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Chemical and Biochemical Analysis

Our research focus is on the design, fabrication, optimization, and application of microscale devices for biomedical, chemical, biochemical, and environmental analysis, with additional work in the area of nanoscale sensors. We also develop microfluidic tools to support inorganic and organic synthesis efforts. This work is highly interdisciplinary and collaborative and is built on a solid foundation of experimental analytical chemistry: chromatography, electrophoresis, spectrometry, spectroscopy, and electrochemistry.

We have established active research in the following areas:

  • lab-on-a-chip technology - fabrication and implementation of analytical instruments in the microchip format
  • nanomaterials-enabled sensors
  • nanostructure and surface chemistry to enable droplet microfluidics
  • molecular recognition technologies - high selectivity sorbents for separations and sensing
  • development of miniaturized, automated assays for clinical chemistry applications
  • development of microscale reactors for nanomaterial synthesis
  • using semiconductor nanoparticles as components of assay systems
  • instrument development to quantify microfluidic detector response

Biothreat Analysis

The development of microscale biosensors for the fast and specific detection of proteins and other biological agents using novel labels for detection that offer enhanced sensitivity. Optical and electromagnetic methods of detection are employed. Previous work involved the development of a sensor that is based on a heterogeneous, sandwich immunoassay and uses bio-functionalized magnetic particles as labels.

Nanoparticles find application in the field of biosensors, both as a label and as a solid support phase for the immunoaffinity reaction. In our group, we synthesize, characterize and tailor the physical-chemical properties of nanoparticles to render them suitable for various biosensing applications.

Microfabrication techniques are employed to build the actual analytical devices. A variety of techniques including, replica molding, thermal embossing, photolithography, nanoimprint lithography are used to fabricate our devices. Our sensors are fabricated using materials like elastomeric PDMS (Poly (dimethylsiloxane)) as well as hard, transparent polymers like PMMA (Poly (methyl methacrylate)).

Developments in microfluidics

The main objective of developing µTAS was to create new means for chemical sensing since sensors at the time could not provide the best results in terms of selectivity and lifetime. Miniaturization was initially intended to enhance analytical performance rather than to reduce its size. It was soon realized that the small size presented the advantage of a smaller consumptions of carrier, reagent, and mobile phase. Additionally, it could provide the integration of sample handling, analysis (i.e. chromatography, electrophoresis), and detection. The concept of a microfluidic chip has been cost effective in terms of reduced reagent consumptions and faster analysis time. In this work, we developed a series of fabrication techniques capable of producing polymer-based microfluidic devices.

A two-stage embossing process was developed to fabricate polymer-based microchips. The microchannel in the master mold was produced by CNC machining or by SU-8 photolithography. In two-stage embossing, two polymer substrates with different glass transition temperatures (Tg) were employed. In the first step, a polymer with a higher Tg was embossed with the master mold to produce a secondary mold. Then the secondary mold can be used to emboss polymers with lower Tg. We have showed that successful feature transfer from the aluminum mold to the final substrates can be achieved reproducibly employing this method. This fabrication approach offers several advantages. The expensive process of producing the primary master only needs to be performed once. Additionally, the life of the primary master can be preserved via the two-stage embossing approach since the replication process can be repeated many times using the secondary mold.

Sealing techniques to form the microchannel are also developed by using different sacrificial layer in solvent bonding. Our bonded PMMA microchips could withstand an internal pressure of > 2000 psi, more than 17 times stronger than the thermally bonded chips. In our current work, we developed a new bonding technique that readily produces complete microfluidic chips, without the need of a sacrificial layer to form complete multilayer microfluidic devices. The advantages of this technique is that it provides a more direct method to generate hard polymer microfluidic chips than classical techniques and therefore is highly amenable to rapid prototyping, which can easily be translated into a production approach. In addition, the technique can readily be applied to many polymers, facilitating device production for a variety of applications, even permitting hybrid polymer chips, and provides a rapid, cost effective, simple, and versatile approach to the production of polymer-based microdevices.

Development of Microfluidic Membrane Filtration Devices for Nanoparticle Concentration and Purification

Solvent resistant nanofiltraion (SRNF) membranes have been recently developed to purify mixtures to smaller than 2nm molecular. It is different from reverse osmosis to permeate only solvents. Each SRNF-membrane has its own molecular weight cutoff (MWCO) which is the molecular weight corresponding to a reference compound that is rejected for 90%. Nowadays commercial SRNF-membranes are developed for different kinds of materials such as polymer and ceramic. Each material property can be used to make SRNF membrane to assemble microfluidic devices. Polymer SRNF membrane can be embed in microfluidic devices. Ceramic SRNF membrane has its own properties to operate in harsh condition in as a wide pH range (2-14), resistant to most polar and non-polar solvents, and even at extremely high temperatures (~ 350ºC).

The synthesis of nanoparticles in a microreactor is developed to get a narrow distribution of particle size in controlled condition. But the purification step is still the same method as a batch scale synthesis such as quenching in a non-polar solvent, filtration through a sintered frit, re-dissolving a solvent and re-crystallizing via solvent evaporation. These sequential steps require more solvent and time than the synthesis step. The development of a SRNF extractor for the purification of nanoparticles will be able to characterize the conditions to yield maximum products and high quality, and reduce the extra solvent and time. On line interfacing with upstream microreactors will be a step for upscaling and industrial implementation.

References:

Rundel, J.T., et al. Journal of Chromatography, A (2007), 1162(2), 167-174

Vandezande, Pieter, Chemical Society Reviews (2008), 37, 365-405

Photoactivable Microfluidic Devices for Selective Extraction of Heavy Metals from Water

A new method has been developed for heavy metals extraction from water using a spiropyran modified PMMA microchip as a photoactivable microfluidic device. Although ion-exchange resins currently play important role in water purifications they, unfortunately, are consumed their used results in an increase in waste stream volume and constitutes a high recurring cost. This work provides a means for the removal of heavy ions from aqueous solution using spiropyran as a photoreversible compound to cycle the chelating moiety between binding and non-binding forms. Rather light will be used to trigger theirs binding and non-binding forms.

Spiro compounds are a well-known class of dyes that exhibit interesting photochromic functionality in that their structure changes reversibly with UV/visible irradiation. The photoinduced reaction of spiropyran involves the cleavage of the spiro carbon-oxygen bond upon UV light irradiation and subsequent isomerization to the open form. Spiropyran chemistry is applicable to extraction of metal ions by first chelating the ions (after the spiro compound is activated using UV light), and subsequently exposing the metal-spiropyran complex to visible light to elute contaminants efficiently in a concentrated plug.

The principle long term goal is the deployment of solar-powered microfluidic devices for the analysis and remediation of ground water.

Nanoscale separations

Microfluidics can be applicable to analytical operations on chip, such as SPE and chromatography, as they offer highly efficient separations and improved sensitivity, decreased sample and reagent consumptions, and reduced analysis time. Beads are normally incorporated as solid supports to further enhance the performance of microfluidic devices by improving the surface to volume ratio for biochemical reactions. Moreover, surface modification can also be easily carried out on these beads to add multiple functionalities to the device. Having solid supports within the systems will therefore enable solid phase extraction and chromatography to be performed on the chip. These advantages are especially important for rapid and accurate determination of clinically important drugs to monitor their levels for diseases treatment.

Magnetic particles have been much use in various fields of study including biomedical applications such as in targeted drug delivery, magnetic resonance imaging, magnetic cell separation, and biosensors. To develop a reproducible synthesis route for the preparation of functionalized magnetic nanoparticles of uniform size and distribution and to explore its potential in bio-related applications has been of our interests. The particles are coated with inorganic molecules, such as silica or gold, to help in binding to the various biological ligands at the particle surface. The functionalized magnetic particles are employed for various analytical applications.

Our aim is to develop new methodologies of performing extraction and separation in a lab-on-a-chip device for medical diagnostics. In particular, the use of magnetic particles as solid support is explored for novel applications. Due to their superparamagnetic properties that they can be externally controlled using permanent magnets, these particles can be employed as solid support for extraction and chromatographic sorbents. The synthesis of magnetic materials with different functionalities together with new approaches for performing extraction and separation is continually being investigated in our lab. Analyses are carried out in a simple prototype microfluidic device fabricated in-house while working towards miniaturization and integration of a total analysis system.