Dan Kelly

Investigation of protein conformation and interactions with salts via X-ray absorption spectroscopy

Nitrogen K-edge spectra of aqueous triglycine were measured using liquid microjets, and the effects of Hofmeister-active salts on the spectra were observed. Spectra simulated using density functional theory, sampled from room temperature classical molecular dynamics trajectories, capture all major features in the measured spectra. The spectrum of triglycine in water is quite similar to that in the presence of chaotropic sodium bromide (and other halides), which raises the solubility of proteins. However, a new feature is found when kosmotropic Na2SO3, which lowers solubility, is present; this feature results from excitations of the nitrogen atom in the terminal amino group of triglycine. Both direct interactions between this salt and the protonated amino terminus, as well as corresponding changes in the conformational dynamics of the system, contribute to this new feature. These molecular measurements support a different mechanism for the Hofmeister effect than has previously been suggested based on thermodynamic measurements. It is also shown that near edge X-ray absorption fine structure (NEXAFS) is sensitive to strong direct interaction between certain salts and charged peptides. However, by investigating the sensitivity of NEXAFS to the extreme structural differences between model β-sheets and α-helices, we conclude that this technique is relatively insensitive to secondary structure of peptides and proteins.

Integrated optical biosensor for detection of multivalent proteins.

We have developed a simple, highly sensitive and specific optical waveguide sensor for the detection of multivalent proteins. The optical biosensor is based on optically tagged glycolipid receptors embedded within a fluid phospholipid bilayer membrane formed upon the surface of a planar optical waveguide. Binding of multivalent cholera toxin triggers a fluorescence resonance energy transfer that results in a two-color optical change that is monitored by measurement of emitted luminescence above the waveguide surface. The sensor approach is highly sensitive and specific and requires no additional reagents and washing steps. Demonstration of protein-receptor recognition by use of planar optical waveguides provides a path forward for the development of fieldable miniaturized biosensor arrays.

Communication: Near edge x-ray absorption fine structure spectroscopy of aqueous adenosine triphosphate at the carbon and nitrogen K-edges

Near edge x-ray absorption fine structure (NEXAFS) spectroscopy at the nitrogen and carbon K-edges was used to study the hydration of adenosine triphosphate in liquid microjets. The total electron yield spectra were recorded as a function of concentration, pH, and the presence of sodium, magnesium, and copper ions (Na(+)/Mg(2+)/Cu(2+)). Significant spectral changes were observed upon protonation of the adenine ring, but not under conditions that promote π-stacking, such as high concentration or presence of Mg(2+), indicating that NEXAFS is insensitive to the phenomenon. Intramolecular inner-sphere association of Cu(2+) did create observable broadening of the nitrogen spectrum, whereas outer-sphere association with Mg(2+) did not.

Surface characterization of oxidative corrosion of U–Nb alloys

We have studied the relative rates of oxidative corrosion of U–Nb alloys containing 2–8 wt. % Nb, using x-ray photoelectron spectroscopy and depth profiling by sputtered neutrals mass spectroscopy. The alloys have been characterized after exposure to dry and humidified air (up to 50% relative humidity) at temperatures from 25 to 125 °C, and after exposure to electrochemical solutions. Oxidation of the U–Nb alloys in a tube furnace results in oxide layers comprised of UO2 and Nb2O5 under all experimental conditions used. The thickness of the oxides increased with treatment time and temperature, but decreased with increasing Nb alloy content. For example, a 48 h treatment at 75 °C and 50% relative humidity results in an oxide layer on U–2% Nb that is approximately 1.5 times as thick as that on U–8% Nb. Electrochemical oxidation of U–Nb alloys facilely generated UO3(⋅nH2O) and Nb2O5 layers ∼1000 A thick, qualitatively similar to thermal oxidation results. U–Nb alloys electrochemically oxidized at low pH exhibit oxide layers with near-surface regions (50 A) enhanced in Nb content, as compared to the bulk material. Surface UO3(⋅nH2O) was not readily reduced upon exposure to molecular D2; however, D atoms facilely reduced UO3(⋅nH2O) to UO2. We have studied the relative rates of oxidative corrosion of U–Nb alloys containing 2–8 wt. % Nb, using x-ray photoelectron spectroscopy and depth profiling by sputtered neutrals mass spectroscopy. The alloys have been characterized after exposure to dry and humidified air (up to 50% relative humidity) at temperatures from 25 to 125 °C, and after exposure to electrochemical solutions. Oxidation of the U–Nb alloys in a tube furnace results in oxide layers comprised of UO2 and Nb2O5 under all experimental conditions used. The thickness of the oxides increased with treatment time and temperature, but decreased with increasing Nb alloy content. For example, a 48 h treatment at 75 °C and 50% relative humidity results in an oxide layer on U–2% Nb that is approximately 1.5 times as thick as that on U–8% Nb. Electrochemical oxidation of U–Nb alloys facilely generated UO3(⋅nH2O) and Nb2O5 layers ∼1000 A thick, qualitatively similar to thermal oxidation results. U–Nb alloys electrochemically oxidized at low pH exhi...

The ACADIA ASIC - detector control and digitization for the Wide-Field Infrared Survey Telescope (WFIRST)

NASAs Wide-Field Infrared Survey Telescope (WFIRST) project has developed the ACADIA ASIC, a next generation detector control and acquisition system-on-a-chip. The purpose of this ASIC is to address the stringent requirements of operating a cryogenic detector in a spacecraft environment. Key performance criteria are low analog noise and low power consumption at temperatures between 150K and 180K while supporting the full dynamic range of the sensor. The ASIC is primarily intended to operate the Teledyne H4RG for WFIRST, but has been designed with considerable flexibility to provide compatibility with a large selection of other detectors. Up to 40 analog sensor outputs can processed in parallel, where each signal is amplified and conditioned by a low-noise pre-amplifier with programmable gain and bandwidth, and then digitized by a 16-bit successive approximation analog-to-digital converter (ADC). The ASIC includes 24 analog output channels that can be configured as programmable voltage or current sources, and are used to generate biases and references to the detector. A simple-to-program sequencer provides timing control for the detector and the ASIC internal circuits, with the option of using an embedded microprocessor for more elaborate readout schemes. This paper presents an overview of the ACADIA ASIC design with detailed descriptions of its analog, mixedsignal, and digital circuit blocks. First prototypes of the ACADIA ASIC have been fabricated, and preliminary test results of functionality and performance have been measured. We discuss the test environment and the obtained results, and conclude by describing the next steps for the project. The ACADIA ASIC is intended to operate the Teledyne H4RG infrared hybrid detector (current baseline for the WFIRST Wide-Field Instrument), but has been designed with considerable flexibility to provide compatibility with a large selection of other detectors. Each analog sensor output is amplified and conditioned by a low-noise pre-amplifier with programmable gain and bandwidth, and then digitized by a 16-bit successive approximation analog-to-digital converter (ADC). Up to 40 signals can be processed in parallel. Some basic math functions like summing, averaging, threshold comparison, and digital gain are available per channel. In addition, the ASIC includes 24 analog output channels that can be configured as programmable voltage or current sources, and are used to provide biases and references to the detector. Overall timing control is provided by a flexible but simple-to-program sequencer, with the option of microprocessor control for more elaborate readout schemes. Further digital capabilities include Direct Memory Access (DMA) engine, timers, Serial Peripheral Interface (SPI), and science data formatting for transmission. All circuitry has been protected against single event effects from ionizing radiation. We will discuss the status of the development effort, with focus on the performance requirements, general design features, and available test results. Over the course of the development, several test chips have been built that have already demonstrated significant improvements in analog performance over prior solutions, and have shown compliance with key WFIRST requirements for both cryogenic and room temperature operation. Prototypes of the full 40-channel ACADIA ASIC have been fabricated and are currently being tested. In addition to the chip itself, the packaging approach, test environment, and control electronics with computer acquisition will be presented.

Detector control and data acquisition for the wide field infrared survey telescope (WFIRST) with a custom ASIC

The Wide-Field Infrared Survey Telescope (WFIRST) will have the largest near-IR focal plane ever flown by NASA, a total of 18 4K x 4K devices. The project has adopted a system-level approach to detector control and data acquisition where 1) control and processing intelligence is pushed into components closer to the detector to maximize signal integrity, 2) functions are performed at the highest allowable temperatures, and 3) the electronics are designed to ensure that the intrinsic detector noise is the limiting factor for system performance. For WFIRST, the detector arrays operate at 90 to 100 K, the detector control and data acquisition functions are performed by a custom ASIC at 150 to 180 K, and the main data processing electronics are at the ambient temperature of the spacecraft, notionally ~300 K. The new ASIC is the main interface between the cryogenic detectors and the warm instrument electronics. Its single-chip design provides basic clocking for most types of hybrid detectors with CMOS ROICs. It includes a flexible but simple-to-program sequencer, with the option of microprocessor control for more elaborate readout schemes that may be data-dependent. All analog biases, digital clocks, and analog-to-digital conversion functions are incorporated and are connected to the nearby detectors with a short cable that can provide thermal isolation. The interface to the warm electronics is simple and robust through multiple LVDS channels. It also includes features that support parallel operation of multiple ASICs to control detectors that may have more capability or requirements than can be supported by a single chip.

Integrated optical toxin sensor

We have developed a method for simple and highly sensitive detection of multivalent proteins using an optical waveguide sensor. The optical biosensor is based on optically tagged glycolipid receptors imbedded within a fluid phospholipid bilayer membrane formed on the surface of a planar optical waveguide. The binding of multivalent toxin initiates a fluorescence resonance energy transfer resulting in a distinctive spectral signature that is monitored by measuring emitted luminescence above the waveguide surface. The sensor methodology is highly sensitive and specific, and requires no additional reagents or washing steps. Demonstration of the utility of protein-receptor recognition using planar optical waveguides is shown here by the detection of cholera toxin.