Pre-concentration by liquid intake by paper (P-CLIP): a new technique for large volumes and digital microfluidics

Abstract

Microfluidic platforms are an attractive option for incorporating complex fluid handling into low-cost and rapid diagnostic tests. A persistent challenge for microfluidics, however, is the mismatch in the "world-to-chip" interface - it is challenging to detect analytes present at low concentrations in systems that can only handle small volumes of sample. Here we describe a new technique termed pre-concentration by liquid intake by paper (P-CLIP) that addresses this mismatch, allowing digital microfluidics to interface with volumes on the order of hundreds of microliters. In P-CLIP, a virtual microchannel is generated to pass a large volume through the device; analytes captured on magnetic particles can be isolated and then resuspended into smaller volumes for further processing and analysis. We characterize this method and demonstrate its utility with an immunoassay for Plasmodium falciparum lactate dehydrogenase, a malaria biomarker, and propose that the P-CLIP strategy may be useful for a wide range of applications that are currently limited by low-abundance analytes.

Microfluidics for Peptidomics, Proteomics, and Cell Analysis

“…However, there is limited knowledge of detergents compatible with LC–MS in DMF [ 155 ]. In this context, using Pluronic F68 [ 156 ] was investigated. This detergent is nontoxic, compatible with cell cultures, aids droplet movement and reduces shear forces.…”

“…The detergent Tetronic 90R4 [ 157 ] showed the best performance in the process of cell lysis and did not cause droplet pinning. Peptide identification is problematic when using Tetronic or Pluronic detergents due to ionization suppression in MS detection [ 156 , 157 ]. The magnetic bead-based sample cleanup technique (SP3) is compatible with high concentrations of salts, detergents, and chaotropes.…”

“…Her primary contributions were in sample cleanup and selection of detergent buffer systems for analysis by LC–MS. SP3 was effective in depleting Pluronic and Tetronic detergents from droplets in samples [ 156 , 157 ]. Another important implication of this research was that detergents compatible with LC–MS were effective in protein digestion in the form of DMF antifouling additives [ 158 ].…”

A digital microfluidic system for serological immunoassays in remote settings

“…In the future, throughput per cartridge could be increased, perhaps using thin-film transistor-based DMF devices with thousands of electrodes (56). Increases in sample throughput should be accompanied by an increase in the number of assay types used on the same cartridge, for example, adding IgM assays for diagnosis or DMFbased assays for other conditions such as malaria (57) or bacterial infections (58,59). In this manner, the user would have the flexibility to conduct many assays on one sample or to conduct a single assay on many samples (or any permutation thereof) depending on the need.…”

Determination of Ascorbic Acid in Commercial Tablets Using Pencil Drawn Electrochemical Paper-based Analytical Devices

“…4 This kind of substrate has become increasingly popular for the scientific community due to its operational simplicity, low instrumental requirements and, most importantly, the possibility to be used in point-of-care testing with the sample-in:answer-out capability. [1][2][3][4] Recent examples of paper-based analytical devices (PADs) for lateral flow or spot test assays, [5][6][7] flow-injection analysis, 8,9 chromatographic and electrophoretic separations, 10,11 digital microfluidics, 12 direct analysis using paper spray ionization mass spectrometry [13][14][15] and electroanalytical measurements 16,17 have been successfully reported.…”