arXiv subjects

William Hale

Publications and source records attributed to William Hale.

4 recordsLinked to original sources

arXiv2022

Direct Production of A Hyperpolarized Metabolite on a Microfluidic Chip

Microfluidic systems hold great potential for the study of live microscopic cultures of cells, tissue samples, and small organisms. Integration of hyperpolarisation would enable quantitative studies of metabolism in such volume limited systems by high-resolution NMR spectroscopy. We demonstrate, for the first time, the integrated generation and detection of a hyperpolarised metabolite on a microfluidic chip. The metabolite 1-$^{13}$C-fumarate is produced in a nuclear hyperpolarised form by (i) introducing para-enriched hydrogen into the solution by diffusion through a polymer membrane, (ii) reaction with a substrate in the presence of a ruthenium-based catalyst, and (iii) conversion of the singlet-polarised reaction product into a magnetised form by the application of a radiofrequency pulse sequence, all on the same microfluidic chip. The microfluidic device delivers a continuous flow of hyperpolarised material at the 2.5 $μ\text{L}/\text{min}$ scale, with a polarisation level of 4%. We demonstrate two methods for mitigating singlet-triplet mixing effects which otherwise reduce the achieved polarisation level.

physics.chem-ph↗

arXiv2021

Synergies between Hyperpolarized NMR and Microfluidics: A Review

Hyperpolarized nuclear magnetic resonance and lab-on-a-chip microfluidics are two dynamic, but until recently quite distinct, fields of research. Recent developments in both areas increased their synergistic overlap. By microfluidic integration, many complex experimental steps can be brought together onto a single platform. Microfluidic devices are therefore increasingly finding applications in medical diagnostics, forensic analysis, and biomedical research. In particular, they provide novel and powerful ways to culture cells, cell aggregates, and even functional models of entire organs. Nuclear magnetic resonance is a non-invasive, high-resolution spectroscopic technique which allows real-time process monitoring with chemical specificity. It is ideally suited for observing metabolic and other biological and chemical processes in microfluidic systems. However, its intrinsically low sensitivity has limited its application. Recent advances in nuclear hyperpolarization techniques may change this: under special circumstances, it is possible to enhance NMR signals by up to 5 orders of magnitude, which dramatically extends the utility of NMR in the context of microfluidic systems. At the same time, hyperpolarization requires complex chemical and/or physical manipulations, which in turn may benefit from microfluidic implementation. In fact, many hyperpolarization methodologies rely on processes that are more efficient at the micro-scale, such as molecular diffusion, penetration electromagnetic radiation into the sample, or restricted molecular mobility on a surface. In this review we examine the confluence between the fields of hyperpolarization-enhanced NMR and microfluidics, and assess how these areas of research have mutually benefited one another, and will continue to do so.

physics.chem-ph↗

arXiv2019

High-Resolution Nuclear Magnetic Resonance Spectroscopy With Picomole Sensitivity by Hyperpolarisation On A Chip

We show that high-resolution NMR can reach picomole sensitivity for micromolar concentrations of analyte by combining parahydrogen induced hyperpolarisation (PHIP)with a high-sensitivity transmission line micro-detector. The para-enriched hydrogen gas is introduced into solution by diffusion through a membrane integrated into a microfluidic chip. NMR microdetectors, operating with sample volumes of a few $μ$L or less, benefit from a favourable scaling of mass sensitivity. However, the small volumes make it very difficult to detect species present at less than millimolar concentrations in microfluidic NMR systems. In view of overcoming this limitation, we implement parahydrogen-induced polarisation (PHIP) on a microfluidic device with 2.5~$\mathrm{μL}$ detection volume. Integrating the hydrogenation reaction into the chip minimises polarisation losses to spin-lattice relaxation, allowing the detection of picomoles of substance. This corresponds to a concentration limit of detection of better than $\mathrm{1\,μM\,\sqrt{s}}$, unprecedented at this sample volume. The stability and sensitivity of the system allows quantitative characterisation of the signal dependence on flow rates and other reaction parameters and permits homo- and heteronuclear 2D NMR experiments at natural $^{13}\mathrm{C}$ abundance.

physics.chem-ph↗

arXiv2016

Remixing as a Pathway to Computational Thinking

Theorists and advocates of "remixing" have suggested that appropriation can act as a pathway for learning. We test this theory quantitatively using data from more than 2.4 million multimedia programming projects shared by more than 1 million users in the Scratch online community. First, we show that users who remix more often have larger repertoires of programming commands even after controlling for the numbers of projects and amount of code shared. Second, we show that exposure to computational thinking concepts through remixing is associated with increased likelihood of using those concepts. Our results support theories that young people learn through remixing, and have important implications for designers of social computing systems.

cs.CY↗