Microdevices for Biological Analyses Recent Advances and Directions for the Future

Abstract

SAMPLE ACQUISITION AND CONTROLBiological sampling is important for drug discovery applications and for the basic biochemical and neurochemical discovery process. Several issues arise when sampling from biological environments. First, important biology can occur in small volumes (nL-pL) and at low concentrations (mM-nM). In order to access this information, the important biochemicals must be detectable and the time of specific biochemical events must be recorded. This means that a sampling and analysis method should be selective for the analyte(s) of interest, without loss or dilution, for efficient analysis. Tremendous accomplishments in biological sampling and analysis have been made, both for sampling and microfluidic manipulation. This article focuses on advances in controlling small volumes of biological samples and the analysis of specific analytes in those samples. FLOW CONTROL BY RADIAL VOLTAGEFluid control of minute amounts of material is of paramount importance to the sampling and analysis of biological systems. Analysis of materials on a small scale has mostly been accomplished with the aid of electrokinetic effects, typically in a capillary electrophoresis (CE) setting. However, the electroosmotic flow (EOF) used in CE to manipulate fluids has proven difficult to control, therefore research has focused on improving electroosmotic flow control. To address the issues of flow control in CE two platforms are used: the microscale, or microfluidic chip approach; and the conventional, or capillary, approach. 1, 2 Because of the importance of EOF to this work, a brief overview of the flow mechanism is given here (also see Figure 1). Electroosmosis is the flow mechanism generated when a buffer interacts with a charged solid interface, such as the capillary wall in CE, in the presence of a lateral potential field. 3 Above pH 3, the wall is negatively charged from the de-protonation of the surface siloxyl groups. The negative charge at the wall attracts cations from the solution. Some of the cations lose their hydration spheres and adhere to the surface (the immobile layer), while some remain hydrated and are free to move despite the attraction to the wall (the diffuse layer). The formation of this layer of charge results in a potential drop near the wall, termed the zeta (z) potential. In the presence of the lateral electric field, the diffuse layer will move toward the more negative electrode. It is this interplay between the wall, the solution, and the applied potential fields that creates EOF. 3 Control of EOF is essential to the resolution, efficiency, and usefulness of separations in both conventional and microscale systems. 3 For these systems to have true flow control, it is necessary to be able to change the flow rate in response to system conditions. Methods of flow control focus on altering the solution/wall interface by changing either the nature of the wall or the composition of the buffer. The use of coatings and buffer additives are common techniques to achieve these changes. 1 However, these metho...