Modeling and measuring glucose diffusion and consumption by colorectal cancer spheroids in hanging drops using integrated biosensors
作者机构：ETH ZürichDepartment of Biosystems Science and EngineeringBio Engineering LaboratoryMattenstrasse 26CH-4058 BaselSwitzerland
出 版 物：《Microsystems & Nanoengineering》 (微系统与纳米工程（英文）)
年 卷 期：2022年第8卷第1期
页 面：193-210页
核心收录：
学科分类：1002[医学-临床医学] 080202[工学-机械电子工程] 08[工学] 100214[医学-肿瘤学] 0802[工学-机械工程] 10[医学]
基 金：N.R.acknowledges financial support from a doctoral scholarship(FRQNT 199851)from the Fonds de Recherche du Québec—Nature et Technologies.R.L.S.acknowledges financial support from a scholarship(LCF/BQ/EU19/11710046)from the“La Caixa”Foundation We acknowledge the help of Christian Lohasz,ETH Zürich,with the cell culture,maintenance,and characterization of HCT116 spheroids.We acknowledge the help of Flavio Bonanini,ETH Zürich,with the determination of cell seeding densities and control of HCT116 growth dynamics We acknowledge the help of Stefan Strebel,University of Basel,and Felix Franke,ETH Zürich,with developing the mathematical models
主 题：diffusion hanging simplicity
摘 要：As 3D in vitro tissue models become more pervasive,their built-in nutrient,metabolite,compound,and waste gradients increase biological relevance at the cost of analysis *** these gradients and the resulting metabolic heterogeneity requires invasive and time-consuming *** alternative is using electrochemical biosensors and measuring concentrations around the tissue model to obtain size-dependent metabolism *** our hanging-dropintegrated enzymatic glucose biosensors,we conducted current measurements within hanging-drop compartments hosting spheroids formed from the human colorectal carcinoma cell line *** developed a physics-based mathematical model of analyte consumption and transport,considering(1)diffusion and enzymatic conversion of glucose to form hydrogen peroxide(H_(2)O_(2))by the glucose-oxidase-based hydrogel functionalization of our biosensors at the microscale;(2)H_(2)O_(2)oxidation at the electrode surface,leading to amperometric H_(2)O_(2)readout;(3)glucose diffusion and glucose consumption by cancer cells in a spherical tissue model at the microscale;(4)glucose and H_(2)O_(2)transport in our hangingdrop compartments at the macroscale;and(5)solvent evaporation,leading to glucose and H_(2)O_(2)*** model relates the measured currents to the glucose concentrations generating the *** low limit of detection of our biosensors(0.4±0.1μM),combined with our current-fitting method,enabled us to reveal glucose dynamics within our *** measuring glucose dynamics in hanging-drop compartments populated by cancer spheroids of various sizes,we could infer glucose distributions within the spheroid,which will help translate in vitro 3D tissue model results to in vivo.
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