Cameron Skinner

Microfluidic devices connected to fused-silica capillaries with minimal dead volume.

Fused-silica capillaries have been connected to microfluidic devices for capillary electrophoresis by drilling into the edge of the device using 200-μm tungsten carbide drills. The standard pointed drill bits create a hole with a conical-shaped bottom that leads to a geometric dead volume of 0.7 nL at the junction, and significant band broadening when used with 0.2-nL sample plugs. The plate numbers obtained on the fused-silica capillary connected to the chip were about 16-25% of the predicted numbers. The conical area was removed with a flat-tipped drill bit and the band broadening was substantially eliminated (on average 98% of the predicted plate numbers were observed). All measurements were made while the device was operating with an electrospray from the end of the capillary. The effective dead volume of the flat-bottom connection is minimal and allows microfluidic devices to be connected to a wide variety of external detectors.

Room temperature bonding of micromachined glass devices for capillary electrophoresis

Abstract We report a simple method to bond glass at room temperature for microfluidic applications, which is based on rigorous cleaning [K. Fluri, G. Fitzpatrick, N. Chiem, D.J. Harrison, Integrated capillary electrophoresis devices with an efficient postcolumn reactor in planar quartz and glass chips, Anal. Chem. 68 (1996) 4285–4290; N. Chiem, D.J. Harrison, Microchip-based capillary, Anal. Chem. 69 (1997) 373–378; D. Sobek, A.M. Young, M.L. Gray, S.D. Senturia, A microfabricated flow chamber for optical measurements influids, Proc. IEEE Micro-Electromechanical Systems Workshop, Fort Lauderdale, FL, Feb 7–10, 1993, pp. 219–224.] of the glass substrates before bonding. Low applied pressure on micromachined glass substrates contacted at 20°C provides devices, which are robustly bonded. These devices are able to withstand routine handling, and be used for capillary electrophoresis for as long as 2 years. Separation efficiencies as high as 90,000 theoretical plates were observed at 6–8 kV applied, comparable to 100,000 observed in devices bonded at 440–650°C. A wide range of the same or different types of commercially available glass can be bonded without heat treatment, alleviating the need for a good match in thermal expansion coefficients between the glasses.

Integrated Serial Dilution on a Microchip for Immunoassay Sample Treatment and Flow Injection Analysis

This paper presents the design and performance of two serial diluters, a 32-fold diluter performing 1:1 dilution in 5 steps and a 1024-fold diluter with ten 1:1 mixing intersections. The simulation package SPICE was used to model the diluter as a network of parallel and serial resistors for flow ratio estimates. Study of the 32-fold diluter showed the expected linear relationship between fluorescein signal and the inverse of overall dilution factor. The dilution factor at each intersection is evaluated to be 1.80 ± 0.02 and 1.89 ± 0.05 in the two devices compared to the nominal value of 2. These results show that integrated serial diluters are possible and the performance data provides foundation for future design of diluters within microchip systems.

Coupling Electrospray Mass Spectrometry to Microfluidic Devices With Low Dead Volume Connections

This work describes a microfluidic device combining a low dead volume connection for coupling to an electrospray mass spectrometry interface. The dead volume expected from the junction was minimized using a flat bottom hole. The band broadening associated with the junction has been investigated with laser induced fluorescence detection and preliminary experiments using a short 5.3 cm capillary demonstrated high separation efficiencies (N=112000). This microfluidic device was coupled via a 15 cm capillary to electrospray mass spectrometry and provided rapid separation of sub micromolar concentrations of synthetic peptides. Peptide fragments arising from the proteolytic digestion of proteins were also characterized using on-line tandem mass spectrometry. This method could be of significant value for the identification and characterization of gel-separated proteins, a key element in the further understanding of functional genomics.

Fluid Mixing Design: Comparison of Simple Versus Complex Modeling Methods

This paper reports on three modeling stages used: a simple lumped element model in which each channel is represented by discrete resistors and the results are calculated using PSPICE; a sheet resistance model, in which each channel is represented by a network of resistors and PSPICE or a home written program is used; a finite element model is solved using Coventor s FlumeCAD software. A detailed evaluation comparing these models with experimental results will be presented.

Multichannel Microchip System for Rapid Calibration and Immunoassay

This paper presents the design and performance of a multiplexed microfluidic system capable of performing six immunoassays simultaneously, based upon on-chip mixing, reaction and affinity capillary electrophoresis. Utilizing a single point, galvanic-scanner based detection system with detection limits of 30 pM for fluorescein (FL), both qualitative and quantitative immunoassays have been performed. Factors governing good quality, quantitative measurements are discussed. The results show a complete estradiol (E2) immunoassay, including calibration, can be performed on chip in about 1 minute.

Design Rule Evaluation for Micro-Scale Flow Restrictions: Comparing Experiment and Theory

Control of the direction of fluid flow within a network of flow paths in a microfluidic device is paramount to its proper operation. Pressure driven flow requires either active valving for control, or passive control through variation of the flow resistance of each intersecting channel by adjusting its geometry. In order to achieve rational design of passive flow control, an accurate model describing fluid flow in micron-scale devices must be available. In this report we compare the predictions of the Navier-Stokes equations with experimental results for three-port devices with flow restrictors. The good agreement seen indicates that flow restrictors with 1-µm dimensions can be designed using solutions to the Navier-Stokes equations.

Automated Microchip Platform for Biochemical Analysis

The development of the components and subsystems of an automated microchipbased platform for bioanalysis by immunoassay and gene probe assay is described. The device uses micromachined glass plates for the fabrication of channel networks and combines electroosmotic pumping and capillary electrophoresis for fluid transport and separation. The complete system enables the on-chip integration of the key elements in analytical processing: injection, mixing, separation, detection and elimination. The analysis platform is being designed for use with an on-line aerosol collector for environmental monitoring.