High-resolution nuclear magnetic resonance spectroscopy in microfluidic droplets

William Hale, Gabriel Rossetto, Rachael Greenhalgh, Graeme Finch and Marcel Utz*

Lab Chip, 2018,18, 3018-3024

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.

Probing the kinetics in supramolecular chemistry and molecular assembly by microfluidic-NMR spectroscopy

Hongxun Fang, Yibin Sun, Xinchang Wang, Manvendra Sharma, Zhong Chen, Xiaoyu Cao*, Marcel Utz* and Zhongqun Tian*

Science China Chemistry, 2018

Microfluidic-NMR spectroscopy has been extended to study the kinetics in supramolecular chemistry and molecular assembly. Kinetics of a multicomponent host-guest supramolecular system containing viologen derivatives, ő≤-cyclodextrins and cucurbit [7]urils are studied by a PMMA based microfluidic chip combined with a dedicated transmission line probe for NMR detection. By combining microfluidic technology with NMR spectroscopy, the amount of material required for a full kinetic study could be minimized. This is crucial in supramolecular chemistry, which often involves highly sophisticated and synthetically costly building blocks. The small size of the microfluidic structure is crucial in bringing the time scale for kinetic monitoring down to seconds. At the same time, the transmission line NMR probe provides sufficient sensitivity to work at low (2 mM) concentrations.

Wirelessly powered and remotely controlled valve-array for highly multiplexed analytical assay automation on a centrifugal microfluidic platform

Saraí M. Torres Delgado, David J. Kinahan, Lourdes Albina Nirupa Julius, Adam Mallette, David Sáenz Ardila, Rohit Mishra, Celina M. Miyazaki, Jan G. Korvink, Jens Ducrée, Dario Mager

Biosensors and Bioelectronics, 2019

In this paper we present a wirelessly powered array of 128 centrifugo-pneumatic valves that can be thermally actuated on demand during spinning. The valves can either be triggered by a predefined protocol, wireless signal transmission via Bluetooth, or in response to a sensor monitoring a parameter like the temperature, or homogeneity of the dispersion. Upon activation of a resistive heater, a low-melting membrane (Parafilm™) is removed to vent an entrapped gas pocket, thus letting the incoming liquid wet an intermediate dissolvable film and thereby open the valve. The proposed system allows up to 12 heaters to be activated in parallel, with a response time below 3‚ÄĮs, potentially resulting in 128 actuated valves in under 30‚ÄĮs. We demonstrate, with three examples of common and standard procedures, how the proposed technology could become a powerful tool for implementing diagnostic assays on Lab-on-a-Disc. First, we implement wireless actuation of 64 valves during rotation in a freely programmable sequence, or upon user input in real time. Then, we show a closed-loop centrifugal flow control sequence for which the state of mixing of reagents, evaluated from stroboscopically recorded images, triggers the opening of the valves. In our last experiment, valving and closed-loop control are used to facilitate centrifugal processing of whole blood.

Murine precision-cut liver slices as a disease model to predict drug-induced cholestasis

Ruby E.H. Karsten. Maciej Grajewski, Gert IJ. Salentijn, Viktoriia Starokozkho, Elisabeth Verpoorte, Peter Olinga

University of Groningen

SLAS 2018

Develop a disease model to study drug-induced cholestasis in precision-cut liver slices (PCLS) in real time

Murine precision-cut liver slices as a disease model to predict drug-induced cholestasis

New Windows into Life: Symposium on Tissue Culture and Magnetic Resonance

A selection of photos from the very successful TISuMR Symposium held 24-27th September at Marwell Hotel, Winchester.

 

Manvendra Sharma

Manvendra Sharma is a senior research fellow in Chemistry at the University of Southampton . ¬†From 2012 to 2016 he was a PhD student at Radboud University, Nijmegen in Prof. Arno Kentgens group. Manvendra’s PhD research was based on Dynamic nuclear polarisation to increase the sensitivity of NMR. In his current project Manvendra will be mainly focusing on development of microfluidic¬†NMR devices for biological samples. His research interests are microfluidics, NMR, NMR hardware, and dynamic nuclear polarisation.

Bishnubrata Patra

Bishnubrata Patra is a research fellow in the Dept of Chemistry at the University of Southampton. He completed his Ph.D. at National Yang-Ming University, Taiwan in Biophotonics and Bio-engineering. Bishnubrata’s main interests are designing microfluidic devices for tissue/ cellular spheroid culture and integrating them with NMR spectroscopy.

Anna Zakhurdaeva

Anna Zakhurdaeva received her BSc degree (2014) in Applied Mathematics and Physics from Moscow Institute of Physics and Technology, Russia, and her MSc degree (2017) in Optics and Photonics from Karlsruhe Institute of Technology, Germany. Her MSc thesis was dedicated to the fabrication and characterization of custom made carbon tips for atomic force microscopy.  In June, 2017 she began her graduate studies under the supervision of Prof. Jan Korvink. Her contribution to the TISuMR project will be the design and fabrication of Lab-On-a-Disc system compatible with NMR/MRI measurements.

TISuMR 1: Symposium Confirmed Speakers

We are delighted to announce the following have accepted an invitation to speak at TISuMR 1: Symposium On Tissue Culture and Magnetic Resonance:

Prof Thomas Gervias,  Montreal Polytechnic

Prof J√ľrgen Hennig, University of Freiburg

Prof Arno Kentgens, Radboud University, Nijmegen

Prof Salim Khakoo, University of Southampton

Dr Viktoriia Starokozhko, University of Groningen

Dr Matthias Worgull, Karlshruhe Institute of Technology

If you are interested in attending the conference please contact us at tisumr@soton.ac.uk

 

 

Groningen’s role in the project

At the University of Groningen, Verpoorte and colleagues will develop an innovative technology platform that integrates nuclear magnetic resonance metabolomics and micro-imaging with microfluidic tissue-slice perfusion culture. This platform is poised to revolutionise life science research by providing unprecedented local insight into physiological processes in intact tissues under highly controlled conditions. The team will focus on liver tissue-slice culture, with the immediate target of elucidating the mechanism of liver damage by drug-induced cholestasis. In the long term, the new technology will find wide application in other tissues, including intestinal, pancreatic, and brain slices. It will form the foundation of a new approach in the life sciences, allowing the detailed metabolic study of tissues at the system level.