Revolutionising Tissue Culture With NMR
Jan G. Korvink, Neil MacKinnon, Vlad Badilita, Mazin Jouda
Journal of Magnetic Resonance, 2019
In this prospective paper we consider the opportunities and challenges of miniaturized nuclear magnetic resonance. As the title suggests, (irreverently borrowing from E.F. Schumacherâs famous book), miniaturized NMR will feature a few small windows of opportunity for the analyst. We look at what these are, speculate on some open opportunities, but also comment on the challenges to progress.
James Eills, William Hale, Manvendra Sharma, Matheus Rossetto, Malcolm H. Levitt and Marcel Utz
Journal of the American Chemical Society, 2019
We show that high-resolution NMR can reach picomole sensitivity for micromolar concentrations of analyte by combining parahydrogen-induced hyperpolarization (PHIP) with a high-sensitivity transmission line microdetector. 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 ÎŒL or less, benefit from a favorable 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 PHIP on a microfluidic device with a 2.5 ÎŒL detection volume. Integrating the hydrogenation reaction into the chip minimizes polarization losses to spinâlattice relaxation, allowing the detection of picomoles of substance. This corresponds to a concentration limit of detection of better than 1 ÎŒM s , unprecedented at this sample volume. The stability and sensitivity of the system allow quantitative characterization of the signal dependence on flow rates and other reaction parameters and permit homo- (1Hâ1H) and heteronuclear (1Hâ13C) 2D NMR experiments at natural 13C abundance.
Yongbo Deng, Zhenyu Liu, Yasi Wang, Huigao Duan, Jan G. Korvink
Aplied Mathematical Modelling, 2019
Robust CassieâBaxter wettability of a rough solid surface with micro-textures is a key factor for stable hydrophobicity. Overlayed micro-textures are potentially more effective in ensuring the robustness of the surface properties, because of the layer-by-layer increase of the duty ratio and their effective approximation of the full hierarchy. However, a design methodology that includes considering manufacturability is lacking. In this article, we address this deficiency and present a monolithic inverse design approach, composed of a series of topology optimizations, to derive micro-textures with hierarchy approximated by overlayed geometries. The optimization are implemented in a dimensionless manner using a periodic regular-polygon tiling of the plane, in which the corresponding dimensionless Young-Laplace equation is used to describe the physics at the liquid/vapor interface. Two sequential and neighboring optimization tasks are linked through the design domain of the downward layer, determined by a conformal extension of the physical density representing the pattern of the upward layer. This ensures the manufacturability e.g. for an overlayed lithography process. Layer-by-layer robustness enhancement is thereby achieved, and the capability to anchor the three-phase contact line after the collapse of the liquid/vapor interface supported by the upward layer. In generating the overlayed micro-textures, a rigorous scaling factor for the patterns was determined, leading to a recursion inequality based on the depth of the liquid/vapor interfaces at the critical static pressures that determines the extrusion distance of the patterns. The trace height and minimal aspect ratio of the micro-textures are specified by the scaling factor and extrusion distance for a layer. This allows a compromise between performance and manufacturability, and thereby avoid instabilities caused by elasto-capillary collapse of the micro-/nano-structures. We computationally confirm the optimality by comparing the derived micro-textures with previously reported designs.
Hossein Davoodi, Mazin Jouda, Jan G. Korvink, Neil MacKinnon, Vlad Badilita
Progress in Nuclear Magnetic Resonance Spectroscopy, 2019
It has always been of considerable interest to study the nuclear magnetic resonance response of multiple nuclei simultaneously, whether these signals arise from internuclear couplings within the same molecule, or from uncoupled nuclei within sample mixtures. The literature contains numerous uncorrelated reports on techniques employed to achieve multi-nuclear NMR detection. This paper consolidates the subset of techniques in which single coil detectors are utilized, and highlights the strengths and weaknesses of each approach, at the same time pointing the way towards future developments in the field of multi-nuclear NMR. We compare the different multi-nuclear NMR techniques in terms of performance, and present a guide to NMR probe designers towards application-based optimum design. We also review the applicability of micro-coils in the context of multi-nuclear methods. Micro-coils benefit from compact geometries and exhibit lower impedance, which provide new opportunities and challenges for the NMR probe designer.
Manvendra Sharma, Marcel Utz
Journal of Magnetic Resonance, 2019
Microfluidic NMR spectroscopy can probe chemical and bio-chemical processes non-invasively in a tightly controlled environment. We present a dual-channel modular probe assembly for high efficiency microfluidic NMR spectroscopy and imaging. It is compatible with a wide range of microfluidic devices, without constraining the fluidic design. It collects NMR signals from a designated sample volume on the device with high sensitivity and resolution. Modular design allows adapting the detector geometry to different experimental conditions with minimal cost, by using the same probe base. The complete probe can be built from easily available parts. The probe body mainly consists of prefabricated aluminium profiles, while the probe circuit and detector are made from printed circuit boards. We demonstrate a double resonance HX probe with a limit of detection of 1.4âŻnmolâŻsâ1/2 for protons at 600âŻMHz, resolution of 3.35âŻHz, and excellent B1homogeneity. We have successfully acquired 1H-13C and 1H-15N heteronuclear correlation spectra (HSQC), including a 1H-15N HSQC spectrum of 1âŻmM 15N labeled ubiquitin in 2.5âŻÎŒl of sample volume.
Complex mixtures, commonly encountered in metabolomics and food analytics, are now routinely measured by nuclear magnetic resonance (NMR) spectroscopy. Since many samples must be measured, onedimensional proton (1D 1H) spectroscopy is the experiment of choice. A common challenge in complex mixture 1H NMR spectroscopy is spectral crowding, which limits the assignment of molecular components to those molecules in relatively high abundance. This limitation is exacerbated when the sample quantity itself is limited and concentrations are reduced even further during sample preparation for routine measurement. To address these challenges, we report a novel microfluidic NMR platform integrating signal enhancement via parahydrogen induced hyperpolarisation. The platform simultaneously addresses the challenges of handling small sample quantities through microfluidics, the associated decrease in signal given the reduced sample quantity by Signal Amplification by Reversible Exchange (SABRE), and overcoming spectral crowding by taking advantage of the chemosensing aspect of the SABRE effect. SABRE at the microscale is enabled by an integrated PDMS membrane alveolus, which provides bubble-free hydrogen gas contact with the sample solution. With this platform, we demonstrate high field NMR chemosensing of microliter sample volumes, nanoliter detection volumes, and micromolar concentrations corresponding to picomole molecular sensitivity.
Mazin Jouda*, Erwin Fuhrer, Pedro Silva, Jan G. Korwink and Neil Mac Kinnon*
The decaying nature of magnetic resonance (MR) signals results in a decreasing signal-to-quantization noise ratio (SQNR) over the acquisition time. Here we describe a method to enhance the SQNR, and thus the overall signal-to-noise ratio (SNR), by dynamically adapting the gain of the receiver before analog-to-digital conversion (ADC). This is in contrast to a standard experiment in which the gain is fixed for a single data acquisition and is thus adjusted only for the first points of the signal. The gain adjustment in our method is done automatically in a closed loop fashion by using the envelope of the MR signal as the control signal. Moreover, the method incorporates a robust mechanism that runs along with signal acquisition to monitor the gain modulation, enabling precise recovery of the signals. The automatic adaptive gain (AGAIN) method requires minimal additional hardware and is thus general and can be implemented in the signal path of any commercial spectrometer system. We demonstrate an SNR enhancement factor of 2.64 when applied to a custom spectrometer, while a factor of 1.4 was observed when applied to a commercial spectrometer.
SaraĂ M. Torres Delgado, Jan G. Korvink, Dario Mager,*
In this paper we present a comprehensive description of the design, fabrication and operation of an electrified Lab-on-a-Disc (eLoaD) system. The smart platform is developed to extend conventional Lab-on-a-Disc applications with an electronic interface, providing additional flow control and sensing capabilities to centrifugal microfluidics platforms. Wireless power is transferred from a Qi-compliant transmitter to the eLoaD platform during rotation. An Arduino-based microcontroller, a Bluetooth communication module, and an on-board SD-card are integrated into the platform. This generalises the applicability of the eLoaD and its modules for performing a wide range of laboratory unit operations, procedures, or diagnostic assays, all controlled wirelessly during spinning. The lightweight platform is fully reusable and modular in design and construction. An interchangeable and non-disposable application disc is fitted with the necessary sensors and/or actuators for a specific assay or experiment to be performed. A particular advantage is the ability to continuously monitor and interact with LoaD experiments, overcoming the limitations of stroboscopy. We demonstrate the applicability of the platform for three sensing experiments involving optical, electrochemical, and temperature detection, and one actuation experiment involving controlled heating/cooling. The complete electronic designs and example programming codes are extensively documented in the supplementary material for easy adaptation.
William Hale, Gabriel Rossetto, Rachael Greenhalgh, Graeme Finch and Marcel Utz*
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 t
