Farzad Pourahmadi

A microfluidic cartridge to prepare spores for PCR analysis

A prototype cartridge system is described that rapidly disrupts Bacillus spores by sonication, adds PCR reagent to the disrupted spores, and dispenses the mixture into a PCR tube. The total time to automatically process the spores in the cartridge and then detect the spore DNA by real-time PCR was 20 min.

Modeling of thermal and mechanical stresses in silicon microstructures

Abstract Modeling of sensors and microstructures using the finite element method (FEM) is described. In this work two modeling techniques are presented which ar

Toward Next Generation Clinical Diagnostic Instruments: Scaling and New Processing Paradigms

Looking toward future clinical diagnostic instruments, there is little debate as to the features that need improvement over the current state-of-the-art. Increasing the speed and sensitivity of the assays, while reducing costs are clear goals. Recently, it has become possible to microminiaturize fluidic and sensing components using micromachining and precision injection molding. There has been a large amount of interest and effort in the area of miniaturization of such systems, yet not all of the properties of fluidics and sensing methods improve as they are drastically reduced in size. It is clear that implementing miniaturized diagnostic instruments is not a matter of simply “shrinking” their conventional counterparts, nor of automating existing manual procedures. What is required to harness the full potential of scaling technologies is the use of design methods that take into account scaling effects and the development of completely new processing approaches. Beginning with a general overview of the relevant scaling principles, sample preparation and detection approaches are addressed in this context.

The effect of corner radius of curvature on the mechanical strength of micromachined single-crystal silicon structures

The burst pressure of typical diaphragm structures is measured for devices that have various radii of curvature at the sharp corner. When pressure is applied to the etched side of the diaphragm, burst pressure is increased by over 50% in devices with radii of curvature as little as 0.2 mu m compared to devices with no measurable radii of curvature. Devices with radii of curvature of 1.5 mu m have burst pressures that are 5* higher than those manufactured with customary methods. Finite element submodeling has been used to simulate the test results, and the models estimate the fracture strength of (100) silicon wafers at 990 kpsi in the (110) direction.<<ETX>>

Low-pressure sensors employing bossed diaphragms and precision etch-stopping

Abstract This paper describes the various critical factors required for the successful design and production of low-pressure silicon micromachined sensors with ranges from 1 psi to 2 in of water. Described in some detail are mechanical modeling and process design and control-related issues. Particular attention is paid to the specialized geometries required for achieving good linearity at low pressures. An example of a plastic housed frequency output sensor with test data is shown.

Single-crysytal silicon pressure sensors with 500 × overpressure protection

Abstract Single-crystal silicon piezoresistive pressure sensors with high overpressure tolerance have been fabricated using the process of silicon fusion bonding. A mechanical stopping surface beneath a conventional diaphragm structure limits diaphragm displacement during overpressure conditions. Uniform and bossed diaphragms in gage and absolute configurations are possible using this process. Sensors with sensitivities as high as 3 mV/ V/psi (typical of sensors used for 5–10 psi full-scale applications) survived overpressures of up to 5000 psi. Finite element modeling is compared to experimental results.

Versatile, Adaptable and Programmable Microfluidic Platforms for DNA Diagnostics and Drug Discovery Assays

A PCR DNA diagnostics system based on a hybrid microfluidic platform is described which offers the advantage of disposability for high DNA concentration PCR. PCR results for a 100 μ1 solution of M13 Bacteriophage DNA as well as a β-Actin human DNA TaqMan® assay show positive amplification after automated sample preparation in the block for both cases. Results have also shown successful follow-up decontamination of the reusable platform after each sample preparation and amplification run. The design and processes utilized in this hybrid system has been leveraged to design and develop a fully disposable cartridge platform for detection of Chlamydia and Gonorrhea from urine samples.

A new generation of PCR instruments and nucleic acid concentration systems

Publisher Summary The polymerase chain reaction (PCR) technique has clearly evolved into an important tool for researchers and clinicians. This has been afforded by the commercialization of robust and dependable instruments for thermal cycling and, recently, with homogenous fluorescence detection.. The state-of-the-art instruments that include real-time, homogeneous, fast thermal cycling, and quantitative detection capabilities still leave significant opportunities for improvements. Efforts to develop PCR on a chip or micromachined/miniaturized systems have shown some interesting capabilities, but still fall short of providing the types of results that surpass or even equal those of commercial systems. However, in the future the development of new nucleic acid systems based on some of the principles from such research devices will probably occur. This chapter describes the extension of previous work based on silicon micromachining that has shown equivalent and improved performance over commercial systems. Other improvements over commercial systems have been discovered. These include new graphical user interface, independent control of each reaction site, modularity, and rapid thermal cycling of large volumes. Ultimately, the chapter concludes with anticipation that one day all the processing and homogenous quantitative detection will occur in one low-cost disposable, integrated system, which will take PCR to the new level of utility.

A Rapid, Flow-through, DNA Extraction Module for Integration into Microfluidic Systems

A reusable flow-through micropillar chip module for efficient, pathogen nucleic acid extraction, purification, and concentration was evaluated on large volume samples. The module was tested on aqueous samples of Francisella tularensis genomic DNA. Only 30 min were required to process a 75-ml sample, resulting in a 1000-fold concentration effect. The data demonstrates the potential of microfluidic approaches for flow-through processing, detection and genetic identification of pathogenic agents at low concentrations in real-world samples.

Microfluidic Bioanalysis Cartridge with Interchangeable Microchannel Separation Components

We have developed a plastic microfluidic cartridge and instrument that processes a sample; aliquots reagents; performs either electrophoretic separation in the case of nucleic acids, or isoelectric focusing in the case of peptides or proteins; and performs time and space-resolved fluorescent detection using solid-state components. The development of this cartridge is but one part of a microfluidic system that includes sample processing, target nucleic acid amplification such as PCR, and separation-based detection of either peptides, proteins or PCR products.