Towards autonomous DNA-based Nanodevices

Molecular recognition, programmability, self-assembling capabilites and biocompatibility are unique features of DNA. The basic approach of DNA nanotechnology is to exploit these properties in order to fabricate novel materials and structures on the nanometer scale. This cumulative dissertation deals with three aspects of this young research area: fast analysis, autonomous control of functional structures, and biocompatible autonomous delivery systems for nanoscale objects. 1. At low temperatures and under favorable buffer conditions, two complementary DNA strands will form a double-helical structure in which the bases of the two strands are paired according to the Watson-Crick rules: adenine bases bind with thymine bases, guanine bases with cytosine bases. The melting temperature TM of a DNA duplex is defined as the temperature at which half of the double strands are separated into single strands. The melting temperature can be calculated for DNA strands of known sequences under standard conditions. However, it has to be determined experimentally for strands of unknown sequences and for applications under extreme buffer conditions. A method for fast and reliable determination of DNA melting temperatures has been developed. Stable gradients of the denaturing agent formamide were generated by means of diffusion in a microfluidic setup. Formamide lowers the melting temperature of DNA and a given formamide concentration can be mapped to a corresponding virtual temperature along the formamide gradient. Differences in the length of complementary sequences of only one nucleotide as well as a single nucleotide mismatch can be detected with this method, which is of great interest for the detection of sequence mutations or variations such as single nucleotide polymorphisms (SNPs). 2. Knowledge of the stability of DNA duplexes is also of great importance for the construction of DNA-based nanostructures and devices. Conformational changes occuring in artificially generated DNA structures can be used to produce motion on the nanometer scale. Usually, DNA devices are driven by the manual addition of fuel molecules or by the periodic variation of buffer conditions. One prominent example of such a conformational change is the formation of the so-called i-motif, which is a folded four-stranded DNA structure characterized by noncanonical hemiprotonated cytosine-cytosine base-pairs. In order to achieve controlled autonomous motion, the oscillating pH-value of a chemical oscillator has been employed to drive the i-motif periodically through its conformational states. The experiments were conducted with the DNA switch in solution and attached to a solid substrate and constitute the first example of DNA-based devices driven autonomously by a chemical non-equilibrium reaction. 3. Finally, a DNA-crosslinked and switchable polyacrylamide hydrogel is introduced, which is used to trap and release fluorescent colloidal quantum dots in response to externally applied programmable DNA signal strands. Trapping and release of the nanoparticles is demonstrated by studying their diffusion properties using single molecule fluorescence microscopy, single particle tracking and fluorescence correlation spectroscopy. Due to the biocompatibility of the polymerized acrylamide and the crosslinking DNA strands, such gels could find application in the context of controlled drug delivery, where the autonomous release of a drug-carrying nanoparticle could be triggered by naturally occurring, potentially disease-related DNA or RNA strands

From timed Dicke states to full inversion

In dieser Arbeit untersuchen wir kollektive Strahlungseffekte in Nanofaser-gekoppelten atomaren Ensembles, die sich über Tausende von optischen Wellenlängen erstrecken. Wir koppeln bis zu 1000 Atome optisch an die geführten Moden einer optischen Nanofaser, die langreichweitige Dipol-Dipol Wechselwirkungen zwischen den Atomen vermittelt. Wir realisieren eine unidirektionale Kopplung und damit ein kaskadiertes Quantensystem, in dem die Dynamik jedes Atoms ausschließlich durch die Dynamik der vorgelagerten Atome bestimmt wird. Wir regen die Atome mit nanofasergeführten optischen Pulsen kohärent an, was uns ermöglicht, den gesamten Parameterbereich von schwacher Anregung bis hin zur voll-ständigen Inversion zu erforschen. Wir stellen fest, dass die kohärente Vorwärtsstreuung, die für die Superradianz im Regime der schwachen Anregung verantwortlich ist, auch nahe voller Inversion eine wichtige Rolle für die Dynamik spielt. Wir beobachten superradiante Puls-Dynamik, die in unserem System trotz des makroskopischen Abstands zwischen den Atomen und einer asymmetrischen Kopplung auftritt. Wir stellen fest, dass die emittierte Spitzenleistung noch schneller mit der Anzahl der Atome skaliert als im Fall der idealen Dicke Superradianz, was auf eine kollektiv erhöhte Sammeleffizienz der nanofasergeführten Mode zurückzuführen ist. Die Analyse der Kohärenz-Eigenschaften des superradianten Pulses erlaubt es uns, zwei Regime der Puls-Dynamik zu identifizieren. Wir entwickeln ein kaskadiertes Wechselwirkungsmodell und zeigen, dass es die kollektive Dynamik unseres Systems über den gesamten in dieser Arbeit untersuchten Parameterbereich akkurat beschreibt. Schließlich untersuchen wir die getriebene Dynamik eines Nanofaser-gekoppelten Ensembles von Drei-Niveau-Atomen. Wir treiben Zwei-Photonen-Rabi-Oszillationen zwischen den beiden Grundzuständen eines $\Lambda$-Systems und beobachten die damit verbundene oszillatorische Raman-Verstärkung und -Absorption.In this thesis, we study collective radiative effects in nanofiber-coupled atomic ensembles that extend over thousands of optical wavelengths. We optically couple up to 1000 atoms to the guided modes of an optical nanofiber, which mediates long-range dipole-dipole interactions between the atoms. We engineer the coupling to be unidirectional, realizing a cascaded quantum system in which the dynamics of each atom is solely determined by the dynamics of upstream atoms. We coherently excite the atoms using nanofiber-guided optical pulses, allowing us to explore the entire parameter regime from weak excitation to full inversion. We find that coherent forward scattering, which is responsible for superradiance in the weak excitation regime, plays an important role for the dynamics even close to full inversion. We observe superradiant burst dynamics, which occurs in our system despite the macroscopic separation between the atoms and an asymmetric coupling. We find that the peak-emitted power scales even faster with the number of atoms than in the case of ideal Dicke superradiance due to a collectively enhanced channeling efficiency into the nanofiber-guided mode. By analyzing the coherence properties of the superradiant burst, we directly identify two regimes of burst dynamics. In the second regime, there is no initial coherence, and the superradiant burst is seeded by vacuum fluctuations. We introduce a cascaded interaction model and find that it accurately describes the collective dynamics of our system over the entire parameter regime explored in this thesis. Finally, we study the driven dynamics of a nanofiber-coupled ensemble of three-level atoms. We drive two-photon Rabi oscillations between the two ground states of a $\Lambda$ system and observe the associated oscillatory Raman gain and absorption

It’s a Bleed: Pediatric Hemophilia and Length of Stay, Rural vs Urban Hospitals

Hemophilia is a rare genetic disorder that requires specialty care and treatment. Pediatric patients with hemophilia have unique medical issues that may lead to permanent disability or death if not properly diagnosed and treated in a timely manner. Due to lack of resources and proper training of staff, rural hospitals are not equipped to properly treat pediatric hemophilia patients. Utilizing the Healthcare Cost and Utilization Project (HCUP) Kids´ Inpatient Database (KID) of the Agency for Healthcare Research and Quality. I have found, across all hospital types, pediatric hemophilia patients have longer lengths of stay, 2.7 days for rural hospitals, 4.6 days for urban hospitals, and 5.1 days for teaching hospitals, compared to the national mean for pediatric LOS of 1.8 days (Heys et al. 2017)

Plasmon-Exciton Coupling Using DNA Templates

Coherent energy exchange between plasmons and excitons is a phenomenon that arises in the strong coupling regime resulting in distinct hybrid states. The DNA-origami technique provides an ideal framework to custom-tune plasmon-exciton nanostructures. By employing this well controlled self-assembly process, we realized hybrid states by precisely positioning metallic nanoparticles in a defined spatial arrangement with fixed nanometer-sized interparticle spacing. Varying the nanoparticle diameter between 30 nm and 60 nm while keeping their separation distance constant allowed us to precisely adjust the plasmon resonance of the structure to accurately match the energy frequency of a J-aggregate exciton. With this system we obtained strong plasmon-exciton coupling and studied far-field scattering at the single-structure level. The individual structures displayed normal mode splitting up to 170 meV. The plasmon tunability and the strong field confinement attained with nanodimers on DNA-origami renders an ideal tool to bottom-up assembly plasmon-exciton systems operating at room temperature.Comment: This document is the unedited Author's version of a Submitted Work that was subsequently accepted for publication in Nano Letters, copyright \copyright American Chemical Society after peer review. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/acs.nanolett.6b03015, Nano Letters 201

Simultaneous microsurgical spermatic vein ligation and sclerotherapy - A combined procedure for the treatment of recurrent or persistent varicocele

Objectives: Microsurgical ligation as well as antegrade sclerotherapy have been established in varicocele treatment. The aim of this study was to evaluate whether a combination of microsurgery. and sclerotherapy can: provide a safe and effective treatment of varicocele recurrence or persistence. Methods. Nine patients with, recurrent or persistent varicoceles were operated by means of the combination method. Under microscopic control varix veins were ligated selectively preserving: lymphatics and arteries. Ectopic veins as a possible source for varicocele persistence or recurrence were also ligated. Finally, an intraoperative venography with subsequent sclerotherapy was, performed through one of the dissected veins. Results. Despite: difficult anatomical situations after previous surgical interventions, the operations were perform, ed successfully without any complications. Clinical controls showed varicocele disappearance without damage of the testis. No varicocele recurrence or persistence was observed. Conclusions. This method combines the advantages of both methods. Precision of the microsurgical technique is combined with velocity of sclerotherapy. Thus, it may represent an Interesting alternative to conventional operation methods especially in the treatment of recurrent or persistent varicoceles. Copyright (C) 2001 S. Karger AG, Basel