Miniaturized real-time monitoring system for l-lactate and glucose using microfabricated multi-enzyme sensors

Perdomo, J.; Hinkers, H.; Sundermeier, C.; Seifert, W.; Morell, O. Martı́nez; Knoll, Meinhard

doi:10.1016/s0956-5663(00)00087-7

Cited by 80 publications

(55 citation statements)

References 13 publications

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“…Miniaturized versions have been used as scanning probes to monitor the glucose and lactate metabolism of single cells 42,43 . Flow-through-type sensor systems have been devised to analyze cell culture conditions and metabolites in liquid samples downstream of cell cultures [44][45][46][47][48][49][50][51] . Silicon-based sensor chips for multi-parameter online monitoring have been mounted in a perfused cell culture unit 52 , and multiple sensing electrodes have been directly incorporated into transparent microfluidic systems to measure the glucose consumption of single cardiac cells 53 or the lactate production of cells of various types 54 and, combined with optical read-out, for monitoring cancer cell metabolism 55 .…”

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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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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“…We obtained a sensitivity of 0.42 nA/µM cm −2 and a detection limit of 216 µM for glutamate, a sensitivity of 0.46 nA/µM cm −2 and a detection limit of 115 µM for glucose, a sensitivity of 1.09 nA/µM cm −2 and a detection limit of 115 µM for lactate. Few works [15], [16] deal with multiple detection of metabolites in cell cultures and none of them has shown the integration of multiple and nanostructured WEs sharing common counter and reference electrode. Instead, the results presented in this work represent a novelty with respect to the state-of-the-art in cell culture monitoring and pave the way to new integrated systems for cell analysis.…”

Section: Discussionmentioning

confidence: 99%

New technologies for nanobiosensing and their applications to real-time monitoring

Boero

Carrara

Micheli

2011

2011 IEEE Biomedical Circuits and Systems Conference (BioCAS)

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Abstract-Amperometric biosensors are complex systems and they require a combination of technologies for their development. The aim of the present work is to exploit existing technologies for new purposes in order to develop nanostructured biosensors for the real-time detection of multiple metabolites in cell culture flasks. The fabrication of five Au working electrodes onto silicon substrate is achieved with CMOS compatible microtechnology. Each working electrode presents an area of 0.25 mm 2 , so structuration with carbon nanotubes and specific functionalization are carried out by using spotting technology, originally developed for microarrays and DNA printing. The electrodes are characterized by cyclic voltammetry and compared with commercially available screen-printed electrodes. Finally, they are functionalized with different enzymes and calibrated for real-time detection of glutamate, glucose and lactate under flow conditions. The developed biosensor for real-time and online detection of multiple metabolites shows very promising results towards its application in cell culture monitoring.

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“…On the other hand, minimizing interferences with cells is much more desirable. Few works [17], [18] deal with multiple detection of metabolites in cell cultures and none of them has shown the integration of multiple and nanostructured working electrodes sharing common counter and reference electrodes. CITSens Bio sensors (C-CIT, Switzerland) are the only device in the market able to perform real-time cell monitoring, even if they do not allow multiple detection on the same platform.…”

Section: Metabolite Detection In Cell Culture Mediummentioning

confidence: 99%

New Approaches for Carbon Nanotubes-Based Biosensors and Their Application to Cell Culture Monitoring

Boero

Olivo

Micheli

et al. 2012

IEEE Trans. Biomed. Circuits Syst.

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Miniaturized real-time monitoring system for l-lactate and glucose using microfabricated multi-enzyme sensors

Cited by 80 publications

References 13 publications

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

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

New technologies for nanobiosensing and their applications to real-time monitoring

New Approaches for Carbon Nanotubes-Based Biosensors and Their Application to Cell Culture Monitoring

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