Extended weightlessness causes numerous deleterious changes in human physiology, including space motion sickness,
cephalad fluid shifts, reduced immune response, and breakdown of muscle tissue with subsequent loss of bone mass and
formation of renal stones. Furthermore, these physiological changes also influence the metabolism of drugs used by
astronauts to minimize these deleterious effects. Unfortunately, the changes in human physiology in space are also
reflected in drug metabolism, and current pre-flight analyses designed to set dosage are inadequate. Furthermore,
current earth-based analytical laboratory methods that employ liquid or gas chromatography for separation and
fluorescence or mass spectrometry for trace detection are labor intensive, slow, massive, and not cost-effective for
operation in space. In an effort to overcome these instrument limitations we have been developing a sampling device to
both separate these drugs and metabolites from urine, and generate surface-enhanced Raman (SER) spectra. The
detailed molecular vibrational information afforded by Raman scattering allows chemical identification, while the
surface-enhancement increases sensitivity by six or more orders of magnitude and allows detection of nanogram per
milliliter concentrations. Generally no more than 1 milliliter of sample is required and complete analysis can be
performed in 5 minutes using a portable, light-weight Raman spectrometer. Here we present the SER analysis of
several drugs used by astronauts measured in synthetic urine and reconstituted urine.
As the war on terrorism in Afghanistan and Iraq continue, future attacks both abroad and in the U.S.A. are expected. In an effort to aid civilian and military personnel, we have been investigating the potential of using a surface-enhanced Raman spectroscopy (SERS) sampling device to detect Bacillus anthracis spores in nasal swab samples. Such a device would be extremely beneficial to medical responders and management in assessing the extent of a bioterrorist attack and making detect-to-treat decisions. The disposable sample device consists of a glass capillary filled with a silver-doped sol-gel that is capable of extracting dipicolinic acid (DPA), a chemical signature of Bacilli, and generating SERS spectra. The sampling device and preliminary measurements of DPA extracted from spores and nasal mucus will be presented.
The United States and its allies have been increasingly challenged by terrorism, and since the September 11, 2001 attacks and the war in Afghanistan and Iraq, homeland security has become a national priority. The simplicity in manufacturing chemical warfare agents, the relatively low cost, and previous deployment raises public concern that they may also be used by terrorists or rogue nations. We have been investigating the ability of surface-enhanced Raman spectroscopy (SERS) to detect extremely low concentrations (e.g. part-per-billion) of chemical agents, as might be found in poisoned water. Since trace quantities of nerve agents can be hydrolyzed in the presence of water, we have expanded our studies to include such degradation products. Our SERS-active medium consists of silver or gold nanoparticles incorporated into a sol-gel matrix, which is immobilized in a glass capillary. The choice of sol-gel precursor allows controlling hydrophobicity, while the porous silica network offers a unique environment for stabilizing the SERS-active metals. Here we present the use of these metal-doped sol-gels to selectively enhance the Raman signal of the hydrolyzed products of the G-series nerve agents.
Chemotherapy drug dosage is based on the limited statistics of the response of previously treated patients and administered according to body surface area. Considerably better dose regulation could be performed if the drug metabolism of each patient could be monitored. Unfortunately, current technologies require multiple withdrawals of blood to determine metabolism, a precious fluid in limited supply. Saliva analysis has long been considered an attractive alternative, but unfortunately standard techniques require large quantities that are difficult to obtain. In an effort to overcome this limitation we have been investigating the ability of metal-doped sol-gels to both separate drugs and their metabolites from saliva and generate surface-enhanced Raman spectra. Surface-enhanced Raman spectroscopy has the potential to perform this analysis with just a few drops of sample due to its extreme sensitivity. Preliminary measurements are presented for the chemotherapy drug, 5-fluorouracil, and its two metabolites 5-fluorouridine and 5-fluoro-2'-deoxyuridine, and the potential of determining metabolism on a patient-by-patient basis.
Pesticides are a key component in protecting crops and producing the quantity of food required by today's world population. However, since excessive concentrations pose a threat to human health, the USA sets strict tolerance levels to ensure public safety. Unfortunately, many other countries ignore these regulations and imported food exceeding these levels or contaminated with banned pesticides is a common occurrence. Furthermore, rapid chemical analysis of pesticide residues is unavailable, and only a very small fraction of foods are inspected. The greatest concern is fruit, for which an estimated 12 million tons were imported in 2003. In an effort to address this need, we have been developing a simple and rapid procedure to analyze for pesticides on fruit surfaces or in the juice of fruits. The procedure employs metal-doped sol-gel filled capillaries that both chemically extracts the pesticide and generates surface-enhanced Raman spectra when irradiated. The SERS-active capillaries, sensitivity, and preliminary fruit analyses are presented.
Modern agriculture depends on pesticides to curb infestations, increase crop yield and to produce the quantity and
quality of food demanded by today's society. However, potential pesticide residue contamination of food is of critical
concern to the food industry and the regulators responsible for health and safety. For example, many pesticides kill
insects by attacking the central nervous system, and the use of these pesticides above the EPA set tolerance levels (from
0.1 to 50 ppm) could pose a threat to humans, in particular infants. Unfortunately, rapid, chemical analysis of pesticide
residues is unavailable, and only a very small fraction of foods are inspected. The greatest concern is food imported
from nations that simply ignore US regulations. In an effort to address this need, we have been developing a simple
device to collect residues from food surfaces, perform a rapid chemical separation, and detect and identify pesticides by
surface-enhanced Raman spectroscopy (SERS). Capillaries are coated with a metal-doped sol-gel that both separates
chemicals and generates SER spectra when irradiated. SERS of pesticides at ppm concentrations, and a preliminary
product to aid inspectors is presented.
Traditional cancer treatment, surgical removal and gamma- or x-ray irradiation, is often augmented by the use of chemotherapy drugs. Theses drugs prevent cancer cell growth through a variety of biochemical mechanisms, but are not target specific and kill other cells. Consequently, the amount administered has a narrow range of safe and effective use. Furthermore, because of the dangerous side-effects of these drugs, clinical trials can not be performed, and a statistical basis for dosage is not available. Instead, the concentration of the drugs and their metabolites are monitored during treatment of cancer patients, Unfortunately current practices require 10-20 mL of blood per analysis, and multiple samples to profile pharmacokinetics may further jeopardize the patient's health. Saliva analysis has long been considered an attractive alternative, but the large sample volumes are difficult to obtain. In an effort to overcome this limitation we have been investigating metal-doped sol-gels to both separate drugs and their metabolites from saliva and generate surface-enhanced Raman spectra. We have incorporated the sol-gel in a disposable pipette format, and generally no more than two drops (100 μL) of sample are required. The detailed molecular vibrational information allows chemical identification, while the increase in Raman scattering by four to six orders of magnitude allows detection of nanomolar concentrations. Preliminary measurements will be presented.
U.S. and Coalition forces fighting terrorism in Afghanistan and Iraq must consider a wide range of attack scenarios in addition to car bombings. Among these is the intentional poisoning of water supplies to obstruct military operations. To counter such attacks, the military is developing portable analyzers that can identify and quantify potential chemical agents in water supplies at microgram per liter concentrations within 10 minutes. To aid this effort we have been investigating the value of a surface-enhanced Raman spectroscopy based portable analyzer. In particular we have been
developing silver-doped sol-gels to generate SER spectra of chemical agents and their hydrolysis products. Here we present SER spectra of methyl phosphonic acid and cyanide as a function of pH, an important factor affecting quantitation measurements, which to our knowledge has not been examined. In addition, dipicolinic acid, a chemical signature associated with anthrax-causing spores, is also presented.
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.
In the past decade, the Unites States and its allies have been challenged by a different kind of warfare, exemplified by
the terrorist attacks of September 11, 2001. Although suicide bombings are the most often used form of terror, military
personnel must consider a wide range of attack scenarios. Among these is the intentional poisoning of water supplies to
obstruct military operations in Afghanistan and Iraq. To counter such attacks, the military is developing portable
analyzers that can identify and quantify potential chemical agents in water supplies at microgram per liter
concentrations within 10 minutes. To aid this effort we have been investigating the value of a surface-enhanced Raman
spectroscopy based portable analyzer. In particular we have been developing silver-doped sol-gels to generate SER
spectra of chemical agents and their hydrolysis products. Here we present SER spectra of several chemical agents
measured in a generic tap water. Repeat measurements were performed to establish statistical error associated with
SERS obtained using the sol-gel coated vials.
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