Label-free detection of single biological molecules using microtoroid optical resonators

Being able to detect a single molecule without the use of labels has been a long standing goal of bioengineers and physicists. This would simplify applications ranging from single molecular binding studies to those involving public health and security, improved drug screening, medical diagnostics, and genome sequencing. One promising technique that has the potential to detect single molecules is the microtoroid optical resonator. The main obstacle to detecting single molecules, however, is decreasing the noise level of the measurements such that a single molecule can be distinguished from background. We have used laser frequency locking in combination with balanced detection and data processing techniques to reduce the noise level of these devices and report the detection of a wide range of nanoscale objects ranging from nanoparticles with radii from 100 to 2.5 nm, to exosomes, ribosomes, and single protein molecules (mouse immunoglobulin G and human interleukin-2). We further extend the exosome results towards creating a non-invasive tumor biopsy assay. Our results, covering several orders of magnitude of particle radius (100 nm to 2 nm), agree with the `reactive' model prediction for the frequency shift of the resonator upon particle binding. In addition, we demonstrate that molecular weight may be estimated from the frequency shift through a simple formula, thus providing a basis for an ``optical mass spectrometer'' in solution. We anticipate that our results will enable many applications, including more sensitive medical diagnostics and fundamental studies of single receptor-ligand and protein-protein interactions in real time. The thesis summarizes what we have achieved thus far and shows that the goal of detecting a single molecule without the use of labels can now be realized.

“Steer-by-wire” software garapena

[EU]Proiektu honek automobilen antzinako direkzio sistemak ordezkatuko dituen steer-by-wire-ren inplementazioa deskribatuko du, software-aren garapena, hain zuzen. Lan hau garatzeko, ezinbestekoa izango da orain arte egindako lanen bilketa eta azterketa egitea, baita nolako zailtasunak, arriskuak egongo diren eta posiblea izango litzatekeen etorkizun batean teknologia hau instalatzea. Programazio, mekanika eta automatika ezagutzaren bidez teknologia berri hau ordenagailu batean simulatuko da eta orain arte erabili izan diren teknologiekin alderatuko dira, ateratako emaitzekin ondorio nabarmenak ezarriz. Programazio eta simulaziorako “Labview” eta “Matlab-Simulink” software-ak erabiliko dira, beharrezkoak diren tresnen ezagutzak aurretik lortuz.

Nuevos phased arrays

[ES]El sistema PAMELA III, con sus correspondientes phased arrays, se diseñó para la detección de daños en aeronaves mediante la tecnología SHM (structural health monitoring). Sin embargo, según los estudios del profesor Tadeusz Stepinski, la distribución de los piezoélectricos utilizada en estos phase arrays producen interferencias. Por ello, este proyecto se basa en el diseño de cuatro phased arrays diferentes, utilizando una de las distribuciones de piezoélectricos estudiada por el profesor Tadeusz. La distribución utilizada es la de cross-shaped (en forma de cruz), con lo que se consigue disminuir las interferencias producidas en los antiguos phased arrays. Además, se ha producido un diseño que es compatible tanto con PAMELA III, como con una futura actualización a PAMELA IV. Con lo que se ha conseguido que se pueda aumentar el tamaño de almacenamiento de la memoria utilizada cambiando la tecnología 1-wire por la de I2C, que sería utilizada solo en el sistema PAMELA IV. Aparte del diseño de los PCBs, también se han diseñado unas piezas de plástico que aportan rigidez a los phased arrays y además, hace que la parte inferior de la tarjeta quede toda a la misma altura y no sobresalgan los piezoélectricos, con lo que aumentará la facilidad de instalación.

Fiber-optic integration and efficient detection schemes for optomechanical resonators

With the advent of the laser in the year 1960, the field of optics experienced a renaissance from what was considered to be a dull, solved subject to an active area of development, with applications and discoveries which are yet to be exhausted 55 years later. Light is now nearly ubiquitous not only in cutting-edge research in physics, chemistry, and biology, but also in modern technology and infrastructure. One quality of light, that of the imparted radiation pressure force upon reflection from an object, has attracted intense interest from researchers seeking to precisely monitor and control the motional degrees of freedom of an object using light. These optomechanical interactions have inspired myriad proposals, ranging from quantum memories and transducers in quantum information networks to precision metrology of classical forces. Alongside advances in micro- and nano-fabrication, the burgeoning field of optomechanics has yielded a class of highly engineered systems designed to produce strong interactions between light and motion.

Optomechanical crystals are one such system in which the patterning of periodic holes in thin dielectric films traps both light and sound waves to a micro-scale volume. These devices feature strong radiation pressure coupling between high-quality optical cavity modes and internal nanomechanical resonances. Whether for applications in the quantum or classical domain, the utility of optomechanical crystals hinges on the degree to which light radiating from the device, having interacted with mechanical motion, can be collected and detected in an experimental apparatus consisting of conventional optical components such as lenses and optical fibers. While several efficient methods of optical coupling exist to meet this task, most are unsuitable for the cryogenic or vacuum integration required for many applications. The first portion of this dissertation will detail the development of robust and efficient methods of optically coupling optomechanical resonators to optical fibers, with an emphasis on fabrication processes and optical characterization.

I will then proceed to describe a few experiments enabled by the fiber couplers. The first studies the performance of an optomechanical resonator as a precise sensor for continuous position measurement. The sensitivity of the measurement, limited by the detection efficiency of intracavity photons, is compared to the standard quantum limit imposed by the quantum properties of the laser probe light. The added noise of the measurement is seen to fall within a factor of 3 of the standard quantum limit, representing an order of magnitude improvement over previous experiments utilizing optomechanical crystals, and matching the performance of similar measurements in the microwave domain.

The next experiment uses single photon counting to detect individual phonon emission and absorption events within the nanomechanical oscillator. The scattering of laser light from mechanical motion produces correlated photon-phonon pairs, and detection of the emitted photon corresponds to an effective phonon counting scheme. In the process of scattering, the coherence properties of the mechanical oscillation are mapped onto the reflected light. Intensity interferometry of the reflected light then allows measurement of the temporal coherence of the acoustic field. These correlations are measured for a range of experimental conditions, including the optomechanical amplification of the mechanics to a self-oscillation regime, and comparisons are drawn to a laser system for phonons. Finally, prospects for using phonon counting and intensity interferometry to produce non-classical mechanical states are detailed following recent proposals in literature.

Cavity-enhanced spectroscopies for applications of remote sensing, chemical kinetics and detection of radical species

This thesis describes applications of cavity enhanced spectroscopy towards applications of remote sensing, chemical kinetics and detection of transient radical molecular species. Both direct absorption spectroscopy and cavity ring-down spectroscopy are used in this work. Frequency-stabilized cavity ring-down spectroscopy (FS-CRDS) was utilized for measurements of spectral lineshapes of O₂ and CO₂ for obtaining laboratory reference data in support of NASA’s OCO-2 mission. FS-CRDS is highly sensitive (> 10 km absorption path length) and precise (> 10000:1 SNR), making it ideal to study subtle non-Voigt lineshape effects. In addition, these advantages of FS-CRDS were further extended for measuring kinetic isotope effects: A dual-wavelength variation of FS-CRDS was used for measuring precise D/H and ¹³C/¹²C methane isotope ratios (sigma>0.026%) for the purpose of measuring the temperature dependent kinetic isotope effects of methane oxidation with O(¹D) and OH radicals. Finally, direct absorption spectroscopic detection of the trans-DOCO radical via a frequency combs spectrometer was conducted in collaboration with professor Jun Ye at JILA/University of Colorado.