High-resolution nuclear magnetic resonance spectroscopy in microfluidic droplets

Abstract

A generic approach is presented that allows high-resolution NMR spectroscopy of water/oil droplet emulsions in microfluidic devices. Microfluidic NMR spectroscopy has recently made significant advances due to the design of micro-detector systems and their successful integration with microfluidic devices. Obtaining NMR spectra of droplet suspensions, however, is complicated by the inevitable differences in magnetic susceptibility between the chip material, the continuous phase, and the droplet phases. This leads to broadening of the NMR resonance lines and results in loss of spectral resolution. We have mitigated the susceptibility difference between the continuous (oil) phase and the chip material by incorporating appropriately designed air-filled structures into the chip. The susceptibilities of the continuous and droplet (aqueous) phases have been matched by doping the droplet phase with a Eu3+ complex. Our results demonstrate that this leads to a proton line width in the droplet phase of about 3 Hz, enabling high-resolution NMR techniques.

Recent Advances on Sorting Methods of High-Throughput Droplet-Based Microfluidics in Enzyme Directed Evolution

“…Raman-activated cell sorting (RACS) would be a good choice if richer information is required apart from the enzymatic reaction itself (Wang et al, 2020 ); meanwhile, the relative low throughput can be compromised. Moreover, another informative sorting method-NMR-based sorting is molecule-informative while of low throughput (Hale et al, 2018 ). Table 1 shows the optimal specification in which different sorting methods have been achieved in recent publications.…”

“…Another challenge that hinders NMR application in microfluidics is the preservation of high spectral resolution, which requires a highly homogenous magnetic field over the sample volume. However, differences in magnetic susceptibility between the chip, the continuous phase, and the droplet phase will lead to a demagnetizing field that varies continuously over the sample volume (Hale et al, 2018 ). Researchers show that susceptibility difference between the chip and the continuous phase could be mitigated by a combination of structural shimming and doping of the less diamagnetic of the liquid phases with a europium compound, such as Eu 3+ compound (Hale et al, 2018 ).…”

Two-dimensional nuclear magnetic resonance spectroscopy with a microfluidic diamond quantum sensor

“…Last, while our microfluidic NMR sensor has an effective detection volume of ∼40 pL, several milliliters of analyte are needed to fill the overall flow apparatus. Future microfluidic chips may miniaturize or omit the prepolarization step, use smaller microfluidic channels for detection, and/or use microdroplets to shuttle small samples within a larger fluidic system ( 49 ).…”

Droplet microfluidics: from proof-of-concept to real-world utility?

“…Unsurprisingly, much recent attention has focused on improving mass (and to a lesser extent concentration) sensitivities, with microcoils proving to be highly adept in measuring mass-limited samples. 44 In this respect, a number of recent studies have demonstrated high-resolution NMR spectroscopy in pL-mL volumes 45,46 and with pmole detection limits. 47 Such advances suggest that contemporary NMR techniques may soon capable of extracting information from single (sub-nL) droplets.…”