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Details of Grant 

EPSRC Reference: EP/W020343/1
Title: Parahydrogen-Induced Hyperpolarisation For Microfluidic Perfusion Culture
Principal Investigator: Utz, Professor M
Other Investigators:
Whitby, Professor RJ Kuprov, Dr I Levitt, Professor MH
Researcher Co-Investigators:
Project Partners:
Max Planck Institutes
Department: Sch of Chemistry
Organisation: University of Southampton
Scheme: Standard Research
Starts: 16 May 2022 Ends: 15 November 2025 Value (£): 1,213,199
EPSRC Research Topic Classifications:
Analytical Science Chemical Synthetic Methodology
Gas & Solution Phase Reactions Microsystems
Quantum Optics & Information
EPSRC Industrial Sector Classifications:
No relevance to Underpinning Sectors
Related Grants:
Panel History:
Panel DatePanel NameOutcome
08 Dec 2021 EPSRC Physical Sciences December 2021 Announced
Summary on Grant Application Form
Nuclear magnetic resonance (NMR) is one of the most powerful tools for

investigating the structure, composition, and dynamics of living and non-living

matter. Its sensitivity is limited by the degree of alignment of nuclear spins,

which is small even in the strongest magnets. Hyperpolarisation techniques

such as parahydrogen-induced polarisation can produce much better spin

alignments, offering corresponding increases in sensitivity.

paraQchip aims provide lab-on-a-chip (LoC) cultures of cells with hyperpolarised

metabolites (pyruvate, fumarate) for high-sensitivity NMR monitoring of metabolism,

by integrating all steps of parahydrogen-induced polarisation (PHIP) onto the

chip. To this end, we propose an interdisciplinary research programme that uses

quantitative modelling of spin dynamics, transport, and kinetic processes

in tandem with experimental quantification of reaction and transport kinetics to

inform the design of the microfluidic chip layout, NMR detector, radiofrequency

pulse sequences, and operation parameters such as flow rates, reagent concentrations,

solvents, and temperature. The main challenge lies in the concerted operation

of the hydrogenation, polarisation transfer, and purification steps, which

must all be completed before nuclear relaxation destroys the hyperpolarisation.

The proposed research consists of four work packages, each led by one

of the Co-PIs. WP 1 (Kuprov) focusses on modelling, using a novel approach

that treats spin and spatial degrees of freedom on an equal footing.

WP 2 (Levitt) deals with the required transfer of polarisation from the

parahydrogen spin order to the target metabolite. This requires design

of a novel microfluidic NMR probe system with separate detectors for

the transfer step and for downstream observation. WP 3 (Whitby) will focus

on the chemical aspects, including hydrogenation, cleavage, and purification.

Finally, WP 4 (Utz) deals with the microfluidic integration of these steps.

LoC devices provide detailed control over the growth conditions of cells,

tissues ("organ-on-a-chip"), and small organisms, providing valuable models

supporting the development of diagnostics and therapies, and drug safety

testing. NMR spectroscopy could be of great use in this context, as it allows

non-invasive quantification of metabolic processes. However, the limited

sensitivity of conventional NMR is exacerbated at the microlitre volume

scale of LoC devices. paraQchip will address that, pushing the limit

of detection from the millimolar concentration range down to micromolar. This will

allow detailed in-situ observation of metabolic processes in microfluidic

cell cultures as well as tissue and organ models, with many applications

in disease modelling, drug testing, and other aspects of the life sciences.

Microfluidic implementation of PHIP will also lead to deeper understanding

of the interplay between the hydrogenation reaction mechanism and nuclear

spin relaxation processes. The computational tools developed and validated

through paraQchip will benefit the development of hyperpolarised magnetic

resonance imaging techniques.

Key Findings
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Potential use in non-academic contexts
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Date Materialised
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Further Information:  
Organisation Website: http://www.soton.ac.uk