Spectrally resolved flow imaging of fluids inside a microfluidic chip with ultrahigh time resolution

Microfluidics has advanced to become a complete lab-on-a-chip platform with applications across many disciplines of scientific research. While optical techniques are primarily used as modes of detection, magnetic resonance (MR) is emerging as a potentially powerful and complementary tool because of its non-invasive operation and analytical fidelity. Two prevailing limitations currently inhibit MR techniques on microfluidic devices: poor sensitivity and the relatively slow time scale of dynamics that can be probed. It is commonly assumed that the time scale of observation of one variable limits the certainty with which one can measure the complementary variable. For example, short observation times imply poor spectral resolution. In this article, we demonstrate a new methodology that overcomes this fundamental limit, allowing in principle for arbitrarily high temporal resolution with a sensitivity across the entire microfluidic device several orders of magnitude greater than is possible by direct MR measurement. The enhancement is evidenced by recording chemically resolved fluid mixing through a complex 3D microfluidic device at 500 frames per second, the highest recorded in a magnetic resonance imaging experiment. The key to this development is combining remote detection with a time ‘slicing’ of its spatially encoded counterpart. Remote detection circumvents the problem of insensitive direct MR detection on a microfluidic device where the direct sensitivity is less than 10^-5 relative to traditional NMR, while the time slicing eliminates the constraints of the limited observation time by converting the time variable into a spatial variable through the use of magnetic field gradients. This method has implications for observing fast processes, such as fluid mixing, rapid binding, and certain classes of chemical reactions with sub millisecond time resolution and as a new modality for on-chip chromatography.