Continuous inline monitoring of glucose in an organ-on-chip using FreeStyle™ libre glucometers

Abstract

Introduction: Organ-on-chips have become an effective platform for studying the physiology of tissues and organs and for evaluating the safety and efficacy of drugs. In these systems, the inline monitoring of key parameters of biological performance (i.e., glucose, oxygen, or lactic acid concentrations) provides valuable information regarding the cell/tissue physiological state. However, significant limitations still exist when attempting to obtain inline information in these systems, and the microsensing technology of on-chip measurement of key parameters is still limited by size, cost, and availability.Methods: Here, we demonstrate the use of a commercially available glucometer (FreestleTM Libre; Abbott), normally used for continuous determination of blood glucose levels, to provide continuous inline measurements of the glucose concentration in tumor-on-chips. Here, we employed a colorectal tumor-on-chip as a first demonstration model and measured the on-chip concentration of glucose continuously for extended culture times (2 weeks).Results and Discussion: We show that inline glucose readings are reproducible and enable the accurate determination of glucose consumption rates (GCRs) by a tumor cell culture. In turn, the GCR measurements provide valuable information regarding the changes in the metabolic activity of the on-chip cultures following inlet perturbations (i.e., delivery of pulses of glucose, culture media additives, and drugs). Inline continuous glucose sensors will be useful tools in organ-on-chip research and will greatly enable cancer research in tumor-on-chip systems.

A 3D-printed tumor-on-chip: user-friendly platform for the culture of breast cancer spheroids and the evaluation of anti-cancer drugs

“…ToCs are built mainly by assembling multiple layers of poly(methyl methacrylate) (PMMA), using screws or by casting polydimethylsiloxane (PDMS) in 3D-printed molds, and these features lead to problems associated with leakage and contamination [10,[31][32][33]. Only recently has 3D printing been used to fabricate microfluidic devices for diverse applications, including cell culture and organ-on-chips or ToCs [12,13,30,34]. In principle, 3D printing can greatly simplify the cycle of designing, prototyping, and testing new microfluidic devices.…”