How Are Sensors Making Organ-on-a-Chip Systems More Accurate?

By Ankit SinghReviewed by Susha Cheriyedath, M.Sc.Oct 28 2026

Electrochemical Sensors Read Cell Activity
Optical Sensors for Oxygen and Drug Responses
Why Continuous Measurements Matter in Drug Research?
Current Challenges
Conclusion
References and Further Reading

Drug developers use animal models and simple cell cultures to predict the behavior of medications in humans. Organ-on-a-chip systems provide a more accurate alternative. These small devices hold living human cells inside tiny channels that mimic the structure and fluid flow of real tissue. Regulators have taken notice, and the U.S. Food and Drug Administration Modernization Act 2.0 opened the door to such models as alternatives to animal testing.

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However, building a realistic chip is only half the job, because researchers also need good measurements from it. Most experiments still end with a single snapshot taken after the cells are destroyed. This article discusses how researchers integrate electrochemical and optical sensors into organ-on-a-chip systems, the significance of continuous readings in drug research, and the existing challenges.¹

Electrochemical Sensors Read Cell Activity

Electrochemical sensors are miniature electrodes that convert a chemical reaction into an electrical current or voltage. In an amperometric oxygen sensor, a platinum electrode held at a fixed voltage reduces dissolved oxygen, and the resulting current increases with oxygen concentration. Potentiometric sensors, on the other hand, operate differently. They measure voltage without drawing current, making them well-suited to tracking pH as cells release acid during metabolism.¹

To detect molecules that do not react at an electrode on their own, researchers add a biological recognition element. For example, a glucose biosensor carries an enzyme that converts glucose into hydrogen peroxide, which the electrode then oxidizes. Similar designs track lactate and glutamate. Because cells burn glucose and release lactate, monitoring both values side by side reveals whether tissue is relying on oxygen or switching to a less efficient energy pathway.¹

Additionally, electrochemical sensors are highly scalable. Electrodes only tens of micrometers across can sit beside a single spheroid, a small ball of cells that serves as a miniature tissue. A team in Freiburg, Germany, built a chip with electrochemical sensors for oxygen, glucose, and lactate around breast cancer organoids. Its oxygen sensors ran for a week in culture medium without measurable drift, providing a steady record of how the growing tissue consumed nutrients.¹

Optical Sensors for Oxygen and Drug Responses

Optical sensors work through a different mechanism. A thin patch or fiber tip coated with a luminescent dye emits a glow when illuminated, and the presence of oxygen diminishes that glow in a predictable manner. A detector outside the chip measures changes in brightness or in the duration of the glow. Because the dye itself consumes no oxygen and needs no wires, one reader can scan many sensor spots in sequence.¹

This wire-free design suits high-throughput screening. A platform reported in RSC Lab on a Chip packs 96 tiny kidney models into a standard plate format, each with its own optical oxygen sensor. It measured oxygen consumption over 11 days and observed how kidney cells reacted to various doses of a chemotherapy drug. The oxygen data gave more robust results than a conventional color-based assay, particularly at the later stages of drug exposure.¹

Optical sensing is also applicable to real tissue. A study published in Analytical Chemistry used fiber-optic oxygen sensors to monitor oxygen consumption in the mouse liver. This rate was closely correlated with cellular energy reserves and declined by 60-70% following exposure to a toxic dose of succinate, a drop later confirmed by tissue staining.²

Why Continuous Measurements Matter in Drug Research?

Most standard assays measure a single endpoint. Scientists treat cells, wait, then stain or break them open to count survivors. However, this approach misses the path the cells took to reach their final state. Sensors record a reversible, time-dependent signal, so researchers can monitor metabolism decline during drug exposure and then assess whether it recovers once the drug is washed out.¹

Continuous data also verifies whether the experiment adheres to its original design. A recent analysis revealed that only 6% of studies provided a fully reproducible description of oxygen conditions. Even in standard incubators, active cancer cells can reduce the oxygen levels around them to near zero between medium changes. A sensor placed beside the cells can detect these subtle shifts, which may otherwise skew the perceived efficacy of a drug.¹

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Moreover, integrated sensing introduces the possibility of active control. When sensor readings feed back into the pumps that drive fluid through a chip, researchers can maintain oxygen at a set level or deliver tailored drug doses over time. This level of monitoring transforms the chip into a controlled experiment that provides real-time feedback, offering scientists a more robust basis for evaluating a compound's effects.¹

Current Challenges

Biofouling is a major challenge in sensor technology. Proteins and cells in culture medium gradually coat electrode surfaces, blocking the electron transfer that produces the signal. This buildup results in decreased sensitivity and fluctuating readings. Researchers are testing porous nanostructured electrodes and water-attracting zwitterionic coatings that resist this buildup. However, current surfaces still offer limited control over these interactions during long-term use.³

Sensor stability poses a related challenge. Enzymes and antibodies responsible for biosensor selectivity tend to degrade over time and with heat, causing many sensors to lose sensitivity during prolonged experiments. Optical dyes also encounter limitations, particularly in terms of accuracy at low oxygen levels. Although meaningful organ models may need to operate for up to 4 weeks, biochemical sensors that stay reliable over that span are rare.¹

Manufacturing adds further complexity. Electrochemical sensors require continuous electrical control, and the circuits that provide it are difficult to scale across dozens of channels. Many biological sensor components cannot withstand the gamma irradiation or autoclaving used in the industry for sterilization. Popular 3D printing methods also struggle to embed electrodes or deliver clear plastics, which pushes developers toward scalable processes borrowed from standard labware.¹

Conclusion

Electrochemical and optical sensors are changing what organ-on-a-chip systems can reveal. Electrodes can measure levels of oxygen, pH, glucose, and lactate in small samples. At the same time, luminescent patches allow a reader to check multiple devices at once. Together, these tools replace single snapshots with continuous records of tissue health, exposing drug effects, recovery, and hidden shifts in culture conditions that endpoint tests can miss.¹

The accuracy of these sensors now depends on their durability. To become standard tools in pharmaceutical labs, antifouling coatings, sturdier recognition elements, and manufacturing methods suited to mass production will be crucial. If engineers can keep sensors stable for weeks in living tissue models, organ-on-a-chip systems will provide the reliable, relevant data that drug developers need to make safer decisions earlier.¹

References and Further Reading

1. Dornhof, J. et al. (2025). Microsensor systems for cell metabolism – from 2D culture to organ-on-chip (2019–2024). Lab on a Chip, 25 (5): 1149–1168. DOI:10.1039/d4lc00437j. https://pubs.rsc.org/lc/article/25/5/1149/853061/Microsensor-systems-for-cell-metabolism-from-2D
2. Karsten, R. E. H. et al. (2024). Real-Time Monitoring of Oxygen-Consumption Rate in Mouse Liver Slices Incubated in Organ-on-a-Chip Devices. Analytical Chemistry, 96 (40): 15871–15879. DOI:10.1021/acs.analchem.4c00355. https://pubs.acs.org/ancham/article/96/40/15871/86635/Real-Time-Monitoring-of-Oxygen-Consumption-Rate-in
3. Carroll, D. P., & Mendes, P. M. (2023). Recent advances in surface modification and antifouling strategies for electrochemical sensing in complex biofluids. Current Opinion in Electrochemistry, 40, 101319. DOI:10.1016/j.coelec.2023.101319. https://www.sciencedirect.com/science/article/pii/S2451910323001126

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