Integrated Microfluidic System for Gene Silencing and Cell Migration

Liu, Zongbin; Han, Xin; Zhou, Qing; Chen, Rui; Fruge, Shelby; Jo, Misung; Ma, Yuan; Li, Ziyin; Yokoi, Kohei; Qin, Lidong

doi:10.1002/adbi.201700054

Cited by 13 publications

(19 citation statements)

References 33 publications

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“…In a subsequent study, the group modified their device architecture to perform siRNA delivery to cancer cells with a repeated pattern of 5 μm constrictions in a reverse wishbone configuration 750 (Figure 16C). Experiments and simulations both indicate that sharper constrictions conferred by the reverse wishbone intensified the local stress on the plasma membrane to increase the magnitude of membrane disruption 750 . Another of their publications featured sharp star-shaped constrictions to facilitate delivery of dextrans, siRNA, and Cas9 RNPs to the intracellular space of hard-to-transfect suspension cell lines and T cells 227 .…”

Section: Intracellular Delivery By Permeabilizationmentioning

confidence: 99%

Intracellular Delivery by Membrane Disruption: Mechanisms, Strategies, and Concepts

2018

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Intracellular delivery is a key step in biological research and has enabled decades of biomedical discoveries. It is also becoming increasingly important in industrial and medical applications ranging from biomanufacture to cell-based therapies. Here, we review techniques for membrane disruption-based intracellular delivery from 1911 until the present. These methods achieve rapid, direct, and universal delivery of almost any cargo molecule or material that can be dispersed in solution. We start by covering the motivations for intracellular delivery and the challenges associated with the different cargo types-small molecules, proteins/peptides, nucleic acids, synthetic nanomaterials, and large cargo. The review then presents a broad comparison of delivery strategies followed by an analysis of membrane disruption mechanisms and the biology of the cell response. We cover mechanical, electrical, thermal, optical, and chemical strategies of membrane disruption with a particular emphasis on their applications and challenges to implementation. Throughout, we highlight specific mechanisms of membrane disruption and suggest areas in need of further experimentation. We hope the concepts discussed in our review inspire scientists and engineers with further ideas to improve intracellular delivery.

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Section: Intracellular Delivery By Permeabilizationmentioning

confidence: 99%

Intracellular Delivery by Membrane Disruption: Mechanisms, Strategies, and Concepts

2018

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“…[ 237 ] In a follow up study performed in Qin lab, an integrated microfluidic chip was designed with repeated fishbone‐shaped arrays of constrictions to achieve on‐chip siRNA‐mediated gene knockdown as well as on‐chip cell migration assay. [ 238 ]…”

Section: Micro‐ and Nanoengineered Intracellular Deliverymentioning

confidence: 99%

A Comprehensive Review on Intracellular Delivery

Rad

Bazaz

et al. 2021

Advanced Materials

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Intracellular delivery is considered an indispensable process for various studies, ranging from medical applications (cell‐based therapy) to fundamental (genome‐editing) and industrial (biomanufacture) approaches. Conventional macroscale delivery systems critically suffer from such issues as low cell viability, cytotoxicity, and inconsistent material delivery, which have opened up an interest in the development of more efficient intracellular delivery systems. In line with the advances in microfluidics and nanotechnology, intracellular delivery based on micro‐ and nanoengineered platforms has progressed rapidly and held great promises owing to their unique features. These approaches have been advanced to introduce a smorgasbord of diverse cargoes into various cell types with the maximum efficiency and the highest precision. This review differentiates macro‐, micro‐, and nanoengineered approaches for intracellular delivery. The macroengineered delivery platforms are first summarized and then each method is categorized based on whether it employs a carrier‐ or membrane‐disruption‐mediated mechanism to load cargoes inside the cells. Second, particular emphasis is placed on the micro‐ and nanoengineered advances in the delivery of biomolecules inside the cells. Furthermore, the applications and challenges of the established and emerging delivery approaches are summarized. The topic is concluded by evaluating the future perspective of intracellular delivery toward the micro‐ and nanoengineered approaches.

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“…Furthermore, decent transfection efficiency (30–60%) of the human lymphoma cell line (SU‐DHL‐1) and mouse embryonic stem cell line (AB2.2) with plasmid DNA encoding enhanced green fluorescent protein (EGFP) was reported; however, key information on DNA concentration and plasmid DNA size was not reported. The same group further modified the constriction shape from diamond‐shaped to star‐ [ 59 ] and branch‐shaped [ 60 ] arrays for CRISPR‐Cas9 RNP delivery (>40% indel efficiency) and siRNA internalization, respectively.…”

Section: Mechanical Plasma Membrane Disruption‐mediated Intracellular Delivery (Mechanoporation)mentioning

confidence: 99%

Microfluidic and Nanofluidic Intracellular Delivery

Hur

Chung

2021

Advanced Science

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Innate cell function can be artificially engineered and reprogrammed by introducing biomolecules, such as DNAs, RNAs, plasmid DNAs, proteins, or nanomaterials, into the cytosol or nucleus. This process of delivering exogenous cargos into living cells is referred to as intracellular delivery. For instance, clustered regularly interspaced short palindromic repeats (CRISPR)‐Cas9 gene editing begins with internalizing Cas9 protein and guide RNA into cells, and chimeric antigen receptor‐T (CAR‐T) cells are prepared by delivering CAR genes into T lymphocytes for cancer immunotherapies. To deliver external biomolecules into cells, tools, including viral vectors, and electroporation have been traditionally used; however, they are suboptimal for achieving high levels of intracellular delivery while preserving cell viability, phenotype, and function. Notably, as emerging solutions, microfluidic and nanofluidic approaches have shown remarkable potential for addressing this open challenge. This review provides an overview of recent advances in microfluidic and nanofluidic intracellular delivery strategies and discusses new opportunities and challenges for clinical applications. Furthermore, key considerations for future efforts to develop microfluidics‐ and nanofluidics‐enabled next‐generation intracellular delivery platforms are outlined.

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Integrated Microfluidic System for Gene Silencing and Cell Migration

Cited by 13 publications

References 33 publications

Intracellular Delivery by Membrane Disruption: Mechanisms, Strategies, and Concepts

Intracellular Delivery by Membrane Disruption: Mechanisms, Strategies, and Concepts

A Comprehensive Review on Intracellular Delivery

Microfluidic and Nanofluidic Intracellular Delivery

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