Tubular cellular biosensors

层状细胞管广泛存在于生物系统和人体中，从微小的血管到乳腺导管，它们对于多组织系统中底物、分泌和排泄产物的有效输送至关重要。本项目旨在设计、制造、建模和验证管状生物传感器，以通过与解剖学相关的设计来探测管状细胞的行为。该项目将生物传感器从固有的平面推进到管状和弯曲环境。它将允许系统地研究生物化学刺激、局部曲率和刚度对管状环境中活细胞功能的个体和组合影响。这项工作的见解将在多个领域发挥作用，包括用于生命系统实时测量的原位生物传感器设计、生物膜、环境暴露和疾病建模的器官芯片模型。曲率产生的应变对细胞行为有明显的影响，并且在矩形截面与圆形截面的管道中流体流动可以显着不同。因此，开发管状管道的组织工程模型，特别是亚毫米直径的管状管道，是细胞生物学和生物工程中一个关键但尚未解决的挑战。本提案旨在结合生物传感器集成和细胞生物学专业知识，创建具有可调尺寸和细胞特征的解剖学相关的管状细胞生物传感器。复杂的和解剖学相关的细胞装载管将大量生产，使用精确的排列和细胞和基质分层，以及基于电子读数的功能性生物传感器。管状和弯曲的集成电分析传感器包括电化学和生化传感器，用于测量物理和化学变量对细胞功能的影响。新的集成生物传感器平台将被开发为模型系统，在解剖学相关的微环境中询问细胞行为对生化刺激的反应。研究将包括不同曲率与平面几何下细胞功能的比较，这对于解决几何在基本细胞生物学和生物医学工程的微环境中所起作用的未解问题至关重要。该提案的更广泛影响包括将3D生物传感器集成原理和几何对生命系统的影响整合到教育课程和K-12，本科和研究生STEM培训以及研究经验中。这些努力将加强工程、生物、化学和医学培训生之间的跨学科合作，PI与这些培训生建立联系，并通过区域、国家和国际科学论坛促进这些主题的研究和创新。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.