Microfluidic devices for the analysis of apoptosis

Qin, Jianhua; Ye, Nannan; Liu, Xin; Lin, Bingcheng

doi:10.1002/elps.200500113

Cited by 46 publications

(36 citation statements)

References 49 publications

(45 reference statements)

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“…Typically, apoptotic cells are characterized by a distinct set of morphological and biochemical characteristics observed exclusively with this mode of cell death [2,3,6]. These features mainly include cell shrinkage, internucleosomal DNA fragmentation, cellular membrane alterations, caspases activation, and mitochondrial membrane changes.…”

Section: Introductionmentioning

confidence: 99%

Characterizing doxorubicin‐induced apoptosis in HepG2 cells using an integrated microfluidic device

Qin

Liu

et al. 2007

Electrophoresis

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Apoptosis has now established its importance in numerous areas of biology and is recently receiving great attention as an important topic related to the development of diseases. In this work, an integrated microfluidic device was developed to characterize doxorubicin-induced apoptosis in human hepatocellular carcinoma (HepG2) cells. A continuous concentration gradient of stimulator (doxorubicin) was generated in the upstream network and used to perfuse downstream cultured HepG2 cells. The appropriate fluorescent dyes were introduced into cells from the inlets connected to the cell culture chambers, allowing one to distinguish apoptotic cells from nonapoptotic or necrotic cells. The resultant fluorescence of cellular population was monitored and quantified with single-cell resolution to infer the apoptosis process being studied. The feasibility of studying apoptosis was demonstrated by measuring several apoptotic events, including morphological alterations, plasma membrane phosphatidylserine externalization, and mitochondrial membrane potential collapse. This microfluidic device, integrating the cell culture, stimulation, staining, and washing steps into a single device, can simultaneously generate a number of experimental conditions and investigate multiple parameters relating stimulation to apoptosis. It offers a unique platform to characterize various cellular responses in a high-throughput fashion, which is otherwise impossible with conventional methods.

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Section: Introductionmentioning

confidence: 99%

Characterizing doxorubicin‐induced apoptosis in HepG2 cells using an integrated microfluidic device

Qin

Liu

et al. 2007

Electrophoresis

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“…Although the gradient system showed sensitivity and specificity similar to those found in a multiwell system, it had several advantages compared to conventional multiwell system and previously developed microfluidic-based gradient generators, [34][35][36] including the short time required for gradient generation, low cost, highthroughput bioanalytical assays, and small amount of biological target and drug candidates. The system also offered features such as simplicity of design, portability, and fast operation.…”

Section: Mechanism Of Cell Death In Response To the 6-ohda Gradientsmentioning

confidence: 99%

A microfluidic-based neurotoxin concentration gradient for the generation of an in vitro model of Parkinson’s disease

et al. 2011

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In this study, we developed a miniaturized microfluidic-based high-throughput cell toxicity assay to create an in vitro model of Parkinson's disease ͑PD͒. In particular, we generated concentration gradients of 6-hydroxydopamine ͑6-OHDA͒ to trigger a process of neuronal apoptosis in pheochromocytoma PC12 neuronal cell line. PC12 cells were cultured in a microfluidic channel, and a concentration gradient of 6-OHDA was generated in the channel by using a back and forth movement of the fluid flow. Cellular apoptosis was then analyzed along the channel. The results indicate that at low concentrations of 6-OHDA along the gradient ͑i.e., approximately less than 260 M͒, the neuronal death in the channel was mainly induced by apoptosis, while at higher concentrations, 6-OHDA induced neuronal death mainly through necrosis. Thus, this concentration appears to be useful for creating an in vitro model of PD by inducing the highest level of apoptosis in PC12 cells. As microfluidic systems are advantageous in a range of properties such as throughput and lower use of reagents, they may provide a useful approach for generating in vitro models of disease for drug discovery applications.

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“…Microfluidic (or lab-on-a-chip) technologies are gaining ground in the biological and medical sciences and offer a suitable platform for high-throughput screening technologies [60][61][62][63]. Proteins present a particular challenge in microfluidic devices because of the need to maintain structural integrity when attached to a number of different surface geometries and chemistries [50].…”

Section: Micro-sicmentioning

confidence: 99%

The use of self‐interaction chromatography in stable formulation and crystallization of proteins

Deshpande

Ahamed

Horst

et al. 2009

Biotechnology Journal

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This paper reviews the basic principles of the recently developed self‐interaction chromatography (SIC) technique with regard to protein solution stability and protein crystallization. It gives experimental protocols for both normal‐scale and micro‐scale SIC experiments and reviews recent developments and current applications of this novel technique in the biopharmaceutical area. This paper aims to be a benchmark in the further proliferation of this highly effective and fast technology for the rational design of stable aqueous formulations of therapeutic proteins and the determination of solution conditions favoring protein crystallization.

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Microfluidic devices for the analysis of apoptosis

Cited by 46 publications

References 49 publications

Characterizing doxorubicin‐induced apoptosis in HepG2 cells using an integrated microfluidic device

Characterizing doxorubicin‐induced apoptosis in HepG2 cells using an integrated microfluidic device

A microfluidic-based neurotoxin concentration gradient for the generation of an in vitro model of Parkinson’s disease

The use of self‐interaction chromatography in stable formulation and crystallization of proteins

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