Abstract: SA-PO039
A High-Throughput Oxygen Biosensing Platform for a Microfluidic In Vitro Kidney Models
Session Information
- Engineering-Based Approaches to Problems in Nephrology
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Bioengineering
- 300 Bioengineering
Authors
- Kann, Samuel H., Boston University, Boston, Massachusetts, United States
- Azizgolshani, Hesham, Draper Laboratory, Cambridge, Massachusetts, United States
- Coppeta, Jonathan, Draper Laboratory, Cambridge, Massachusetts, United States
- Zhang, Xin, Boston University, Boston, Massachusetts, United States
- Vedula, Else M., Draper Laboratory, Cambridge, Massachusetts, United States
- Charest, Joseph L., Draper Laboratory, Cambridge, Massachusetts, United States
Background
Oxygen concentration and dynamics directly influence renal cell function in vivo. For example, low oxygen tension plays a significant role in both acute and chronic kidney disease. In addition, decreased cellular oxygen consumption in the kidney has been linked to mitochondrial and metabolic dysfunction. Therefore, monitoring oxygen levels within in vitro kidney models will enable physiologically accurate oxygen conditions for the models and allow assessment of metabolic function for normal tissue or metabolic changes due to toxic insults, disease states, or therapy administration. Current microfluidic in vitro kidney models control flow to generate tissue with kidney-specific functionality, however, such systems lack high-throughput oxygen sensing capabilities.
Methods
We integrated optical luminescence based oxygen sensors into a high-throughput microfluidic in vitro kidney model platform (PREDICT-96), previously developed at Draper, for real-time and non-destructive monitoring of dissolved oxygen in the tissue microenvironment. PREDICT-96 supports renal co-cultures under flow in a 96 tissue replicate device. The oxygen sensor probes, deposited in each microfluidic channel, are excited by red-light transmitted via a fiber optic cable resulting in near infrared emission with an oxygen dependent phase-shift. The O2 measurement system was adapted to fit a standard microscope stage. High-throughput readings are accomplished by programming the stage to align the optic fiber with each sensor probe and to cycle through all 96 devices.
Results
Oxygen consumption rates for co-cultured human renal proximal tubule epithelial and human microvascular endothelial cells under flow and static conditions were quantified. A COMSOL-based computational model indicates the ability to regulate oxygen concentration via controlling flow of the PREDICT-96 pumps. In this way, oxygen levels will be characterized for varying in vitro model parameters, resulting in both physiologically accurate renal co-culture conditions of normal tissue and hypoxic or ischemic injury tissue.
Conclusion
The PREDICT-96 oxygen biosensing platform will enhance in vitro renal tissue function and provide a high-throughput respirometric platform for studying renal metabolic dynamics in response to nephrotoxic drugs or disease progression.
Funding
- Other U.S. Government Support –