scholarly journals A Review of Advanced Impedance Biosensors with Microfluidic Chips for Single-Cell Analysis

Biosensors ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 412
Author(s):  
Soojung Kim ◽  
Hyerin Song ◽  
Heesang Ahn ◽  
Taeyeon Kim ◽  
Jihyun Jung ◽  
...  

Electrical impedance biosensors combined with microfluidic devices can be used to analyze fundamental biological processes for high-throughput analysis at the single-cell scale. These specialized analytical tools can determine the effectiveness and toxicity of drugs with high sensitivity and demonstrate biological functions on a single-cell scale. Because the various parameters of the cells can be measured depending on methods of single-cell trapping, technological development ultimately determine the efficiency and performance of the sensors. Identifying the latest trends in single-cell trapping technologies afford opportunities such as new structural design and combination with other technologies. This will lead to more advanced applications towards improving measurement sensitivity to the desired target. In this review, we examined the basic principles of impedance sensors and their applications in various biological fields. In the next step, we introduced the latest trend of microfluidic chip technology for trapping single cells and summarized the important findings on the characteristics of single cells in impedance biosensor systems that successfully trapped single cells. This is expected to be used as a leading technology in cell biology, pathology, and pharmacological fields, promoting the further understanding of complex functions and mechanisms within individual cells with numerous data sampling and accurate analysis capabilities.

Lab on a Chip ◽  
2021 ◽  
Author(s):  
Huichao Chai ◽  
Yongxiang Feng ◽  
Fei Liang ◽  
Wenhui Wang

Successful single-cell isolation is a pivotal technique for subsequent biological and chemical analysis of single cells. Although significant advances have been made in single-cell isolation and analysis techniques, most passive...


Lab on a Chip ◽  
2017 ◽  
Vol 17 (23) ◽  
pp. 4077-4088 ◽  
Author(s):  
Lindong Weng ◽  
Felix Ellett ◽  
Jon Edd ◽  
Keith H. K. Wong ◽  
Korkut Uygun ◽  
...  

A passive pumping, single-cell trapping microarray was developed to monitor volumetric change of multiple, single cells following hypertonic exposure.


Author(s):  
Kyohei Terao ◽  
Murat Gel ◽  
Atsuhito Okonogi ◽  
Takaaki Suzuki ◽  
Fumikazu Oohira ◽  
...  

We propose a novel cell stimulation device for the analysis of cell responses to chemical stimuli. In order to deliver chemical substances to target single cells, we developed a microfluidic device having microchannels and apertures in the side wall to subject stimuli to laterally trapped cells. The channels were designed to allow simple flow control with single syringe pump. We demonstrated single cell trapping and culturing of pancreatic β cell with the device. To test its feasibility in cell stimulation assay, intracellular response of the cell to glucose stimulation was demonstrated.


Lab on a Chip ◽  
2016 ◽  
Vol 16 (13) ◽  
pp. 2440-2449 ◽  
Author(s):  
Soo Hyeon Kim ◽  
Teruo Fujii

The electroactive double well-array consists of trap-wells for highly efficient single-cell trapping using dielectrophoresis (cell capture efficiency of 96 ± 3%) and reaction-wells that confine cell lysates for analysis of intracellular materials from single cells.


Sensors ◽  
2018 ◽  
Vol 18 (11) ◽  
pp. 3672 ◽  
Author(s):  
Yang Liu ◽  
Dahai Ren ◽  
Xixin Ling ◽  
Weibin Liang ◽  
Jing Li ◽  
...  

Single-cell capture plays an important role in single-cell manipulation and analysis. This paper presents a microfluidic device for deterministic single-cell trapping based on the hydrodynamic trapping mechanism. The device is composed of an S-shaped loop channel and thousands of aligned trap units. This arrayed structure enables each row of the device to be treated equally and independently, as it has row periodicity. A theoretical model was established and a simulation was conducted to optimize the key geometric parameters, and the performance was evaluated by conducting experiments on MCF-7 and Jurkat cells. The results showed improvements in single-cell trapping ability, including loading efficiency, capture speed, and the density of the patterned cells. The optimized device can achieve a capture efficiency of up to 100% and single-cell capture efficiency of up to 95%. This device offers 200 trap units in an area of 1 mm2, which enables 100 single cells to be observed simultaneously using a microscope with a 20× objective lens. One thousand cells can be trapped sequentially within 2 min; this is faster than the values obtained with previously reported devices. Furthermore, the cells can also be recovered by reversely infusing solutions. The structure can be easily extended to a large scale, and a patterned array with 32,000 trap sites was accomplished on a single chip. This device can be a powerful tool for high-throughput single-cell analysis, cell heterogeneity investigation, and drug screening.


2021 ◽  
Author(s):  
Wenbo Wei ◽  
Miao Zhang ◽  
Zhongyuan Xu ◽  
Weifeng Li ◽  
Lixin Cheng ◽  
...  

A microfluidic array was constructed for trapping single cell and loading identical dynamic biochemical stimulation for gain a better understanding of Ca2+ signalling in single cells by applying extracellular dynamic biochemical stimulus. This microfluidic array consists of multiple radially aligned flow channels with equal intersection angles, which was designed by a combination of stagnation point flow and physical barrier. Numerical simulation results and trajectory analysis shown the effectiveness of this single cell trapping device. Fluorescent experiment results demonstrated the effects of flow rate and frequency of dynamic stimulus on the profiles of biochemical concentration which exposed on captured cells. In this array chip, the captured single cells in each trapping channels were able to receive identical extracellular dynamic biochemical stimuli which being transmitted from the entrance at the middle of the microfluidic array. Besides, after loading dynamic Adenosine Triphosphate (ATP) stimulation on captured cells by this device, consistent average intracellular Ca2+ dynamics phase and cellular heterogeneity were observed in captured single K562 cells. Furthermore, this device is able to be used for investigating cellular respond in single cells to temporally varying environments by modulating the stimulation signal in terms of concentration, pattern, and duration of exposure.


Author(s):  
L. Ferrara ◽  
F. Bragheri ◽  
P. Minzioni ◽  
I. Cristiani ◽  
K. C. Vishnubhatla ◽  
...  

2019 ◽  
Author(s):  
Wenfa Ng

While many microbes could be cultivated on common nutrient medium from environmental samples, there is perhaps a larger consortium of microbes that could not be brought under cultivation. Known as viable but non-culturable (VBNC) microbes, many facets of cell biology, biochemistry and physiology remain hidden from view given the inability to culture them in the laboratory. Without the ability to culture VBNC, many modern genetic tools could not be used to interrogate intrinsic metabolic capabilities and regulatory mechanisms of the cells. A more important question is perhaps what defines the VBNC state. Specifically, what is the level of metabolic activity in such cells and which branch of metabolism remains active in helping cells maintain cellular sensory system essential to understanding extracellular nutrition and environmental conditions crucial for activating vegetative growth under the right conditions? To answer the questions, we first need to develop methods for identifying cells in the VBNC state. One possibility involves screening environmental microbes for their ability to grow in rich medium under standard laboratory incubation conditions using 96 well plate assay where single cells are inoculated into each well. Cells that fail to grow would subsequently be selected for single cell RNA sequencing to understand the transcriptome that could be correlated to the VBNC state. In parallel, single cell whole genome sequencing could also be conducted to obtain the reference genome on which expression of different genes in the transcriptome could be assessed. Specifically, automated gene annotation pipelines could be used for gene detection; thereby, yielding an ensemble of genes useful for understanding the transcriptome. But, detection of mRNA transcripts does not mean the successful translation of mRNA into proteins. More importantly, while single cell proteomics might be achievable on a routine basis in future, conventional methods lack the sensitivity for profiling cellular proteome at the global level in single cell given the inability to massively amplify proteins unlike the case for DNA or RNA. Similarly, single cell metabolomics, which is essential to obtaining a complete picture of cellular metabolism in VBNC state faces challenges associated with sensitivity and detection of a broad range of intermediates and compounds. Thus, at present, efforts to access the metabolic state associated with VBNC would most likely stop at probing the global transcriptome at the single cell level. But, future developments in single cell proteomics and metabolomics would hopefully provide new tools for biologists to revisit the important question on what is the metabolic status of cells in VBNC, and more importantly, which metabolic branch remain active in maintaining sensory awareness of the cell’s immediate environment.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
B. Deng ◽  
X. F. Li ◽  
D. Y. Chen ◽  
L. D. You ◽  
J. B. Wang ◽  
...  

Microfluidic cell-based arraying technology is widely used in the field of single-cell analysis. However, among developed devices, there is a compromise between cellular loading efficiencies and trapped cell densities, which deserves further analysis and optimization. To address this issue, the cell trapping efficiency of a microfluidic device with two parallel micro channels interconnected with cellular trapping sites was studied in this paper. By regulating channel inlet and outlet status, the microfluidic trapping structure can mimic key functioning units of previously reported devices. Numerical simulations were used to model this cellular trapping structure, quantifying the effects of channel on/off status and trapping structure geometries on the cellular trapping efficiency. Furthermore, the microfluidic device was fabricated based on conventional microfabrication and the cellular trapping efficiency was quantified in experiments. Experimental results showed that, besides geometry parameters, cellular travelling velocities and sizes also affected the single-cell trapping efficiency. By fine tuning parameters, more than 95% of trapping sites were taken by individual cells. This study may lay foundation in further studies of single-cell positioning in microfluidics and push forward the study of single-cell analysis.


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