Continuous-flow Ferrohydrodynamic Sorting of Cells in Microfluidic Devices with Permanent Magnets
- 详细技术说明
- Microfluidicdevices for microparticle and cellular separation are becoming increasinglyimportant in miniaturized biological applications. Existing separation methods,including techniques based on channel geometry and obstacle design, opticalforce, dielectrophoresis, and magnetic bead labeling, have their ownshortcomings. Techniques based on geometries use appropriate channel andobstacle design to direct particles of different sizes into separate flowstreamlines. The dimensions of the channels and obstacles have implications forthe applicable separation size range, and a significant amount of fine-tuningis often necessary for the separation of small particles. The optical tweezertechnique employs the forces exerted by a focused laser beam to manipulatenano- to micro-scale objects. This method is usually applied to move and trap asingle object. The heating due to the focused laser beam can potentially damageliving systems. Dielectrophoresis has the potential to realize integrateddevices for high-throughput manipulation of microparticles or cells. However,its performance usually depends on the electrical properties of the specificliquid medium, particle shape, and its effective dielectric constant. Thealternating electric fields may polarize the cell membranes and lead to celldeath. The magnetic bead labeling technique, on the other hand, usesfunctionalized magnetic beads to label and separate target particles and cells.This approach takes long incubation time and is manually intensive. There isalso the difficulty of removing the magnetic labels from the target particlesor cells prior to further analysis.
- *Abstract
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In an attemptto address some of the aforementioned limitations, UGA researchers havedeveloped a novel microfluidic device that can continuously separatenon-magnetic microparticles (e.g., cells) based on their sizes insidewater-based ferrofluids, with the use of a simple permanent magnet. Theiringenuous approach uses the ferrofluid asa uniform magnetic environment that surrounds the non-magnetic particles withinthe microfluidic channel. Non-magnetic microparticles mixed with water-basedferrofluids were introduced into the microfluidic channel and hydrodynamicallyfocused by the ferrofluid sheath flow. Once entering the separation region,deflections of non-magnetic particles from their flow paths occurred because ofthe magnetic buoyancy forces on them . As a result, larger particles weredeflected more than small ones. This phenomenon can be used to continuouslyseparate non-magnetic particles inside ferrofluid based on their sizes.Size-based separation (1 µm and 9.9 µm, 1.9 µm and 9.9 µm, 3.1 µm and 9.9 µm,etc.) of microparticles close to 100% separation efficiency. Cell throughputsbetween 106 and 108 cells/h were achieved when the systemwas tested with a variety of cells such as E. coli, S. cerevisiae,L. casei, HeLa and Jurkat cells, andcancer cells. The system is also applicable to other materials, such as - forinstance—polymer beads, microparticulates in liquids– and waterbornecontaminants.
Characteristics
· Inexpensive and of easy construction
· High throughput of analytes (cells,microparticles, etc.)
· Does not induce cell death or lysis
· Requires little or no sample preparation
· Requires no specialized training tooperate, nor complex circuitry or additional equipment
· Water-based process
References and Intellectual Property
US Patent 9,517,474
Wujun Zhao, Rui Cheng, Brittany D. Jenkins,Taotao Zhu, Nneoma E. Okonkwo, Courtney E. Jones, Melissa B. Davis, Sravan K.Kavuri, Zhonglin Hao, Carsten Schroeder and Leidong Mao,“Label-freeferrohydrodynamic cell separation of circulating tumor cells”, Labon a Chip, 2017, DOI:: 10.1039/c7lc00680b
Wujun Zhao, Rui Cheng, So Hyun Lim, Joshua R.Miller, Weizhong Zhang, Wei Tang, Jin Xie and Leidong Mao,“Biocompatible andlabel-free separation of cancer cells from cell culture lines from white bloodcells in ferrofluids”, Labon a Chip, 2017, DOI: 10.1039/c7lc00327g
Wujun Zhao, Rui Cheng, Joshua Miller andLeidong Mao, “Label-Free Microfluidic Manipulation of Particles and Cells inMagnetic Liquids”, AdvancedFunctional Materials, 2016
Wujun Zhao*, Taotao Zhu*, Rui Cheng, YufeiLiu, Jian He, Hong Qiu, Lianchun Wang, Tamas Nagy, Troy D. Querec, Elizabeth R.Unger and Leidong Mao, “Label-Free and Continuous-Flow FerrohydrodynamicSeparation of HeLa Cells and Blood Cells in Biocompatible Ferrofluids”, AdvancedFunctional Materials, 2015.
- 国家/地区
- 美国
