Assessing thermochromatography as a separation method for nuclear forensics: current capability vis-à-vis forensic requirements

Nuclear forensic science has become increasingly important for global nuclear security. However, many current laboratory analysis techniques are based on methods developed without the imperative for timely analysis that underlies the post-detonation forensics mission requirements. Current analysis of actinides, fission products, and fuel-specific materials requires time-consuming chemical separation coupled with nuclear counting or mass spectrometry. High-temperature gas-phase separations have been used in the past for the rapid separation of newly created elements/isotopes and as a basis for chemical classification of that element. We are assessing the utility of this method for rapid separation in the gas-phase to accelerate the separations of radioisotopes germane to post-detonation nuclear forensic investigations. The existing state of the art for thermochromatographic separations, and its applicability to nuclear forensics, will be reviewed.     

Analytical methods for separating and isolating magnetic nanoparticles

Despite the large body of literature describing the synthesis of magnetic nanoparticles, few analytical tools are commonly used for their purification and analysis. Due to their unique physical and chemical properties, magnetic nanoparticles are appealing candidates for biomedical applications and analytical separations. Yet in the absence of methods for assessing and assuring their purity, the ultimate use of magnetic particles and heterostructures is likely to be limited. In this review, we summarize the separation techniques that have been initially used for this purpose. For magnetic nanoparticles, it is the use of an applied magnetic flux or field gradient that enables separations. Flow based techniques are combined with applied magnetic fields to give methods such as magnetic field flow fractionation and high gradient magnetic separation. Additional techniques have been explored for manipulating particles in microfluidic channels and in mesoporous membranes. Further development of these and new analytical tools for separation and analysis of colloidal particles is critically important to enable the practical use of these, particularly for medicinal purposes.     

Two‐dimensional separation techniques using supercritical fluid chromatography

High‐resolution separation systems are essential for the analysis of complex mixtures in a wide variety of application areas. To increase resolution, multidimensional chromatographic techniques have been one key solution. Supercritical fluid chromatography provides a unique opportunity in these multidimensional separations based on its potential for high solvent compatibility, rapid duty cycles, and orthogonality to other separation modes. This review focuses on two‐dimensional chromatography methods from the past decade that use supercritical fluid chromatography because of these advantages. Valving schemes and modulation strategies used to interface supercritical fluid chromatography with other liquid chromatography and gas chromatography techniques are described. Particular applications of multidimensional separations using supercritical fluid chromatography for the analysis of oils and chiral separations of pharmaceutical compounds are highlighted. Limitations of and a potential trajectory for supercritical fluid chromatography in this field are also discussed.     

Nuclear forensic analysis of thorium

A comprehensive radiochemical isolation procedure and data analysis/interpretation method for the nuclear forensic investigation of Th has been developed. The protocol includes sample dissolution, chemical separation, nuclear counting techniques, consideration of isotopic parent-daughter equilibria, and data interpretation tactics. Practical application of the technology was demonstrated by analyses of a questioned specimen confiscated at an illegal drug synthesis laboratory by law enforcement authorities.     

Determination of rare-earth elements in uranium-bearing materials by inductively coupled plasma mass spectrometry

A novel and simple analytical procedure has been developed for the trace-level determination of lanthanides (rare-earth elements) in uranium-bearing materials by inductively coupled plasma sector-field mass spectrometry (ICP-SFMS). The method involves a selective extraction chromatographic separation of lanthanides using TRU™ resin followed by ICP-SFMS analysis. The limits of detection of the method proposed is in the low pg g⁻¹ range, which are approximately two orders of magnitude better than that of without chemical separation. The method was validated by the measurement of reference material and applied for the analysis of uranium ore concentrates (yellow cakes) for nuclear forensic purposes, as a potential application of the methodology.     

Continuous gas phase chemical separations

Gas-phase chemical separations have been used for the study of short-lived fission products. Often the chemical separation is achieved in a few seconds. The articles reviews the techniques used in fast, gas-phase separations.     

Determination of technetium-99 in environmental samples: A review

Due to the lack of a stable technetium isotope, and the high mobility and long half-life, ⁹⁹Tc is considered to be one of the most important radionuclides in safety assessment of environmental radioactivity as well as nuclear waste management. ⁹⁹Tc is also an important tracer for oceanographic research due to the high technetium solubility in seawater as TcO₄⁻. A number of analytical methods, using chemical separation combined with radiometric and mass spectrometric measurement techniques, have been developed over the past decades for determination of ⁹⁹Tc in different environmental samples. This article summarizes and compares recently reported chemical separation procedures and measurement methods for determination of ⁹⁹Tc. Due to the extremely low concentration of ⁹⁹Tc in environmental samples, the sample preparation, pre-concentration, chemical separation and purification for removal of the interferences for detection of ⁹⁹Tc are the most important issues governing the accurate determination of ⁹⁹Tc. These aspects are discussed in detail in this article. Meanwhile, the different measurement techniques for ⁹⁹Tc are also compared with respect to advantages and drawbacks. Novel automated analytical methods for rapid determination of ⁹⁹Tc using solid extraction or ion exchange chromatography for separation of ⁹⁹Tc, employing flow injection or sequential injection approaches are also discussed.     

Development of rapid methodologies for the isolation and quantitation of drug metabolites by differential mobility spectrometry – mass spectrometry

Clinical and forensic toxicology laboratories are inundated with thousands of samples requiring lengthy chromatographic separations prior to mass spectrometry. Here, we employ differential mobility spectrometry (DMS) interfaced to nano-electrospray ionization-mass spectrometry to provide a rapid ion filtration technique for the separation of ions in gas phase media prior to mass spectral analysis on a DMS-integrated AB SCIEX API 3000 triple-quadrupole mass spectrometer. DMS is efficient at the rapid separation of ions under ambient conditions and provides many advantages when used as an ion filtration technique in tandem with mass spectrometry (MS) and MS/MS. Our studies evaluated DMS-MS/MS as a rapid, quantitative platform for the analysis of drug metabolites isolated from urine samples. In targeted applications, five metabolites of common drugs of abuse were effectively and rapidly separated using isopropanol and ethyl acetate as transport gas modifiers, eliminating the gas chromatography or liquid chromatography-based separations commonly employed in clinical and forensic toxicology laboratories. Calibration curves were prepared for the selected drug metabolites utilizing deuterated internal standards for quantitative purposes. The feasibility of separating and quantitating drug metabolites in a rapid fashion was evaluated by compensation voltage stepping followed by multiple reaction monitoring (MRM) detection. Rapid profiling of clinical and forensic toxicology samples could help to address an urgent need within the scientific community by developing high-throughput analytical methodologies, which could reduce significant case backlogs present within these laboratories.     

Two-dimensional separations with electrospray ionization ambient pressure high-resolution ion mobility spectrometry/quadrupole mass spectrometry

The coupling of ion mobility spectrometry (IMS) instruments with mass spectrometers has been described since early in IMS development, most commonly with quadrupole mass analyzers. The recent development of IMS with time-of-flight (TOF) instruments has demonstrated that the time compatibility (IMS milliseconds and TOFMS microseconds) of the two techniques enables rapid two-dimensional separations to be performed, theoretically in the order of seconds for a complete analysis. This study presents a unique way to operate a traditional IMS/QMS system to attain separations similar to those achieved with IMS/TOF. For this new approach, the quadrupole was slowly scanned in the single-ion monitoring mode while IMS spectra were continually embedded in each m/z step. In this way, two-dimensional separations (IMS drift times and m/z) were obtained using the traditional IMS/QMS arrangement. An example of a five amino acid separation (quadrupole scan of 40 m/z values at a rate of approximately 7 steps/min) led to a complete two-dimensional analysis within 6 min, comparable to rapid chromatographic separations with mass spectrometry. Proposed approaches to reduce the analysis time are discussed and a reduction in the analysis time to less than 1 min is feasible when the IMS/QMS separation conditions are optimized.     

Enantioselective capillary electrochromatography: recent developments and new trends

Since its development in the early 1970s, CEC has been studied quite extensively, but unfortunately its use is still mostly located at an academic level. Reasons for this are the limited availability of commercially available stationary phases (SPs) and columns, along with some practical limitations, such as column fragility, lack of column robustness and reproducibility. Nevertheless, CEC maintains a place among the separation techniques, probably because of its unique feature to combine two separation principles. Also in the field of chiral separations, CEC is often used as a separation technique and already showed its potential for this kind of analyses. This overview will focus on the recent applications, i.e. between 2006 and 2010, in enantioselective analysis by means of CEC. For the selected applications, the used SPs (chiral selectors) and their potential for future method development or screening purposes will be evaluated and critically discussed.     

State of practice and emerging application of analytical techniques of nuclear forensic analysis: highlights from the 5th Collaborative Materials Exercise of the Nuclear Forensics International Technical Working Group (ITWG)

The Nuclear Forensics International Technical Working Group (ITWG), a community of nuclear forensic practitioners who respond to incidents involving nuclear and other radioactive material out of regulatory control, completed its fifth Collaborative Materials Exercise in 2017 (CMX-5). Forensic laboratories from 19 countries and one multinational organization aimed to advance nuclear forensic science and improve international cooperation in the event of a nuclear material security incident. In all, over 30 analytical techniques were utilized to investigate the samples, many techniques applying novel methods or offering improvements in turnaround time. An objective review of the state of practice and emerging application of analytical techniques of nuclear forensic analysis based upon this exercise is provided.

     

Size-exclusion chromatography—from high-performance to ultra-performance

Size-exclusion chromatography (SEC) enables measurement of the average molecular weights and molecular-weight distributions of polymers. Because these characteristics may, in turn, be correlated with important performance characteristics of plastics, SEC is an essential analytical technique for characterization of macromolecules. Although SEC is one of the oldest instrumental chromatographic techniques, it is still under continuous development, as a result of the great demand for increased resolution and faster analysis in SEC. Ultra-high-pressure size-exclusion chromatography (UHPSEC) was recently introduced to satisfy the growing demands of analytical chemists. Using instrumentation capable of generating very high pressures and columns packed with small particles, this technique enables greater separation efficiency and faster analysis than are achieved with conventional SEC. UHPSEC is especially advantageous for high-resolution analysis of oligomers, for very rapid polymer separations, and as a second dimension in comprehensive two-dimensional liquid chromatography of polymers. In this paper we discuss the benefits of UHPSEC for separation of macromolecules, with examples from the literature.     

Recent applications in CEC

In this review, research papers on CEC are summarized that have been published between May 2005 and May 2007. Application-oriented research is discussed in which CEC is used in biochemical and pharmaceutical studies, in the analysis of food and natural products, and in industrial, environmental, and forensic analysis. Some trends and developments in separation science that may increase the applicability of the separation technique CEC are highlighted: 2-D separation systems and the application of nano- and microfluidic devices in separations.     

Ion chromatography for the separation of heparin and structurally related glycoaminoglycans: A review

The global crisis resulting from adulterated heparin in late 2007 and early 2008 revived the importance of analytical techniques for the purity analysis of heparin products. The utilization of ion chromatography techniques for the separation, detection, and structural determination of heparin and structurally related glycoaminoglycans, including their corresponding oligosaccharides, has become increasingly important. This review summarizes the primary HPLC approaches, particularly strong anion exchange, weak ion exchange, and reversed‐phase ion‐pair, used for heparin purity analysis as well as structural characterization. Strong anion exchange HPLC has been studied most extensively and currently offers the best separation of crude heparin and heparin‐like compounds. Weak anion exchange HPLC has been shown to provide shorter analysis times with lower salt concentrations in the mobile phase but is not as widely developed for the separation of all glycoaminoglycans of interest. Reversed‐phase ion‐pair HPLC offers fast and effective separations of oligosaccharides derived from glycoaminoglycans that can be coupled to mass spectrometry for structural analysis. However, this method generally does not provide sufficient retention of intact glycoaminoglycans.     

Detection method for microchip separations

The features of analytical systems utilizing microfluidic devices, especially detection methods, are described. Electrochemical detection (EC), laser-induced fluorescence (LIF), mass spectrometry (MS), and chemical luminescence (CL) methods are covered. EC enables detection without labeling and has been used in recent years because of its low cost and sensitivity. LIF is the most generally used detection method in microchip separations. Use of LED as an excitation source for fluorescence measurement was also developed for the purpose of miniaturization of the entire system, including detection and separation. Although MS enables highly sensitive analysis, the interface between MS and micro channels is still under examination. This review with fifty-two references introduces interesting detection methods for microchip separations. Related separation methods using microfluidic devices are also discussed.     

Stabilized phospholipid membranes in chromatography: toward membrane protein-functionalized stationary phases

Transmembrane protein (TMP)-functionalized materials have resulted in powerful new methods in chemical analysis. Of particular interest is the development of high-throughput, TMP-functionalized stationary phases for affinity chromatography of complex mixtures of analytes. Several natural and synthetic phospholipids and lipid mimics have been used for TMP reconstitution, although the resulting membranes often lack the requisite chemical and temporal stability for long-term use, a problem that is exacerbated in flowing separation systems. Polymerizable lipids with markedly increased membrane stability and TMP functionality have been developed over the past two decades. More recently, these lipids have been incorporated into a range of analytical methods, including separation techniques, and are now poised to have a significant impact on TMP-based separations. Here, we describe current methods for preparing TMP-containing stationary phases and examine the potential utility of polymerizable lipids in TMP affinity chromatography.     

Rapid analysis of membrane glycopeptides by gel permeation high-performance liquid chromatography

A rapid procedure for the analysis of glycopeptides has been developed using gel permeation high-performance liquid chromatography (HPLC). Glycopeptides derived by exhaustive pronase digestion of glycoproteins from radiolabeled human tumor and normal cell lines were chromatographed on DuPont GF-250 and GF-450 gel permeation columns in buffers containing non-ionic detergents. Effective separations of glycopeptides ranging in molecular mass from less than 600 daltons to more than 20,000 daltons, equivalent to the separation range of Sephadex G50 chromatography, were achieved in 7 min. The separations were dependent upon the use of an isocratic mobile phase, that contained a low-ionic-strength Tris buffer and Nonidet P-40 or Triton X-100. The mobilities of protein standards indicated the occurrence of a biphasic elution system, which favored the separation of species with molecular masses below 20,000 daltons. Glycopeptides isolated by this method could be applied directly to lectin or ion-exchange columns or could be digested with neuraminidase, endo H or other enzymes without further treatment. Removal of sialic acid from the glycopeptides caused a dramatic increase in retention time. Using this method, glycopeptides could be isolated rapidly and in high yield. The ease, speed and reproducibility of the separations and compatibility of the solvent systems with affinity or ion-exchange chromatography techniques make this gel permeation HPLC method an ideal initial step in the purification of glycopeptides.     

Determination of Am and Cm in spent nuclear fuels by isotope dilution inductively coupled plasma mass spectrometry and isotope dilution thermal ionization mass spectrometry after separation by high-performance liquid chromatography

Elemental and isotopic determination of americium and curium in spent nuclear fuels is necessary to validate neutronic calculation codes and for nuclear waste disposal purposes. Prior to mass spectrometric analysis, it is mandatory to perform separations in order to eliminate isobaric interferences between U, Pu, Am and Cm. In the spent fuels samples analyzed, a separation of U and Pu has been first realized with an anion-exchange resin. Then a rapid Am/Cm separation has been developed by high-performance liquid chromatography (HPLC) with an on-line detection using the Am and Cm α-emission. The influence of the different parameters on the chromatographic separation are described and discussed. Inductively coupled plasma mass spectrometry (ICP-MS) and thermal-ionization mass spectrometry (TIMS) have been used to measure the isotopic composition of U, Am and Cm and to determine the ²⁴¹Am/²³⁸U and ²⁴⁴Cm/²³⁸U ratios with the double spike isotope dilution method. The measurement procedures and the accuracy and precision of the results obtained with a quadrupole ICP-MS on different spent fuels samples are discussed and compared with those obtained by TIMS, used as a reference technique. Received: 30 November 1998 / Revised: 8 January 1999 / Accepted: 12 January 1999     

Determination of Am and Cm in spent nuclear fuels by isotope dilution inductively coupled plasma mass spectrometry and isotope dilution thermal ionization mass spectrometry after separation by high-performance liquid chromatography

Elemental and isotopic determination of americium and curium in spent nuclear fuels is necessary to validate neutronic calculation codes and for nuclear waste disposal purposes. Prior to mass spectrometric analysis, it is mandatory to perform separations in order to eliminate isobaric interferences between U, Pu, Am and Cm. In the spent fuels samples analyzed, a separation of U and Pu has been first realized with an anion-exchange resin. Then a rapid Am/Cm separation has been developed by high-performance liquid chromatography (HPLC) with an on-line detection using the Am and Cm α-emission. The influence of the different parameters on the chromatographic separation are described and discussed. Inductively coupled plasma mass spectrometry (ICP-MS) and thermal-ionization mass spectrometry (TIMS) have been used to measure the isotopic composition of U, Am and Cm and to determine the ²⁴¹Am/²³⁸U and ²⁴⁴Cm/²³⁸U ratios with the double spike isotope dilution method. The measurement procedures and the accuracy and precision of the results obtained with a quadrupole ICP-MS on different spent fuels samples are discussed and compared with those obtained by TIMS, used as a reference technique. Received: 30 November 1998 / Revised: 8 January 1999 / Accepted: 12 January 1999