Gravimetric deposition of microliter drops with radiometric confirmation.

A manual microliter gravimetric dispensing technique is demonstrated using a micropipettor modified for use with removeable microcapillaries. Liquid scintillation sources were prepared from a well-characterized 241Am reference solution, providing a radiometric check of dispensed masses. Further experiments confirmed controlled dispensing of drops onto gold foils with losses ≤0.34(4) % of the total drop activity. A detailed measurement equation for the weighing technique, including the corrections for evaporation, is presented with a full accounting of associated uncertainties.

Sub-picoliter Traceability of Microdroplet Gravimetry and Microscopy.

Gravimetry typically lacks the resolution to measure single microdroplets, whereas microscopy is often inaccurate beyond the resolution limit. To address these issues, we advance and integrate these complementary methods, introducing simultaneous measurements of the same microdroplets, comprehensive calibrations that are independently traceable to the International System of Units (SI), and Monte-Carlo evaluations of volumetric uncertainty. We achieve sub-picoliter agreement of measurements of microdroplets in flight with volumes of approximately 70 pL, with ensemble gravimetry and optical microscopy both yielding 95% coverage intervals of ±0.6 pL, or relative uncertainties of ±0.9%, and root-mean-square deviations of mean values between the two methods of 0.2 pL or 0.3%. These uncertainties match previous gravimetry results and improve upon previous microscopy results by an order of magnitude. Gravimetry precision depends on the continuity of droplet formation, whereas microscopy accuracy requires that optical diffraction from an edge reference matches that from a microdroplet. Applying our microscopy method, we jet and image water microdroplets suspending fluorescent nanoplastics, count nanoplastic particles after deposition and evaporation, and transfer volumetric traceability to the number concentrations of single microdroplets. We expect that our methods will impact diverse fields involving dimensional metrology and volumetric analysis of microdroplets, including inkjet microfabrication, disease transmission, and industrial sprays.

Toward a New Primary Standardization of Radionuclide Massic Activity Using Microcalorimetry and Quantitative Milligram-Scale Samples.

We present a new paradigm for the primary standardization of radionuclide activity per mass of solution (Bq/g). Two key enabling capabilities are 4π decay-energy spectrometry using chip-scale sub-Kelvin microcalorimeters and direct realization of mass by gravimetric inkjet dispensing using an electrostatic force balance. In contrast to traditional traceability, which typically relies on chemical separation of single-radionuclide samples, 4π integral counting, and additional spectrometry methods to verify purity, the system described here has both 4π counting efficiency and spectroscopic resolution sufficient to identify multiple radionuclides in the same sample at once. This enables primary standardization of activity concentrations of mixed-radionuclide samples. A major benefit of this capability, beyond metrology, is in assay of environmental and forensics samples, for which the quantification of multiplenuclide samples can be achieved where presently inhibited by interferences. This can be achieved without the need for chemical separations or efficiency tracers, thereby vastly reducing time, radioactive waste, and resulting measurement uncertainty.

Discriminative potential of ion mobility spectrometry for the detection of fentanyl and fentanyl analogues relative to confounding environmental interferents.

The opioid crisis and emergence of fentanyl, fentanyl analogues, and other synthetic opioids has highlighted the need for sensitive and robust detection for interdiction at screening points, notably vehicles at border crossings and packages at postal facilities. This work investigates the discriminative potential, sensitivity and specificity, of ion mobility spectrometry (IMS) for the detection of fentanyl and fifteen (15) fentanyl-related compounds (analogues, other opioids, and metabolites) relative to confounding environmental interferents. The environmental background interferent levels, frequency and intensity, were derived from over 10 000 screening samples collected from delivery vehicles entering a federal site. A receiver operating characteristic (ROC) curve methodology was employed to quantify the relationship between sensitivity and specificity for these target compounds on two instruments/configurations. These instrument configurations differed in desorption and drift tube temperatures, reactant ion dopant chemistry, and analysis time. This work identified reduced mobility areas of high interference that resulted in increased false positive rates (FPR), effectively reducing sensitivity (true positive rate: TPR) in those regions. Except for a few target compounds on either of the instruments that exhibited elevated FPRs, detection of fentanyl and fentanyl-related species was achieved at single to tens of nanograms with ≥90% TPR and ≤2% FPR. This work established the importance of systematic environmental background characterization at each specific screening setting in evaluating a platform's true performance.

Correction to: Metrology for stable isotope reference materials: 13C/12C and 18O/16O isotope ratio value assignment of pure carbon dioxide gas samples on the Vienna PeeDee Belmnite-CO2 scale using dual-inlet mass spectrometry.

The authors would like to call the reader's attention to the fact that unfortunately the formula for the O17 correction parameter "a" is reported incorrectly as.

Inkjet metrology II: resolved effects of ejection frequency, fluidic pressure, and droplet number on reproducible drop-on-demand dispensing.

We report highly reproducible gravimetric and optical measurements of microdroplets that lend insights into the fundamentals of drop-on-demand (DOD) printing. Baseline fluidic pressure within the DOD dispenser was controlled to within 0.02 hPa, enabling long-term stability in dispensed droplet mass with observed variations near 1% (RSD) for isobutanol. The gravimetric measurements were sensitive enough to detect and avoid unwanted effects from air bubbles within the dispenser. The gravimetric and optical velocity measurements enabled consistent determination of droplet kinetic energy that governed baseline behavior across the operational variables. Mass and velocity were influenced in a nonlinear manner by the frequency of droplet ejection, the fluidic pressure within the dispensing device, and the number of droplets dispensed in a burst. Resolved effects were attributable to several possible mechanisms including acoustic resonances, energy partitioning from systematic orifice refill dynamics, pressure wavelets created within the dispenser cavity during "first-drop" formation, and residual ring-down after last-drop emergence.

Inkjet metrology: high-accuracy mass measurements of microdroplets produced by a drop-on-demand dispenser.

We describe gravimetric methods for measuring the mass of droplets generated by a drop-on-demand (DOD) microdispenser. Droplets are deposited, either continuously at a known frequency or as a burst of known number, into a cylinder positioned on a submicrogram balance. Mass measurements are acquired precisely by computer, and results are corrected for evaporation. Capabilities are demonstrated using isobutyl alcohol droplets. For ejection rates greater than 100 Hz, the repeatability of droplet mass measurements was 0.2%, while the combined relative standard uncertainty (u(c)) was 0.9%. When bursts of droplets were dispensed, the limit of quantitation was 72 microg (1490 droplets) with u(c) = 1.0%. Individual droplet size in a burst was evaluated by high-speed videography. Diameters were consistent from the tenth droplet onward, and the mass of an individual droplet was best estimated by the average droplet mass with a combined uncertainty of about 1%. Diameters of the first several droplets were anomalous, but their contribution was accounted for when dispensing bursts. Above the limits of quantitation, the gravimetric methods provided statistically equivalent results and permit detailed study of operational factors that influence droplet mass during dispensing, including the development of reliable microassays and standard materials using DOD technologies.

New guidelines for delta13C measurements.

Consistency of delta13C measurements can be improved 39-47% by anchoring the delta13C scale with two isotopic reference materials differing substantially in 13C/12C. It is recommended that delta13C values of both organic and inorganic materials be measured and expressed relative to VPDB (Vienna Peedee belemnite) on a scale normalized by assigning consensus values of -46.6 per thousand to L-SVEC lithium carbonate and +1.95 per thousand to NBS 19 calcium carbonate. Uncertainties of other reference material values on this scale are improved by factors up to two or more, and the values of some have been notably shifted: the delta13C of NBS 22 oil is -30.03 per thousand.

Isotopic metrology of carbon dioxide. I. Interlaboratory comparison and empirical modeling of inlet equilibration time, inlet pressure, and ion source conductance.

We report a pilot study of high-precision differential isotope ratio measurements made on replicate samples of pure carbon dioxide using three instruments of identical manufacture. Measurement protocols were designed to explore the effects of sample size, ion source conductance, and inlet changeover equilibration time on the raw measurements. Our goal was better understanding of factors that influence these measurements in order to establish procedures for highly reproducible and accurate determinations of Reference Material (RM) isotopic compositions. Evaluation and modeling of reported data illuminated effects consistent with two instrumental memory sources--one short-lived (t((1/2)) approximately 10 s) and the other long-lived (t((1/2)) approximately 6-10 min), uncompensated by normal background measurements--that can significantly influence measurements made by the dual inlet method. These biases, proportional to the difference in isotopic compositions between the measured sample and reference gases, decrease in magnitude with increasing sample size, source conductance, and equilibration time. We observed biases as high as 0.1 per thousand per 10 per thousand difference between sample and reference gases. These memory sources may be responsible for measured delta(13)C values of RMs generally being highly reproducible within any single laboratory but less reproducible among independent laboratories. The magnitude of the bias is consistent with the ranges of delta(13)C values reported in prior laboratory intercomparisons. Uncertainties are most likely due to high and variable long-lived memory among the instruments tested.

Isotopic metrology of carbon dioxide. II. Effects of ion source materials, conductance, emission, and accelerating voltage on dual-inlet cross contamination.

We report high-precision isotopic carbon dioxide measurements, made before and after ion source modification to gas isotope ratio mass spectrometry (IRMS) instruments. Measurement protocols were designed to explore the effects of ion source material substitution, source conductance, inlet pressure, electron emission, acceleration potential, and inlet changeover equilibration time. After modification of the IRMS instruments at the National Institute of Standards and Technology (NIST) and the Max-Planck-Institute for Chemistry (MPI-Mainz), immediate changes were observed. At NIST, measurements were no longer sensitive to inlet equilibration times greater than 15 s, and different settings of ion source conductance resulted in delta(13)C shifts of about 0.04 per thousand per 10 per thousand measurement difference between sample and reference, a five-fold improvement. No significant changes in machine performance were observed after a month of use. After a year, performance had degraded slightly, but was controlled by ion source cleaning and the use of low-energy ion acceleration to minimize sputtering. At MPI-Mainz, results were very similar. We report cross-contamination coefficients measured since 1996, and discuss the role of adsorption, ion implantation, and sputtering on cross contamination in mass spectrometry systems. We recommend that users of high-precision IRMS instruments test for and minimize the effects described.