Orientation-Based Control of Microfluidics

Norouzi, Nazila; Bhakta, Heran C.; Grover, William H.

doi:10.1371/journal.pone.0149259

Cited by 11 publications

(6 citation statements)

References 15 publications

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“…In previous work, we showed that when two fluids of different densities flow together horizontally in a microfluidic chip, the fluids quickly reorient themselves relative to gravity (locating the more-dense fluid on the bottom and the less-dense fluid on the top) and form two stable flowing fluid layers of different densities [ 12 ]. In this work we show that any number of different-density fluids can be combined in this manner to create a continuously-flowing micron-scale on-chip density gradient capable of sorting cells by their densities.…”

Section: Introductionmentioning

confidence: 99%

Sorting cells by their density

2017

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Sorting cells by their type is an important capability in biological research and medical diagnostics. However, most cell sorting techniques rely on labels or tags, which may have limited availability and specificity. Sorting different cell types by their different physical properties is an attractive alternative to labels because all cells intrinsically have these physical properties. But some physical properties, like cell size, vary significantly from cell to cell within a cell type; this makes it difficult to identify and sort cells based on their sizes alone. In this work we continuously sort different cells types by their density, a physical property with much lower cell-to-cell variation within a cell type (and therefore greater potential to discriminate different cell types) than other physical properties. We accomplish this using a 3D-printed microfluidic chip containing a horizontal flowing micron-scale density gradient. As cells flow through the chip, Earth’s gravity makes each cell move vertically to the point where the cell’s density matches the surrounding fluid’s density. When the horizontal channel then splits, cells with different densities are routed to different outlets. As a proof of concept, we use our density sorter chip to sort polymer microbeads by their material (polyethylene and polystyrene) and blood cells by their type (white blood cells and red blood cells). The chip enriches the fraction of white blood cells in a blood sample from 0.1% (in whole blood) to nearly 98% (in the output of the chip), a 1000x enrichment. Any researcher with access to a 3D printer can easily replicate our density sorter chip and use it in their own research using the design files provided as online Supporting Information. Additionally, researchers can simulate the performance of a density sorter chip in their own applications using the Python-based simulation software that accompanies this work. The simplicity, resolution, and throughput of this technique make it suitable for isolating even rare cell types in complex biological samples, in a wide variety of different research and clinical applications.

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Section: Introductionmentioning

confidence: 99%

Sorting cells by their density

2017

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“…Computer-based simulation is becoming increasingly important in the design of microfluidic devices. Finite element analysis (FEA) software enables researchers to study microfluidic phenomena in their chips [ 1 , 2 ], optimize existing chip designs [ 3 ], and even automate the design of new devices [ 4 ]. However, existing simulation tools suffer from several notable drawbacks which have unnecessarily raised the barrier to entry and slowed widespread adoption of these tools in the microfluidics community.…”

Section: Introductionmentioning

confidence: 99%

Instantaneous simulation of fluids and particles in complex microfluidic devices

et al. 2017

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Microfluidics researchers are increasingly using computer simulation in many different aspects of their research. However, these simulations are often computationally intensive: simulating the behavior of a simple microfluidic chip can take hours to complete on typical computing hardware, and even powerful workstations can lack the computational capabilities needed to simulate more complex chips. This slows the development of new microfluidic chips for new applications. To address this issue, we present a microfluidic simulation method that can simulate the behavior of fluids and particles in some typical microfluidic chips instantaneously (in around one second). Our method decomposes the chip into its primary components: channels and intersections. The behavior of fluid in each channel is determined by leveraging analogies with electronic circuits, and the behavior of fluid and particles in each intersection is determined by querying a database containing nearly 100,000 pre-simulated channel intersections. While constructing this database takes a nontrivial amount of computation time, once built, this database can be queried to determine the behavior of fluids and particles in a given intersection in a fraction of a second. Using this approach, the behavior of a microfluidic chip can be simulated in just one second on a standard laptop computer, without any noticeable degradation in the accuracy of the simulation. While our current technique has some constraints on the designs of the chips it can simulate (namely, T- or cross-shaped intersections, 90 degree channel turns, a fixed channel width, fluid flow rates between 0 and 2 cm/s, and particles with diameters between 1 and 20 microns), we provide several strategies for increasing the range of possible chip designs that can be simulated using our technique. As a proof of concept, we show that our simulation method can instantaneously simulate the paths followed by particles in both simple and complex microfluidic chips, with results that are essentially indistinguishable from simulations that took hours or even days to complete using conventional approaches.

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“…Norouzi et al reported the orientation-based control of on-chip fluid flow and mixing with no off-chip hardware or power using only gravity and fluids of differing density. 41 While promising, these approaches still require complicated microchip design, some power or external hardware, or require further advances to allow for implementation in practical/relevant bioanalytical assays.…”

Section: Introductionmentioning

confidence: 99%

Magnetic-adhesive based valves for microfluidic devices used in low-resource settings

et al. 2016

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Since the introduction of micro total analytical systems (μTASs), significant advances have been made toward development of lab-on-a-chip platforms capable of performing complex biological assays that can revolutionize public health, among other applications. However, use of these platforms in low-resource environments (e.g. developing countries) has yet to be realized as the majority of technologies used to control microfluidic flow rely on off-device hardware with non-negligible size, cost, power requirements and skill/training to operate. In this paper we describe a magnetic-adhesive based valve that is simple to construct and operate, and can be used to control fluid flow and store reagents within a microfluidic device. The design consists of a port connecting two chambers on different planes in the device that is closed by a neodymium disk magnet seated on a thin ring of adhesive. Bringing an external magnet into contact with the outer surface of the device unseats and displaces the valve magnet from the adhesive ring, exposing the port. Using this configuration, we demonstrate on-device reagent storage and on-demand transport and reaction of contents between chambers. This design requires no power or external instrumentation to operate, is extremely low cost ($0.20 materials cost per valve), can be used by individuals with no technical training, and requires only a hand-held magnet to actuate. Additionally, valve actuation does not compromise the integrity of the completely sealed microfluidic device, increasing safety for the operator when toxic or harmful substances are contained within. This valve concept has the potential to simplify design of μTASs, facilitating development of lab-on-a-chip systems that may be practical for use in point-of-care and low-resource settings.

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Orientation-Based Control of Microfluidics

Cited by 11 publications

References 15 publications

Sorting cells by their density

Sorting cells by their density

Instantaneous simulation of fluids and particles in complex microfluidic devices

Magnetic-adhesive based valves for microfluidic devices used in low-resource settings

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