Optical oxygen sensors for applications in microfluidic cell culture

Abstract

The presence and concentration of oxygen in biological systems has a large impact on the behavior and viability of many types of cells, including the differentiation of stem cells or the growth of tumor cells. As a result, the integration of oxygen sensors within cell culture environments presents a powerful tool for quantifying the effects of oxygen concentrations on cell behavior, cell viability, and drug effectiveness. Because microfluidic cell culture environments are a promising alternative to traditional cell culture platforms, there is recent interest in integrating oxygen-sensing mechanisms with microfluidics for cell culture applications. Optical, luminescence-based oxygen sensors, in particular, show great promise in their ability to be integrated with microfluidics and cell culture systems. These sensors can be highly sensitive and do not consume oxygen or generate toxic byproducts in their sensing process. This paper presents a review of previously proposed optical oxygen sensor types, materials and formats most applicable to microfluidic cell culture, and analyzes their suitability for this and other in vitro applications.

Keywords: cell culture; lab-on-a-chip; luminescence; microfluidics; optical oxygen sensors.

Figure 1.

Simplified example setup for intensity-based optical oxygen sensing.

Figure 2.

Simplified example setup for lifetime-based optical oxygen sensing. Example excitation modulation and emission waveforms are also shown.

Figure 3.

Illustration of “pulse-and-gate” time-domain luminescence lifetime detection. The transparent colored boxes indicate the windows of data acquisition; the decay constant and luminescence lifetime can be determined from the data acquired in these windows (figure adapted from [28]).

Figure 4.

(a) Thin film sensor. (b) Patterned thin-film sensor. (c) Tapered optical fiber sensor without and with opaque polymer optical isolation (shown as partially transparent for figure clarity). (d) Micro/nanoparticle sensors suspended in aqueous media. (e) Micro/nanoparticle sensors suspended in a thin film. (f) Water-soluble sensor compound dissolved in aqueous media.

Figure 5.

Illustration of enclosed PDMS microfluidic system for cell culture with possible designs for integrated optical oxygen sensors.

Figure 6.

Photograph of the fabricated three-chamber microfluidic cell culture analog device with integrated optical oxygen sensor. Reprinted from [81] with permission from John Wiley and Sons.

Figure 7.

(a) Schematic diagram of the microfluidic oxygenator with integrated oxygen sensors. (b) Photograph of the fabricated oxygenator device. (c) Microscope image of the microfluidic multiplexor and oxygen concentration gradient generator. Reprinted from [55] with permission from the American Chemical Society.