Untersuchung von Magnetostriktiven und Piezotronischen Mikrostrukturen und Materialien für biomagnetische Sensoren mittels Röntgenstrahlen

Detecting electric potential differences from the human physiology is an established technique in medical diagnosis, e.g., as electrocardiogram. It arises from a changing electrical polarization of living cells. Simultaneously, biomagnetism is induced and can be utilized for medical examinations, as well. Benefits in using magnetic signals are, no need for direct skin contact and an increased spatial resolution, e.g., for mapping brain activity, especially in combination with electrical examinations. But biomagnetic signals are very weak and, thus, highly sensitive devices are necessary. The development of small and easy to use biomagnetic sensors, with a sufficient sensitivity, is the goal of the Collaborative Research Centre 1261 - Magnetoelectric Sensors: From Composite Materials to Biomagnetic Diagnostics. This thesis was written as part of this collaboration, with the main focus on the investigation of crystalline structures and structure related properties of piezotronic and magnetostrictive materials by utilizing a selection of X-ray techniques, i.e., X-ray diffraction (XRD), X-ray reflectivity (XRR) and coherent X-ray diffraction imaging (CXDI). Piezotronics, realized by combining piezoelectricity and Schottky contacts in one structure, provides a promising path to enhance sensor sensitivity. A first study investigated the crystalline structure of three piezotronic ZnO rods, spatially resolved by scanning nano XRD and combined with electrical examinations of their Schottky contact properties. It is found that the crystalline quality has a clear impact on the electrical properties of the related Schottky contact, probably due to crystalline defects. A complementary transmission electron microscopy (TEM) and XRD study performed on hybride vapor phase epitaxy (HVPE) grown GaN showed a slight, photoelectrochemical etching related relaxion of strain originating from crystal growth. In a separate study, CXDI was utilized for three-dimensional visualization of strain in a gold coated ZnO rod, with spatial resolution below 30 nm. A distinct strain distribution was found inside the rod, denoted to depletion and screening effects occurring in bent piezotronic structures, and a high strain at the interface may be related to Schottky contact formation. This interface strain agrees with results obtained from TEM. A succeeding CXDI study was conducted on a ZnO rod coated with magnetostrictive FeCoSiB and the possibility for the investigation of the Schottky contacts electrical properties. It was found that FeCoSiB sputtered on ZnO results in an ohmic contact and that an external magnetic field causes a change of the electrical properties, probably due to a strain change, visualized by CXDI. In a fifth study, magnetostrictive FeCo/TiN multilayer structures were investigated by a combined TEM and XRD/XRR approach, showing a relaxation of the structure due to an annealing process and a cube-on-cube structure of the FeCo and TiN layers

Bio-sensing using toroidal microresonators & theoretical cavity optomechanics

In this thesis we report on two matters, (i) time-resolved single particle bio-sensing using a cavity enhanced refractive index sensor with unmatched sensitivity, and (ii) the theoretical analysis of parametric normal mode splitting in cavity optomechanics, as well as the quantum limit of a displacement transducer that relies on multiple cavity modes. It is the unifying element of these studies that they rely on a high-Q optical cavity transducer and amount to a precision measurement of an optical frequency. In the first part, we describe an experiment where a high-Q toroidal microcavity is used as a refractive index sensor for single particle studies. The resonator supports whispering gallery modes (WGM) that feature an evanescent fraction, probing the environment close to the toroid's surface. When a particle with a refractive index, different from its environment, enters the evanescent field of the WGM, the resonance frequency shifts. Here, we monitor the shift with a frequency resolution of df/f=7.7e-11 at a time resolution of 100µs , which constitutes a x10 improvement of the sensitivity and a x100 improvement in time resolution, compared to the state of the art. This unprecedented sensitivity is the key to real-time resolution of single lipid vesicles with 25nm radius adsorbing onto the surface. Moreover -- for the first time within one distinct measurement -- a record number of up to 200 identifiable events was recorded, which provides the foundation for a meaningful statistical analysis. Strikingly, the large number of recorded events and the high precision revealed a disagreement with the theoretical model for the single particle frequency shift. A correction factor that fully accounts for the polarizability of the particle, and thus corrects the deviation, was introduced and establishes a quantitative understanding of the binding events. Directed towards biological application, we introduce an elegant method to cover the resonator surface with a single lipid bilayer, which creates a universal, biomimetic interface for specific functionalization with lipid bound receptors or membrane proteins. Quantitative binding of streptavidin to biotinylated lipids is demonstrated. Moving beyond the detection limit, we provide evidence that the presence of single IgG proteins (that cannot be resolved individually) manifests in the frequency noise spectrum. The theoretical analysis of the thermo-refractive noise floor yields a fundamental limit of the sensors resolution. The second part of the thesis deals with the theoretical analysis of the coupling between an optical cavity mode and a mechanical mode of much lower frequency. Despite the vastly different resonance frequencies, a regime of strong coupling between the mechanics and the light field can be achieved, which manifests as a hybridization of the modes and as a mode splitting in the spectrum of the quadrature fluctuations. The regime is a precondition for coherent energy exchange between the mechanical oscillator and the light field. Experimental observation of optomechanical mode splitting was reported shortly after publication of our results [cf. Gröblacher et al., Nature 460, 724--727]. Dynamical backaction cooling of the mechanical mode can be achieved, when the optical mode is driven red-detuned from resonance. We use a perturbation and a covariance approach to calculate both, the power dependence of the mechanical occupation number and the influence of excess noise in the optical drive that is used for cooling. The result was one to one applied for data analysis in a seminal article on ground state cooling of a mechanical oscillator [cf. Teufel et al., Nature 475, 359--363]. In addition we investigate a setting, where multiple optical cavity modes are coupled to a single mechanical degree of freedom. Resonant build-up of the motional sidebands amplifies the mechanical displacement signal, such that the standard quantum limit for linear position detection can be reached at significantly lower input power.In dieser Dissertation werden zwei Themen behandelt. Im ersten Teil widmen wir uns experimentell der zeitaufgelösten Messung von Liposomen mit Hilfe eines Nahfeld-Brechungsindex-Sensors. Der zweite Teil handelt von der theoretischen Beschreibung des Regimes der starken Kopplung zwischen einem mechanischen Oszillator und dem Feld eines optischen Resonators. Des Weiteren erörtern wir ein Messschema, das es erlaubt eine mechanische Bewegung, mit Hilfe von mehreren optischen Resonatormoden genauer auszulesen. Die Gemeinsamkeit beider Arbeiten besteht darin, dass es sich jeweils um eine Präzisionsmessung einer optischen Frequenz handelt. Im experimentellen Teil benutzen wir Toroid-Mikroresonatoren mit extrem hoher optischer Güte als Biosensoren. Dabei handelt es sich um eine ringförmige Glasstruktur, entlang welcher Licht im Kreis geleitet wird. Dazu muss eine Resonanzbedingung erfüllt sein, die besagt, dass der (effektive) Umfang des Rings einem ganzzahligen Vielfachen der optischen Wellenlänge entspricht. Ein Teil des zirkulierenden Lichts ist als evaneszente Welle empfänglich für Brechungsindexänderungen nahe der Oberfläche des Resonators. Ein Partikel, dessen Brechungsindex sich von dem der Umgebung unterscheidet, induziert beim Eintritt in das evaneszente Feld eine Frequenzverschiebung der optischen Resonanz. Im Rahmen dieser Arbeit lösen wir relative Frequenzverschiebungen mit einer Genauigkeit von df/f=7.7e-11 und einer Zeitkonstante von 100µs auf. Dies stellt eine Verbesserung des derzeitigen Stands der Technik um einen Faktor x10 in der Frequenz und einen Faktor x100 in der Zeit dar. Diese bisher unerreichte Empfindlichkeit der Messmethode ist der Schlüssel zur Echtzeitdetektion einzelner Lipidvesikel mit einem Radius von 25nm . Zudem gelingt es uns innerhalb einer Messung, bis zu 200 Einzelteilchenereignisse aufzunehmen, welche die Basis für eine aussagekräftige Statistik liefern. Bemerkenswerterweise konnten wir Dank der außerordentlichen Präzision und der Vielzahl der Ereignisse eine Abweichung zur bis dato akzeptierten und angewandten Theorie feststellen. Wir ergänzen das Model um einen Korrekturfaktor, der die Polarisierbarkeit des Teilchens vollständig berücksichtigt und erlangen dadurch ein umfassendes und quantitatives Verständnis der Messergebnisse. Im Hinblick auf biologisch relevante Fragestellungen zeigen wir eine elegante Methode auf, die es erlaubt, den Resonator mit einer einzelnen Lipidmembran zu beschichten. Wir kreieren somit eine biomimetische Schnittstelle, welche das Grundgerüst für eine spezifische Funktionalisierung mit lipidgebundenen Rezeptoren, Antikörpern oder Membranproteinen darstellt. Des Weiteren zeigen wir, dass der Empfindlichkeit eine fundamentale Grenze durch thermische Brechungsindexfluktuationen gesetzt ist. Hierzu wird ein theoretisches Modell speziell für den relevanten niederfrequenten Bereich errechnet. Im zweiten Teil der Arbeit beschäftigen wir uns mit der theoretischen Beschreibung eines optischen Resonators, dessen Lichtfeld an eine mechanische Schwingung gekoppelt ist. Obwohl sich die Resonanzfrequenzen der Optik und der Mechanik typischerweise um mehrere Größenordnungen unterscheiden, existiert ein Regime der starken Kopplung, in dem die Fluktuationen des Lichts und die mechanischen Vibrationen hybridisieren. Dies offenbart sich zum Beispiel im Phasenspektrum, wo sich das ursprüngliche Maximum der Resonanz in zwei Maxima aufspaltet. Die starke Kopplung stellt die Grundlage für kohärenten Energie- und Informationsaustausch zwischen Licht und Mechanik dar und ist daher von besonderem technischen und wissenschaftlichen Interesse. Es ist anzumerken, dass die starke Kopplung und die einhergehende Aufspaltung der Resonanz bereits kurz nach Veröffentlichung unserer theoretischen Beschreibung im Experiment beobachtet wurde [vgl. Gröblacher et al., Nature 460, 724--727]. Wenn der optische Resonator (zur längeren Wellenlänge hin) verstimmt von der Resonanz angeregt wird, kann über dynamische Rückkopplung eine effektive Kühlung der mechanischen Schwingung erreicht werden. Wir berechnen die thermische Besetzungszahl der mechanischen Mode (und somit die Temperatur) mit Hilfe eines störungstheoretischen und eines Kovarianzansatzes. Dabei berücksichtigen wir sowohl ein klassisches Rauschen des optischen Feldes als auch den Einfluss der optomechanischen Kopplung auf die Grenztemperatur. Der hergeleitete Ausdruck für die finale Besetzungszahl wurde eins zu eins für die Datenanalyse in dem wegweisenden Artikel über das Kühlen eines mechanischen Oszillators in den Quantengrundzustand verwendet [vgl. Teufel et al., Nature 475, 359--363]. Abschließend betrachten wir ein Schema, bei dem die Lichtfelder mehrerer optischer Resonanzen an eine mechanischen Schwingung gekoppelt sind. Die resonante Verstärkung der Information über die mechanische Bewegung in den optischen Seitenbändern ermöglicht es, eine durch das Standard Quantenlimit begrenzte Empfindlichkeit bei signifikant niedriger Eingangsleistung zu erreichen

The molecular landscape of developmental pausing in mammals

Many mammals can control the timing of birth by temporarily suspending development which is marked by a reduction of metabolic activity. This interruption in the development process is called diapause is specific to blastocyst-stage embryos and is an apparent response to tide over adverse environmental and nutritional conditions. The establishment of diapause is an active process involving extensive rewiring of the epigenetic, transcriptomic and metabolic landscape of the embryo. How the above three cellular processes are coordinately re-wired during dormancy entry is not known. Here I show that the regulatory function of miRNAs is indispensable for the mouse embryos entering into the diapause state. Without the miRNA function mouse ESCs and embryos suffer developmental collapse upon mTORi-mediated diapause induction. Small RNA sequencing of single mouse embryos showed specific miRNAs to be upregulated during diapause induction. In silico miRNA-protein network of diapause was developed by the integration of small RNA sequencing data together with computationally predicted miRNA targets. The network showed miRNA-mediated regulation of nuclear and cytoplasmic bodies along with RNA splicing which are perturbed in miRNA null mouse ESCs. The study also shows nutrient and autophagy regulator TFE3 to be the upstream regulator for the expression of dormancy-associated miRNAs, linking cytoplasmic mTOR activity to nuclear miRNA biogenesis. It is unknown whether the capacity to pause is a conserved trait across mammals, more specifically in humans. Mouse and humans show similar patterns of mTOR expression during pre-implantation development, suggesting the involvement of the primordial pathway in blastocyst development and timing in both species. Here I show human blastoids and pluripotent cells in naïve and naïve-like states retain the capacity to pause via mTOR inhibition and the pausing is functionally reversible even at the molecular level. Taken together the above findings suggest that the development of human embryos may be controllable and that miRNAs play a critical regulatory role in bringing transcriptional re-wiring in mouse embryos for successful entry into dormancy

Flexible ZnO thin film-based surface acoustic wave devices for environmental and biomedical sensing applications

Flexible ZnO thin film on aluminium foil-based SAW devices have been investigated for the first time as sensors for temperature, UV light, and humidity as well as breath and apnoea detection, and these devices were performing sensing while they were placed in flat and bending (curved) positions. Flexible SAW devices offer a promising technology of low cost, highly sensitive and bendable sensors. They also exhibit high potential for wearable, point of care and microfluidics and lab-on-chips applications. The ZnO thin film was deposited on the aluminium foil and ZnO nanorods were grown on the surface of selected samples. The SAW sensors were fabricated by patterning Au/Cr IDTs with various wavelengths. Film and nanorods possessed the preferred structure and piezoelectric properties. Lamb modes were identified, and they were in a good agreement with the FEA results. The maximum value of TCF was -773 ppm/K which is among the highest values mentioned in the literature. The sensors showed excellent linearity and repeatability during temperature cycling test. The maximum value of sensitivity to UV light was 63 ppm (mW/cm2)-1. ZnO nanorods enhanced the sensitivity by 1.76 times. The sensors showed excellent repeatability and reliability during UV light cycling in flat, bent-up and bent-down positions. The maximum values of sensitivity to humidity were 47.7 kHz at 90%RH for nanorodenhanced device and the maximum frequency shift was -57 kHz. The sensors exhibited good repeatability in response to humidity cycling. Besides, the devices exhibited an excellent response, sensitivity, and reliability for various breath patterns (e.g., healthy breathing, apnoea, slow and fast breathing)

All-optical interrogation of neural circuits during behaviour

This thesis explores the fundamental question of how patterns of neural activity encode information and guide behaviour. To address this, one needs three things: a way to record neural activity so that one can correlate neuronal responses with environmental variables; a flexible and specific way to influence neural activity so that one can modulate the variables that may underlie how information is encoded; a robust behavioural paradigm that allows one to assess how modulation of both environmental and neural variables modify behaviour. Techniques combining all three would be transformative for investigating which features of neural activity, and which neurons, most influence behavioural output. Previous electrical and optogenetic microstimulation studies have told us much about the impact of spatially or genetically defined groups of neurons, however they lack the flexibility to probe the contribution of specific, functionally defined subsets. In this thesis I leverage a combination of existing technologies to approach this goal. I combine two-photon calcium imaging with two-photon optogenetics and digital holography to generate an “all-optical” method for simultaneous reading and writing of neural activity in vivo with high spatio-temporal resolution. Calcium imaging allows for cellular resolution recordings from neural populations. Two-photon optogenetics allows for targeted activation of individual cells. Digital holography, using spatial light modulators (SLMs), allows for simultaneous photostimulation of tens to hundreds of neurons in arbitrary spatial locations. Taken together, I demonstrate that this method allows one to map the functional signature of neurons in superficial mouse barrel cortex and to target photostimulation to functionally-defined subsets of cells. I develop a suite of software that allows for quick, intuitive execution of such experiments and I combine this with a behavioural paradigm testing the effect of targeted perturbations on behaviour. In doing so, I demonstrate that animals are able to reliably detect the targeted activation of tens of neurons, with some sensitive to as few as five cortical cells. I demonstrate that such learning can be specific to targeted cells, and that the lower bound of perception shifts with training. The temporal structure of such perturbations had little impact on behaviour, however different groups of neurons drive behaviour to different extents. In order to probe which characteristics underly such variation, I tested whether the sensory response strength or correlation structure of targeted ensembles influenced their behavioural salience. Whilst these final experiments were inconclusive, they demonstrate their feasibility and provide us with some key actionable improvements that could further strengthen the all-optical approach. This thesis therefore represents a significant step forward towards the goal of combining high resolution readout and perturbation of neural activity with behaviour in order to investigate which features of the neural code are behaviourally relevant

Two-photon all-optical interrogation of mouse barrel cortex during sensory discrimination

The neocortex supports a rich repertoire of cognitive and behavioural functions, yet the rules, or neural ‘codes’, that determine how patterns of cortical activity drive perceptual processes remain enigmatic. Experimental neuroscientists study these codes through measuring and manipulating neuronal activity in awake behaving subjects, which allows links to be identified between patterns of neural activity and ongoing behaviour functions. In this thesis, I detail the application of novel optical techniques for simultaneously recording and manipulating neurons with cellular resolution to examine how tactile signals are processed in sparse neuronal ensembles in mouse somatosensory ‘barrel’ cortex. To do this, I designed a whisker-based perceptual decision-making task for head-fixed mice, that allows precise control over sensory input and interpretable readout of perceptual choice. Through several complementary experimental approaches, I show that task performance is exquisitely coupled to barrel cortical activity. Using two- photon calcium imaging to simultaneously record from populations of barrel cortex neurons, I demonstrate that different subpopulations of neurons in layer 2/3 (L2/3) show selectivity for contralateral and ipsilateral whisker input during behaviour. To directly test whether these stimulus-tuned groups of neurons differentially impact perceptual decision-making I performed patterned photostimulation experiments to selectively activate these functionally defined sets of neurons and assessed the resulting impact on behaviour and the local cortical network in layer 2/3. In contrast with the expected results, stimulation of sensory-coding neurons appeared to have little perceptual impact on task performance. However, activation of non- stimulus coding neurons did drive decision biases. These results challenge the conventional view that strongly sensory responsive neurons carry more perceptual weight than non-responsive sensory neurons during perceptual decision-making. Furthermore, patterned photostimulation revealed and imposed potent surround suppression in L2/3, which points to strong lateral inhibition playing a dominant role in shaping spatiotemporally sparse activity patterns. These results showcase the utility of combined patterned photostimulation methods and population calcium imaging for revealing and testing neural circuit function during sensorimotor behaviour and provide new perspectives on sensory coding in barrel cortex

An In-Shoe Laser Doppler Sensor for Assessing Plantar Blood Flow in the Diabetic Foot

An in-shoe laser Doppler sensor for assessing plantar blood flow in the diabetic foot. Jonathan Edwin Cobb Plantar ulceration is a complication of the diabetic foot prevalent in adults with type 11 diabetes mellitus. Although neuropathy, microvascular disease and biornechanical factors are all implicated, the mechanism by which the tissue becomes pre-disposed to damage remains unclear. Recent theories suggest that the nutritional supply to the tissue is compromised, either by increased flow through the arteriovenous anastomoses ('capillary steal' theory) or through changes in the micro vascu I ature (haemodynamic hypothesis). Clinical data to support these ideas has been limited to assessment of the unclad foot under rest conditions. A limitation of previous studies has been the exclusion of static and dynamic tissue loading, despite extensive evidence that these biornechanical factors are essential in the development of plantar ulceration. The present study has overcome these problems by allowing assessment of plantar blood flow, in-shoe, during standing and walking. The system comprises a laser Doppler blood flux sensor operating at 780nm, load sensor, measurement shoe, instrumentation, and analysis software. In-vitro calibration was performed using standard techniques. An in-vivo study of a small group of diabetic subjects indicated differences in the blood flux response between diabetic neuropaths, diabetics with vascular complications and a control group. For example, following a loading period of 120s, relative increases in response from rest to peak were: Control (150% to 259%), Vascular (-70% to 242%), Neuropathic (109%-174%) and recovery times to 50% of the peak response were: Control (33s to 45s), Vascular (43s to >120s), Neuropathic (>120s). Dynamic re-perfusion rates (arbitrary units per millisecond) obtained for the swing phase of gait were: Control (6.1 a. u/ms to 7.9 a. u/ms), Vascular (4 a. u/ms to 6.2 a. u/ms), Neuropathic (2.3 a. u/ms to 4.5 a. u/ms)

Intelligent Circuits and Systems

ICICS-2020 is the third conference initiated by the School of Electronics and Electrical Engineering at Lovely Professional University that explored recent innovations of researchers working for the development of smart and green technologies in the fields of Energy, Electronics, Communications, Computers, and Control. ICICS provides innovators to identify new opportunities for the social and economic benefits of society.　 This conference bridges the gap between academics and R&D institutions, social visionaries, and experts from all strata of society to present their ongoing research activities and foster research relations between them. It provides opportunities for the exchange of new ideas, applications, and experiences in the field of smart technologies and finding global partners for future collaboration. The ICICS-2020 was conducted in two broad categories, Intelligent Circuits & Intelligent Systems and Emerging Technologies in Electrical Engineering