Particle Focusing in Staged Inertial Microfluidic Devices for Flow Cytometry

Oakey, John; Applegate, Robert W.; Arellano, Erik; Carlo, Dino Di; Graves, Steven W.; Toner, Mehmet

doi:10.1021/ac100387b

Cited by 209 publications

(217 citation statements)

References 29 publications

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“…For practical purposes, particle focusing at high flow rates is essential for high-throughput analysis 12,13,23 , but the previous particle focusing using synthetic polymers were limited to low flow rates (B200 ml h À 1 ) 19,20 . The maximum attainable flow rate in this DNA-based method is comparable with those of inertia-based approaches implemented in a single-layer microchannel 23,24 and commercial flow cytometers. On the other hand, we expect that DNA molecules in the working media are not problematic in most applications such as cell identification and deformability measurements 12,13 .…”

Section: Resultsmentioning

confidence: 61%

DNA-based highly tunable particle focuser

et al. 2013

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DNA is distinguished by both long length and structural rigidity. Classical polymer theories predict that DNA enhances the non-Newtonian elastic properties of its dilute solution more significantly than common synthetic flexible polymers because of its larger size and longer relaxation time. Here we exploit this property to report that under Poiseuille microflow, rigid spherical particles laterally migrate and form a tightly focused stream in an extremely dilute DNA solution (0.0005 (w/v)%). By the use of the DNA solution, we achieve highly efficient focusing (499.5%) over an unprecedented wide range of flow rates (ratio of maximum to minimum flow rates B400). This highly tunable particle-focusing technique can be used in the design of cost-effective portable flow cytometers, high-throughput cell analysis and also for cell sorting by size. We demonstrate that DNA is an efficient elasticity enhancer, which originates from its unique structural properties.

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Section: Resultsmentioning

confidence: 61%

DNA-based highly tunable particle focuser

et al. 2013

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“…31 Their device allows easier operation, accurate detection, and differentiation of cells at higher sample concentrations than traditional flow cytometers will allow, while operating at a throughput of around 1 ϫ 10 6 cells/ s ͑over ten channels͒. 32 Most recently, Oakey et al 33 fabricated a staged device including both curved and straight channels to confine particles into a single streamline without sheath flow ͑Fig. 5͒.…”

Section: B Inertial Effect "Nonzero Re…mentioning

confidence: 99%

Review Article: Recent advancements in optofluidic flow cytometer

Cho¹,

Godin²,

Chen³

et al. 2010

Biomicrofluidics

143

105

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There is an increasing need to develop optofluidic flow cytometers. Optofluidics, where optics and microfluidics work together to create novel functionalities on a small chip, holds great promise for lab-on-a-chip flow cytometry. The development of a low-cost, compact, handheld flow cytometer and microfluorescence-activated cell sorter system could have a significant impact on the field of point-of-care diagnostics, improving health care in, for example, underserved areas of Africa and Asia, that struggle with epidemics such as HIV/AIDS. In this paper, we review recent advancements in microfluidics, on-chip optics, novel detection architectures, and integrated sorting mechanisms.

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“…The strength of this secondary flow is characterized by the inertia of the fluid and the curvature of the channel, or the non-dimensional Dean number defined as De 5 Re C d 1/2 , where d is the curvature ratio d 5 D h /2r, where r is the radius of curvature of the channel. This secondary flow imparts an additional drag force on particles thereby adjusting the number and locations of inertial focusing equilibrium positions 9,[19][20][21][22][23][24][25][26][27][28][29][30] . A review of these effects and the field of inertial microfluidics in general is available elsewhere 18 .…”

mentioning

confidence: 99%

Particle Focusing in Curved Microfluidic Channels

Martel

Toner

2013

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The decoupled effects of Reynolds and Dean numbers are examined in inertial focusing flows. In doing so, a complex set of inertial focusing behavioral regimes is discovered within curved microfluidic channels over a range of channel Reynolds numbers, curvature ratios and particle confinement ratios. These regimes are characterized by particle migration either towards or away from the center of curvature as the channel Reynolds number is increased. The transition between these two regimes is shown to be a set of conditions where single-point equilibrium position focusing of particles of different sizes is achieved. A mechanism describing the observed motion of particles in such flows is hypothesized incorporating the redistribution of the main flow velocities caused by Dean flow and its effect on the balance forces on suspended particles.I nertial focusing is an area of significant interest in the realm of microfluidics because it combines high throughput capability with precision particle positioning and offers theoretical intrigue due to the seemingly endless surprises that accompany experimental results. Inertial focusing occurs under certain conditions as particles flowing through a microchannel migrate across streamlines to equilibrium positions within the flow. This migration is due to inertial effects of the fluid motion around the particle and the interaction of this flow field with the walls of the channel 1-5 . Equilibrium positions arise from a balance between two distinct effects; a shear gradient lift force directed towards the walls of the channel and an opposing wall effect 6,7 . These forces allow for the precise alignment of particles in a flow at throughputs orders of magnitudes higher than in previous microfluidic technologies. The high throughput nature of inertial focusing has enabled a range of microfluidic technologies for biomedical applications from separation technologies [8][9][10][11][12] , to automated sample preparations 13,14 , to novel cell analysis techniques such as cell deformability cytometry 15 and the isolation of circulating tumor cells from blood 16,17 .It is generally accepted that inertial focusing in straight channels is dependent on two main parameters: Reynolds number, defined as Re C 5 rU Max D h /m, where r is the fluid density, m is the fluid viscosity, U Max > 3/2U Avg is the maximum velocity of the fluid and D h is the hydraulic diameter of the channel defined as D h 5 2hw/(h 1 w) where h and w are the height and width of the channel cross section respectively, and the particle confinement ratio, l 5 a/D h , where a, is the particle size. Prior research has determined a minimum threshold for inertial focusing to occur such that l . 0.07 and Re C l 2 , also known as the particle Reynolds number, Re P , is $1 18 . The equilibrium positions can be further controlled using curved channels, where a secondary flow called Dean flow is established at finite Re C . The strength of this secondary flow is characterized by the inertia of the fluid and the curvature of the cha...

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Particle Focusing in Staged Inertial Microfluidic Devices for Flow Cytometry

Cited by 209 publications

References 29 publications

DNA-based highly tunable particle focuser

DNA-based highly tunable particle focuser

Review Article: Recent advancements in optofluidic flow cytometer

Particle Focusing in Curved Microfluidic Channels

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