Microfluidics-based diagnostics of infectious diseases in the developing world

Abstract

One of the great challenges in science and engineering today is to develop technologies to improve the health of people in the poorest regions of the world. Here we integrated new procedures for manufacturing, fluid handling and signal detection in microfluidics into a single, easy-to-use point-of-care (POC) assay that faithfully replicates all steps of ELISA, at a lower total material cost. We performed this 'mChip' assay in Rwanda on hundreds of locally collected human samples. The chip had excellent performance in the diagnosis of HIV using only 1 μl of unprocessed whole blood and an ability to simultaneously diagnose HIV and syphilis with sensitivities and specificities that rival those of reference benchtop assays. Unlike most current rapid tests, the mChip test does not require user interpretation of the signal. Overall, we demonstrate an integrated strategy for miniaturizing complex laboratory assays using microfluidics and nanoparticles to enable POC diagnostics and early detection of infectious diseases in remote settings.

Rapid fabrication of pressure-driven open-channel microfluidic devices in omniphobic RF paper

“…Silanization of paper with an alkyl or fluoroalkyl trichlorosilane makes it hydrophobic; the reaction occurs readily with the silanizing agent in the vapor phase, and requires no 30 equipment apart from a low-pressure chamber and a source of heat. 21 The cost of the materials used for functionalization with a long fluoroalkyl trichlorosilane is ~$0.80 per m 2 of paper (for reagents purchased in small quantities), slightly less than rendering paper hydrophobic by wax printing ($1 per m 2 ).…”

“…Two separate fluid streams (0.05% solutions of Tartrazine or Methylene Blue in water) entered through a Y-junction at a flow rate of 10 µL/min. Repeating C-shaped units turned the fluid through 180° to induce chaotic advection and passively enhance the mixing of the 30 streams. Thus close to the inlet we observed two clearly delineated blue and yellow co-flowing liquid streams that then became a single stream of green liquid 18 mm downstream from the inlet (Fig.…”

“…18,19 Despite their advantages, current paper microfluidic 25 technologies share some common disadvantages: limited minimum feature sizes (channel widths are generally greater than 200 µm) and inefficient delivery of sample within the device. Due to sample retention in the porous cellulose matrix, the volume that reaches the detection zones is usually less than 50% 30 of the total volume within the device. 7 Moreover, applications that require low Reynolds number, pressure-driven flows in open channels-for example, multiphase flows involving drops or bubbles, or flows of complex fluids such as whole blood or colloidal suspensions that contain particulates-are generally as 45 µm, using, as matrix for fabrication, omniphobic R F paper prepared by silanization of cellulose paper with a fluoroalkyl 50 silanizing reagent.…”

From the Bench to the Field in Low‐Cost Diagnostics: Two Case Studies

“…The development of a test for HIV by Sia (at Columbia) and Linder (at Claros, now OPKO) provides an alternative example. [40] Chin, Linder, and Sia also provide a helpful review of many of the companies working to commercialize POC diagnostics and their different funding structures. [4] )…”

Microfluidic barcode assay for antibody-based confirmatory diagnostics

“…Yet, microfluidic heterogeneous immunoassays specifically developed for immunoglobulin detection are limited. [20][21][22][23][24] A significant challenge stems from the high concentration levels of total immunoglobulin in serum (6-18 mg ml 21 ). [25][26][27] Underpinning the high clinical sensitivity and specificity of HCV blotting confirmatory diagnostics is the capacity to detect multiple immunoglobulin molecules in one biospecimen (i.e., multiplexing).…”