Mentors
Project Description
The renal proximal tubule is a segment of the kidney’s nephron that actively carries out endocrine and regulatory functions, most notably filtration. The proximal tubule also serves as the primary site of local interstitial accumulation of drugs within the kidney. Nephrotoxicity induced by this accumulation, as well as kidney injury, typically account for 20% of drug attrition during phase III clinical trials. This late detection of nephrotoxicity is largely due to the poor predictive value of animal models resulting from interspecies variability, and a lack of widely accepted human cell line in vitro models. Therefore, optimized methods for renal toxicity prediction are fundamental to maximizing patient safety and improving the drug development success rate.
In this project, we will develop a microfluidic biosensor for monitoring cilia formation on the surface of renal epithelial cells. Tissue level viability will be observed through confocal microscopy of tight junctions and primary cilia. Students will explore the dynamics of embedded microelectronics and correlate electrical readouts of the cells to changes in these physiological parameters.
Research Participants
Program: INM
Aanahita Ervin, Research Experiences for Undergraduates.
Hear what Aanahita’s taking with her from her time at BU.
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Dr. Kimberly Stieglitz, Research Experiences for Teachers.
Hear how Dr. Kimberly Stieglitz took what she learned back to her classroom.
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Research Goals
- To develop an embedded microelectrode array capable of noninvasively sensing cilia formation in real-time with a microfluidic biochip.
- Validate methods to measure electric field changes within the microfluidic channel.
- Develop methods for automated counting of primary cilia from confocal images.
- Measure cilia formation and epithelium viability using impedance measurements.
- Correlate confocal and electrical measurements.
Learning Goals
- Learn about conventional microelectrode fabrication techniques.
- Learn about the nephron and renal proximal tubule epithelium physiology.
- Learn how immunochemistry and confocal microscopy observe cell viability.
- Learn about software for simulating electric field distributions.
- Learn the basics of impedance sensing and its application in microfluidic biosensing.
Timeline
Weeks 1-2: Delve into the literature of biosensing and microfluidic devices for monitoring epithelial tissue layers.
Weeks 2-3: Begin initial multiphysics simulations with COMSOL to validate adequate electric field distribution across the apical surface of the cell layer.
Weeks 4-6: Introduction to microfabrication. Students will learn the basics of fabricating microelectrode arrays for biosensors while preparing microfluidic devices for confocal and impedance monitoring experiments.
Week 5: Teachers will begin to expose themselves to the biosensing literature and familiarize themselves with the student’s progress. Students will be responsible for explaining the microfabrication process employed in this project to the teachers as they continue to learn together in the cleanroom.
Week 6: Students and teachers will work together to assemble completed bilayer microfluidic devices.
Weeks 7-8: Initial biological experiments. Renal cell seeding into microfluidic devices and continuous electrical measurement recording. Periodic confocal imaging.
Week 9: Correlation analysis of physiological parameters and impedance measurements.
Week 1o: Wrap up final experiments and prepare for REU/RET poster session.
