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Unformatted text preview: Detection Limits for Nanoscale Biosensors Paul E. Sheehan* and Lloyd J. Whitman Chemistry Di V ision, Na V al Research Laboratory, Washington, D.C. 20375 Received February 15, 2005 ABSTRACT We examine through analytical calculations and finite element simulations how the detection efficiency of disk and wire-like biosensors in unmixed fluids varies with size from the micrometer to nanometer scales. Specifically, we determine the total flux of DNA-like analyte molecules on a sensor as a function of time and flow rate for a sensor incorporated into a microfluidic system. In all cases, sensor size and shape profoundly affect the total analyte flux. The calculations reveal that reported femtomolar detection limits for biomolecular assays are very likely an analyte transport limitation, not a signal transduction limitation. We conclude that without directed transport of biomolecules, individual nanoscale sensors will be limited to picomolar-order sensitivity for practical time scales. Tremendous progress is being made in the development of microanalytical systems for biosensing, driven by parallel advances in biotechnology, microtechnology, and micro- fluidics. 1,2 The advantages of small, highly integrated systems include more rapid and multiplexed analysis and reagent sample volumes reduced to the microliter range. When combined with innovative signal transduction technology, microsystems have recently achieved specific biomolecular detection at roughly femtomolar (fM) concentrations, cor- responding to just a few thousand (or even a few hundred) analyte molecules in the sample volume. 3- 5 Concurrently, many research groups have been developing micrometer or nanometer scale sensing elements based on novel transduc- tion mechanisms. 5- 11 Many researchers of nanometer-scale phenomena focus on the fact that miniaturizing a sensor often increases its signal-to-noise ratio (S:N), an inherent advantage for signal transduction, but the effect of nanoscale miniaturization on the overall sensitivity, which includes mass transport effects, has not been widely considered. For example, whether nanometer-scale sensors are intrinsically more sensitive overall than micrometer-scale sensors has not been fully examined. In this letter, we use experimentally verified 12- 14 analytical solutions to examine the maximum sensitivity with which micro-to-nanoscale sensors of various geometries can detect biomolecules from solution. Our principal goal is to explicitly examine mass transport effects on biosensing at the nanoscale; however, the calculations also lead us to conclude that reported femtomolar detection limits for bioassays are likely an analyte transport limitation, not a signal transduction limitation. The implication is that, without methods to actively direct biomolecules to a sensor surface, individual nanoscale sensors will be subject to picomolar- order detection limits for practical time scales....
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This document was uploaded on 08/16/2010.
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