Microsensor systems for cell metabolism - from 2D culture to organ-on-chip (2019-2024).

Cell cultures, organs-on-chip and microphysiological systems become increasingly relevant as models, , in drug development, disease modelling, toxicology or cancer research. It has been underlined repeatedly that culture conditions and metabolic cues have a strong or even essential influence on the reproducibility and validity of such experiments but are often not appropriately measured or controlled. Here we review microsensor systems for cell metabolism for the continuous measurement of culture conditions in microfluidic and lab-on-chip platforms.

Reference Electrode Types for Zero-Gap CO Electrolyzers: Benefits and Limitations.

Integrated reference electrodes allow to deconvolute voltage contributions of anode and cathode and contribute to a better understanding of CO electrolyzers. However, in zero-gap cell configurations, this integration can be challenging and obtaining error-free data with such a setup is a non-trivial task. This study compares five different methods to integrate a reference electrode into an alkaline zero-gap CO electrolysis cell.

In Situ Performance Monitoring of Electrochemical Oxygen and Hydrogen Peroxide Sensors in an Additively Manufactured Modular Microreactor.

Miniaturized and microstructured reactors in process engineering are essential for a more decentralized, flexible, sustainable, and resilient chemical production. Modern, additive manufacturing methods for metals enable complex reactor-geometries, increased functionality, and faster design iterations, a clear advantage over classical subtractive machining and polymer-based approaches. Integrated microsensors allow online, in situ process monitoring to optimize processes like the direct synthesis of hydrogen peroxide.

Electrochemical Methods in the Cloud: FreiStat, an IoT-Enabled Embedded Potentiostat.

Embedded potentiostats enable electrochemical measurements in the Internet-of-Things (IoT) or other decentralized applications, such as remote environmental monitoring, electrochemical energy systems, and biomedical point-of-care applications. We report on Freiburg's Potentiostat (FreiStat) based on the AD5941 potentiostat circuit from Analog Devices, together with custom firmware, as the key to precise and advanced electrochemical methods. We demonstrated its analytical performance by various cyclic voltammetry measurements, advanced techniques such as differential pulse voltammetry, and a lactate biosensor measurement with currents in the nA range and a resolution of 54 pA.

Advanced electrochemical potential monitoring for improved understanding of electrical neurostimulation protocols.

Current-controlled neurostimulation is increasingly used in the clinical treatment of neurological disorders and widely applied in neural prostheses such as cochlear implants. Despite its importance, time-dependent potential traces of electrodes during microsecond-scale current pulses, especially with respect to a reference electrode (RE), are not precisely understood. However, this knowledge is critical to predict contributions of chemical reactions at the electrodes, and ultimately electrode stability, biocompatibility, and stimulation safety and efficacy.

Bioprinting-based automated deposition of single cancer cell spheroids into oxygen sensor microelectrode wells.

Three-dimensional (3D) cell agglomerates, such as microtissues, organoids, and spheroids, become increasingly relevant in biomedicine. They can provide models that recapitulate functions of the original tissue in the body and have applications in cancer research. For example, they are widely used in organ-on-chip systems.

In situ stability monitoring of platinum thin-film electrodes for neural interfaces in the presence of proteins.

The long-term stability of platinum electrodes is a key factor that determines the life-time of biomedical devices, such as implanted neural interfaces like brain stimulation or recording electrodes, cochlear implants, and biosensors. The downsizing of such devices relies on the usage of microfabricated thin-film electrodes. In order to determine and investigate the causal degradation processes for platinum electrodes, it is essential to use potential-controlled experiments, which allow selectable polarization of the electrode without exceeding the water stability window boundaries.

Electrochemical microelectrode degradation monitoring:investigation of platinum corrosion at neutral pH.

. The stability of platinum and other noble metal electrodes is critical for neural implants, electrochemical sensors, and energy sources. Beyond the acidic or alkaline environment found in most electrochemical studies, the investigation of electrode corrosion in neutral pH and chloride containing electrolytes is essential, particularly regarding the long-term stability of neural interfaces, such as brain stimulation electrodes or cochlear implants.

Standard cochlear implants as electrochemical sensors: Intracochlear oxygen measurements in vivo.

Cochlear implants are the most successful neural prostheses worldwide and routinely restore sensorineural hearing loss by direct electrical stimulation of the auditory nerve. Enhancing this standard implant by chemical sensor functionality opens up new possibilities, ranging from access to the biochemical microenvironment of the implanted electrode array to the long-term study of the electrode status. We developed an electrochemical method to turn the platinum stimulation microelectrodes of cochlear implants into electrochemical sensors.

Microfluidic organ-on-chip system for multi-analyte monitoring of metabolites in 3D cell cultures.

Three-dimensional cell cultures using patient-derived stem cells are essential models for a more efficient and individualized cancer therapy. Currently, culture conditions and metabolite concentrations, especially hypoxia, are often not accessible continuously and within microphysiological systems. However, understanding and standardizing the cellular microenvironment are the key to successful models.

Electrochemical methods for neural interface electrodes.

. Neural interfaces often rely on charge transfer processes between electrodes and the tissue or electrolyte. Electrochemical processes are at the core of electrode function and, therefore, the key to neural interface stability, electrode performance characterization, and utilization of electrodes as chemical sensors.

Electrochemical Microsensor for Microfluidic Glyphosate Monitoring in Water Using MIP-Based Concentrators.

Glyphosate (GLY) is a broad-spectrum herbicide and is the most used pesticide worldwide. This vast usage has raised strong interest in the ecotoxicological impacts and human risks, with contamination of water being a major concern. Decentralized analytical techniques for water monitoring are of high importance.

In Situ Mapping of H, O, and HO in Microreactors: A Parallel, Selective Multianalyte Detection Method.

Determining local concentrations of the analytes in state-of-the-art microreactors is essential for the development of optimized and safe processes. However, the selective, parallel monitoring of all relevant reactants and products in a multianalyte environment is challenging. Electrochemical microsensors can provide unique information on the reaction kinetics and overall performance of the hydrogen peroxide synthesis process in microreactors, thanks to their high spatial and temporal resolution and their ability to measure in situ, in contrast to other techniques.

Microsensor Electrodes for 3D Inline Process Monitoring in Multiphase Microreactors.

We present an electrochemical microsensor for the monitoring of hydrogen peroxide direct synthesis in a membrane microreactor environment by measuring the hydrogen peroxide and oxygen concentrations. In prior work, for the first time, we performed in situ measurements with electrochemical microsensors in a microreactor setup. However, the sensors used were only able to measure at the bottom of the microchannel.

New life for old wires: electrochemical sensor method for neural implants.

Objective: Electrochemical microsensors based on noble metals can give essential information on their microenvironment with high spatio-temporal resolution. However, most advanced chemo- and biosensors lack the long-term stability for physiological monitoring of brain tissue beyond an acute application. Noble metal electrodes are widely used as neural interfaces, particularly for stimulating in the central nervous system.

On-chip photodynamic therapy - monitoring cell metabolism using electrochemical microsensors.

We introduce a new system which combines metabolic monitoring using electrochemical microsensors with photodynamic therapy on-chip for the first time. Oxygen consumption of T-47D breast cancer cells was measured during therapy with protoporphyrin IX. We determined the efficacy of the therapy and revealed its recovery effects, which underlines the high relevance of continuous monitoring.

Active Potentiometry for Dissolved Oxygen Monitoring with Platinum Electrodes.

Potentiometric oxygen monitoring using platinum as the electrode material was enabled by the combination of conventional potentiometry with active prepolarization protocols, what we call . The obtained logarithmic transfer function is well-suited for the measurement of dissolved oxygen in biomedical applications, as the physiological oxygen concentration typically varies over several decades. We describe the application of active potentiometry in phosphate buffered salt solution at different pH and ion strength.

Sensor Access to the Cellular Microenvironment Using the Sensing Cell Culture Flask.

The Sensing Cell Culture Flask (SCCF) is a cell culture monitoring system accessing the cellular microenvironment in 2D cell culture using electrochemical microsensors. The system is based on microfabricated sensor chips embedded in standard cell culture flasks. Ideally, the sensor chips could be equipped with any electrochemical sensor.

Microsensor systems for cell metabolism - from 2D culture to organ-on-chip.

Microsensor systems for cell metabolism are essential tools for investigation and standardization in cell culture. Electrochemical and optical read-out schemes dominate, which enable the marker-free, continuous, online recording of transient effects and deliver information beyond microscopy and end-point tests. There has been much progress in microfluidics and microsensors, but the translation of both into standard cell culture procedures is still limited.

In-vivo monitoring of infection via implantable microsensors: a pilot study.

The most common complication after implantation of foreign material is infection, leading to implant failure and severe patient discomfort. Smoldering-infections proceed inapparently and might not get verified by radiological diagnostics. Early identification of this type of infection might significantly reduce the rate of complications.

Multianalyte Antibiotic Detection on an Electrochemical Microfluidic Platform.

The excessive use of antibiotics in human and veterinary medicine causes the emergence of multidrug resistant bacteria. In this context, the surveillance of many different antibiotics provokes a worldwide challenge. Hence, fast and versatile multianalyte single-use biosensors are of increasing interest for many fields such as medical analysis or environmental and food control.

Accessing 3D microtissue metabolism: Lactate and oxygen monitoring in hepatocyte spheroids.

3D hepatic microtissues, unlike 2D cell cultures, retain many of the in-vivo-like functionalities even after long-term cultivation. Such 3D cultures are increasingly applied to investigate liver damage due to drug exposure in toxicology. However, there is a need for thorough metabolic characterization of these microtissues for mechanistic understanding of effects on culture behaviour.

Microfabricated, amperometric, enzyme-based biosensors for in vivo applications.

Miniaturized electrochemical in vivo biosensors allow the measurement of fast extracellular dynamics of neurotransmitter and energy metabolism directly in the tissue. Enzyme-based amperometric biosensing is characterized by high specificity and precision as well as high spatial and temporal resolution. Aside from glucose monitoring, many systems have been introduced mainly for application in the central nervous system in animal models.

Lift-Off Free Fabrication Approach for Periodic Structures with Tunable Nano Gaps for Interdigitated Electrode Arrays.

We report a simple, low-cost and lift-off free fabrication approach for periodic structures with adjustable nanometer gaps for interdigitated electrode arrays (IDAs). It combines an initial structure and two deposition process steps; first a dielectric layer is deposited, followed by a metal evaporation. The initial structure can be realized by lithography or any other structuring technique (e.

Targeting tumour hypoxia to prevent cancer metastasis. From biology, biosensing and technology to drug development: the METOXIA consortium.

The hypoxic areas of solid cancers represent a negative prognostic factor irrespective of which treatment modality is chosen for the patient. Still, after almost 80 years of focus on the problems created by hypoxia in solid tumours, we still largely lack methods to deal efficiently with these treatment-resistant cells. The consequences of this lack may be serious for many patients: Not only is there a negative correlation between the hypoxic fraction in tumours and the outcome of radiotherapy as well as many types of chemotherapy, a correlation has been shown between the hypoxic fraction in tumours and cancer metastasis.