Browsing by Subject "Lab-on-a-chip"
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Item Electrokinetic and acoustic manipulations of colloidal and biological particles(2009-05-15) Park, SeungkyungRecent advances in microfluidic technologies have enabled integration of the functional units for biological and chemical analysis onto miniaturized chips, called Labon- a-Chip (LOC). However, the effective manipulation and control of colloidal particles suspended in fluids are still challenging tasks due to the lack of clear characterization of particle control mechanisms. The aim of this dissertation is to develop microfluidic techniques and devices for manipulating colloids and biological particles with the utilization of alternating current (AC) electric fields and acoustic waves. The dissertation presents a simple theoretical tool for predicting the motion of colloidal particles in the presence of AC electric field. Dominant electrokinetic forces are explained as a function of the electric field conditions and material properties, and parametric experimental validations of the model are conducted with particles and biological species. Using the theoretical tool as an effective framework for designing electrokinetic systems, a dielectrophoresis (DEP) based microfluidic device for trapping bacterial spores from high conductivity media is developed. With a simple planar electrode having well defined electric field minima that can act as the targetattachment/ detection sites for integration of biosensors, negative DEP trapping of spores on patterned surfaces is successfully demonstrated. A further investigation of DEP colloidal manipulation under the effects of electrothermal flow induced by Joule heating of the applied electric field is conducted. A periodic structure of the electrothermal flow that enhances DEP trapping is numerically simulated and experimentally validated. An acoustic method is investigated for continuous sample concentration in a microscale device. Fast formation of particle streams focused at the pressure nodes is demonstrated by using the long-range forces of the ultrasonic standing waves (USW). High frequency actuation suitable for miniaturization of devices is successfully applied and the device performance and key parameters are explained. Further extension and integration of the technologies presented in this dissertation will enable a chip scale platform for various chemical and biological applications such as drug delivery, chemical analyses, point-of-care clinical diagnosis, biowarfare and biochemical agent detection/screening, and water quality control.Item Next generation transduction pathways for nano-bio-chip array platforms(2009-05) Jokerst, Jesse Vincent; McDevitt, John ThomasIn the following work, nanoparticle quantum dot (QD) fluorophores have been exploited to measure biologically relevant analytes via a miniaturized sensor ensemble to provide key diagnostic and prognostic information in a rapid, yet sensitive manner—data essential for effective treatment of many diseases including HIV/AIDS and cancer. At the heart of this “nano-bio-chip” (NBC) sensor is a modular chemical/cellular processing unit consisting of either a polycarbonate membrane filter for cell-based assays, or an agarose bead array for detection of biomarkers in serum or saliva. Two applications of the NBC sensor system are described herein, both exhibiting excellent correlation to reference methods ((R² above 0.94), with analysis times under 30 minutes and sample volumes below 50 [mu]L. First, the NBC sensor was employed for the sequestration and enumeration of T lymphocytes, cells specifically targeted by HIV, from whole blood samples. Several different conjugation methods linking QDs to recognition biomolecules were extensively characterized by biological and optical methods, with a thiol-linked secondary antibody labeling scheme yielding intense, specific signal. Using this technique, the photostability of QDs was exploited, as was the ability to simultaneously visualize different color QDs via a single light pathway, effectively reducing optical requirements by half. Further, T-cell counts were observed well below the 200/[mu]L discriminator between HIV and AIDS and across the common testing region, demonstrating the first reported example of cell counting via QDs in an enclosed, disposable device. Next, multiplexed bead-based detection of cancer protein biomarkers CEA, Her-2/Neu, and CA125 in serum and saliva was examined using a sandwich immunoassay with detecting antibodies covalently bound to QDs. This nano-based signal was amplified 30 times versus molecular fluorophores and cross talk in multiplexed experiments was less than 5%. In addition, molecular-level tuning of recognition elements (size, concentration) and agarose porosity resulted in NBC limits of detection two orders of magnitude lower than ELISA, values competitive with the most sensitive methods yet reported (0.021 ng/mL CEA). Taken together, these efforts serve to establish the valuable role of QDs in miniaturized diagnostic devices with potential for delivering biomedical information rapidly, reliably, and robustly.