High-Speed microfluidic differential manometer for cellular-scale hydrodynamics

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High-Speed microfluidic differential manometer for cellular-scale hydrodynamics, M. Abkarian, M. Faivre, H.A. Stone, PNAS vol.103 no.3 (2006)[1]

Soft Matter Keywords

Compliance, Cell Stiffness, Lysis, Microfluidics, Pressure Sensing

Brief Summary

A microfluidic differential pressure sensor is fabricated using soft lithography techniques and is used to investigate the mechanical properties of red- and white blood cells.

Soft Matter

Figure 1: A: Optical micrograph of device with lower half of the exit pool labelled with dye. C: Calibration of device. This plot shows the change in interface position as a function of applied pressure difference.

The mechanical compliance of blood cells is of central importance with regards to understanding the physics of circulatory disease. Additionally, recent research shows that cancer cells also display a markedly different mechanical response than their healthy counterparts. Presently, the measurement of the stiffness of cells is accomplished by passing cells through a sieve like device and measuring the cell passage time. The authors note that this is an inherently averaged technique which does not have the ability of single cell/pore resolution.

The authors present a device consisting of twin microchannels connected to a common exit pool. As cells pass through one of the small microchannels (that is - smaller than the cell itself), the cell is deformed so that it fits into the channel. The cell partially blocks flow through that channel leading to a reduced flow rate and hence a smaller pressure drop from one end to the other. The other channel remains pressurized at the original level and so the fluid level in the common exit pool is displaced upwards (see Figure 1). The device can be calibrated by driving with a known pressure difference across the twin channel structure. The difference between driving pressures is varied from roughly -1 to 0.5 psi for original driving pressures of 5 and 10 psi, with the lower driving pressure giving a larger displacement per psi and hence greater pressure sensing resolution.

Figure 2: Variation of pressure drop as a RBC and then a WBC traverse the upper microchannel.

To test the applicability of the device to measuring cell mechanics, red blood cells are flown through the upper channel. A typical pressure difference trace is shown in Figure 2 as a function of time as the cell traverses the channel. The effect of cell membrane stiffening on the pressure drop is depicted in Figure 3. Cells treated with glutaraldehyde (a substance known to stiffen the cell membrane) produce a significantly enhanced pressure drop across the channel (roughly a factor of 2). Near the end of the paper, the authors describe the observation of a hemolytic event occuring when a RBC blocks the microchannel. A RBC nears the entry into the top microchannel and subsequently completely plugs the flow. Stress builds up on the cell membrane until it ruptures at which point the additional pressure drop is measured to be ~ 1.1 psi which is close to typical values of 0.6 psi (4kPa) observed using a micropipette technique. The authors go on to mention that this type of measurement may be of interest when investigating lysis of malaria infected RBCs which are known to be more stiff that healthy RBCs.

Figure 3: The open symbols represent pressure drop traces for membrane-stiffened cells whereas the crosses represent a healthy, more compliant cell.

This work furthers efforts towards supplying a high throughput device for measuring the mechanical characteristics of cells. This is becoming more and more important as it is discovered that many illnesses such as cancer, malaria and circulatory diseases have drastic impacts on cell rigidity. Perhaps these types of microfluidic networks can not only used as research tools but as diagnostic screening devices.