Microfluidic Apparatus Research Articles

Delivering More Than Charge

CHEMISTRY A small platinum or carbon wire inserted into a solution environment can yield substantial chemical insight through charge exchange with local compounds. One limitation of such electrode sensing, however, is that only electrons can be shuttled back and forth. Chen et al. have engineered a microfluidic apparatus, which they term a chemistrode, that can deliver or remove complex molecules from specific sites with a spatial resolution of 15 μm. The system relies on a fluorocarbon carrier fluid that pulls well-separated aqueous droplets through a channel that briefly opens to contact a substrate surface for molecular exchange. Analytes absorbed from the substrate can then be subjected to a wide range of traditional spectrometric probing techniques. The authors demonstrate the device through a measurement of insulin secretion kinetics by murine islet of Langerhans cells. — JSY Proc. Natl. Acad. Sci. U.S.A. 105 , 16843 (2008).

Microfluidic Capillary System for Immunoaffinity Separations of C-Reactive Protein in Human Serum and Cerebrospinal Fluid

A miniaturized system based on microfluidic capillaries is presented for point-of-care testing and clinical assessment. The approach relies on microsyringe pump-generated flow to deliver reagents and immunoaffinity chromatography to isolate the antigen from biological matrixes. Capillary sandwich immunoassays for C-reactive protein (CRP) were demonstrated in human serum and cerebrospinal fluid (CSF), which are relevant matrixes for cardiovascular disease risk and meningitis research, respectively. Capillaries packed with antibody-coated silica beads were used to capture CRP from the matrix and a second, dye-labeled antibody was introduced to form a sandwich complex. An acidic elution buffer dissociated the antibody-antigen complexes, and the labeled antibody was detected with diode laser-induced fluorescence. Four parameter logistic functions and % relative error plots were used to model and assess the data. The calibration ranges for CRP were 0.05-3.0 microg/mL in 1:10 diluted serum and 0.01-30 microg/mL in undiluted CSF. The microfluidic apparatus employed a flow rate of 2 microL/min and a sample injection volume of 250 nL. Since it was not necessary to reach antibody-antigen reaction equilibrium and the assay platform dimensions were minimal, run times were as short as 10 min.

Purely Elastic Flow Asymmetries

Using a numerical technique we demonstrate that the flow of the simplest differential viscoelastic fluid model (i.e., the upper-convected Maxwell model) goes through a bifurcation to a steady asymmetric state when flowing in a perfectly symmetric "cross-slot" geometry. We show that this asymmetry is purely elastic in nature and that the effect of inertia is a stabilizing one. Our results are in qualitative agreement with very recent experimental visualizations of a similar flow in the microfluidic apparatus of Arratia et al.

Microfluidic Deletion/Insertion Analysis for Rapid Screening of KIT and PDGFRA Mutations in CD117-Positive Gastrointestinal Stromal Tumors : Diagnostic Applications and Report of a New KIT Mutation

Gastrointestinal stromal tumors (GISTs) frequently harbor mutations in the KIT and PDGFRA genes, the presence and type of which correlate with the response to the kinase inhibitor imatinib mesylate. Because most GIST mutations are deletions/insertions, we used a microfluidic apparatus to detect these size variations in polymerase chain reaction-amplified DNA. This approach, termed microfluidic deletion/insertion analysis (MIDIA), identified mutations in 30 of 50 DNA samples from paraffin-embedded CD117-positive GISTs (60%), comprising 25 deletions and five insertions. Sequencing of 14 MIDIA-positive samples confirmed the deletions/insertions, including two 3-bp alterations. Sequencing of all 20 MIDIA-negative samples also showed highly consistent results with MIDIA because 10 cases were wild type and eight displayed a single base substitution in which detection by MIDIA was not expected. Sequencing also revealed a 3-bp deletion undetected by MIDIA, thus establishing the resolution limit of MIDIA at deletions/insertions >or=3 bp. Denaturing high-pressure liquid chromatography analysis confirmed all mutations detected by MIDIA and sequencing. We pro-pose MIDIA as the first step in mutational screening of GIST because it allowed the detection of 75% of mutated cases (94% of deletions/insertions) in less than 30 minutes after polymerase chain reaction amplification and at a lower cost compared with denaturing high-pressure liquid chromatography and sequencing, which might then be used only for MIDIA-negative cases.

A polymeric microfluidic valve employing a pH-responsive hydrogel microsphere as an actuating source

In this paper, we propose a new fabrication method for pH-responsive microfluidic valves. Conventionally, an in situ photopolymerization method has been employed to build the micro functional structure inside a microfluidic channel. Here, we suggest a new method that allows the mass production of a stimuli-responsive microsystem through the use of a pre-made microstructure as an actuating element, like the assembly of commercial products in a factory. We have massively fabricated pH-responsive microspheres that act as an actuating component through the use of PDMS-based microfluidic apparatus and an ‘on the fly’ photopolymerization method. By incorporation of this microsphere into the microvalve during the fabrication process, we have produced a pH-responsive microfluidic valve in a simple way. The operation and the function of the fabricated microvalve were evaluated through diverse experiments. The microvalve was successfully fabricated, and functioned well according to the pH change.

Hydrodynamic microfabrication via “on the fly” photopolymerization of microscale fibers and tubes

A microfluidic apparatus capable of creating continuous microscale cylindrical polymeric structures has been developed. This system is able to produce microstructures (e.g. fibers, tubes) by employing 3D multiple stream laminar flow and "on the fly"in-situ photopolymerization. The details of the fabrication process and the characterization of the produced microfibers are described. The apparatus is constructed by merging pulled glass pipettes with PDMS molding technology and used to manufacture the fibers and tubes. By controlling the sample and sheath volume flow rates, the dimensions of the microstructures produced can be altered without re-tooling. The fiber properties including elasticity, stimuli responsiveness, and biosensing are characterized. Responsive woven fabric and biosensing fibers are demonstrated. The fabrication process is simple, cost effective and flexible in materials, geometries, and scales.