Wayne Smith

Drug Stability Analysis by Raman Spectroscopy

Pharmaceutical drugs are available to astronauts to help them overcome the deleterious effects of weightlessness, sickness and injuries. Unfortunately, recent studies have shown that some of the drugs currently used may degrade more rapidly in space, losing their potency before their expiration dates. To complicate matters, the degradation products of some drugs can be toxic. Here, we present a preliminary investigation of the ability of Raman spectroscopy to quantify mixtures of four drugs; acetaminophen, azithromycin, epinephrine, and lidocaine, with their primary degradation products. The Raman spectra for the mixtures were replicated by adding the pure spectra of the drug and its degradant to determine the relative percent contributions using classical least squares. This multivariate approach allowed determining concentrations in ~10 min with a limit of detection of ~4% of the degradant. These results suggest that a Raman analyzer could be used to assess drug potency, nondestructively, at the time of use to ensure crewmember safety.

Microshutter arrays for near-infrared applications on the James Webb Space Telescope

Magnetically actuated MEMS microshutter arrays are being developed at the NASA Goddard Space Flight Center for use in a multi-object spectrometer on the James Webb Space Telescope (JWST), formerly Next Generation Space Telescope (NGST). The microshutter arrays are designed for the selective transmission of light with high efficiency and high contrast. The JWST environment requires cryogenic operation at 45K. Microshutter arrays are fabricated out of silicon-on-insulator (SOI) wafers. Arrays consist of close-packed shutters made on silicon nitride (nitride) membranes with a pixel size of 100 × 100 m. Individual shutters are patterned with a torsion flexure permitting shutters to open 90°, with a minimized mechanical stress concentration. Shutters operated this way have survived fatigue life test. The mechanical shutter arrays are fabricated using MEMS technologies. The processing includes a multi-layer metal deposition, patterning of shutter electrodes and magnetic pads, reactive ion etching (RIE) of the front side to form shutters in a nitride film, an anisotropic back-etch for wafer thinning, and a deep RIE (DRIE) back-etch, down to the nitride shutter layer, to form support frames and relieve shutters from the silicon substrate. An additional metal deposition and patterning has recently been developed to form electrodes on the vertical walls of the frame. Shutters are actuated using a magnetic force, and latched electrostatically. One-dimensional addressing has been demonstrated.

Analysis of Twenty-Two Performance Properties of Diesel, Gasoline, and Jet Fuels Using a Field-Portable Near-Infrared (NIR) Analyzer

The change in custody of fuel shipments at depots, pipelines, and ports could benefit from an analyzer that could rapidly verify that properties are within specifications. To meet this need, the design requirements for a fuel analyzer based on near-infrared (NIR) spectroscopy, such as spectral region and resolution, were examined. It was found that the 1000 to 1600 nm region, containing the second CH overtone and combination vibrational modes of hydrocarbons, provided the best near-infrared to fuel property correlations when path length was taken into account, whereas 4 cm−1 resolution provided only a modest improvement compared to 16 cm−1 resolution when four or more latent variables were used. Based on these results, a field-portable near-infrared fuel analyzer was built that employed an incandescent light source, sample compartment optics to hold 2 mL glass sample vials with ∼1 cm path length, a transmission grating, and a 256 channel InGaAs detector that measured the above stated wavelength range with 5–6 nm (∼32 cm−1) resolution. The analyzer produced high signal-to-noise ratio (SNR) spectra of samples in 5 s. Twenty-two property correlation models were developed for diesel, gasoline, and jet fuels with root mean squared error of correlation – cross-validated values that compared favorably to corresponding ASTM reproducibility values. The standard deviations of predicted properties for repeat measurements at 4, 24, and 38℃ were often better than ASTM documented repeatability values. The analyzer and diesel property models were tested by measuring seven diesel samples at a local ASTM certification laboratory. The standard deviations between the analyzer determined values and the ASTM measured values for these samples were generally better than the model root mean squared error of correlation—cross-validated values for each property.

Complex MEMS device: microshutter array system for space applications

A complex MEMS device, microshutter array system, is being developed at NASA Goddard Space Flight Center for use as an aperture array for a Near-Infrared Spectrometer (NirSpec). The instrument will be carried on the James Webb Space Telescope (JWST), the next generation of space telescope after Hubble Space Telescope retires. The microshutter arrays (MSAs) are designed for the selective transmission of light with high efficiency and high contrast. Arrays are close-packed silicon nitride membranes with a pixel size close to 100x200 &mgr;m. Individual shutters are patterned with a torsion flexure permitting shutters to open 90 degrees with a minimized mechanical stress concentration. Light shields are made on to each shutter for light leak prevention so to enhance optical contrast. Shutters are actuated magnetically, latched and addressed electrostatically. The shutter arrays are fabricated using MEMS bulk-micromachining technologies and packaged using single-sided indium flip-chip bonding technology. The MSA flight concept consists of a mosaic of 2 x 2 format of four fully addressable 365 x 171 arrays placed in the JWST optical path at the focal plane.

A portable fuel analyzer

Fuel is the single most import supply during war. Consider that the US Military is employing over 25,000 vehicles during Operation Iraqi Freedom. Most fuel is obtained locally, and must be characterized to ensure proper operation of these vehicles. Determination of fuel properties is currently determined using a deployed chemical laboratory. Unfortunately, each sample requires in excess of 5 hours to characterize. To overcome this limitation, we have developed a portable fuel analyzer capable of determine 7 fuel properties that allow determining fuel usage. The analyzer uses Raman spectroscopy to measure the fuel samples without preparation in 2 minutes. The challenge, however, is that as distilled fractions of crude oil, all fuels are composed of hundreds of hydrocarbon components that boil at similar temperatures, and performance properties can not be simply correlated to a single component, and certainly not to specific Raman peaks. To meet this challenge, we measured over 500 diesel and jet fuels from around the world and used chemometrics to correlate the Raman spectra to fuel properties. Critical to the success of this approach is laser excitation at 1064 nm to avoid fluorescence interference (many fuels fluoresce) and a rugged interferometer that provides 0.1 cm-1 wavenumber (x-axis) accuracy to guarantee accurate correlations. Here we describe the portable fuel analyzer, the chemometric models, and the successful determination of these 7 fuel properties for over 30 unknown samples provided by the US Marine Corps, US Navy, and US Army.

Pharmaceutical process applications of Raman spectroscopy

In the past decade Raman spectroscopy (Raman) has moved out of the shadow of infrared spectroscopy (IR) and has become a routine analytical tool and is finding value in pharmaceutical process applications. Raman offers several advantages over IR vibrational information in identifying and quantifying chemicals, such as linear response to concentration independent of path length, ability to measure aqueous solutions without interference from water bands, and ease of sampling provided by fiber optic probes. However, process measurements, such as continuous monitoring or raw materials identification have been slow to develop due to instability of the wavenumber axis. Commercial suppliers of dispersive based Raman systems employ calibration references and software approaches to solve this difficult problem. To overcome this difficulty, just as dispersive IRs have been replaced by FT-IRs, we have developed an industrial hardened FT-Raman system. Furthermore, we have increased sensitivity by 25 times by employing an Si detector instead of an InGaAs detector. Here we present the abilities of this Raman system to address a number of pharmaceutical applications, including identifying raw materials in less than one minute using spectral library matching, process monitoring during early stage optimization, analyzing blended materials, and determining polymorphism.

A military grade, field usable, Raman analyzer: measurement of captured fuel

Portable Raman analyzers have emerged during the first part of this century as an important field tool for crime scene and forensic analysis, primarily for their ability to identify unknown substances. This ability is also important to the US military, which has been investigating such analyzers for identification of explosive materials that may be used to produce improvised explosive devices, chemicals that may be used to produce chemical warfare agents, and fuels in storage tanks that may be used to power US military vehicles. However, the use of such portable analyzers requires that they meet stringent military standards (specifically MIL-STD 810G). These requirements include among others: 1) light weight and small size (< 35 pounds, < 3 cu. ft.), 2) vibration and shock resistant (26 four foot drops), 3) operation from -4 to 110 oF, 4) operation in blowing dust, sand and rain, 5) battery operation, and of course 6) safe operation (no laser or shock hazards). Here we describe a portable Raman analyzer that meets all of these requirements, and its use to determine if captured fuels are suitable for use.

Drug stability analyzer for long duration spaceflights

Crewmembers of current and future long duration spaceflights require drugs to overcome the deleterious effects of weightlessness, sickness and injuries. Unfortunately, recent studies have shown that some of the drugs currently used may degrade more rapidly in space, losing their potency well before their expiration dates. To complicate matters, the degradation products of some drugs can be toxic. Consequently there is a need for an analyzer that can determine if a drug is safe at the time of use, as well as to monitor and understand space-induced degradation, so that drug types, formulations, and packaging can be improved. Towards this goal we have been investigating the ability of Raman spectroscopy to monitor and quantify drug degradation. Here we present preliminary data by measuring acetaminophen, and its degradation product, p-aminophenol, as pure samples, and during forced degradation reactions.

Portable Raman spectroscopy using retina-safe (1550 nm) laser excitation

The use of portable Raman analyzers to identify unknown substances in the field has grown dramatically during the past decade. Measurements often require the laser beam to exit the confines of the sample compartment, which increases the potential of eye or skin damage. This is especially true for most commercial analyzers, which use 785 nm laser excitation. To overcome this safety concern, we have built a portable FT-Raman analyzer using a 1550 nm retina-safe excitation laser. Excitation at 1550 nm falls within the 1400 to 2000 nm retina-safe range, so called because the least amount of damage to the eye occurs in this spectral region. In contrast to wavelengths below 1400 nm, the retina-safe wavelengths are not focused by the eye, but are absorbed by the cornea, aqueous and vitreous humor. Here we compare the performance of this system to measurements of explosives at shorter wavelengths, as well as its ability to measure surface-enhanced Raman spectra of several chemicals, including the food contaminant melamine.

Identifying bacterial spores and anthrax hoax materials by Raman spectroscopy

The distribution of Bacillus anthracis spores through the US postal system in the autumn of 2001, initiated a secondary form of terror, the mailing of hoax materials. In the past three years nearly 20,000 letters containing harmless powders have been mailed, creating additional anxiety. Thus, there is a need for analyzers that can not only identify anthrax-causing spores to save lives, but also identify hoax materials to eliminate time-consuming and costly shutdowns. Recently, we established that Raman spectroscopy has the ability to identify both Bacilli endospores and hoax materials. Here we present Raman spectra of several Bacilli spores along with the dipicolinate salts, to further define the abilities of this technology to not only identify hoax materials, but also identify spores at the genus and species level.