Development of an integrated microfluidic platform for dynamic oxygen sensing and delivery in a flowing medium

Abstract

This paper describes a platform for real-time sensing of dissolved oxygen in a flowing microfluidic environment using an oxygen-sensitive luminescent dye (platinum octaethylporphyrin ketone) integrated into a micro-oxygenator device. Using a phase-based detection method, the luminescent decay lifetime of the dye was consistent with the linear Stern-Volmer relationship using both gaseous and aqueous samples. Maximum sensor resolution varied between 120-780 ppb across a range of dissolved oxygen (DO) concentrations ranging from 0-42.5 ppm. The sensor was subsequently used to determine the convective mass-transfer characteristics of a multilayer polydimethylsiloxane (PDMS) microfluidic oxygenator. The membrane-based oxygenator showed excellent agreement with an analytical convection model, and the integrated oxygen sensor was accurate across a wide range of tested flow rates (0.05-5 mL min 21). The device is unique for its ease of fabrication and highly flexible configuration, as well as the novel incorporation of oxygen delivery and detection in a single micro-device. Potential applications include tissue engineering, cell culturing, and miniaturized bio-assays that require the delivery and/or detection of precise quantities of oxygen within a microfluidic construct.

A microfluidic optical platform for real-time monitoring of pH and oxygen in microfluidic bioreactors and organ-on-chip devices

“…25 Microfluidic detection methods are highly suited for integration with organ-on-chip devices due to their potential for the analysis of low-volume liquids and high degree of automation. 29 A variety of microfluidic optical and electrochemical techniques have been developed to measure oxygen 22,[30][31][32][33][34][35][36][37][38] and pH 31,34,37,[39][40][41][42][43][44] for cell-based studies. Moreover, in some instances, the optical methods are preferred over electrical methods since they do not require electrical connections and electrodes which may be prone to biofouling and corrosion.…”

Patterning, integration and characterisation of polymer optical oxygen sensors for microfluidic devices

“…18 It exhibits both a long wavelength shift and an extended long-term photostability compared to other fluorescent dyes. 13,19 This allows for the use of standard optical filters and makes sample handling less critical. PS was chosen as polymer matrix because it provides good oxygen permeability, bio-compatibility and low autofluorescence.…”

“…20 Furthermore, removal of the photoresist with acetone after exposure and development lead to the destruction of the PtOEPK/PS film surface. Photoresist lift-off in combination with pipetting of individual sensor patches has been demonstrated, 13 but is potentially limited in throughput and minimum feature size due to the manual handling required. Previously we have suggested the use of spin-coating and dry-etching to enable wafer-level processing of polymer-encapsulated fluorescent-dye sensors.…”

“…For flow rates below this value the operating range decreases slightly due to parasitic convective losses to the surrounding PDMS. 13 Depending on the initial concentration entering the device, oxygen is either added or removed from the DI water by mass transfer through the device walls. This effect is due to the high permeability of oxygen in PDMS and can be reduced by use of a less permeable polymer or by encapsulation of the final device.…”

A microfluidic device to study cancer metastasis under chronic and intermittent hypoxia

“…[45][46][47][48] These sensors are used in place of conventional Clark-type electrodes due to their adaptability, rapid response to changing oxygen and their non-invasiveness; i.e., they do not consume oxygen during operation. We chose Ru(Ph 2 phen 3 )Cl 2 due to its high quantum yield and stability at low oxygen concentrations.…”