Microfluidic control over topological states in channel-confined nematic flows

Compared to isotropic liquids, orientational order of nematic liquid crystals makes their rheological properties more involved, and thus requires fine control of the flow parameters to govern the orientational patterns. In microfluidic channels with perpendicular surface alignment, nematics discontinuously transition from perpendicular structure at low flow rates to flow-aligned structure at high flow rates. Here we show how precise tuning of the driving pressure can be used to stabilize and manipulate a previously unresearched topologically protected chiral intermediate state which arises before the homeotropic to flow-aligned transition. We characterize the mechanisms underlying the transition and construct a phenomenological model to describe the critical behaviour and the phase diagram of the observed chiral flow state, and evaluate the effect of a forced symmetry breaking by introduction of a chiral dopant. Finally, we induce transitions on demand through channel geometry, application of laser tweezers, and careful control of the flow rate

Functional soft materials from blue phase liquid crystals

Blue phase (BP) liquid crystals are chiral fluids wherein millions of molecules self-assemble into cubic lattices that are on the order of hundred nanometers. As the unit cell sizes of BPs are comparable to the wavelength of light, they exhibit selective Bragg reflections in the visible. The exploitation of the photonic properties of BPs for technological applications is made possible through photopolymerization, a process that renders mechanical robustness and thermal stability. We review here the preparation and characterization of stimuli-responsive, polymeric photonic crystals based on BPs. We highlight recent studies that demonstrate the promise that polymerized BP photonic crystals hold for colorimetric sensing and dynamic light control. We review using Landau–de Gennes simulations for predicting the self-assembly of BPs and the potential for using theory to guide experimental design. Finally, opportunities for using BPs to synthesize new soft materials, such as highly structured polymer meshes, are discussed

Sculpting stable structures in pure liquids

Pure liquids in thermodynamic equilibrium are structurally homogeneous. In liquid crystals, flow and light pulses are used to create reconfigurable domains with polar order. Moreover, through careful engineering of concerted microfluidic flows and localized optothermal fields, it is possible to achieve complete control over the nucleation, growth, and shape of such domains. Experiments, theory, and simulations indicate that the resulting structures can be stabilized indefinitely, provided the liquids are maintained in a controlled nonequilibrium state. The resulting sculpted liquids could find applications in microfluidic devices for selective encapsulation of solutes and particles into optically active compartments that interact with external stimuli

Alterations in immunophenotype and metabolic profile of mononuclear cells during follow up in children with multisystem inflammatory syndrome (MIS-C)

IntroductionAlthough children seem to be less susceptible to COVID-19, some of them develop a rare but serious hyperinflammatory condition called multisystem inflammatory syndrome in children (MIS-C). While several studies describe the clinical conditions of acute MIS-C, the status of convalescent patients in the months after acute MIS-C is still unclear, especially the question of persistence of changes in the specific subpopulations of immune cells in the convalescent phase of the disease.MethodsWe therefore analyzed peripheral blood of 14 children with MIS-C at the onset of the disease (acute phase) and 2 to 6 months after disease onset (post-acute convalescent phase) for lymphocyte subsets and antigen-presenting cell (APC) phenotype. The results were compared with six healthy age-matched controls.ResultsAll major lymphocyte populations (B cells, CD4 + and CD8+ T cells, and NK cells) were decreased in the acute phase and normalized in the convalescent phase. T cell activation was increased in the acute phase, followed by an increased proportion of γ/δ-double-negative T cells (γ/δ DN Ts) in the convalescent phase. B cell differentiation was impaired in the acute phase with a decreased proportion of CD21 expressing, activated/memory, and class-switched memory B cells, which normalized in the convalescent phase. The proportion of plasmacytoid dendritic cells, conventional type 2 dendritic cells, and classical monocytes were decreased, while the proportion of conventional type 1 dendritic cells was increased in the acute phase. Importantly the population of plasmacytoid dendritic cells remained decreased in the convalescent phase, while other APC populations normalized. Immunometabolic analysis of peripheral blood mononuclear cells (PBMCs) in the convalescent MIS-C showed comparable mitochondrial respiration and glycolysis rates to healthy controls.ConclusionsWhile both immunophenotyping and immunometabolic analyzes showed that immune cells in the convalescent MIS-C phase normalized in many parameters, we found lower percentage of plasmablasts, lower expression of T cell co-receptors (CD3, CD4, and CD8), an increased percentage of γ/δ DN Ts and increased metabolic activity of CD3/CD28-stimulated T cells. Overall, the results suggest that inflammation persists for months after the onset of MIS-C, with significant alterations in some immune system parameters, which may also impair immune defense against viral infections

Optothermal manipulation of pressure-driven nematic liquid crystal microflows in microfluidic environment

V doktorski disertaciji sem raziskal optične in temperaturne vplive zunanjih polj na direktorsko polje nematskega tekočega kristala v različnih tokovnih režimih znotraj mikrofluidičnih kanalčkov z močnim homeotropnim sidranjem. Uporabljal sem polarizacijski optični mikroskop, opremljen z lasersko pinceto, ki pri večjih močeh laserske svetlobe zaradi absorpcije v prevodnem substratu mikrokanalčka povzroči lokalno segrevanje nematika v izotropno fazo in ob hipnem ugašanju posledično sproži hiter fazni prehod v nematsko fazo. Na ta način sem pokazal, da je z laserskim snopom optične pincete v toku nematika mogoče nukleirati in stabilizirati topološko ograjene, orientacijske domenske strukture. Raziskal sem dinamiko teh struktur pri različnih hitrostih toka in skonstruiral fazni diagram prehodov med podkritičnim in nadkritičnim območjem parametrov, ki kvantitativno ločijo krčenje in širjenje domen v dani geometriji. Osredotočil sem se na frekvenčne modulacije tokovnih režimov in relaksacijske procese ob zaustavitvi tokov, ki povzročijo reorientacijo v domeno ujetega direktorskega polja in nastanek točkastih defektov s solitoni. Pokazal sem, da je orientacijske domenske strukture, razen v nematiku 5CB, mogoče tvoriti in stabilizirati tudi v tekočem kristalu CCN z negativno dielektrično anizotropijo in majhno optično dvolomnostjo. Izkazalo se je, da temperaturne spremembe v mikrofluidičnem kanalčku znatno vplivajo na stabilnost z laserjem segretih nematskih plasti, tvorjenje domenskih struktur in na tokovne režime, zato sem te pojave podrobneje raziskal pri višji temperaturi. Pri faznem prehodu toka tekočega kristala iz izotropne v nematsko fazo sem zasledil soobstoj nematskih in izotropnih domen. Nato sem z različnimi geometrijami mikrokanalčkov kontrolirano vplival na obliko, velikost in življenjski čas domen, saj ima takšna manipulacija anizotropne tekočine potencial za uporabo v kompleksnejših mikrofluidičnih vezjih, senzorjih tlaka in nastavljivih optičnih filtrih. S tokom potujoče domene lahko tudi razcepimo, združujemo in sortiramo. V sodelovanju s teoretičnimi fiziki sem kot prvi pokazal obstoj novega kiralnega stanja v toku homeotropnega nematika, ki je doslej, zaradi premalo natančne regulacije tokov, ostalo neopaženo. Nazadnje sem preučil vpliv električnega polja na tokovne režime in domenske strukture. Zaradi dielektrične anizotropije in polarizabilnosti tekočekristalnih molekul lahko z električnim poljem spreminjamo obliko domenskih struktur, jih pri tem razpolavljamo, usmerjamo ali pa jih z močnejšim preklapljanjem električnega polja celo tvorimo. Precizna frekvenčna modulacija električnega polja je nenazadnje uporabna za tvorbo kiralnih domenskih stanj brez uporabe laserske pincete.In the thesis I examine optical and thermal effects on the nematic director field configurations in various flow regimes confined to microfluidic channels with homeotropic surface alignment. Polarizing optical microscopy in combination with laser tweezers is applied to locally heat the nematic flow into the isotropic phase and quench it back to the nematic phase. Thereby, realigned phase domains with encircled defect loops are nucleated, stabilized and transported in a flowing nematic phase. I study the dynamic evolution of orientational phase domains in stationary nematic microflows to construct a phase diagram of shrinking and growing loops for a wide range of flow velocities. Further, I focus on careful tuning and active control of the flow to reveal reorientational dynamics of the flow-aligned director field in oscillatory flows, followed by a nucleation of solitons and point defects as it seeks relaxation to equilibrium. I demonstrate the phenomena in single component liquid crystal 5CB, as well as in a mixture of two CCN liquid crystals with negative dielectric anisotropy and very low birefringence. The laser light interaction with the confined nematic flow is further explored at higher temperatures that approach the nematic to the isotropic phase transition. The study shows impacts of heating on the stability of applied optical traps, nucleation and coexistence of oriented nematic and isotropic domains, and evolution of flow regimes after cooling back to the nematic phase. Next, I demonstrate the dynamic control over the growth and shape of nematic domains by varying only the shape of the channels. This way, splitting and coalescence of the domains can be achieved without use of the laser tweezers. The complete control over domain size manipulation and their birefringent colors may find applications in highly sensitive microfluidic pressure sensors or tunable optofluidic filters. In collaboration with theoretical physicists, I present a hidden pre-transitional state with broken chiral symmetry which can occur before the homeotropic to flow-aligned transition, and characterize the underlying mechanisms of its formation. Lastly, I study effect of external electric field on different flow regimes and domain structure formation. Due to the dielectric anisotropy and the polarizability of liquid-crystalline molecules, applied electric field can reorient, split or nucleate the before-studied flow-aligned domains. Finally, precise frequency modulation of an alternating electric field can produce a sequence of chiral domains in a steady nematic flow

Model prediction of forced expiratory volume in first second (FEV1) before and after ingestion of non-steroidal anti-inflammatory drugs

Skupina zdravil nesteroidni antirevmatiki (NSAR) lahko po zaužitju pri posameznih osebah povzroči značilne klinične znake, poznane kot aspirinska intoleranca. Astmatika, ki je preobčutljiv na NSAR in ima dva značilna klinična znaka – bronhokonstrikcijo in nosne polipe, imenujemo aspirinsko intolerantni astmatik. Za pojav aspirinske intolerance je ključna razgradnja arahidonske kisline (AA) v belih krvnih celicah. V splošnem ta poteka po ciklooksigenazni in lipoksigenazni poti. Po prvi poti se tvorijo prostanoidi, po drugi pa cisteinil levkotrieni. NSAR učinkujejo na ciklooksigenazno pot tako, da inhibirajo encime in posledično zmanjšujejo produkcijo prostanoidov, kar naj bi vodilo do povišanja produkcije cisteinil levkotrienov. Znižana produkcija prostanoidov in zvišana produkcija cisteinil levkotrienov sta tipični značilnosti aspirinske intolerance na metabolomski ravni. Raziskave, ki ločujejo aspirinsko intolerantne astmatike od aspirinsko tolerantnih astmatikov in neastmatikov, potekajo na različnih nivojih človeškega organizma. Na proteomskem nivoju potekajo raziskave v smeri študija razlik v ekspresiji posameznih ključnih encimov v metabolni mreži AA, na metabolomskem nivoju pa potekajo raziskave v smeri meritev in analize razmerij med posameznimi eikozanoidi. Raziskave na nivoju tkiv in organov so usmerjene v določanje povečane bronhialne reaktivnosti in preobčutljivosti pacientov na vrste in doze NSAR. To se izvaja s t. i. provokacijskimi testi, pri čemer se s spirometrijo meri forsirani izdihani volumen zraka v prvi sekundi (FEV1). V magistrski nalogi smo s fizikalno-matematičnim modelom povezali proteomski in metabolomski nivo na ravni celice ter napovedali dogajanje na ravni tkiva in organa virtualnega pacienta. Na celičnem nivoju smo z modelom napovedali koncentracije eikozanoidov za različna stanja ekspresij ključnih encimov v procesu metabolizma AA, ki bi naj karakterizirale različne skupine in podskupine pacientov – neastmatike ter astmatike tolerantne in intolerantne na aspirin. Na podlagi teh rezultatov smo najprej na celičnem nivoju napovedali razvito silo v gladkih mišičnih celicah dihalnih poti, nato pa še polmer tipične dihalne poti in končno FEV1. Vse izračune smo izvedli v bazalnem stanju (tj. brez zaužitega zdravila) in po simulaciji oralnega zaužitja različnih vrst NSAR z različnimi dozami. Z modelom smo določili mejne doze simuliranih NSAR (indometacina, ibuprofena, naproksena in celecoxiba) in paracetamola ter ovrednotili njihovo potentnost v smislu povzročitve bronhokonstrikcije in tveganja astmatičnega napada pri različnih modelnih populacijah aspirinsko intolerantnih astmatikov. Vse modelne simulacije smo izvedli v dveh modelnih stanjih. Prvo simulira stanje neinflamacije, drugo pa stanje inflamacije. Na tak način smo z modelom napovedali in simulirali, kako bi se individualni pacient ali skupina pacientov z razpoznavnim vzorcem v produkciji eikozanoidov in z značilnimi razlikami v ekspresiji posameznih ključnih encimov v metabolni mreži AA lahko odzivali na NSAR v primerih nezdravljene in kontrolirane astme, npr. s kortikosteroidi.In some individuals ingestion of non-steroidal anti-inflammatory drugs (NSAIDs) induces typical clinical signs known as aspirin intolerance. Asthmatics with two typical symptoms – bronchoconstriction and nasal polyps, and with hypersensitivity to NSAIDs are identified as aspirin intolerant asthmatics. Degradation of arachidonic acid (AA) in white blood cells is essential for the occurrence of aspirin intolerance. Metabolism of AA is generally divided into the cyclooxygenase and the lipoxygenase pathway revealing prostanoids and leukotrienes as metabolites, respectively. NSAIDs have inhibitory impact on the enzymes of the cyclooxygenase pathway resulting in the reduction of the prostanoids production. As a consequence, this might result in higher cysteinyl leukotrienes production. Low prostanoid levels and high cisteinil leukotrienes levels are typical characteristics of aspirin intolerance at the metabolomic level. The occurrence of aspirin intolerance is studied on different levels of human organism. On the proteomic level, study is focused on detecting the differences in the expression of important enzymes in the AA metabolic pathway, and, on the metabolomic level, the ratios between particular eicosanoids are measured and analysed. Research on the tissue and organ level is oriented in determining the patients’ bronchial hyperreactivity and hypersensitivity towards the type and the dose of different NSAIDs. This is carried out with provocation tests, whereby forced expiratory volume in first second (FEV1) is measured by spirometry technique. With our mathematical model, presented in this master’s thesis, we coupled proteomic and metabolomic properties at the cellular level, and gave predictions at the tissue and organ level of a virtual patient. On the cellular level we predicted absolute concentrations of eicosanoids for different expressions of the key enzymes in the metabolism of AA, which characterize different groups and subgroups of patients – non-asthmatics as well as asthmatics tolerant and intolerant to aspirin. Based on these results, we first predicted stress developed in the airway smooth muscle cells, then the diameter of a typical airway, and, finally, FEV1. All calculations were carried out in the basal state (i.e. without drug) and after the simulated oral dosing of different NSAIDs with different doses. We determined and evaluated the limiting doses of each of the studied NSAIDs (indomethacin, ibuprofen, naproxen and celecoxib) and paracetamol in terms of the potency for the occurrence of bronchoconstriction and the risk for asthmatic attack in cases of different model populations of aspirin intolerant asthmatics. All model simulations were carried out in two different model statesthe first one, simulating the state of no-inflammation, and the second one, simulating the state of inflammation. In this way we predicted and simulated, how an individual patient or a patient group with a distinguishing pattern in eicosanoid production as well as with characteristic differences in the expression of the key enzymes within the AA metabolic pathway would respond to NSAIDs in cases of untreated and treated asthma, e.g. with corticosteroids

Viskoelastični model izometrične kontrakcije gladkih mišic

V seminarju obravnavamo mehanizme razvoja sile v gladki mišični celici dihalnih poti ob holinergični stimulaciji. Pri tem obravnavamo od kalcija odvisen razvoj sile, ki upošteva podroben opis od kalcija in kalmodulina odvisne aktivacije encima kinaze lahkih verig miozina in aktivnost fosfataze lahkih verig miozina. Obstoječi model nadgradimo z elementi, ki opisujejo viskoelastične lastnosti gladkih mišičnih celic arterij. Modelni rezultati napovejo zakasnitve v razvoju sile, kar je bolj v skladu z meritvami kot pri predhodnih modelih.In this work we study mechanisms of stress development in an airway smooth muscle cell upon the cholinergic stimulation. In this case, the stress development is calcium dependent and includes activation of the calcium - calmodulin dependent myosin light chain kinase and activation of a myosin light chain phosphatase. The existing model is upgraded by the viscoelastic elements, that describe viscoelastic properties of smooth muscle cells of arteries. The model predicts a delay in the development of stress which gives better agreement with experimental results than the previous models

Clinical and MRI outcome of cervical spine lesions in children with juvenile idiopathic arthritis treated with anti-TNFα drugs early in disease course

Abstract Backgrounds The purpose of the study was to evaluate the clinical and magnetic resonance imaging (MRI) outcome of cervical spine arthritis in children with juvenile idiopathic arthritis (JIA), who received anti-TNFα early in the course of cervical spine arthritis. Methods Medical charts and imaging of JIA patients with cervical spine involvement were reviewed in this retrospective study. Data, including age at disease onset, JIA type, disease activity, treatment and clinical outcome were collected. Initial and followup MRI examinations of cervical spine were performed according to the hospital protocol to evaluate the presence of inflammation and potential chronic/late changes. Results Fifteen JIA patients with MRI proved cervical spine inflammation (11 girls, 4 boys, median age 6.3y) were included in the study: 9 had polyarthritis, 3 extended oligoarthritis, 2 persistent oligoarthritis and 1 juvenile psoriatic arthritis. All children were initially treated with high-dose steroids and methotrexate. In addition, 11 patients were treated with anti-TNFα drug within 3 months, and 3 patients within 7 months of cervical spine involvement confirmed by MRI. Mean observation time was 2.9y, mean duration of anti-TNFα treatment was 2.2y. Last MRI showed no active inflammation in 12/15 children, allowing to stop biological treatment in 3 patients, and in 3/15 significant reduction of inflammation. Mild chronic changes were found on MRI in 3 children. Conclusions Early treatment with anti-TNFα drugs resulted in significantly reduced inflammation or complete remission of cervical spine arthritis proved by MRI, and prevented the development of serious chronic/late changes. Repeated MRI examinations are suggested in the follow-up of JIA patients with cervical spine arthritis

Crystalline solid retains memory of anisotropy in precursor liquid crystalline phase

From chemical reactivity to mechanical strength, crystal texture plays a central role in determining the key properties of solids. In organic electronics, texture determines the charge carrier mobility of the active layer in devices such as organic field effect transistors (OFETs). Current methods of controlling the texture of thin films of organic crystals through solution processing are restricted by the stochastic nucleation that accompanies rapid solvent evaporation. We report here a facile method to create biaxially textured crystals of thin films of discotic organic semiconductor, HAT6 (2,3,6,7,10,11-Hexakis(hexyloxy)triphenylene). We first direct the self-assembly of the precursor discotic liquid crystalline (DLC) state; the columnar hexagonal (ColH) phase of HAT6 is biaxially aligned in lithographically fabricated microchannels. Synchrotron X-ray scattering measurements reveal the direction of π-stacking is perpendicular to the channel walls. The biaxial alignment and the directionality of π-stacking in the liquid crystalline phase are transferred to the crystalline state through rapid cooling. Contrary to previous reports, we observe preservation of anisotropy upon crystallization of DLCs. As a significant fraction of organic semiconductors exhibit a liquid crystalline phase, we expect our method of creating textured crystals to be of broad interest