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A pillar-based microfilter for isolation of white blood cells on elastomeric substrate.

ABSTRACT: Our goal is to design, fabricate, and characterize a pillar-based microfluidic device for size-based separation of human blood cells on an elastomeric substrate with application in the low-cost rapid prototyping of lab-chip devices. The single inlet single outlet device is using parallel U-shape arrays of pillars with cutoff size of 5.5 μm for trapping white blood cells (WBCs) in a pillar chamber with internal dead-volume of less than 1.0 μl. The microstructures are designed to limit the elastomeric deformation against fluid pressures. Numerical analysis showed that at maximum pressure loss of 15 kPa which is lower than the device conformal bonding strength, the pillar elastomeric deformation is less than 5% for flow rates of up to 1.0 ml min(-1). Molding technique was employed for device prototyping using polyurethane methacrylate (PUMA) resin and polydimethylsiloxane (PDMS) mold. Characterization of the dual-layer device with beads and blood samples is performed. Tests with blood injection showed that ∼18%-25% of WBCs are trapped and ∼84%-89% of red blood cells (RBCs) are passed at flow rates of 15-50 μl min(-1) with a slight decrease of WBCs trap and improve of the RBCs pass at higher flow rates. Similar results were obtained by separation of mixed microspheres of different size injected at flow rates of up to 400 μl min(-1). Tests with blood samples stained by fluorescent gel demonstrated that the WBCs are accumulated in the arrays of pillars that later end up to blockage of the device. Filtration results of using elastomeric substrate present a good consistency with the trend of separation efficiencies of the similar silicon-based filters.

SUBMITTER: Alvankarian J

PROVIDER: S-EPMC3555971 | biostudies-other | 2013

REPOSITORIES: biostudies-other

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Project description:BACKGROUND:High blood pressure (BP) is a risk factor for cardiovascular morbidity and mortality. While BP is regulated by the function of kidney, vasculature, and sympathetic nervous system, recent experimental data suggest that immune cells may play a role in hypertension. METHODS:We studied the relationship between major white blood cell types and blood pressure in the UK Biobank population and used Mendelian randomization (MR) analyses using the ?750?000 UK-Biobank/International Consortium of Blood Pressure-Genome-Wide Association Studies to examine which leukocyte populations may be causally linked to BP. RESULTS:A positive association between quintiles of lymphocyte, monocyte, and neutrophil counts, and increased systolic BP, diastolic BP, and pulse pressure was observed (eg, adjusted systolic BP mean±SE for 1st versus 5th quintile respectively: 140.13±0.08 versus 141.62±0.07 mm?Hg for lymphocyte, 139.51±0.08 versus 141.84±0.07 mm?Hg for monocyte, and 137.96±0.08 versus 142.71±0.07 mm?Hg for neutrophil counts; all P<10-50). Using 121 single nucleotide polymorphisms in MR, implemented through the inverse-variance weighted approach, we identified a potential causal relationship of lymphocyte count with systolic BP and diastolic BP (causal estimates: 0.69 [95% CI, 0.19-1.20] and 0.56 [95% CI, 0.23-0.90] of mm?Hg per 1 SD genetically elevated lymphocyte count, respectively), which was directionally concordant to the observational findings. These inverse-variance weighted estimates were consistent with other robust MR methods. The exclusion of rs3184504 SNP in the SH2B3 locus attenuated the magnitude of the signal in some of the MR analyses. MR in the reverse direction found evidence of positive effects of BP indices on counts of monocytes, neutrophils, and eosinophils but not lymphocytes or basophils. Subsequent MR testing of lymphocyte count in the context of genetic correlation with renal function or resting and postexercise heart rate demonstrated a positive association of lymphocyte count with urine albumin-to-creatinine ratio. CONCLUSIONS:Observational and genetic analyses demonstrate a concordant, positive and potentially causal relationship of lymphocyte count with systolic BP and diastolic BP.

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A pillar-based microfilter for isolation of white blood cells on elastomeric substrate.

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