On-chip integrated label-free optical biosensing

This thesis investigates the design and implementation of a label-free optical biosensing system utilizing a robust on-chip integrated platform. The goal has been to transition optical micro-resonator based label-free biosensing from a laborious and delicate laboratory demonstration to a tool for the analytical life scientist. This has been pursued along four avenues: (1) the design and fabrication of high-$Q$ integrated planar microdisk optical resonators in silicon nitride on silica, (2) the demonstration of a high speed optoelectronic swept frequency laser source, (3) the development and integration of a microfluidic analyte delivery system, and (4) the introduction of a novel differential measurement technique for the reduction of environmental noise.

The optical part of this system combines the results of two major recent developments in the field of optical and laser physics: the high-$Q$ optical resonator and the phase-locked electronically controlled swept-frequency semiconductor laser. The laser operates at a wavelength relevant for aqueous sensing, and replaces expensive and fragile mechanically-tuned laser sources whose frequency sweeps have limited speed, accuracy and reliability. The high-$Q$ optical resonator is part of a monolithic unit with an integrated optical waveguide, and is fabricated using standard semiconductor lithography methods. Monolithic integration makes the system significantly more robust and flexible compared to current, fragile embodiments that rely on the precarious coupling of fragile optical fibers to resonators. The silicon nitride on silica material system allows for future manifestations at shorter wavelengths. The sensor also includes an integrated microfluidic flow cell for precise and low volume delivery of analytes to the resonator surface. We demonstrate the refractive index sensing action of the system as well as the specific and nonspecific adsorption of proteins onto the resonator surface with high sensitivity. Measurement challenges due to environmental noise that hamper system performance are discussed and a differential sensing measurement is proposed, implemented, and demonstrated resulting in the restoration of a high performance sensing measurement.

The instrument developed in this work represents an adaptable and cost-effective platform capable of various sensitive, label-free measurements relevant to the study of biophysics, biomolecular interactions, cell signaling, and a wide range of other life science fields. Further development is necessary for it to be capable of binding assays, or thermodynamic and kinetics measurements; however, this work has laid the foundation for the demonstration of these applications.

Diffraction-limited imaging on the 200-inch telescope

We have used the technique of non-redundant masking at the Palomar 200-inch telescope and radio VLBI imaging software to make optical aperture synthesis maps of two binary stars, β Corona Borealis and σ Herculis. The dynamic range of the map of β CrB, a binary star with a separation of 230 milliarcseconds is 50:1. For σ Her, we find a separation of 70 milliarcseconds and the dynamic range of our image is 30:1. These demonstrate the potential of the non-redundant masking technique for diffraction-limited imaging of astronomical objects with high dynamic range.

We find that the optimal integration time for measuring the closure phase is longer than that for measuring the fringe amplitude. There is not a close relationship between amplitude errors and phase errors, as is found in radio interferometry. Amplitude self calibration is less effective at optical wavelengths than at radio wavelengths. Primary beam sensitivity correction made in radio aperture synthesis is not necessary in optical aperture synthesis.

The effects of atmospheric disturbances on optical aperture synthesis have been studied by Monte Carlo simulations based on the Kolmogorov theory of refractive-index fluctuations. For the non-redundant masking with τ_c-sized apertures, the simulated fringe amplitude gives an upper bound of the observed fringe amplitude. A smooth transition is seen from the non-redundant masking regime to the speckle regime with increasing aperture size. The fractional reduction of the fringe amplitude according to the bandwidth is nearly independent of the aperture size. The limiting magnitude of optical aperture synthesis with τ_c-sized apertures and that with apertures larger than τ_c are derived.

Monte Carlo simulations are also made to study the sensitivity and resolution of the bispectral analysis of speckle interferometry. We present the bispectral modulation transfer function and its signal-to-noise ratio at high light levels. The results confirm the validity of the heuristic interferometric view of image-forming process in the mid-spatial-frequency range. The signal-to- noise ratio of the bispectrum at arbitrary light levels is derived in the mid-spatial-frequency range.

The non-redundant masking technique is suitable for imaging bright objects with high resolution and high dynamic range, while the faintest limit will be better pursued by speckle imaging.

Part 1: Longitudinal static and dynamic effects in semiconductor lasers. Part II: Spectral characteristics of passively mode-locked quantum well lasers

In the first part of this thesis a study of the effect of the longitudinal distribution of optical intensity and electron density on the static and dynamic behavior of semiconductor lasers is performed. A static model for above threshold operation of a single mode laser, consisting of multiple active and passive sections, is developed by calculating the longitudinal optical intensity distribution and electron density distribution in a self-consistent manner. Feedback from an index and gain Bragg grating is included, as well as feedback from discrete reflections at interfaces and facets. Longitudinal spatial holeburning is analyzed by including the dependence of the gain and the refractive index on the electron density. The mechanisms of spatial holeburning in quarter wave shifted DFB lasers are analyzed. A new laser structure with a uniform optical intensity distribution is introduced and an implementation is simulated, resulting in a large reduction of the longitudinal spatial holeburning effect.

A dynamic small-signal model is then developed by including the optical intensity and electron density distribution, as well as the dependence of the grating coupling coefficients on the electron density. Expressions are derived for the intensity and frequency noise spectrum, the spontaneous emission rate into the lasing mode, the linewidth enhancement factor, and the AM and FM modulation response. Different chirp components are identified in the FM response, and a new adiabatic chirp component is discovered. This new adiabatic chirp component is caused by the nonuniform longitudinal distributions, and is found to dominate at low frequencies. Distributed feedback lasers with partial gain coupling are analyzed, and it is shown how the dependence of the grating coupling coefficients on the electron density can result in an enhancement of the differential gain with an associated enhancement in modulation bandwidth and a reduction in chirp.

In the second part, spectral characteristics of passively mode-locked two-section multiple quantum well laser coupled to an external cavity are studied. Broad-band wavelength tuning using an external grating is demonstrated for the first time in passively mode-locked semiconductor lasers. A record tuning range of 26 nm is measured, with pulse widths of typically a few picosecond and time-bandwidth products of more than 10 times the transform limit. It is then demonstrated that these large time-bandwidth products are due to a strong linear upchirp, by performing pulse compression by a factor of 15 to a record pulse widths as low 320 fs.

A model for pulse propagation through a saturable medium with self-phase-modulation, due to the a-parameter, is developed for quantum well material, including the frequency dependence of the gain medium. This model is used to simulate two-section devices coupled to an external cavity. When no self-phase-modulation is present, it is found that the pulses are asymmetric with a sharper rising edge, that the pulse tails have an exponential behavior, and that the transform limit is 0.3. Inclusion of self-phase-modulation results in a linear upchirp imprinted on the pulse after each round-trip. This linear upchirp is due to a combination of self-phase-modulation in a gain section and absorption of the leading edge of the pulse in the saturable absorber.

Electrical, electrochemical, and optical characterization of ceria films

Acceptor-doped ceria has been recognized as a promising intermediate temperature solid oxide fuel cell electrode/electrolyte material. For practical implementation of ceria as a fuel cell electrolyte and for designing model experiments for electrochemical activity, it is necessary to fabricate thin films of ceria. Here, metal-organic chemical vapor deposition was carried out in a homemade reactor to grow ceria films for further electrical, electrochemical, and optical characterization. Doped/undoped ceria films are grown on single crystalline oxide wafers with/without Pt line pattern or Pt solid layer. Deposition conditions were varied to see the effect on the resultant film property. Recently, proton conduction in nanograined polycrystalline pellets of ceria drew much interest. Thickness-mode (through-plane, z-direction) electrical measurements were made to confirm the existence of proton conductivity and investigate the nature of the conduction pathway: exposed grain surfaces and parallel grain boundaries. Columnar structure presumably favors proton conduction, and we have found measurable proton conductivity enhancement. Electrochemical property of gas-columnar ceria interface on the hydrogen electrooxidation is studied by AC impedance spectroscopy. Isothermal gas composition dependence of the electrode resistance was studied to elucidate Sm doping level effect and microstructure effect. Significantly, preferred orientation is shown to affect the gas dependence and performance of the fuel cell anode. A hypothesis is proposed to explain the origin of this behavior. Lastly, an optical transmittance based methodology was developed to obtain reference refractive index and microstructural parameters (thickness, roughness, porosity) of ceria films via subsequent fitting procedure.

Mitigating Scarring and Inflammation during Corneal Wound Healing using Nanofiber-Hydrogel Scaffolds

Due to the universal lack of donor tissue, there has been emerging interest in engineering materials to stimulate living cells to restore the features and functions of injured organs. We are particularly interested in developing materials for corneal use, where the necessity to maintain the tissue’s transparency presents an additional challenge. Every year, there are 1.5 – 2 million new cases of monocular blindness due to irregular healing of corneal injuries, dwarfing the approximately 150,000 corneal transplants performed. The large gap between the need and availability of cornea transplantation motivates us to develop a wound-healing scaffold that can prevent corneal blindness.

To develop such a scaffold, it is necessary to regulate the cells responsible for repairing the damaged cornea, namely myofibroblasts, which are responsible for the disordered and non-refractive index matched scar that leads to corneal blindness. Using in vitro assays, we identified that protein nanofibers of certain orientation can promote cell migration and modulate the myofibroblast phenotype. The nanofibers are also transparent, easy to handle and non-cytotoxic. To adhere the nanofibers to a wound bed, we examined the use of two different in situ forming hydrogels: an artificial extracellular matrix protein (aECM)-based gel and a photo-crosslinkable heparin-based gel. Both hydrogels can be formed within minutes, are transparent upon gelation and are easily tunable.

Using an in vivo mouse model for epithelial defects, we show that our corneal scaffolds (nanofibers together with hydrogel) are well-tolerated (no inflammatory response or turbidity) and support epithelium regrowth. We developed an ex vivo corneal tissue culture model where corneas that are wounded and treated with our scaffold can be cultured while retaining their ability to repair wounds for up to 21 days. Using this technique, we found that the aECM-based treatment induced a more favorable wound response than the heparin-based treatment, prompting us to further examine the efficacy of the aECM-based treatment in vivo using a rabbit model for stromal wounds. Results show that treated corneas have fewer myofibroblasts and immune cells than untreated ones, indicating that our corneal scaffold shows promise in promoting a calmer wound response and preventing corneal haze formation.

Electrical and optical investigations of beta-gallium oxide

An experimental investigation of the optical properties of β–gallium oxide has been carried out, covering the wavelength range 220-2500 nm.

The refractive index and birefringence have been determined to about ± 1% accuracy over the range 270-2500 nm, by the use of a technique based on the occurrence of fringes in the transmission of a thin sample due to multiple internal reflections in the sample (ie., the "channelled spectrum" of the sample.)

The optical absorption coefficient has been determined over the range 220 - 300 nm, which range spans the fundamental absorption edge of β – Ga₂O₃. Two techniques were used in the absorption coefficient determination: measurement of transmission of a thin sample, and measurement of photocurrent from a Schottky barrier formed on the surface of a sample. Absorption coefficient was measured over a range from 10 to greater than 10⁵, to an accuracy of better than ± 20%. The absorption edge was found to be strongly polarization-dependent.

Detailed analyses are presented of all three experimental techniques used. Experimentally determined values of the optical constants are presented in graphical form.