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Micromachines
Special Issues
Bioprocess Microfluidics
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Bioprocess Microfluidics

A special issue of Micromachines (ISSN 2072-666X). This special issue belongs to the section "B：Biology and Biomedicine".

Deadline for manuscript submissions: closed (15 July 2021) | Viewed by 12090

Special Issue Editors

Dr. Marco P.C. Marques

E-Mail Website
Guest Editor
Department of Biochemical Engineering, University College London, London WC1E 6BT, UK
Interests: flow biocatalysis; enzyme kinetic modeling; reactor design and scale-up; continuous flow; microfluidic reactors; green/sustainable synthesis
Prof. Dr. Nicolas Szita

E-Mail Website
Guest Editor
Department of Biochemical Engineering, University College London, London WC1E 6BT, UK
Interests: multi-enzyme microreactors; microfluidic cell culture devices; microbioreactors; system-wide integration of novel analytical tools; whole bioprocess sequences

Special Issue Information

Dear Colleagues,

Scale-down approaches have long been applied in bioprocessing to resolve scale-up problems. In early-stage process development, miniaturized bioreactors have thrived as tools to process relevant data with a minimum amount of labor and at a minimum cost. Microfluidic devices are an attractive alternative in bioprocessing development due to the high degree of control over process variables afforded by the laminar flow and the possibility to reduce time and cost factors. Data quality obtained with these devices is high when integrated with sensing technology and is invaluable for scale-translation and to assess the economical viability of bioprocesses. Microfluidic devices as upstream process development tools have been developed in the area of small molecules, therapeutic proteins, and cellular therapies. More recently, they have also been applied to mimic downstream unit operations (Marques and Szita, Curr Opin Chem Eng, 18, 61–68).

This Special Issue aims to host original contributions dealing with advances in the new field of bioprocess microfluidics. This encompasses the application of microfluidics to all fields of bioprocessing (small molecules, therapeutic proteins, cell and gene therapies), either relating to individual unit operations, whole process sequences, or continuous manufacturing.

We are looking in particular for contributions (experimental or modeling) that clearly demonstrate how microfluidics can address the current challenges of bioprocessing, and we request that the authors highlight the expected impact on bioprocessing clearly in their contribution.

Dr. Marco P.C. Marques
Prof. Dr. Nicolas Szita
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Micromachines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2100 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Microfluidics
  • Bioprocessing
  • Monitoring
  • Modeling
  • Biocatalysis
  • Cell and Gene Therapy
  • Therapeutic Proteins
  • Upstream and Downstream Unit Operations
  • Continuous Flow

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Published Papers (3 papers)

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Research

14 pages, 3502 KiB  
Article
3D Printed Microfluidic Spiral Separation Device for Continuous, Pulsation-Free and Controllable CHO Cell Retention
by Anton Enders, John-Alexander Preuss and Janina Bahnemann
Micromachines 2021, 12(9), 1060; https://doi.org/10.3390/mi12091060 - 31 Aug 2021
Cited by 15 | Viewed by 4133
Abstract
The development of continuous bioprocesses—which require cell retention systems in order to enable longer cultivation durations—is a primary focus in the field of modern process development. The flow environment of microfluidic systems enables the granular manipulation of particles (to allow for greater focusing [...] Read more.
The development of continuous bioprocesses—which require cell retention systems in order to enable longer cultivation durations—is a primary focus in the field of modern process development. The flow environment of microfluidic systems enables the granular manipulation of particles (to allow for greater focusing in specific channel regions), which in turn facilitates the development of small continuous cell separation systems. However, previously published systems did not allow for separation control. Additionally, the focusing effect of these systems requires constant, pulsation-free flow for optimal operation, which cannot be achieved using ordinary peristaltic pumps. As described in this paper, a 3D printed cell separation spiral for CHO-K1 (Chinese hamster ovary) cells was developed and evaluated optically and with cell experiments. It demonstrated a high separation efficiency of over 95% at up to 20 × 106 cells mL−1. Control over inlet and outlet flow rates allowed the operator to adjust the separation efficiency of the device while in use—thereby enabling fine control over cell concentration in the attached bioreactors. In addition, miniaturized 3D printed buffer devices were developed that can be easily attached directly to the separation unit for usage with peristaltic pumps while simultaneously almost eradicating pump pulsations. These custom pulsation dampeners were closely integrated with the separator spiral lowering the overall dead volume of the system. The entire device can be flexibly connected directly to bioreactors, allowing continuous, pulsation-free cell retention and process operation. Full article
(This article belongs to the Special Issue Bioprocess Microfluidics)
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16 pages, 3553 KiB  
Article
Transesterification of Sunflower Oil over Waste Chicken Eggshell-Based Catalyst in a Microreactor: An Optimization Study
by Stefan Pavlović, Gordana Šelo, Dalibor Marinković, Mirela Planinić, Marina Tišma and Miroslav Stanković
Micromachines 2021, 12(2), 120; https://doi.org/10.3390/mi12020120 - 23 Jan 2021
Cited by 17 | Viewed by 3448
Abstract
The statistical experimental design (DoE) and optimization (Response Surface Methodology combined with Box–Behnken design) of sunflower oil transesterification catalyzed by waste chicken eggshell-based catalyst were conducted in a custom-made microreactor at 60 °C. The catalyst was synthesized by the hydration–dehydration method and subsequent [...] Read more.
The statistical experimental design (DoE) and optimization (Response Surface Methodology combined with Box–Behnken design) of sunflower oil transesterification catalyzed by waste chicken eggshell-based catalyst were conducted in a custom-made microreactor at 60 °C. The catalyst was synthesized by the hydration–dehydration method and subsequent calcination at 600 °C. Comprehensive characterization of the obtained catalyst was conducted using: X-ray powder diffractometry (XRD), X-ray fluorescence (XRF), Fourier-transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), N2 physisorption, and Hg-porosimetry. Structural, morphological, and textural results showed that the obtained catalyst exhibited high porosity and regular dispersity of plate-like CaO as an active species. The obtained optimal residence time, catalyst concentration, and methanol/oil volume ratio for the continuous reaction in microreactor were 10 min, 0.1 g g−1, and 3:1, respectively. The analysis of variance (ANOVA) showed that the obtained reduced quadratic model was adequate for experimental results fitting. The reaction in the microreactor was significantly intensified compared to a conventional batch reactor, as seen through the fatty acid methyl esters (FAMEs) content after 10 min, which was 51.2% and 18.6%, respectively. Full article
(This article belongs to the Special Issue Bioprocess Microfluidics)
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11 pages, 3326 KiB  
Article
Slipstreaming Mother Machine: A Microfluidic Device for Single-Cell Dynamic Imaging of Yeast
by David C. Durán, César A. Hernández, Elizabeth Suesca, Rubén Acevedo, Ivón M. Acosta, Diana A. Forero, Francisco E. Rozo and Juan M. Pedraza
Micromachines 2021, 12(1), 4; https://doi.org/10.3390/mi12010004 - 22 Dec 2020
Cited by 5 | Viewed by 3852
Abstract
The yeast Saccharomyces cerevisiae is one of the most basic model organisms for studies of aging and other phenomena such as division strategies. These organisms have been typically studied with the use of microfluidic devices to keep cells trapped while under a flow [...] Read more.
The yeast Saccharomyces cerevisiae is one of the most basic model organisms for studies of aging and other phenomena such as division strategies. These organisms have been typically studied with the use of microfluidic devices to keep cells trapped while under a flow of fresh media. However, all of the existing devices trap cells mechanically, subjecting them to pressures that may affect cell physiology. There is evidence mechanical pressure affects growth rate and the movement of intracellular components, so it is quite possible that it affects other physiological aspects such as aging. To allow studies with the lowest influence of mechanical pressure, we designed and fabricated a device that takes advantage of the slipstreaming effect. In slipstreaming, moving fluids that encounter a barrier flow around it forming a pressure gradient behind it. We trap mother cells in this region and force daughter cells to be in the negative pressure gradient region so that they are taken away by the flow. Additionally, this device can be fabricated using low resolution lithography techniques, which makes it less expensive than devices that require photolithography masks with resolution under 5 µm. With this device, it is possible to measure some of the most interesting aspects of yeast dynamics such as growth rates and Replicative Life Span. This device should allow future studies to eliminate pressure bias as well as extending the range of labs that can do these types of measurements. Full article
(This article belongs to the Special Issue Bioprocess Microfluidics)
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