High-throughput on-chip flow cytometry system using “microfluidic drifting” based three-dimensional (3D) hydrodynamic focusing

Author(s):  
X. Mao ◽  
S.-C. S. Lin ◽  
T.J. Huang
Lab on a Chip ◽  
2009 ◽  
Vol 9 (11) ◽  
pp. 1583 ◽  
Author(s):  
Xiaole Mao ◽  
Sz-Chin Steven Lin ◽  
Cheng Dong ◽  
Tony Jun Huang

2005 ◽  
Author(s):  
Jeffrey T. Coleman ◽  
Bob M. Lansdorp ◽  
David Sinton

Hydrodynamic focusing is commonly employed to reduce the cross-sectional area of a microfluidic sample stream. Two-dimensional focusing is achieved by combining a central sample stream with a buffer sheathing flow on adjacent sides of a standard microfluidic cross chip. This method of on-chip hydrodynamic focusing is the most common, perhaps due to the relative ease and popularity of planar microfluidic chip fabrication methods. The application of two-dimensional focusing to on-chip flow cytometry is limited for two reasons: Firstly, the degree of focusing obtained is limited by the microchannel depth. Secondly, many biological analytes adhere to channel walls mitigating the optical measurements. Three-dimensional focusing can both increase the focus intensity, and minimize interaction between the analyte stream and the channel walls in the viewed region. In this work, a new method is presented for obtaining three-dimensional hydrodynamic focusing on a planar microfluidic geometry using strategically placed surface charge patches. Numerical simulations are employed to show the concentration profiles resulting from the local flow circulations induced by the surface patches in an electrokinetically-driven flow.


2016 ◽  
Vol 113 (52) ◽  
pp. 14915-14920 ◽  
Author(s):  
Yih Yang Chen ◽  
Pamuditha N. Silva ◽  
Abdullah Muhammad Syed ◽  
Shrey Sindhwani ◽  
Jonathan V. Rocheleau ◽  
...  

On-chip imaging of intact three-dimensional tissues within microfluidic devices is fundamentally hindered by intratissue optical scattering, which impedes their use as tissue models for high-throughput screening assays. Here, we engineered a microfluidic system that preserves and converts tissues into optically transparent structures in less than 1 d, which is 20× faster than current passive clearing approaches. Accelerated clearing was achieved because the microfluidic system enhanced the exchange of interstitial fluids by 567-fold, which increased the rate of removal of optically scattering lipid molecules from the cross-linked tissue. Our enhanced clearing process allowed us to fluorescently image and map the segregation and compartmentalization of different cells during the formation of tumor spheroids, and to track the degradation of vasculature over time within extracted murine pancreatic islets in static culture, which may have implications on the efficacy of beta-cell transplantation treatments for type 1 diabetes. We further developed an image analysis algorithm that automates the analysis of the vasculature connectivity, volume, and cellular spatial distribution of the intact tissue. Our technique allows whole tissue analysis in microfluidic systems, and has implications in the development of organ-on-a-chip systems, high-throughput drug screening devices, and in regenerative medicine.


Sensors ◽  
2019 ◽  
Vol 19 (12) ◽  
pp. 2761 ◽  
Author(s):  
Byeongyeon Kim ◽  
Dayoung Kang ◽  
Sungyoung Choi

Miniaturizing flow cytometry requires a comprehensive approach to redesigning the conventional fluidic and optical systems to have a small footprint and simple usage and to enable rapid cell analysis. Microfluidic methods have addressed some challenges in limiting the realization of microflow cytometry, but most microfluidics-based flow cytometry techniques still rely on bulky equipment (e.g., high-precision syringe pumps and bench-top microscopes). Here, we describe a comprehensive approach that achieves high-throughput white blood cell (WBC) counting in a portable and handheld manner, thereby allowing the complete miniaturization of flow cytometry. Our approach integrates three major components: a motorized smart pipette for accurate volume metering and controllable liquid pumping, a microfluidic cell concentrator for target cell enrichment, and a miniaturized fluorescence microscope for portable flow cytometric analysis. We first validated the capability of each component by precisely metering various fluid samples and controlling flow rates in a range from 219.5 to 840.5 μL/min, achieving high sample-volume reduction via on-chip WBC enrichment, and successfully counting single WBCs flowing through a region of interrogation. We synergistically combined the three major components to create a handheld, integrated microflow cytometer and operated it with a simple protocol of drawing up a blood sample via pipetting and injecting the sample into the microfluidic concentrator by powering the motorized smart pipette. We then demonstrated the utility of the microflow cytometer as a quality control means for leukoreduced blood products, quantitatively analyzing residual WBCs (rWBCs) in blood samples present at concentrations as low as 0.1 rWBCs/μL. These portable, controllable, high-throughput, and quantitative microflow cytometric technologies provide promising ways of miniaturizing flow cytometry.


Lab on a Chip ◽  
2021 ◽  
Vol 21 (1) ◽  
pp. 75-82
Author(s):  
Yingdong Luo ◽  
Jinwu Yang ◽  
Xinqi Zheng ◽  
Jianjun Wang ◽  
Xin Tu ◽  
...  

We present real-time quantitative phase microscopy (RT-QPM) that can be used for on-chip three-dimensional visualization of droplets and high-throughput quantitative molecular measurement via real-time extraction of sample-induced phase variation.


Author(s):  
N Fang

Traditionally, cutting tools made of sintered carbides or high-speed steels are used to cut a variety of metal materials in the experimental study on chip control. One of the existing problems is that, in most cases, it is difficult to make, in a laboratory, cutting tools with a three-dimensionally shaped chip breaking groove for use in the follow-up experiments. Turning to tool manufacturers, who use the powder metallurgy techniques of tool making for help, usually leads to a long experimental period and high cost. An auxiliary approach to the experimental study on chip control, called a kinematically simulated test (KST), is proposed in this present work to overcome the above shortcoming of the traditional method employed in the experimental study on chip control. A plexiglass-made cutting tool is employed to cut a commercially available paraffin wax to simulate some kinematic phenomena (such as chip flow and chip curl) which take place during practical machining processes. After the applied range of KST has been illustrated, two examples of applying KST are given. One is the application of KST to chip flow research. The other is optimizing the geometry of the chip breaking groove of a tool insert by means of KST. Both examples involve the making of the chip breaking grooves with the three-dimensional shape and geometry.


2012 ◽  
pp. 1913-1923 ◽  
Author(s):  
Shady Gawad ◽  
Ana Valero ◽  
Thomas Braschler ◽  
David Holmes ◽  
Philippe Renaud ◽  
...  
Keyword(s):  

Lab on a Chip ◽  
2020 ◽  
Vol 20 (12) ◽  
pp. 2228-2236 ◽  
Author(s):  
Xuejia Hu ◽  
Shukun Zhao ◽  
Ziyi Luo ◽  
Yunfeng Zuo ◽  
Fang Wang ◽  
...  

Multicellular aggregates in three-dimensional (3D) environments provide novel solid tumor models that can provide insight into in vivo drug resistance.


2020 ◽  
Vol 15 (5) ◽  
pp. 296-301
Author(s):  
Salini Krishna ◽  
Fadi Alnaimat ◽  
Ali Hilal‐Alnaqbi ◽  
Saud Khashan ◽  
Bobby Mathew
Keyword(s):  

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