A portable cell culture system with a simple microscope, oxygen sensor and MEA amplifier

Abstract

Cell culture in-vitro is a well-known method to develop cell and disease models for studying physiologically relevant mechanisms and responses for various applications in life sciences. Conventional methods for instance, using static culture flasks or well plates, have limitations, as these cannot provide accurate tractable models for advanced studies. However, microscale systems can overcome this since they mimic the cells' natural microenvironment adequately. We have developed a portable live-cell imaging system with an invert-upright-convertible architecture and a mini-bioreactor for long-term simultaneous cell imaging and analysis, chemical sensing and electrophysiological recording. Our system integrates biocompatible cell-friendly materials with modular measurement schemes and precise environment control and can be automated. High quality time-lapse cell imaging is hugely useful in cell/disease models. However, integration of advanced in-vitro systems into benchtop microscopes for in-situ imaging is tricky and challenging. This is especially true with device based biological systems, such as lab/organ/body-on-chips, or mini-bioreactors/microfluidic systems. They face issues ranging from optical and physical geometry incompatibilities to difficulties in connectivity of flow and perfusion systems. However, the novel modular system we have developed either as an inverted or as an upright system can easily accommodate virtually any in-vitro devices. Furthermore, it can accept additional sensor or measurement devices quite freely. Cell characterization, differentiation, chemical sensing, drug screening, microelectrode-array-electrophysiological recordings, and cell stimulation can be carried out with simultaneous in-situ imaging and analysis. Moreover, our system can be configured to capture images from regions that are otherwise inaccessible by conventional microscopes, for example, cells cultured on physical or biochemical sensor systems. We demonstrate the system for video-based beating analysis of cardiomyocytes, cell orientation analysis on nanocellulose, and simultaneous long-term in-situ microscopy with pO2 and temperature sensing. The compact microscope as such is comparable to standard phase-contrast-microscopes without any detectable aberrations and is useful practically for any in-situ microscopy demands. [1] D. K. Rajan et al., "A Portable Live-Cell Imaging System With an Invert-Upright-Convertible Architecture and a Mini-Bioreactorfor Long-Term Simultaneous Cell Imaging, Chemical Sensing, and Electrophysiological Recording," in IEEE Access, vol. 6,pp. 11063-11075, 2018. doi: 10.1109/ACCESS.2018.2804378. [2] Antti-Juhana Mäki et al., "A Portable Microscale Cell Culture System with Indirect Temperature Control"SLAS TECHNOLOGY: Translating Life Sciences Innovation 2018 23:6, 566-579. [3] Hannu Välimäki et al.,Fluorimetric oxygen sensor with an efficient optical read-out for in vitro cellmodels,Sensors and Actuators B: Chemical,Volume 249,2017,pp.738-746,ISSN 0925-4005,https://doi.org/10.1016/j.snb.2017.04.182.