An Autonomous Microfluidic Device for Generating Volume-Defined Dried Plasma Spots

Abstract

Obtaining plasma from a blood sample and preparing it for subsequent analysis is currently a laborious process involving experienced health-care professionals and centrifugation. We circumvent this by utilizing capillary forces and microfluidic engineering to develop an autonomous plasma sampling device that filters and stores an exact amount of plasma as a dried plasma spot (DPS) from a whole blood sample in less than 6 min. We tested 24 prototype devices with whole blood from 10 volunteers, various input volumes (40− 80 μL), and different hematocrit levels (39−45%). The resulting mean plasma volume, assessed gravimetrically, was 11.6 μL with a relative standard deviation similar to manual pipetting (3.0% vs 1.4%). LC-MS/MS analysis of caffeine concentrations in the generated DPS (12 duplicates) showed a strong correlation (R 2 = 0.99) to, but no equivalence with, concentrations prepared from corresponding plasma obtained by centrifugation. The presented autonomous DPS device may enable patient-centric plasma sampling through minimally invasive finger-pricking and allow generatation of volume-defined DPS for quantitative blood analysis.

Simultaneous Quantification of BCR-ABL and Bruton Tyrosine Kinase Inhibitors in Dried Plasma Spots and Its Application to Clinical Sample Analysis

“…22 Several microsampling devices have been developed to collect a fixed volume of plasma from finger-prick blood without centrifugation. [28][29][30] The combination of these devices with our method would be an option to conduct routine TDM based on DPS prepared at patients' homes.…”

Alternative Sampling Devices to Collect Dried Blood Microsamples: State-of-the-Art

“…The excess plasma is removed through the drainage valve. 92,93 Some proof-of-principle measurements demonstrated the capability of the device to generate DPS of a fixed volume, within a limited Hct range (39%-45%) and a blood input volume range of 40-80 mL. This initial evaluation also revealed that, compared with plasma obtained through centrifugation, 73% 6 8% of the plasma proteins were recovered after filtration of venous and capillary blood.…”

A microfluidic device for TEM sample preparation

“…The devices were fabricated using lamination technology where the device is formed by stacking several layers of different materials, as described previously. 17,18 The cross section in Fig. 1a shows the different layers.…”

“…The PVA film was fabricated, as previously reported, 17,18 from an aqueous solution of 20 wt% of granular PVA. Using a thin-film applicator (4340, Elcometer, Manchester, UK) the PVA films were uniformly transferred to laminating pouches (3385694, Office Depot, LA Venlo, Netherlands) and dried at room temperature.…”