Microfluidics for Biotechnology: Bridging Gaps to Foster Microfluidic Applications

Ortseifen, Vera; Viefhues, Martina; Wobbe, Lutz; Grünberger, Alexander

doi:10.3389/fbioe.2020.589074

Cited by 71 publications

(49 citation statements)

References 108 publications

(121 reference statements)

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“…A third challenge is to further improve the accessibility of the technology. While the device itself is relatively simple and so is its operation through the use of a commercially available pressure pump, integrating and automating all workflows into a ready‐to‐use “chip‐in‐a‐box” [ 46 ] is required to facilitate widespread adoption by biotechnologists and bioprocess engineers. All in all, given the ease of operation, the potential for scale out and incorporation of analytics, the presented droplet nanobioreactor provides a solid base for the screening of microorganisms or process conditions under industrially relevant fed‐batch conditions.…”

Section: Discussionmentioning

confidence: 99%

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Fed‐Batch Droplet Nanobioreactor for Controlled Growth of Cyberlindnera (Pichia) jadinii: A Proof‐Of‐Concept Demonstration

Totlani

Wang

Bisschops

et al. 2021

Adv Materials Technologies

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Improvement of the microorganism's product yield on feedstock is possible by targeted genetic modification, which requires a solid understanding of the species metabolism and genetics. Alternatively, genetic modifications can be introduced randomly such that the chance that a resulting mutant performs better than the original one is small. Consequently, many mutants need to be created and subsequently screened in order to identify the best performing ones. [1] Given the large number of experiments, it is common practice to grow and study all the different mutants in individual microliter-sized wells on microtiter plates. While this allows for parallel screening in an automated fashion using pipetting robots and plate readers, conventional microtiter plates lack the ability to feed nutrients and control pH by base or acid addition. It is indeed challenging to feed liquids at flow rates in the nanoliter per hour range to all the individual wells of a microtiter plate and to do so accurately. Therefore, screening of mutants is commonly performed under batch conditions with all feedstock present from the start and no further control over feedstock concentration and pH. In contrast, more than 80% of the processes in industrial biotechnology are operated under so called fed-batch conditions with control over feedstock concentration and pH. [2,3] This incompatibility between the physiological conditions during screening and industrial operation not only leads to selection of false positives which fail to generate competitive yields at industrial scale, but also fails to identify the best mutants for fed-batch conditions. [4][5][6] The effectiveness of screening hence greatly benefits from a technology that enables growing and studying a large number of microorganisms under precisely controlled conditions representative of industrial bioreactors. Besides screening of mutants, optimization of process conditions, a second important aspect in bioprocess development, also benefits from such a technology. [7] Although there has been progress in recent years, there remains both need and opportunity to cost-effectively and with fidelity miniaturize fermentation to screen under fed-batch conditions.Several strategies have been developed to study microorganisms under controlled growth conditions. One strategy is to A key bottleneck in bioprocess development is that state-of-the-art tools used for screening of cells and optimization of cultivation conditions do not represent the conditions enforced at industrial scale. At industrial scale, cell growth is strictly controlled ("fed-batch") to optimize the metabolites produced by the cells. In contrast, cell growth is uncontrolled ("batch") in microwells commonly used for bioprocess development due to the difficulty to continuously supply minute amounts of nutrients to the cells in these wells over the course of the cultivation experiment. This work addresses this bottleneck through the development of a droplet-based fed-batch nanobioreactor.A key challenge addressed in this work is ...

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Section: Discussionmentioning

confidence: 99%

“…A benefit over microtiter‐based fed‐batch systems such as the BioLectorPro is the ability to perform these screens at single cell resolution and characterize cell heterogeneity. [ 46 ]…”

Section: Discussionmentioning

confidence: 99%

Fed‐Batch Droplet Nanobioreactor for Controlled Growth of Cyberlindnera (Pichia) jadinii: A Proof‐Of‐Concept Demonstration

Totlani

Wang

Bisschops

et al. 2021

Adv Materials Technologies

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“…Microfluidic platforms enable various tests in a fast and low-cost fashion, using miniaturized or portable devices. This is of great importance for applications, such as single-cell analysis, drug encapsulation, drug and toxicity testing, separation and detection of biomarkers, and cell sorting [2][3][4][5][6]. The latter has attracted more attention recently due to the microfluidic systems' high precision and ease of performing steps, such as culturing, mixing, labeling, attachment to nano-and micro-particles, immune-or aptamer-based capturing, and separation of cells and stem cells.…”

Section: Introductionmentioning

confidence: 99%

Recent Microfluidic Innovations for Sperm Sorting

et al. 2021

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Sperm selection is a clinical need for guided fertilization in men with low-quality semen. In this regard, microfluidics can provide an enabling platform for the precise manipulation and separation of high-quality sperm cells through applying various stimuli, including chemical agents, mechanical forces, and thermal gradients. In addition, microfluidic platforms can help to guide sperms and oocytes for controlled in vitro fertilization or sperm sorting using both passive and active methods. Herein, we present a detailed review of the use of various microfluidic methods for sorting and categorizing sperms for different applications. The advantages and disadvantages of each method are further discussed and future perspectives in the field are given.

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“…The thorough characterisation of the physical parameters related to device geometry [17,18] allows system optimisation to favour cell growth and molecular delivery. For these reasons, these platforms allow to perform molecular, pharmaceutical, diagnostic or high-throughput analyses in controlled and reproducible conditions [18][19][20][21]. They also contribute to overcome the ethical issues related to models [22] and have the potential to be employed in the early stages of clinical trials [23].…”

Section: Introductionmentioning

confidence: 99%

A Microfluidic Platform for Cavitation-Enhanced Drug Delivery

et al. 2021

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An endothelial-lined blood vessel model is obtained in a PDMS (Polydimethylsiloxane) microfluidic system, where vascular endothelial cells are grown under physiological shear stress, allowing -like maturation. This experimental model is employed for enhanced drug delivery studies, aimed at characterising the increase in endothelial permeability upon microbubble-enhanced ultrasound-induced (USMB) cavitation. We developed a multi-step protocol to couple the optical and the acoustic set-ups, thanks to a 3D-printed insonation chamber, provided with direct optical access and a support for the US transducer. Cavitation-induced interendothelial gap opening is then analysed using a customised code that quantifies gap area and the relative statistics. We show that exposure to US in presence of microbubbles significantly increases endothelial permeability and that tissue integrity completely recovers within 45 min upon insonation. This protocol, along with the versatility of the microfluidic platform, allows to quantitatively characterise cavitation-induced events for its potential employment in clinics.

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Microfluidics for Biotechnology: Bridging Gaps to Foster Microfluidic Applications

Cited by 71 publications

References 108 publications

Fed‐Batch Droplet Nanobioreactor for Controlled Growth of Cyberlindnera (Pichia) jadinii: A Proof‐Of‐Concept Demonstration

Fed‐Batch Droplet Nanobioreactor for Controlled Growth of Cyberlindnera (Pichia) jadinii: A Proof‐Of‐Concept Demonstration

Recent Microfluidic Innovations for Sperm Sorting

A Microfluidic Platform for Cavitation-Enhanced Drug Delivery

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