Oxygen Measurement in Microdevices

Abstract

Oxygen plays a fundamental role in respiration and metabolism, and quantifying oxygen levels is essential in many environmental, industrial, and research settings. Microdevices facilitate the study of dynamic, oxygen-dependent effects in real time. This review is organized around the key needs for oxygen measurement in microdevices, including integrability into microfabricated systems; sensor dynamic range and sensitivity; spatially resolved measurements to map oxygen over two- or three-dimensional regions of interest; and compatibility with multimodal and multianalyte measurements. After a brief overview of biological readouts of oxygen, followed by oxygen sensor types that have been implemented in microscale devices and sensing mechanisms, this review presents select recent applications in organs-on-chip in vitro models and new sensor capabilities enabling oxygen microscopy, bioprocess manufacturing, and pharmaceutical industries. With the advancement of multiplexed, interconnected sensors and instruments and integration with industry workflows, intelligent microdevice-sensor systems including oxygen sensors will have further impact in environmental science, manufacturing, and medicine.

Bright and Photostable TADF‐Emitting Zirconium(IV) Pyridinedipyrrolide Complexes: Efficient Dyes for Decay Time‐Based Temperature Sensing and Imaging

“…Nanosensors play an important role in understanding fundamental chemical processes in human and non-human cells and can help us to develop new drugs and therapies against diseases. [1][2][3][4][5] Among others, luminescent nanosensors have been reported for many important parameters such as pH, [6][7][8] oxygen, [9,10] ions, [11][12][13] and temperature. [14][15][16] Temperature is recognized as a fundamental parameter that can be altered by external and homeostatic causes.…”

Live microscopy of multicellular spheroids with the multi-modal near-infrared nanoparticles reveals differences in oxygenation gradients

“…[18][19][20][21] Typically, tumour spheroids larger than 300-500 µm in diameter are expected to consist of three concentric layers: [22][23][24] the proliferating, quiescent, and necrotic cores, due to nutrients and oxygen diffusion limits concomitant with accumulation of waste products, lactate, and decreasing pH. 25,26 Traditional methods for (intra)cellular oxygen measurements and oxygen consumption rates (OCR) in such 3D models as spheroids, neurospheres, organoids, and (micro)scaffold-grown structures include microelectrodes, 27 redox-sensitive nitroimidazole derivatives, 28 indirect staining with antibodies and hypoxia markers (such as HIF-1α), 29 genetically encoded fluorescent reporters, 30,31 organ-on-a-chip devices coupled with solid-state sensors, 32,33 opticalbased multi-well plate systems, 34,35 and optical methods using fluorescent [36][37][38] and phosphorescent [39][40][41][42][43][44] probes. Optical sensing of molecular oxygen (O 2 ) has gained significant interest as it allows for live monitoring of cell metabolism, OCR, and oxygen gradient in a direct, 2 d e t, non-invasive, non-chemical, and highly sensitive manner with broad possibilities for multiplexing.…”

“…While some progress has been achieved with the dye- and fluorescent protein-based structures, their use in ratiometric measurements in imaging 3D microtissues is still rare. 41,67–70 Here, we demonstrate the red/near infrared-emitting nanoparticle probes, which provide non-toxic, stable, and cell line-dependent staining, and can be used for long-term monitoring of rapid changes in oxygenation in multicellular spheroids. We also validate the detection of observed gradients with the label-free two-photon FLIM microscopy of NAD(P)H. Collectively, the presented approach should help to standardise studies probing hypoxia in 3D tissue models.…”

Live Microscopy of Multicellular Spheroids with the Multimodal Near-Infrared Nanoparticles Reveals Differences in Oxygenation Gradients

“…Surprisingly, there has been little attention to the use of deep-red and near-infrared (NIR) dyes in O 2 imaging so far. − Using such structures with long-wave excitation and emission would provide decreased phototoxicity, ensure better filtering of the autofluorescence, and provide deeper light penetration across the volume of multicellular spheroids. While some progress has been achieved with the dye- and fluorescent protein-based structures, their use in ratiometric measurements in imaging of 3D microtissues is still rare. ,− Here, we demonstrate the red/NIR-emitting NP probes, which provide nontoxic, stable, and cell line-dependent staining and can be used for long-term monitoring of rapid changes in oxygenation in multicellular spheroids. We also validate the detection of observed gradients with the label-free two-photon FLIM microscopy of NAD(P)H. Collectively, the presented approach should help to standardize studies probing hypoxia in 3D tissue models.…”

“…Traditional methods for (intra)­cellular oxygen measurements and oxygen consumption rates (OCR) in such 3D models as spheroids, neurospheres, organoids, and (micro)­scaffold-grown structures include microelectrodes, redox-sensitive nitroimidazole derivatives, indirect staining with antibodies and hypoxia markers (such as HIF-1α), genetically encoded fluorescent reporters, , organ-on-a-chip devices coupled with solid-state sensors, , optical-based multiwell plate systems, , and optical methods using fluorescent − and phosphorescent − probes. Optical sensing of molecular oxygen (O 2 ) has gained significant interest, as it allows for live monitoring of cell metabolism, OCR, and oxygen gradient in a direct, noninvasive, nonchemical, and highly sensitive manner with broad possibilities for multiplexing .…”