Microfluidics, a technology characterized by the engineered manipulation of fluids at the submillimetre scale, has shown considerable promise for improving diagnostics and biology research. Certain properties of microfluidic technologies, such as rapid sample processing and the precise control of fluids in an assay, have made them attractive candidates to replace traditional experimental approaches. Here we analyse the progress made by lab-on-a-chip microtechnologies in recent years, and discuss the clinical and research areas in which they have made the greatest impact. We also suggest directions that biologists, engineers and clinicians can take to help this technology live up to its potential.

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The present and future role of microfluidics in biomedical research

The standard centrifuge is a laboratory instrument widely used by biologists and medical technicians for preparing cell samples. Efforts to automate the operations of concentration, cell separation, and solution exchange that a centrifuge performs in a simpler and smaller platform have had limited success. Here, we present a microfluidic chip that replicates the functions of a centrifuge without moving parts or external forces. The device operates using a purely fluid dynamic phenomenon in which cells selectively enter and are maintained in microscale vortices. Continuous and sequential operation allows enrichment of cancer cells from spiked blood samples at the mL min−1 scale, followed by fluorescent labeling of intra- and extra-cellular antigens on the cells without the need for manual pipetting and washing steps. A versatile centrifuge-analogue may open opportunities in automated, low-cost and high-throughput sample preparation as an alternative to the standard benchtop centrifuge in standardized clinical diagnostics or resource poor settings.

Automated cellular sample preparation using a Centrifuge-on-a-Chip

Microfluidics, a toolbox comprising methods for precise manipulation of fluids at small length scales (micrometers to millimeters), has become useful for manipulating cells. Its uses range from dynamic management of cellular interactions to high-throughput screening of cells, and to precise analysis of chemical contents in single cells. Microfluidics demonstrates a completely new perspective and an excellent practical way to manipulate cells for solving various needs in biology and medicine. This review introduces and comments on recent achievements and challenges of using microfluidics to manipulate and analyze cells. It is believed that microfluidics will assume an even greater role in the mechanistic understanding of cell biology and, eventually, in clinical applications.

Microfluidics for Manipulating Cells

We report that a droplet dispensed from a micropipette almost always has a considerable electrical charge of a magnitude dependent on the constituents of the droplet, on atmospheric humidity and on the coating material of pipette tip. We show that this natural electrification of a droplet originates from the charge separation between a droplet and pipette tip surface by contact with water due to the ionization of surface chemical groups. Charge on a droplet can make it difficult to detach the droplet from the pipette tip, can decrease its surface tension, can affect the chemical characteristics of solutions due to interactions with charged molecules, and can influence the combination and localization of charged bio-molecules; in all cases, the charge may affect results of experiments in which any of these factors is important. Thus, these findings reveal experimental parameters that should be controlled in experiments that use micropipettes.

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Spontaneous electrical charging of droplets by conventional pipetting

Continuous flow microfluidic separation and processing of rare cells and bioparticles found in blood - A review.

Cell concentration via centrifugation is a ubiquitous step in many cell culture procedures. At the macroscale, centrifugation suffers from a number of limitations, particularly when dealing with small numbers of cells (e.g., less than 50 000). On the other hand, typical microscale methods for cell concentration can affect cell physiology and bias readouts of cell behavior and function. In this paper, we present a microfluidic concentrator device that utilizes the effects of gravity to allow cells to gently settle out of a suspension into a collection region without the use of specific adhesion ligands. Dimensional analysis was performed to compare different device designs and was verified with flow modeling to optimize operational parameters. We are able to concentrate low-density cell suspensions in a microfluidic chamber, achieving a cell loss of only 1.1 ± 0.6% (SD, n = 7) with no observed loss during a subsequent cell staining protocol which incorporates ∼36 complete device volume replacements. This m...

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A Microfluidic Cell Concentrator

Laminar flow patterning (LFP) is a characteristic method of microfluidic systems that allows two (or more) different solutions to flow side-by-side in a channel without convective mixing. This fluid behavior can be used to pattern cell suspensions, particles, and treatments as well as to create chemical gradients. LFP is typically implemented using syringe pumps and, for this reason, is most effective in constant flow scenarios such as long-term gradient generation. However, the complexity of using syringe pumps for patterning cell suspensions typically makes it a less attractive option than other standard patterning methods. We present a passive microfluidic method that enables short-term LFP of multiple fluids using a single pipette and allows each sample to be loaded in any sequence, at any point in time relative to one another. The proposed method is well-suited for cell-based assays, reduces the complexity of LFP to be on a similar level as other cell patterning methods, can be scaled to include more than two streams of fluid, and enables arrays of individually addressable devices for LFP on a single chip.

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Pipette-friendly laminar flow patterning for cell-based assays

The various embodiments described herein relate to fabricating and using open microfluidic networks according to methods, systems, and devices that can be used in applications ranging from home-testing, diagnosis, and research laboratories. Open microfluidic networks allow the input, handling, and extraction of fluids or components of the fluid into or out of the open microfluidic network. Fluids can be inserted into an open microfluidic channel by using open sections of the open microfluidic network. Passive valves can be created in the microfluidic network, allowing the creation of logic circuits and conditional flow and volume valves. The fluid can be presented via the microfluidic network to diagnostic and analysis components. Fluids and components of the fluid can be extracted from the open microfluidic network via functional open sections that are easily interfaced with other microfluidic networks or common laboratory tools.

Methods, Systems, and Devices Relating to Open Microfluidic Channels

A handheld device for drawing, collecting, and analyzing bodily fluid includes a body having a lumen defined therein, a plunger configured to be user-actuated, and a base. Multiple needles are fixed to the plunger, and at least one of the needles is configured to pass through the apertures of the base and penetrate a subject's skin to release bodily fluid when the plunger is actuated. After the plunger is actuated, a mechanism retracts the plunger from the subject's skin and creates a vacuum within the lumen. A network of passages on the base is configured to collect at least some of the bodily fluid and communicate the bodily fluid to one or more sensing areas for analysis.

Handheld Device for Drawing, Collecting, and Analyzing Bodily Fluid

The disclosed apparatus, systems and methods relate to the collection of bodily fluids through the use of gravity and microfluidic properties by way of a collector. The collector can make use of microfluidic networks connected to collection sites on the skin of a subject to gather and shuttle blood into a reservoir by a combination of capillary action and gravitational forces. The collected fluid is moved through the microfluidic networks and into the reservoir by a variety of approaches.

Ben Casavant

Papers

A Microfluidic Cell Concentrator

Pipette-friendly laminar flow patterning for cell-based assays

Methods, Systems, and Devices Relating to Open Microfluidic Channels

Handheld Device for Drawing, Collecting, and Analyzing Bodily Fluid

Devices, systems and methods for gravity-enhanced microfluidic collection, handling and transferring of fluids