CFPS reaction and increasing protein yield. Membrane permeability can be altered by plasma-enhanced chemical vapor deposition and atomic layer deposition to tune the exchange rate of small molecules. This allows for extended reaction times and improved yields. Further, the reaction product and higher molecular weight components of the transcription/translation machinery in the reactor channel can be retained. As a result, we show that the microscale bioreactor design produces higher protein yields than conventional tube-based batch formats, and that product yields can be dramatically improved by facilitating small molecule exchange withinmore » the dual-channel bioreactor.« less

Authors:

Timm, Andrea C. ^[1]; Shankles, Peter G. ^[2]; Foster, Carmen M. ^[1]; Doktycz, Mitchel John ^[2]; Retterer, Scott T. ^[2]

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+ Show Author Affiliations

1. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
2. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Univ. of Tennessee, Knoxville, TN (United States)

Publication Date:

Tue Dec 22 00:00:00 EST 2015

Research Org.:

Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Org.:

Work for Others (WFO)

OSTI Identifier:

1238743

Grant/Contract Number:  

AC05-00OR22725

Resource Type:

Accepted Manuscript

Journal Name:

Small

Additional Journal Information:

Journal Volume: 12; Journal Issue: 6; Journal ID: ISSN 1613-6810

Publisher:

Wiley

Country of Publication:

United States

Language:

English

Subject:

60 APPLIED LIFE SCIENCES