Tubular cellular biosensors

Johns Hopkins University, Baltimore MD

Investigators

Abstract

Layered cellular tubes widely occur in biological systems and the human body, ranging from tiny blood vessels to mammary ducts, and these are essential for the efficient delivery of substrates, secretory, and excretory products in multi-tissue systems. This project aims to design, fabricate, model, and validate tubular biosensors to probe the behavior of cells in tubes with anatomically relevant design. The project advances biosensors from inherently planar to tubular and curved environments. It will allow the systematic study of the individual and combinatorial impact of biochemical stimuli, local curvature, and stiffness on the function of live cells in tubular environments. Insights from this work will be useful in diverse fields, including in situ biosensor design for real-time measurements in living systems, biofilms, and organ-on-chip models of environmental exposures and disease modeling. Strain produced by curvature has a pronounced effect on cellular behavior, and fluid flow can be significantly different in tubes with rectangular vs. circular cross-sections. Hence, developing tissue-engineered models for tubular ducts, especially at sub-millimeter diameters, is a critical yet unmet challenge in cell biology and bioengineering. This proposal aims to combine biosensor integration and cell biology expertise to create anatomically relevant tubular cellular biosensors with tunable dimensions and cellular characteristics. Complex and anatomically relevant cell-laden tubes will be mass-produced using accurate alignment and layering of cells and matrix, along with functional biosensors based on electrical readouts. Tubular and curved integrated electroanalytical sensors include electrochemical and biochemical sensors that measure the effects of the physical and chemical variables on cellular function. New integrated biosensor platforms will be developed as model systems to interrogate cell behavior in response to biochemical stimuli in anatomically relevant microenvironments. Studies will include comparisons of cell function in varying curvature vs. planar geometries, which is vital for addressing unanswered questions on the role of geometry in the microenvironment on fundamental cell biology and biomedical engineering. The broader impacts of the proposal include integrating principles of 3D biosensor integration and the effect of geometry on living systems into educational curricula and K-12, undergraduate and graduate STEM training, and research experiences. These efforts will enhance interdisciplinary cooperativity among the pools of engineering, biology, chemistry, and medicine trainees that the PI’s interface with and serve as a template for catalyzing investigation and innovation on these topics through regional, national, and international scientific forums. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.