1 |
Microfluidic Devices and BiosensorsTsai, Long-Fang 01 February 2016 (has links)
My research broadly covers various important aspects of microfluidic devices and biosensors. Specifically, this dissertation reports: (1) a new and effective room temperature method of bonding polydimethylsiloxane (PDMS) microfluidics to substrates such as silicon and glass, (2) a new microfluidic pump concept and implementation specifically designed to repeatedly drive a small sample volume (<1 µL) very rapidly (~500 µL/min) through a sensor-containing flow channel to significantly decrease sensor response time through advection-driven rather than diffusion-driven mass transport, (3) use of a new microfluidic material based on polyethylene glycol diacrylate (PEGDA) to implement impedance-based dynamic nanochannel sensors for protein sensing, and (4) an investigation of galvanoluminescence and how to avoid it for conditions important to fluorescence-based dielectrophoresis (DEP) microfluidic biosensors. Over the last decade, the Nordin research group has developed a lab-on-a-chip (LOC) biosensor based on silicon photonic microcantilever arrays integrated with polydimethylsiloxane (PDMS) microfluidics for protein biomarker detection. Integration requires reliable bonding at room temperature with adequate bond strength between the PDMS element and microcantilever sensor substrate. The requirement for a room temperature process is particularly critical because microcantilevers must be individually functionalized with antibody-based receptor molecules prior to bonding and cannot withstand significant heating after functionalization. I developed a new room temperature bonding method using PDMS curing agent as an intermediate adhesive layer. Two curing agents (Sylgard 184 and 182) were compared, as well as an alternate UV curable adhesive (NOA 75). The bond strength of Sylgard 184 was found to be stronger than Sylgard 182 under the same curing conditions. Overnight room temperature curing with Sylgard 184 yields an average burst pressure of 433 kPa, which is more than adequate for many PDMS sensor devices. In contrast, UV curable epoxy required a 12 hour bake at 50 °C to achieve maximum bond strength, which resulted in a burst pressure of only 124 kPa. In many biosensing scenarios it is desirable to use a small sample volume (<1 µL) to detect small analyte concentrations in as short a time as possible. I report a new microfluidic pump to address this need, which we call a reflow pump. It is designed to rapidly pump a small sample volume back and forth in a flow channel. Ultimately, the flow channel would contain functionalized sensor surfaces. The rapid flow permits use of advection-driven mass transport to the sensor surfaces to dramatically reduce sensor response times compared to diffusion-based mass transport. Normally such rapid flow would have the effect of decreasing the fraction of analyte molecules in the volume that would see the sensor surfaces. By configuring the pump to reflow fluid back and forth in the flow channel, the analyte molecules in the small sample volume are used efficiently in that they have many opportunities to make it to the sensor surfaces. I describe a 3-layer PDMS reflow pump that pumps 300 nL of fluid at 500 µL/min for 15 psi actuation pressure, and demonstrate a new two-layer configuration that significantly simplifies pump fabrication. Impedance-based nanochannel sensors operate on the basis of capturing target molecules in nanochannels such that impedance through the nanochannels is increased. While simple in concept, the response time can be quite long (8~12 hours) because the achievable flow rate through a nanochannel is very limited. An approach to dramatically increase the flow rate is to form nanochannels only during impedance measurements, and otherwise have an array of nanotrenches on the surface of a conventional microfluidic flow channel where they are exposed to normal microfluidic flow rates. I have implemented such a dynamic nanochannel approach with a recently-developed microfluidic material based polyethylene glycol diacrylate (PEGDA). I present the design, fabrication, and testing of PEGDA dynamic nanochannel array sensors, and demonstrate an 11.2 % increase in nanochannel impedance when exposed to 7.2 µM bovine serum albumin (BSA) in phosphate buffered saline (PBS). Recently, LOC biosensors for cancer cell detection have been demonstrated based on a combination of dielectrophoresis (DEP) and fluorescence detection. For fluorescence detection it is critical to minimize other sources of light in the system. However, reported devices use a non-noble metal electrode, indium tin oxide (ITO), to take advantage of its optical transparency. Unfortunately, use of non-noble metal electrodes can result in galvanoluminescence (GL) in which the AC voltage applied to the electrodes to achieve DEP causes light emission, which can potentially confound the fluorescence measurement. I designed and fabricated two types of devices to examine and identify conditions that lead to GL. Based on my observations, I have developed a method to avoid GL that involves measuring the impedance spectrum of a DEP device and choosing an operating frequency in the resistive portion of the spectrum. I also measure the emission spectrum of twelve salt solutions, all of which exhibited broadband GL. Finally, I show that in addition to Au, Cr and Ni do not exhibit GL, are therefore potentially attractive as low cost DEP electrode materials.
|
Page generated in 0.0464 seconds