What we Do

CE-TDA

As an analytical metric, mass-to-charge ratio (m/z) is so information-rich that mass spectrometry (MS) is often viewed as the Swiss army knife of chemical analysis. It seems sensible that size (i.e. hydrodynamic radius, Rh) describes molecular structure in similar ways as mass, yet charge-to-size ratio (i.e. electrophoretic mobility, μ) is not typically used for structurally descriptive analyses analogous to m/z. The key difference is that mass is an intrinsic property of an analyte, while Rh is a composite property of the analyte and its environment, making precise and reproducible measurements challenging.

Taylor dispersion analysis (TDA) provides absolute determinations of Rh, requiring no calibration nor comparison to known standards. With sufficient precision and sensitivity, absolute Rh determinations can provide structurally descriptive information.

Combining μ determination by capillary electrophoresis (CE) and Rh determination by TDA presents opportunities for structurally descriptive analyses with high sensitivity from nL samples under native solution conditions. Put another way: CE-TDA has the potential for MS-like analyses within micro- and nanofluidic devices.

We develop new instrumentation and methodologies to push the boundaries of precision and sensitivity in CE, TDA, and the online integration of CE-TDA.

Brain-on-chip models

Microfluidic perfusion culture is a powerful tool for modeling complex biological systems with precise control of solution conditions, and enriched sampling of cellular secretions. Ex vivo tissue culture offers especially powerful models, as they preserve aspects of native cytoarchitecture. Discovery in molecular neuroscience has benefitted from robust methods for ex vivo brain tissue culture and analysis, but few of these offer the advantages inherent to microfluidic perfusion systems. Meeting the high oxygen demand of neural tissue adequately to support long-term tissue culture is a particular challenge for integrating brain slice culture with microfluidic perfusion.

Enriched secretion sampling by microfluidic perfusion offers unique benefits for molecular neuroscience, since most brain function is mediated by the release of neurotransmitters and other signaling molecules. While in vivo perfusion sampling is established technology, it doesn’t provide the environmental control that microfluidic models do, among other limitations.

We have developed a unique microfluidic “bubble perfusion” system for ex vivo brain slice culture. The system delivers precision segmented flow of oxygen microbubbles and aqueous nutrient microdroplets to brain tissue explants. Gaseous oxygen provides more effective tissue oxygenation, and segmented flow offers advantages for maintaining temporal resolution in downstream analyses.

We continue to improve this technology while developing advanced analyses that leverage the unique properties of bubble perfusion to enable discovery in molecular neuroscience. These include developments in fluorescence microscopy analyses, and assay development for quantifying under-explored modes of neurotransmission.

Accessible Research Technologies

“The miracle is this: The more we share the more we have.”
— Leonard Nimoy

In the Baker Bioanalysis Lab, we’re primarily tool makers. We develop new technologies to help answer questions that interest us, but our principal motivation is to produce technologies that enable the broadest possible impact. Our technology development is guided by two key principles:

Hammers not can openers
The most exciting applications of technology are the ones you don’t see coming. Developing technologies that operate on simple and robust principles, and have the broadest envelope of use cases ensures that we’re putting something new in the world with the potential to answer questions we never thought of. A hammer can be used to frame a house, hang a picture, or open a coconut. A can opener may be a staple in the kitchen, but its specificity and complexity doesn’t present many creative use cases.

Access is impact
Creativity isn’t a closed ecosystem. The more hands that can hold a tool, the more minds there are to find the unexpected uses. This is why we develop technologies to be as broadly accessible to the scientific community as possible. Our design strategies leverage open and accessible fabrication methods, with an emphasis on consumer-grade 3D printing and digital distribution. Interested in your own CE-TDA instrument? Just download and print one yourself!

While we’re pursuing the questions of neuroscience, chemical separations, and bioanalytical chemistry that most intrigue us, we are also seeking new opportunities to broaden our horizons, especially when it opens doors to developing new, broadly accessible tools for biomolecular research.