Microfluidic SlipChip device for multistep multiplexed biochemistry on a nanoliter scale

Zhukov, Dmitriy V.; Khorosheva, Eugenia M.; Khazaei, Tahmineh; Du, Wei; Selck, David A.; Shishkin, A.A.; Ismagilov, Rustem F.

doi:10.1039/c9lc00541b

Cited by 27 publications

(18 citation statements)

References 53 publications

(111 reference statements)

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“…To overcome this limitation, a slip-over method can be used. 48 In general, the microfluidic plates used in slip molding can be produced with relatively fast turnaround times and low cost.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Slip Molding for Precision Fabrication of Microparts

et al. 2019

Langmuir

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Microparts with precise sizes, custom shapes, and a wide selection of materials have various applications, including biomedical microelectromechanical systems (MEMS), drug delivery, single-cell studies, and tissue engineering. Janus microparts containing multiple components are also demonstrated for biomolecule analysis, cell–cell interaction studies, and self-assembly. Small-footprint, affordable, and rapid technologies to fabricate microparts with customized morphologies and a wide selection of materials are highly desired. This paper reports on a SlipChip-based microfluidic molding method to control the interface for the synthesis of microparts-on-demand (mPods) with fast and easy loading–slipping–solidification operations that do not require pumps, masks, or other auxiliary fluidic control instruments. This method is based on the relative movement of two microfluidic plates that are in close contact, and the size and shape of the microparts can be accurately controlled by the geometry of the microcavities imprinted on the contacting surfaces of these microfluidic plates. To demonstrate the capability of this method, mPods of different sizes and various shapes are presented with photosensitive resin via a photopolymerization reaction. The synthesis of two-layer Janus microparts is also demonstrated by a slip overmolding method. This SlipChip-based molding method can offer new opportunities for producing customized microparts with great flexibility for a broad spectrum of applications.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Slip Molding for Precision Fabrication of Microparts

et al. 2019

Langmuir

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“…Scaled-up fabrication is critical to conducting experiments at moderate scale (dozens of devices) and for propagating such technology to collaborators. In particular, this scale of fabrication would be useful for SlipChips, which are two-phase, reconfigurable microfluidic devices [ 4 , 5 , 6 , 7 , 8 , 9 ]. SlipChips usually comprise two planar components that can be “slipped” relative to one another, contain recessed features to hold droplets or streams of aqueous solution, and are separated by a thin layer of oil [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…SlipChips usually comprise two planar components that can be “slipped” relative to one another, contain recessed features to hold droplets or streams of aqueous solution, and are separated by a thin layer of oil [ 4 ]. SlipChip devices were first developed in the Ismagilov lab [ 4 ] as a new technology to perform in low-resource settings [ 5 , 6 , 7 ]. The first SlipChips were fabricated from glass plates, which offer ideal surface properties and optical clarity but require wet etching with HF, a hazardous procedure that requires a skilled technician [ 4 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Rapid Fabrication by Digital Light Processing 3D Printing of a SlipChip with Movable Ports for Local Delivery to Ex Vivo Organ Cultures

2021

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SlipChips are two-part microfluidic devices that can be reconfigured to change fluidic pathways for a wide range of functions, including tissue stimulation. Currently, fabrication of these devices at the prototype stage requires a skilled microfluidic technician, e.g., for wet etching or alignment steps. In most cases, SlipChip functionality requires an optically clear, smooth, and flat surface that is fluorophilic and hydrophobic. Here, we tested digital light processing (DLP) 3D printing, which is rapid, reproducible, and easily shared, as a solution for fabrication of SlipChips at the prototype stage. As a case study, we sought to fabricate a SlipChip intended for local delivery to live tissue slices through a movable microfluidic port. The device was comprised of two multi-layer components: an enclosed channel with a delivery port and a culture chamber for tissue slices with a permeable support. Once the design was optimized, we demonstrated its function by locally delivering a chemical probe to slices of hydrogel and to living tissue with up to 120 µm spatial resolution. By establishing the design principles for 3D printing of SlipChip devices, this work will enhance the ability to rapidly prototype such devices at mid-scale levels of production.

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“…Apart from slow release approaches, microchannels controlled through pneumatic valves have been added to or incorporated in microtiter plates for nutrient supply and pH regulation. [11][12][13] A second strategy is to integrate the wells and fluidic supply lines all in a single microfluidic device , [14][15][16][17][18][19] see the comprehensive reviews by Grunberger's group. [20][21][22] A third strategy is to grow and study cells by compartmentalizing them inside aqueous microdroplets instead of inside solid wells.…”

Section: Introductionmentioning

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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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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Microfluidic SlipChip device for multistep multiplexed biochemistry on a nanoliter scale

Abstract: Using interfacial energy between carrier and sample phases, this manually operated device accurately meters and merges nanoliter scale reagent droplets repeatedly.

Cited by 27 publications

References 53 publications

Slip Molding for Precision Fabrication of Microparts

Slip Molding for Precision Fabrication of Microparts

Rapid Fabrication by Digital Light Processing 3D Printing of a SlipChip with Movable Ports for Local Delivery to Ex Vivo Organ Cultures

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

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