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Unformatted text preview: Quantitative sensing of nanoscale colloids using a microchip Coulter counter O. A. Saleh and L. L. Sohn a) Department of Physics, Princeton University, Princeton, New Jersey 08544 ~ Received 27 June 2001; accepted for publication 20 September 2001 ! We have fabricated a microchip Coulter counter on a quartz substrate, and have used it to detect individual nanoscale colloidal particles with a sensitivity proportional to each particle’s size. We demonstrate the ability of this device to sense colloids as small as 87 nm diameter, and to distinguish between colloids whose diameters differ by less than 10%. Further reductions in the pore size, easily done with current nanofabrication techniques, make our device applicable to measuring biological macromolecules, such as DNA and proteins. © 2001 American Institute of Physics. @ DOI: 10.1063/1.1419224 # I. INTRODUCTION Quantitative measurements of the size and concentration of nanoscale particles are critical for studies of colloidal and macromolecular solutions. Traditionally, this is accomplished through ultracentrifugation, chromatography, gel electrophoresis, 1 or dynamic light scattering. 2 Here we dis- cuss an alternative method based on the Coulter technique of particle sensing. 3 Coulter counters typically consist of two reservoirs of particle-laden solution separated by a mem- brane and connected by a single pore through that mem- brane. By monitoring changes in the electrical current through the pore as individual particles pass from one reser- voir to another, a Coulter counter can measure the size of particles whose dimensions are on the order of the pore di- mensions. While this method has long been used to charac- terize cells several microns in diameter, 4,5 its relative sim- plicity has led to many efforts to employ it to detect nanoscale particles, 6–9 including viruses. 10 In this article, we present the first working realization of a Coulter counter on a microchip. Our device, fabricated on top of a quartz substrate using standard microfabrication techniques, utilizes a four-point measurement of the current through the pore. We are able to control precisely the pore dimensions, which we can easily measure using optical and atomic force microscopies. Knowing the exact pore dimen- sions allows us to predict quantitatively the response of the device to various sized particles. We have fabricated pores with lateral dimensions between 400 nm and 1 m m, and used them to detect latex colloidal particles as small as 87 nm in diameter. Furthermore, we demonstrate the ability of the de- vice to detect ; 500 nm diam colloids with a resolution of 6 10 nm. The device has numerous applications in sizing and separating nanoscale particles in solution, and is easily inte- grated with other on-chip analysis systems....
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