An Analog Phase Interpolation Based Fractional-N PLL

A novel phase-locked loop topology is presented. Compared to conventional designs, this architecture aims to increase frequency resolution and reduce quantization noise while maintaining the fractional-N benefits of high bandwidth and low phase noise up-conversion. This is achieved utilizing a feedforward mechanism for offset cancellation from the integer-N frequency. The design is implemented in a 0.13μm CMOS process technology. A frequency resolution of 1.16Hz is achieved on a 5GHz differential delay cell VCO with a 100MHz reference oscillator. A ping-pong swallow counter topology alleviates pipeline latency to achieve 1-64 divide ratios. A digital pulse generator and nested phase-frequency detector provide tunable offset cancellation. A 5-bit current-steering DAC capable of 200ps pulses reduces output spurs. Theoretical calculations and Simulink modeling provides insight to the effects of non idealities in the system. Test structures and loop configurability are programmed via SPI interface through a custom GUI and prototype PCB

An Integrated-Photonics Optical-Frequency Synthesizer

Integrated-photonics microchips now enable a range of advanced functionalities for high-coherence applications such as data transmission, highly optimized physical sensors, and harnessing quantum states, but with cost, efficiency, and portability much beyond tabletop experiments. Through high-volume semiconductor processing built around advanced materials there exists an opportunity for integrated devices to impact applications cutting across disciplines of basic science and technology. Here we show how to synthesize the absolute frequency of a lightwave signal, using integrated photonics to implement lasers, system interconnects, and nonlinear frequency comb generation. The laser frequency output of our synthesizer is programmed by a microwave clock across 4 THz near 1550 nm with 1 Hz resolution and traceability to the SI second. This is accomplished with a heterogeneously integrated III/V-Si tunable laser, which is guided by dual dissipative-Kerr-soliton frequency combs fabricated on silicon chips. Through out-of-loop measurements of the phase-coherent, microwave-to-optical link, we verify that the fractional-frequency instability of the integrated photonics synthesizer matches the $7.0*10^{-13}$ reference-clock instability for a 1 second acquisition, and constrain any synthesis error to $7.7*10^{-15}$ while stepping the synthesizer across the telecommunication C band. Any application of an optical frequency source would be enabled by the precision optical synthesis presented here. Building on the ubiquitous capability in the microwave domain, our results demonstrate a first path to synthesis with integrated photonics, leveraging low-cost, low-power, and compact features that will be critical for its widespread use.Comment: 10 pages, 6 figure

A Versatile Mixed-Signal Controller for Optoelectronic Frequency Synthesis

Self-referenced optical combs have proven pivotal for numerous metrology applications including precision navigation, LiDAR, and molecular spectroscopy. While plenty of research has improved and broadened the scope of this instrument, most implementations to date have been lab-scale setups that require kilowatts of power. The size, weight and power (SWaP) needs to shrink in order to fully realize the potential of this technology.Silicon chip-based Photonic Integrated Circuits (PICs) provide a platform to exploit the same optical phenomena in a reduced SWaP. However, these miniature devices are inherently prone to fabrication variation and environmental fluctuations during operation. An associated issue is the coupling of precision and power. Where bench top implementations can circumvent many issues by increasing the laser power to mitigate downstream losses in optical elements, an integrated solution requires novel electronic signal estimation, detection and stabilization architectures to maintain precision under a low power budget.This dissertation presents a mixed-signal controller designed to handle the challenges of achieving parts-per-trillion frequency stability in an integrated optoelectronic frequency synthesizer. I discuss the development of a heterodyne-based architecture and highlight experimental results from a PCB prototype using commercial-off-the-shelf electronics. The limitations present at the board-level are further mitigated by the development of a custom IC. Results from an application-specific integrated circuit (ASIC) designed in 55nm CMOS show the potential of integration in reducing the SWaP. Ultimately, this architecture achieves state-of-the-art performance, producing a 193 THz output with 5.6 mHz average deviation (2.9e-17 ADEV @ 1000s). The synthesizer is tunable >40 nm across the C-band with 745 mHz setpoint resolution, capable of full configurability in real-time via a custom Graphical User Interface (GUI)

A Versatile Mixed-Signal Controller for Optoelectronic Frequency Synthesis

Self-referenced optical combs have proven pivotal for numerous metrology applications including precision navigation, LiDAR, and molecular spectroscopy. While plenty of research has improved and broadened the scope of this instrument, most implementations to date have been lab-scale setups that require kilowatts of power. The size, weight and power (SWaP) needs to shrink in order to fully realize the potential of this technology.Silicon chip-based Photonic Integrated Circuits (PICs) provide a platform to exploit the same optical phenomena in a reduced SWaP. However, these miniature devices are inherently prone to fabrication variation and environmental fluctuations during operation. An associated issue is the coupling of precision and power. Where bench top implementations can circumvent many issues by increasing the laser power to mitigate downstream losses in optical elements, an integrated solution requires novel electronic signal estimation, detection and stabilization architectures to maintain precision under a low power budget.This dissertation presents a mixed-signal controller designed to handle the challenges of achieving parts-per-trillion frequency stability in an integrated optoelectronic frequency synthesizer. I discuss the development of a heterodyne-based architecture and highlight experimental results from a PCB prototype using commercial-off-the-shelf electronics. The limitations present at the board-level are further mitigated by the development of a custom IC. Results from an application-specific integrated circuit (ASIC) designed in 55nm CMOS show the potential of integration in reducing the SWaP. Ultimately, this architecture achieves state-of-the-art performance, producing a 193 THz output with 5.6 mHz average deviation (2.9e-17 ADEV @ 1000s). The synthesizer is tunable >40 nm across the C-band with 745 mHz setpoint resolution, capable of full configurability in real-time via a custom Graphical User Interface (GUI)

Avidity and Bystander Suppressive Capacity of Human Regulatory T Cells Expressing De Novo Autoreactive T-Cell Receptors in Type 1 Diabetes.

The ability to alter antigen specificity by T-cell receptor (TCR) or chimeric antigen receptor (CAR) gene transfer has facilitated personalized cellular immune therapies in cancer. Inversely, this approach can be harnessed in autoimmune settings to attenuate inflammation by redirecting the specificity of regulatory T cells (Tregs). Herein, we demonstrate efficient protocols for lentiviral gene transfer of TCRs that recognize type 1 diabetes-related autoantigens with the goal of tissue-targeted induction of antigen-specific tolerance to halt β-cell destruction. We generated human Tregs expressing a high-affinity GAD555-567-reactive TCR (clone R164), as well as the lower affinity clone 4.13 specific for the same peptide. We demonstrated that de novo Treg avatars potently suppress antigen-specific and bystander responder T-cell (Tresp) proliferation in vitro in a process that requires Treg activation (P < 0.001 versus unactivated Tregs). When Tresp were also glutamic acid decarboxylase (GAD)-reactive, the high-affinity R164 Tregs exhibited increased suppression (P < 0.01) with lower Tresp-division index (P < 0.01) than the lower affinity 4.13 Tregs. These data demonstrate the feasibility of rapid expansion of antigen-specific Tregs for applications in attenuating β-cell autoimmunity and emphasize further opportunities for engineering cellular specificities, affinities, and phenotypes to tailor Treg activity in adoptive cell therapies for the treatment of type 1 diabetes

Avidity and Bystander Suppressive Capacity of Human Regulatory T Cells Expressing De Novo Autoreactive T-Cell Receptors in Type 1 Diabetes

The ability to alter antigen specificity by T-cell receptor (TCR) or chimeric antigen receptor (CAR) gene transfer has facilitated personalized cellular immune therapies in cancer. Inversely, this approach can be harnessed in autoimmune settings to attenuate inflammation by redirecting the specificity of regulatory T cells (Tregs). Herein, we demonstrate efficient protocols for lentiviral gene transfer of TCRs that recognize type 1 diabetes-related autoantigens with the goal of tissue-targeted induction of antigen-specific tolerance to halt β-cell destruction. We generated human Tregs expressing a high-affinity GAD555–567-reactive TCR (clone R164), as well as the lower affinity clone 4.13 specific for the same peptide. We demonstrated that de novo Treg avatars potently suppress antigen-specific and bystander responder T-cell (Tresp) proliferation in vitro in a process that requires Treg activation (P < 0.001 versus unactivated Tregs). When Tresp were also glutamic acid decarboxylase (GAD)-reactive, the high-affinity R164 Tregs exhibited increased suppression (P < 0.01) with lower Tresp-division index (P < 0.01) than the lower affinity 4.13 Tregs. These data demonstrate the feasibility of rapid expansion of antigen-specific Tregs for applications in attenuating β-cell autoimmunity and emphasize further opportunities for engineering cellular specificities, affinities, and phenotypes to tailor Treg activity in adoptive cell therapies for the treatment of type 1 diabetes