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Biomedical Engineering – From Theory to Applications

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Design Principles for Microfluidic <strong>Biomedical</strong> Diagnostics in Space<br />

= 75 dynes/cm 2, they found that a suspension of isolated platelets with viscosity<br />

=1.1 mPa·s was significantly more likely <strong>to</strong> become activated (similarly for whole blood at<br />

=83 dynes/cm 2, =3.8 mPa·s). Even a few seconds of exposure can be sufficient <strong>to</strong> sensitize<br />

platelets (Dayananda et al., 2010). The viscosity of the fluid medium is important because it<br />

is the shear stress, not the shear rate reported in many studies, that governs the behavior.<br />

(In a homogeneous fluid, shear stress is the shear rate multiplied by viscosity.) Clearly, the<br />

microfluidic design must avoid such levels of shear stress. But given the dependence on<br />

shear stress his<strong>to</strong>ry, the sample should avoid wall proximity <strong>to</strong> limit the potential for<br />

adhesion. This is a strong argument for rigorously avoiding fluid separations (recirculating<br />

flow cells), which may occur near sharp bends, corners, and steps. It also suggests that<br />

sample dilution can be beneficial by lowering fluid viscosity and reducing protein and cell<br />

concentration.<br />

Fig. 2. Solids found in blood and urine samples: (a) blood cells; (b) erythrocyte, activated<br />

platelet, and leukocyte; (c) urinary erythrocyte cast; (d) calcium oxalate crystals (arrows)<br />

(e) uric acid crystals; (f) triple phosphate crystals with amorphous phosphate.<br />

(a)-(b) reprinted from the National Cancer Institute, Frederick, Md.; (c)-(f) reprinted from<br />

the National Institutes of Health Clinical Center Department of Labora<strong>to</strong>ry Medicine,<br />

Bethesda, Md.<br />

Urine separation presents a different set of challenges. Although the solids content is far<br />

less than blood, the size and other properties of the particulates vary more widely. These<br />

can include cells, casts (which include blood and tissue cells that have passed through the<br />

renal system, retaining the renal tubule’s shape, Fig. 2(c)), proteins, and a wide array of<br />

crystals (Fig. 2(d)-(f)). Size, electromagnetic properties, rigidity, and staining propensities<br />

are also quite variable. Obtaining well-filtered urine should be straightforward with<br />

branching techniques (§3.2.2). Examination of urinary sediment can also yield critical<br />

diagnostic information, but it is somewhat more challenging <strong>to</strong> accommodate in a<br />

microfluidic context. Typically, a urine sample of 10-15 mL is centrifuged at ~2000-3000<br />

rpm for five minutes <strong>to</strong> concentrate the solids content. Pure fluid is withdrawn until ~0.2-<br />

0.5 mL remains. A drop of this fluid is then examined under a microscope (Simerville et<br />

al., 2005). To examine urinary sediment in the space environment, an effective<br />

microfluidic concentra<strong>to</strong>r would be required as well as a means of staining and imaging<br />

the concentrated sample.<br />

Saliva is of interest <strong>to</strong> space biodiagnostics because of its ready availability and marginal<br />

invasiveness <strong>to</strong> the astronaut, particularly since wound healing proceeds more slowly in<br />

space (Delp, 2008). Saliva’s non-New<strong>to</strong>nian viscoelastic behavior is a result of its high mucin<br />

139

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