A novel broadband high-speed impedance spectrometer has been developed for the analysis of single biological particles in a high-throughput microfluidic cytometer. The technique is based on obtaining the impulse response of the system using maximum length sequences (MLS) as the excitation signal. The impulse response is converted into the frequency domain using Fast Fourier Transform (FFT). Theoretical modeling and simulation of a single cell suspended in the cytometer show that the MLS technique is capable of high precision single particle analysis.
The control and handling of fluids and fluid-based samples is central to the majority of applications in the areas of Micro Analysis systems and the Lab-on-a-chip. As a result, there is a great deal of research and industrial interest in developing specific technologies for this purpose: micropumps, micromixers, microstirrers, etc. One widely used technology in these systems is electrokinetics, the use of electric fields for the manipulation and control of fluids and particles. In DC electrokinetic systems, high voltages (typically ~1kV) are required for controlled manipulation and separation. The use of AC electric fields presents a range of different potential applications as well as the potential for better integration into microsystems. AC Electrokinetic devices for the handling of fluid require significantly lower voltages (~10V) and therefore a four order of magnitude reduction in power requirements. This paper presents devices based on AC electroosmosis and Electrothermal Electrohydrodynamics. The first mechanism involves the interaction of the Electrical Double Layer induced on electrodes by an applied potential and the electric field generated by the same potential. The second involves the interaction of an electric field with gradients in polarisability of the fluid produced by non-uniform heating. Several different designs are presented with applications in pumping, mixing and the general area of micro AC electric field microfluidic control. A specific example is presented: the use of the technique for the local modification of streamlines and deflection of fluids is presented and applications to analysis and sensing are discussed.
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.
The precise control and manipulation of small masses of liquids is an important requirement in the lab-on-a-chip technology. Net fluid flows induced by ac potentials applied to arrays of co-planar interdigitated microelectrodes are reported. Two types of microelectrode structures have been studied: arrays of unequal width electrodes subjected to a single ac signal, and arrays of identical electrodes subjected to a travelling-wave potential. Experiments were performed using solutions of KCl in water of conductivities around 1mS/m placed on top of the electrodes. Fluorescent latex particles were used as tracers. In both microstructures, two fluid flow regimes have been observed: at small voltage amplitudes the fluid moves in a certain direction, and at higher voltage amplitudes the fluid flow is reversed. The fluid flow seems to be driven at the level of the electrodes in the two regimes. A theoretical model of ac electroosmosis is described. The model is based upon the Gouy-Chapman-Stern theory of the double layer. The theoretical results are in qualitative accordance with the experimental observations at low voltages.
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.