Blood-on-a-Chip

Abstract

Accurate, fast, and affordable analysis of the cellular component of blood is of prime interest for medicine and research. Yet, most often sample preparation procedures for blood analysis involve handling steps prone to introducing artifacts, whereas analysis methods commonly require skilled technicians and well-equipped, expensive laboratories. Developing more gentle protocols and affordable instruments for specific blood analysis tasks is becoming possible through the recent progress in the area of microfluidics and lab-on-a-chip-type devices. Precise control over the cell microenvironment during separation procedures and the ability to scale down the analysis to very small volumes of blood are among the most attractive capabilities of the new approaches. Here we review some of the emerging principles for manipulating blood cells at microscale and promising high-throughput approaches to blood cell separation using microdevices. Examples of specific single-purpose devices are described together with integration strategies for blood cell separation and analysis modules.

In vitro blood flow in a rectangular PDMS microchannel: experimental observations using a confocal micro-PIV system

“…Table 1. The lateral and axial resolutions of both conventional and confocal microscopes and optical slice thickness of confocal microscopes (Willhelm et al 2003, Park et al 2004 Progress in microfabricated technologies has attracted the attention of the biomedical research community to the development of diagnostic, microfluidic devices (so-called bio-microelectromechanical systems or a lab-on-a-chip) (Sutton et al 1997, Gomez et al 2001, Beebe et al 2002, Minas et al 2004, Toner and Irimia 2005, Faivre et al 2006) capable of providing useful information about the general health status of patients. However, most of the information provided by blood analysis in microchannels is based on conventional visual observations on the area and volume of the RBCs (Sutton et al 1997.…”

“…By using a soft lithography technique it is possible to generate extremely precise, reproducible and versatile rectangular microchannels. Although, rectangular microchannels may not be the best models to simulate in vivo microvessels geometry, many phenomena of blood flow behavior through this kind of microchannels exhibits certain features characteristic with those investigated in living microvessels (Beebe et al 2002, Shevkoplyas et al 2003, ,Toner and Irimia 2005, Faivre et al 2006. Furthermore, experiments with this kind of microchannels enable not only precise control of experimental parameters but also obtain more accurate measurements.…”

Cell handling using microstructured membranes

“…3 Volumes of blood as small as a few microliters can be precisely sampled using syringes and micropipettes. However, smaller volumes, like those used in microfabricated devices, require different approaches not always suited to complex cell-rich fluids like blood.…”

“…[28][29][30] The new cell enrichment procedure may also be useful for the isolation of cells from dissociated tissues and removal of debris, 31 or for separating cells in particles based on size, in an approach comparable to mechanical filtering of blood cells. 3 The study of cellular responses to chemical stimulation is of fundamental importance for many biology studies. While macroscopic techniques using pipettes and Petri dishes are still widely used in biology laboratories, there is increasing interest in the more precise methods available through microfluidics.…”

Continuous-flow ferrohydrodynamic sorting of particles and cells in microfluidic devices

“…Microfluidic particle and cell sorting plays an important role in environmental monitoring (Liu et al 2004;Beyor et al 2008;Dharmasiri et al 2010), disease diagnostics (Nagrath et al 2007;Adams et al 2008;Hoshino et al 2011), and therapeutics (Toner and Irimia 2005;Yung et al 2009). Compared to high-specificity and label-based cell sorting techniques such as 0fluorescence-activated cell sorter (FACS) (Bonner et al 1972) and magnetic-activated cell sorter (MACS) (Miltenyi et al 1990), microfluidic sortings are mostly label-free, relying on cells' intrinsic properties such as size, shape, density, deformability, electric and magnetic properties for manipulation specificity (Pamme 2007;Tsutsui and Ho 2009;Gossett et al 2010;Lenshof and Laurell 2010).…”