Microfluidic Surgery in Single Cells and Multicellular Systems

Zhang, Kevin S.; Nadkarni, Ambika V.; Paul, Rajorshi; Martin, Adrian M.; Tang, Susan

doi:10.1021/acs.chemrev.1c00616

Cited by 13 publications

(7 citation statements)

References 352 publications

(730 reference statements)

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“…As a typical category of chemical stimulation, subcellular damage could trigger wound healing and regeneration behaviors. However, effective methods for in situ chemical damage to subcellular regions of living single cells , are still absent. Herein, we used sodium dodecyl sulfate (SDS), a surfactant, as an example to perform subcellular damage, which could provide opportunities to study important wound healing and regeneration behaviors , of single cells.…”

Section: Results and Discussionmentioning

confidence: 99%

Microfluidic Aqueous Two-Phase Focusing of Chemical Species for In Situ Subcellular Stimulation

Zhang,

Xie,

et al. 2023

ACS Appl. Mater. Interfaces

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Confinement of chemical species in a controllable micrometer-level (several to a dozen micrometers) space in an aqueous environment is essential for precisely manipulating chemical events in subcellular regions. However, rapid diffusion and hard-to-control micrometer-level fluids make it a tough challenge. Here, a versatile open microfluidic method based on an aqueous two-phase system (ATPS) is developed to restrict species inside an open space with micron-level width. Unequal standard chemical potentials of the chemical species in two phases and space-time correspondence in the microfluidic system prevent outward diffusion across the phase interface, retaining the target species inside its preferred phase flow and creating a sharp boundary with a dramatic concentration change. Then, the chemical flow (the preferred phase with target chemical species) is precisely manipulated by a microfluidic probe, which can be compressed to a micron-level width and aimed at an arbitrary position of the sample. As a demonstration of the feasibility and versatility of the strategy, chemical flow is successfully applied to subcellular regions of various kinds of living single cells. Subcellular regions are successfully labeled (cytomembrane and mitochondria) and damaged. Healing−regeneration behaviors of living single cells are triggered by subcellular damage and analyzed. The method is relatively general regarding the species of chemicals and biosamples, which could promote deeper cell research.

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Section: Results and Discussionmentioning

confidence: 99%

Microfluidic Aqueous Two-Phase Focusing of Chemical Species for In Situ Subcellular Stimulation

Zhang,

Xie,

et al. 2023

ACS Appl. Mater. Interfaces

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“…There has been significant recent progress in single cell analysis due to the importance of cellular heterogeneity in drug discovery, disease diagnosis, and therapy design. − The complex nature of cell-to-cell heterogeneity has motivated the development of tools for single cell analysis, including patch clamping, , in situ fluorescence hybridization, , flow cytometry, , immunospot assays, microfluidics, − single cell sequencing, , etc. These methods provide valuable information on basic biological processes in living cells, which promotes our understanding of cellular heterogeneity.…”

Section: Introductionmentioning

confidence: 99%

Specially Resolved Single Living Cell Perfusion and Targeted Fluorescence Labeling Based on Nanopipettes

Wang

Zhou

et al. 2022

Anal. Chem.

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Targeted delivery and labeling of single living cells in heterogeneous cell populations are of great importance to understand the molecular biology and physiological functions of individual cells. However, it remains challenging to perfuse fluorescence markers into single living cells with high spatial and temporal resolution without interfering neighboring cells. Here, we report a single cell perfusion and fluorescence labeling strategy based on nanoscale glass nanopipettes. With the nanoscale tip hole of 100 nm, the use of nanopipettes allows special perfusion and high-resolution fluorescence labeling of different subcellular regions in single cells of interest. The dynamic of various fluorescent probes has been studied to exemplify the feasibility of nanopipette-dependent targeted delivery. According to experimental results, the cytoplasm labeling of Sulfo-Cyanine5 and fluorescein isothiocyanate is mainly based on the Brownian movement due to the dyes themselves and does not have a targeting ability, while the nucleus labeling of 4′,6-diamidino-2-phenylindole (DAPI) is originated from the adsorption between DAPI and DNA in the nucleus. From the finite element simulation, the precise manipulation of intracellular delivery is realized by controlling the electro-osmotic flow inside the nanopipettes, and the different delivery modes between nontargeting dyes and nucleus-targeting dyes were compared, showcasing the valuable ability of nanopipette-based method for the analysis of specially defined subcellular regions and the potential applications for single cell surgery, subcellular manipulation, and gene delivery.

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“…Microdissection of small organisms, which involves cutting or splitting the organisms into smaller fragments, has traditionally been performed manually. 28,29 From the late 1800s to today, microdissection of single cells has primarily utilized manually controlled microneedles for cutting while the process is monitored under an optical microscope. [30][31][32] Manual surgery using microneedles poses a few challenges.…”

Section: Introductionmentioning

confidence: 99%

“…Second, manual surgery is a slow process. 29,31,33 Depending on the skill of the operator, cutting each cell can take as long as 3 minutes. 9 Analyses such as proteomics and RNA sequencing often require hundreds of cells.…”

Section: Introductionmentioning

confidence: 99%