In this work we report on the development of biochips for the rapid analysis of single cells and other particles. We have developed a device that can simultaneously measure the optical and electrical properties of single cells or other micron-scale particles. The micro flow-cytometer chip consists of a planar electrode array onto which a micro-fluidic channel is fabricated from polyimide. The electrodes are used to measure the impedance of single cells flowing through the channel at hundreds per second. The impedance of single particles is simultaneously measured at typically two separate frequencies (e.g. 0.5MHz and 2MHz) using a lock-in system and high specification instrumentation amplifiers mounted on top of the micro-fluidic chip. The impedance data provides information on the membrane characteristics of cells and also the size of the particle. In addition a three-wavelength confocal optical system has been developed which is used to simultaneously interrogate the optical properties of particles. The device can detect small numbers of fluorescently labelled rare particles in a sample and has been used for the analysis of blood and suspensions of latex beads.
Microfluidic analysis devices, often referred to as Micro Total Analysis Systems or the Lab-on-a-chip, are often based on the manipulation of small volumes of fluid. These devices require the design and fabrication of components for fluid handling, control and measurement, such as micropumps, micromixers and flow sensors. The fabrication of miniature versions of large scale components such as pressure sensors and flow rate meters has been demonstrated. However, complicated fabrication is prohibitive and devices which involve flow constriction can be prone to blocking if particle containing samples are used. This paper presents results of the design and fabrication of a microimpedance measurement cell, designed to measure the impedance of sub-nanolitre volumes of fluids. The measurement system was designed to measure the electrical impedance at several different frequencies, allowing identification and analysis of the material contained within the sample volume. Measurements of different fluids at different flow rates through a microchannel containing the measurement cell are presented. The use of this system as a solid state flow rate sensor is then discussed.
A polymer microfluidic device for the formation of artificial bilayer lipid membranes (BLMs) on-chip is described. The device is fabricated from thin, transparent films of poly(methyl methacrylate), allowing for optical monitoring of the BLM. In addition, detection of single fluorescently-labeled lipid molecules using conventional epifluorescence microscopy is described.