NMR imaging of flow:mapping velocities inside microfluidic devices and sequence development

Abstract The subject of this thesis is flow imaging by methods based on the nuclear magnetic resonance (NMR) phenomenon. The thesis consists of three related topics: In the first one the feasibility of measuring velocity maps and distributions inside a microfluidic device by pulsed field gradient (PFG) NMR has been demonstrated. The second topic was to investigate microfluidic gas flow using a combination of a special detection technique and a powerful signal enhancement method. The third topic is related to the unambiguous determination of velocities under challenging experimental conditions and introduces a new, improved velocity imaging sequence. In the first part, well established imaging methods have been used to study water flow inside a micromixer. A surface coil matching the region of interest of the mixer was home built and used in the measurements in order to gain a better signal-to-noise ratio. Velocities inside the mixer have been measured by phase-encoding velocity, with unprecedented spatial resolution. Two dimensional NMR imaging and velocity maps revealed clogging and different manufacturing qualities of the mixers. In addition to the velocity maps, which display an average velocity for spins within one pixel, complete velocity distributions (so called average propagators) were measured. It was found that in the absence of spatial resolution in the third dimension, the propagator data can provide valuable insight to the flow system by revealing overlapping flow passages. The next topic was gas flow inside a microfluidic device. It was investigated by time-of-flight flow imaging. The measurement of the weak gas signal was enabled by the use of two signal enhancement techniques: remote detection NMR and parahydrogen induced polarization (PHIP). The results demonstrate that a very significant signal enhancement can be achieved by this technique. In the future it may enable the investigation of interesting chemical reactions inside microreactors. The third and last topic of the thesis deals with measuring flow by the so called multiecho sequences. When multiecho sequences are used in combination with phase encoding velocity, an error may be introduced: the multiecho sequence may produce a cumulative error to the phase of the magnetization, if it is sensitive to RF pulse imperfections. The problem has been elaborately explained and various solutions discussed, among the newly proposed one. Experimental results demonstrate the performance of the new velocity imaging sequence and show that the new sequence enables the unambiguous determination of velocities even in challenging experimental conditions resulting from inhomogeneous radio frequency fields of the measurement coils

Digitaalista pedagogiikkaa:opettaja ja oppija muuttuvissa työskentely-ympäristöissä

Abstract This work focuses on digital pedagogy in changing work environments from the perspectives of the teacher and the learner. Digitalization has strongly shaped the practices of the education sector, which has created increasing pressure for change, especially for teachers. Smooth practices and functional digital pedagogy are more important than ever before. This work is intended as learning material for teachers who wish to develop their own digital pedagogical competence and skills to operate in diverse learning environments in a way that serves learning. The contents of this work are based on the “Teacher's digital pedagogical skills in distance and hybrid environments (‘DigiPeda’)” project at the University of Oulu, which was funded by the European Social Fund and the Northern Ostrabothnian Centre for Economic Development, Transport, and the Environment. The project aimed to support the professional development and well-being of teachers in changing working environments. The authors of the publication are teachers, experts in learning research and personnel of the DigiPeda project. The work is divided into four parts, the first of which focuses on digital pedagogical perspectives and the use of technology in teaching during distance and hybrid education, as well as on the teacher's digital competence frameworks. Part 2 provides a research-based overview of learning skills, well-being, and emotions, as well as the growth mindset as part of distance and hybrid education. Part 3 consists of case reports of teachers during the distance education transition and a description of the continuing learning course implemented in the DigiPeda project. Finally, an outlook of a new learning culture encouraged by diversifying modes of teaching is provided. The chapters include a diverse range of perspectives from experts on digital pedagogy as part of the teacher's work. The central cross-cutting theme of this publication is the change in working and learning environments. Teachers' and learners' skills required to operate in diverse working environments are constantly evolving, and new practices are laying the foundation for future education.Tiivistelmä Tämä teos käsittelee digipedagogiikkaa muuttuvissa työympäristöissä opettajan ja oppijan näkökulmista. Digitalisaatio on muokannut koulutussektorin käytänteitä voimakkaasti, mikä on luonut kasvavia muutospaineita erityisesti opettajille. Sujuvat käytännöt ja toimiva digipedagogiikka ovat tärkeämpiä kuin koskaan ennen. Tämä teos on suunnattu oppimateriaaliksi opettajille, jotka haluavat kehittää omaa digipedagogista osaamistaan ja taitojaan toimia monimuotoisissa oppimisympäristöissä oppimista palvelevalla tavalla. Teoksen sisältö pohjaa vuoden 2020 koronaviruspandemian siivittämään etä- ja hybridiopetussiirtymään sekä Euroopan sosiaalirahaston ja Pohjois-Pohjanmaan ELY-keskuksen rahoittamaan Oulu yliopiston Opettajan digipedagogiset taidot etä- ja hybridityöskentelyssä (”DigiPeda”) -hankkeeseen, jonka tavoitteena oli tukea opettajien ammattitaidon kehittymistä ja hyvinvointia muuttuvissa työskentely-ympäristöissä. Julkaisun kirjoittajat ovat opettajia, oppimisen tutkimuksen asiantuntijoita sekä DigiPeda-hankkeen henkilöstöä. Teos jakautuu neljään osaan, joista ensimmäinen keskittyy digipedagogisiin näkökulmiin ja teknologian hyödyntämiseen opetuksessa etä- ja hybridiopetuksen aikana sekä opettajan digitaalisen osaamisen viitekehyksiin. Toisessa osassa tehdään tutkimustietoon perustuva katsaus erityisesti oppimisen taitoihin, hyvinvointiin ja tunteisiin sekä kasvun ajattelutapaan osana etä- ja hybridiopetusta. Kolmas osa koostuu opettajien tapauskertomuksista etäopetussiirtymän ajalta sekä DigiPeda-hankkeessa toteutetun täydennyskoulutuksen kuvauksesta. Lopuksi luodaan katse kohti monimuotoistuvan opetuksen kannustamaa uudenlaista oppimiskulttuuria. Osiot sisältävät monipuolisen kattauksen asiantuntijoiden näkökulmia digipedagogiikkaan osana opettajan työtä. Julkaisun keskeisenä läpileikkaavana teemana on työ- ja oppimisympäristöjen muutos. Opettajien ja oppijoiden tarvitsemat taidot monimuotoisissa työskentely-ympäristöissä toimimiseen kehittyvät jatkuvasti, ja uudet käytänteet luovat pohjan tulevaisuuden koulutukselle

Ultrafast NMR diffusion measurements exploiting chirp spin echoes

Abstract Standard diffusion NMR measurements require the repetition of the experiment multiple times with varying gradient strength or diffusion delay. This makes the experiment time-consuming and restricts the use of hyperpolarized substances to boost sensitivity. We propose a novel single-scan diffusion experiment, which is based on spatial encoding of two-dimensional data, employing the spin-echoes created by two successive adiabatic frequency-swept chirp π pulses. The experiment is called ultrafast pulsed-field-gradient spin-echo (UF-PGSE). We present a rigorous derivation of the echo amplitude in the UF-PGSE experiment, justifying the theoretical basis of the method. The theory reveals also that the standard analysis of experimental data leads to a diffusion coefficient value overestimated by a few per cent. Although the overestimation is of the order of experimental error and thus insignificant in many practical applications, we propose that it can be compensated by a bipolar gradient version of the experiment, UF-BP-PGSE, or by corresponding stimulated-echo experiment, UF-BP-pulsed-field-gradient stimulated-echo. The latter also removes the effect of uniform background gradients. The experiments offer significant prospects for monitoring fast processes in real time as well as for increasing the sensitivity of experiments by several orders of magnitude by nuclear spin hyperpolarization. Furthermore, they can be applied as basic blocks in various ultrafast multidimensional Laplace NMR experiments

Ultrafast Laplace NMR with hyperpolarized xenon gas

Abstract Laplace NMR, consisting of diffusion and relaxation experiments, provides detailed information about dynamics of fluids in porous materials. Recently, we showed that two-dimensional Laplace NMR experiments can be carried out with a single scan based on spatial encoding. The method shortens the experiment time by one to three orders of magnitude, and therefore it is called ultrafast Laplace NMR. Furthermore, the single-scan approach facilitates significantly the use of nuclear spin hyperpolarization for boosting the sensitivity of the experiment, because a laborious hyperpolarization procedure does not need to be repeated. Here, we push the limits of the ultrafast Laplace NMR method by applying it, for the first time, in the investigation of a gas phase substance, namely hyperpolarized xenon gas. We show that, regardless of the fast diffusion of gas, layer-like spatial encoding is feasible, and an ultrafast diffusion — T2 relaxation correlation experiment reveals significantly different signals of free gas and gas adsorbed in a mesoporous controlled pore glass (CPG). The observed diffusion coefficients are many orders of magnitude larger than those detected earlier from liquid phase substances, emphasizing the extended application range of the method. The challenges in the methodology, caused by the fast diffusion, are also discussed

²¹Ne and ¹³¹Xe NMR study of electric field gradients and multinuclear NMR study of the composition of a ferroelectric liquid crystal

Abstract This study has two goals. First, the electric field gradient (EFG) present in the liquid-crystalline phases of ferroelectric FELIX-R&D is determined using NMR spectroscopy of noble gases ²¹Ne and ¹³¹Xe. The ²¹Ne and ¹³¹Xe NMR spectra were recorded over a temperature range, which covers all the mesophases of FELIX-R&D: nematic N*, smectic A, and smectic C*. The spin quantum number of both ²¹Ne and ¹³¹Xe is 3/2. Their electric quadrupole moment interacts with the EFG at the nuclear site, which in liquid-crystalline phases results in the NMR spectra of the triplet structure, instead of a singlet detectable in the isotropic phase. The total EFG experienced by the noble gas nuclei consists of two contributions; one arises from the quadrupole moments of the liquid crystal molecules (external contribution) and the other one from the deformation of the electron distribution of the atoms (deformational contribution). The total EFGs determined from the ¹³¹Xe and ²¹Ne quadrupole splittings are very similar in the nematic and smectic A phases but differ in the smectic C* phase, being about twice larger in the ²¹Ne case which stems from the larger deformation of the xenon electron cloud than that of neon. For the first time, EFG was determined also in the smectic C* phase applying noble gas NMR spectroscopy. Second, the structure of molecules which, as a mixture, compose the used ferroelectric liquid crystal, FELIX-R&D, is determined by applying a number of various NMR methods and sophisticated spectral analysis. In this part, NMR spectra were recorded from FELIX-R&D/CDCl3 solution. The NMR spectral analysis was divided into four subsystems with over 13 000 000 nonzero intensity transitions. It appeared that FELIX-R&D is composed of three phenyl pyrimidine derivatives and a chiral dopant with fluorine in the asymmetric carbon atom

Identification of intracellular and extracellular metabolites in cancer cells using ¹³C hyperpolarized ultrafast laplace NMR

Abstract Ultrafast Laplace NMR (UF-LNMR), which is based on the spatial encoding of multidimensional data, enables one to carry out 2D relaxation and diffusion measurements in a single scan. Besides reducing the experiment time to a fraction, it significantly facilitates the use of nuclear spin hyperpolarization to boost experimental sensitivity, because the time-consuming polarization step does not need to be repeated. Here we demonstrate the usability of hyperpolarized UF-LNMR in the context of cell metabolism, by investigating the conversion of pyruvate to lactate in the cultures of mouse 4T1 cancer cells. We show that ¹³C ultrafast diffusion–T₂ relaxation correlation measurements, with the sensitivity enhanced by several orders of magnitude by dissolution dynamic nuclear polarization (D-DNP), allows the determination of the extra- vs intracellular location of metabolites because of their significantly different values of diffusion coefficients and T₂ relaxation times. Under the current conditions, pyruvate was located predominantly in the extracellular pool, while lactate remained primarily intracellular. Contrary to the small flip angle diffusion methods reported in the literature, the UF-LNMR method does not require several scans with varying gradient strength, and it provides a combined diffusion and T₂ contrast. Furthermore, the ultrafast concept can be extended to various other multidimensional LNMR experiments, which will provide detailed information about the dynamics and exchange processes of cell metabolites

Characterization of the decay process of Scots pine caused by Coniophora puteana using NMR and MRI

Abstract Wood decay is an economically significant process, as it is one of the major causes of wood deterioration in buildings. In this study, the decay process of Scots pine (Pinus sylvestris) samples caused by cellar fungus (Coniophora puteana) was followed by nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging (MRI) methods. Altogether, 30 wood sample pieces were exposed to fungus for 10 weeks. Based on the decrease of the dry mass, the samples were categorized into three classes: decomposed (mass decrease 50–70%), slightly decomposed (10–50%), and nondecomposed (<10%). MRI made it possible to identify the active regions of fungus inside the wood samples based on the signal of free water brought by the fungus and arisen from the decomposition of wood carbohydrates. MRI implies that free water is not only created by the decay process, but fungal hyphae also transports a significant amount of water into the sample. Two-dimensional ¹H T₁-T₂ relaxation correlation NMR measurements provided detailed information about the changes in the microstructure of wood due to fungal decomposition. Overall, this study paves the way for noninvasive NMR and MRI detection of fungal decay at early stages as well as the related structural changes

Ultrafast diffusion exchange nuclear magnetic resonance

Abstract The exchange of molecules between different physical or chemical environments due to diffusion or chemical transformations has a crucial role in a plethora of fundamental processes such as breathing, protein folding, chemical reactions and catalysis. Here, we introduce a method for a single-scan, ultrafast NMR analysis of molecular exchange based on the diffusion coefficient contrast. The method shortens the experiment time by one to four orders of magnitude. Consequently, it opens the way for high sensitivity quantification of important transient physical and chemical exchange processes such as in cellular metabolism. As a proof of principle, we demonstrate that the method reveals the structure of aggregates formed by surfactants relevant to aerosol research

Structure and dynamics elucidation of ionic liquids using multidimensional Laplace NMR

Abstract We demonstrate the ability of multidimensional Laplace NMR (LNMR), comprising relaxation and diffusion experiments, to reveal essential information about microscopic phase structures and dynamics of ionic liquids that is not observable using conventional NMR spectroscopy or other techniques

Ultrafast multidimensional Laplace NMR for a rapid and sensitive chemical analysis

Abstract Traditional nuclear magnetic resonance (NMR) spectroscopy relies on the versatile chemical information conveyed by spectra. To complement conventional NMR, Laplace NMR explores diffusion and relaxation phenomena to reveal details on molecular motions. Under a broad concept of ultrafast multidimensional Laplace NMR, here we introduce an ultrafast diffusion-relaxation correlation experiment enhancing the resolution and information content of corresponding 1D experiments as well as reducing the experiment time by one to two orders of magnitude or more as compared with its conventional 2D counterpart. We demonstrate that the method allows one to distinguish identical molecules in different physical environments and provides chemical resolution missing in NMR spectra. Although the sensitivity of the new method is reduced due to spatial encoding, the single-scan approach enables one to use hyperpolarized substances to boost the sensitivity by several orders of magnitude, significantly enhancing the overall sensitivity of multidimensional Laplace NMR