Metabolic Multianalyte Microphysiometry Reveals Extracellular Acidosis is an Essential Mediator of Neuronal Preconditioning

McKenzie, Jennifer R.; Palubinsky, Amy M.; Brown, Jacquelynn E.; McLaughlin, BethAnn; Cliffel, David E.

doi:10.1021/cn300003r

Cited by 18 publications

(17 citation statements)

References 38 publications

(67 reference statements)

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“…The resulting linear ranges and limit of detection (LOD) are listed in Table 1. Figures of merit for GOx and LOx sensors used in a recent work with the original MAMP 20 are listed for comparison. The hand-cast LOx films featured a LOD comparable to LODs found for the 20 mg/mL LOx SPE sensors.…”

Section: Resultsmentioning

confidence: 99%

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Real-Time Monitoring of Cellular Bioenergetics with a Multianalyte Screen-Printed Electrode

et al. 2015

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Real-time monitoring of changes to cellular bioenergetics can provide new insights into mechanisms of action for disease and toxicity. This work describes the development of a multi-analyte screen-printed electrode for the detection of analytes central to cellular bioenergetics: glucose, lactate, oxygen, and pH. Platinum screen-printed electrodes were designed in-house and printed by Pine Research Instrumentation. Electrochemical plating techniques were used to form quasi-reference and pH electrodes. A Dimatix materials inkjet printer was used to deposit enzyme and polymer films to form sensors for glucose, lactate, and oxygen. These sensors were evaluated in bulk solution and microfluidic environments, and found to behave reproducibly and possess a lifetime of up to six weeks. Linear ranges and limits of detection for enzyme-based sensors were found to have an inverse relationship with enzyme loading, and iridium oxide pH sensors were found to have super-Nernstian responses. Preliminary measurements where the sensor was enclosed within a microfluidic channel with RAW 264.7 macrophages were performed to demonstrate the sensors’ capabilities for performing real-time microphysiometry measurements.

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Section: Resultsmentioning

confidence: 99%

“…20 To counteract bubble formation by BSA, the BSA-PB solution was lowered to a concentration of 31 mg/mL BSA. The BSA-PB solution was then used to dissolve either stabilized GOx or LOx.…”

Section: Methodsmentioning

confidence: 99%

Real-Time Monitoring of Cellular Bioenergetics with a Multianalyte Screen-Printed Electrode

et al. 2015

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“…132-135 It is a great advantage that, typically, the signal-to-noise ratio of electrochemical sensors does not increase as the electrodes are miniaturized, 136 and it has been shown possible to make electrochemical measurements of single cells and small cell populations. 134,135,137,138 …”

Section: Engineering Challengesmentioning

confidence: 99%

Scaling and systems biology for integrating multiple organs-on-a-chip

et al. 2013

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Coupled systems of in vitro microfabricated organs-on-a-chip containing small populations of human cells are being developed to address the formidable pharmacological and physiological gaps between monolayer cell cultures, animal models, and humans that severely limit the speed and efficiency of drug development. These gaps present challenges not only in tissue and microfluidic engineering, but also in systems biology: how does one model, test, and learn about the communication and control of biological systems with individual organs-on-chips that are one-thousandth or one-millionth of the size of adult organs, or even smaller, i.e., organs for a milliHuman (mHu) or microHuman (μHu)? Allometric scaling that describes inter-species variation of organ size and properties provides some guidance, but given the desire to utilize these systems to extend and validate human pharmacokinetic and pharmacodynamic (PK/PD) models in support of drug discovery and development, it is more appropriate to scale each organ functionally to ensure that it makes the suitable physiological contribution to the coupled system. The desire to recapitulate the complex organorgan interactions that result from factors in the blood and lymph places a severe constraint on the total circulating fluid (~5 mL for a mHu and ~5 μL for a μHu) and hence on the pumps, valves, and analytical instruments required to maintain and study these systems. Scaling arguments also provide guidance on the design of a universal cell-culture medium, typically without red blood cells. This review presents several examples of scaling arguments and discusses steps that should ensure the success of this endeavour.

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“…Many multi-sensor systems were designed as probes, mostly comprising electrochemical biosensors, and have been applied to conventional cell culture assays to monitor microphysiological conditions over time [38][39][40][41] . Miniaturized versions have been used as scanning probes to monitor the glucose and lactate metabolism of single cells 42,43 .…”

Section: Introductionmentioning

confidence: 99%

Multi-analyte biosensor interface for real-time monitoring of 3D microtissue spheroids in hanging-drop networks

et al. 2016

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Microfluidics is becoming a technology of growing interest for building microphysiological systems with integrated read-out functionalities. Here we present the integration of enzyme-based multi-analyte biosensors into a multi-tissue culture platform for 'body-on-a-chip' applications. The microfluidic platform is based on the technology of hanging-drop networks, which is designed for the formation, cultivation, and analysis of fluidically interconnected organotypic spherical three-dimensional (3D) microtissues of multiple cell types. The sensor modules were designed as small glass plug-ins featuring four platinum working electrodes, a platinum counter electrode, and an Ag/AgCl reference electrode. They were placed directly into the ceiling substrate from which the hanging drops that host the spheroid cultures are suspended. The electrodes were functionalized with oxidase enzymes to enable continuous monitoring of lactate and glucose through amperometry. The biosensors featured high sensitivities of 322 ± 41 nA mM − 1 mm − 2 for glucose and 443 ± 37 nA mM − 1 mm − 2 for lactate; the corresponding limits of detection were below 10 μM. The proposed technology enabled tissue-size-dependent, real-time detection of lactate secretion from single human colon cancer microtissues cultured in the hanging drops. Furthermore, glucose consumption and lactate secretion were monitored in parallel, and the impact of different culture conditions on the metabolism of cancer microtissues was recorded in real-time.

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Metabolic Multianalyte Microphysiometry Reveals Extracellular Acidosis is an Essential Mediator of Neuronal Preconditioning

Cited by 18 publications

References 38 publications

Real-Time Monitoring of Cellular Bioenergetics with a Multianalyte Screen-Printed Electrode

Real-Time Monitoring of Cellular Bioenergetics with a Multianalyte Screen-Printed Electrode

Scaling and systems biology for integrating multiple organs-on-a-chip

Multi-analyte biosensor interface for real-time monitoring of 3D microtissue spheroids in hanging-drop networks

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