Microfluidic chemostat and turbidostat with flow rate, oxygen, and temperature control for dynamic continuous culture

Lee, Kevin M.; Boccazzi, Paolo; Sinskey, Anthony J.; Ram, Rajeev J.

doi:10.1039/c1lc20019d

Cited by 98 publications

(113 citation statements)

References 27 publications

(32 reference statements)

Supporting

Mentioning

111

Contrasting

Order By: Relevance

“…Alternatively, mechanical flow actuation seems to be a more feasible approach. For example, Lee et al (2011b) worked on a micro-mixer composed of three interconnected deformable growth chambers. The corresponding mixing was achieved through deflections of the PDMS membranes in a peristaltic manner.…”

Section: Electronic Supplementary Materialsmentioning

confidence: 99%

Mixing in an enclosed microfluidic chamber through moving boundary motions

Yang

Sun

et al. 2015

Microfluid Nanofluid

View full text Add to dashboard Cite

show abstract

Section: Electronic Supplementary Materialsmentioning

confidence: 99%

Mixing in an enclosed microfluidic chamber through moving boundary motions

Yang

Sun

et al. 2015

Microfluid Nanofluid

View full text Add to dashboard Cite

show abstract

“…These microfluidic bioreactors allow environmental control but do not facilitate single cell resolution for longer time periods. 19 Secondly, microfluidic devices for biotechnological single cell studies including, e.g., phenotypic population heterogeneity 20 and single cell growth. 20,21 Our intention is a combination of both approaches, to be specific, a microfluidic device allowing environmental reactor control at a defined culture volume and continuous single cell observation simultaneously.…”

Section: Introductionmentioning

confidence: 99%

A disposable picolitre bioreactor for cultivation and investigation of industrially relevant bacteria on the single cell level

et al. 2012

View full text Add to dashboard Cite

In the continuously growing field of industrial biotechnology the scale-up from lab to industrial scale is still a major hurdle to develop competitive bioprocesses. During scale-up the productivity of single cells might be affected by bioreactor inhomogeneity and population heterogeneity. Currently, these complex interactions are difficult to investigate. In this report, design, fabrication and operation of a disposable picolitre cultivation system is described, in which environmental conditions can be well controlled on a short time scale and bacterial microcolony growth experiments can be observed by time-lapse microscopy. Three exemplary investigations will be discussed emphasizing the applicability and versatility of the device. Growth and analysis of industrially relevant bacteria with single cell resolution (in particular Escherichia coli and Corynebacterium glutamicum) starting from one single mother cell to densely packed cultures is demonstrated. Applying the picolitre bioreactor, 1.5-fold increased growth rates of C. glutamicum wild type cells were observed compared to typical 1 litre labscale batch cultivation. Moreover, the device was used to analyse and quantify the morphological changes of an industrially relevant L-lysine producer C. glutamicum after artificially inducing starvation conditions. Instead of a one week lab-scale experiment, only 1 h was sufficient to reveal the same information. Furthermore, time lapse microscopy during 24 h picolitre cultivation of an arginine producing strain containing a genetically encoded fluorescence sensor disclosed time dependent single cell productivity and growth, which was not possible with conventional methods.

show abstract

“…23 Many microfluidic cell culture devices contain membranes to provide nutrients to the cells or control movement of cells through the device. [24][25][26][27][28][29][30] Microhabitat patches developed by the Austin group were used to limit transport of nutrients in order to study bacterial competition. 27,[31][32][33] However, a majority of current microfluidic cell culture chambers either deal with larger mammalian cells rather than smaller bacterial cells, 25 or are fabricated in silicon, 27,29 which are slower to fabricate and limit the use of transmitted light microscopy compared to polydimethylsiloxane (PDMS) devices.…”

Section: Introductionmentioning

confidence: 99%

Fabrication of nanoporous membranes for tuning microbial interactions and biochemical reactions

Shankles

Timm

Doktycz

et al. 2015

Journal of Vacuum Science &Amp; Technology B, Nanotechnology and Microelectronics: Materials, Processing, Measurement, and Phen

View full text Add to dashboard Cite

New strategies for combining conventional photo-and soft-lithographic techniques with highresolution patterning and etching strategies are needed in order to produce multiscale fluidic platforms that address the full range of functional scales seen in complex biological and chemical systems. The smallest resolution required for an application often dictates the fabrication method used. Micromachining and micropowder blasting yield higher throughput, but lack the resolution needed to fully address biological and chemical systems at the cellular and molecular scales. In contrast, techniques such as electron beam lithography or nanoimprinting allow nanoscale resolution, but are traditionally considered costly and slow. Other techniques such as photolithography or soft lithography have characteristics between these extremes. Combining these techniques to fabricate multiscale or hybrid fluidics allows fundamental biological and chemical questions to be answered. In this study, a combination of photolithography and electron beam lithography are used to produce two multiscale fluidic devices that incorporate porous membranes into complex fluidic networks in order to control the flow of energy, information, and materials in chemical form. In the first device, materials and energy were used to support chemical reactions. A nanoporous membrane fabricated with e-beam lithography separates two parallel, serpentine channels. Photolithography was used to pattern microfluidic channels around the membrane. The pores were written at 150 nm and reduced in size with silicon dioxide deposition from plasma enhanced chemical vapor deposition and atomic layer deposition. Using this method, the molecular weight cutoff of the membrane can be adapted to the system of interest. In the second approach, photolithography was used to fabricate 200 nm thin pores. The pores confined microbes and allowed energy replenishment from a media perfusion channel. The same device can be used for study of intercellular communication via the secretion and uptake of signal molecules. Pore size was tested with 750 nm fluorescent polystyrene beads and fluorescein dye. The 200 nm polydimethylsiloxane pores were shown to be robust enough to hold 750 nm beads while under pressure, but allow fluorescein to diffuse across the barrier. Further testing showed that extended culture of bacteria within the chambers was possible. These two examples show how lithographically defined porous membranes can be adapted to two unique situations and used to tune the flow of chemical energy, materials, and information within a microfluidic network.

show abstract

Microfluidic chemostat and turbidostat with flow rate, oxygen, and temperature control for dynamic continuous culture

Cited by 98 publications

References 27 publications

Mixing in an enclosed microfluidic chamber through moving boundary motions

Mixing in an enclosed microfluidic chamber through moving boundary motions

A disposable picolitre bioreactor for cultivation and investigation of industrially relevant bacteria on the single cell level

Fabrication of nanoporous membranes for tuning microbial interactions and biochemical reactions

Contact Info

Product

Resources

About