Characterization of Microfluidic Gas Reactors Using Remote-Detection MRI and Parahydrogen-Induced Polarization

Nuclear magnetic resonance (NMR) is an extremely powerful method for in situ monitoring of chemical reactions and mass transport processes. However, the low intrinsic sensitivity of NMR resulting from low thermal nuclear spin polarization limits the use of the method. Several hyperpolarization techniques have been developed for boosting the sensitivity. Among them, parahydrogen-induced polarization (PHIP) has a direct relation to chemistry, as the hyperpolarization is naturally produced in the course of a chemical reaction proceeding through the addition of parahydrogen. Originally, PHIP was discovered in a homogeneous catalytic hydrogenation, and since then many homogeneous catalytic systems have been shown to produce PHIP. Within the past five years, several catalysts have been found to enable the production of PHIP in heterogeneously catalyzed hydrogenations. 5] Catalyst–product separation is much easier in the heterogeneous than in the homogeneous processes, and therefore, continuous production of hyperpolarized molecules is facilitated. Herein, we consider a miniaturized packed-bed reactor, which produces a continuous flow of gaseous catalyst-free hyperpolarized molecules, as a microfluidic nuclear spin polarizer based on PHIP achieved in a heterogeneous hydrogenation reaction. Microfluidics deals with the control and manipulation of fluids in channels with dimensions below one millimeter. Microfluidic devices provide control over a process with capabilities that exceed those of large-scale systems. In the production of hyperpolarized molecules utilizing PHIP, the advantages of using microfluidic flow reactors instead of large reactors are low-scale production, fast transport times through the device, highly controllable heat exchange, and much safer pressurization of the reactor. Furthermore, microfluidic flow reactors can be easily mounted inside the magnet of an NMR spectrometer, whereas large-scale polarizers have to be placed outside the magnet, leading to significant losses of polarization during the transport of the molecules to the magnet. Microfluidic reactor could be even included in a lab-on-a-chip device in which it would produce hyperpolarized substances for NMR characterization of the processes in the following modules of the device. As the performance of the reactor is characterized by NMR, the size of a radio-frequency (RF) coil in a conventional NMR experiment is dictated by the size of an entire microfluidic device (the reactor in this case). Typically, the dimensions of the device are orders of magnitude larger than the dimensions of the flow channels inside it. In general, a small coil is more sensitive than a large coil. Therefore, the poor sensitivity resulting from the large coil and a low filling factor make conventional NMR experiments very challenging, especially when gases with a low spin density are studied. Remote-detection (RD) NMR based on the spatial separation of signal encoding and detection provides an elegant solution to the sensitivity issues. In the RD MRI experiments carried out herein, the encoding of spatial information is performed by a large coil that surrounds the microfluidic reactor, while signal detection is done by an ultrasensitive microcoil with an optimized filling factor outside the device as the fluid flows out (Figure 1a). Consequently, the RD method increases significantly the sensitivity of the experiment when compared to a conventional NMR experiment. The travel time from the encoding region to the detector depends on the spatial position of fluid molecules during the encoding, and thus RD NMR provides time-offlight (TOF) information. Consequently, TOF flow images measured by RD MRI reveal mass transport characteristics of the device under investigation. In our previous study, we showed that the sensitivity enhancement of several orders of magnitude can be achieved by combining PHIP and RD NMR, allowing gas flow visualization in microfluidic devices. PHIP was produced by a relatively large polarizer outside the magnet. Herein, we demonstrate that miniaturized microfluidic gas reactors can provide significant polarization enhancement compared to thermal polarization of nuclear spins inside the NMR magnet, and the high polarization degree combined with RD MRI technique enable characterization of the reactors. Recently, Bouchard et al. visualized hydrogenation in a larger reactor utilizing PHIP and conventional MRI. However, the sensitivity boost given by RD technique used in our work enables the investigation of much smaller reactors, and the method [*] Dr. V. V. Zhivonitko, Prof. I. V. Koptyug Laboratory of Magnetic Resonance Microimaging International Tomography Center SB RAS 3A Institutskaya St., Novosibirsk 630090 (Russia) E-mail: v_zhivonitko@tomo.nsc.ru