Biological/Biomedical Accelerator Mass Spectrometry Targets. 1. Optimizing the CO2 Reduction Step Using Zinc Dust

Biological and biomedical applications of accelerator mass spectrometry (AMS) use isotope ratio mass spectrometry to quantify minute amounts of long-lived radioisotopes such as 14C. AMS target preparation involves first the oxidation of carbon (in sample of interest) to CO2 and second the reduction of CO2 to filamentous, fluffy, fuzzy, or firm graphite-like substances that coat a −400-mesh spherical iron powder (−400MSIP) catalyst. Until now, the quality of AMS targets has been variable; consequently, they often failed to produce robust ion currents that are required for reliable, accurate, precise, and high-throughput AMS for biological/biomedical applications. Therefore, we described our optimized method for reduction of CO2 to high-quality uniform AMS targets whose morphology we visualized using scanning electron microscope pictures. Key features of our optimized method were to reduce CO2 (from a sample of interest that provided 1 mg of C) using 100 ± 1.3 mg of Zn dust, 5 ± 0.4 mg of −400MSIP, and a reduction temperature of 500 °C for 3 h. The thermodynamics of our optimized method were more favorable for production of graphite-coated iron powders (GCIP) than those of previous methods. All AMS targets from our optimized method were of 100% GCIP, the graphitization yield exceeded 90%, and δ13C was −17.9 ± 0.3‰. The GCIP reliably produced strong 12C− currents and accurate and precise Fm values. The observed Fm value for oxalic acid II NIST SRM deviated from its accepted Fm value of 1.3407 by only 0.0003 ± 0.0027 (mean ± SE, n = 32), limit of detection of 14C was 0.04 amol, and limit of quantification was 0.07 amol, and a skilled analyst can prepare as many as 270 AMS targets per day. More information on the physical (hardness/color), morphological (SEMs), and structural (FT-IR, Raman, XRD spectra) characteristics of our AMS targets that determine accurate, precise, and high-hroughput AMS measurement are in the companion paper

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 (uc) was 0.9%. When bursts of droplets were dispensed, the limit of quantitation was 72 μg (1490 droplets) with uc = 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

All-inkjet-printed thin-film transistors: manufacturing process reliability by root cause analysis

We report on the detailed electrical investigation of all-inkjet-printed thin-film transistor (TFT) arrays focusing on TFT failures and their origins. The TFT arrays were manufactured on flexible polymer substrates in ambient condition without the need for cleanroom environment or inert atmosphere and at a maximum temperature of 150 degrees C. Alternative manufacturing processes for electronic devices such as inkjet printing suffer from lower accuracy compared to traditional microelectronic manufacturing methods. Furthermore, usually printing methods do not allow the manufacturing of electronic devices with high yield (high number of functional devices). In general, the manufacturing yield is much lower compared to the established conventional manufacturing methods based on lithography. Thus, the focus of this contribution is set on a comprehensive analysis of defective TFTs printed by inkjet technology. Based on root cause analysis, we present the defects by developing failure categories and discuss the reasons for the defects. This procedure identifies failure origins and allows the optimization of the manufacturing resulting finally to a yield improvement

Quality of Graphite Target for Biological/Biomedical/Environmental Applications of 14C-Accelerator Mass Spectrometry

Catalytic graphitization for 14C-accelerator mass spectrometry (14C-AMS) produced various forms of elemental carbon. Our high-throughput Zn reduction method (C/Fe = 1:5, 500 °C, 3 h) produced the AMS target of graphite-coated iron powder (GCIP), a mix of nongraphitic carbon and Fe3C. Crystallinity of the AMS targets of GCIP (nongraphitic carbon) was increased to turbostratic carbon by raising the C/Fe ratio from 1:5 to 1:1 and the graphitization temperature from 500 to 585 °C. The AMS target of GCIP containing turbostratic carbon had a large isotopic fractionation and a low AMS ion current. The AMS target of GCIP containing turbostratic carbon also yielded less accurate/precise 14C-AMS measurements because of the lower graphitization yield and lower thermal conductivity that were caused by the higher C/Fe ratio of 1:1. On the other hand, the AMS target of GCIP containing nongraphitic carbon had higher graphitization yield and better thermal conductivity over the AMS target of GCIP containing turbostratic carbon due to optimal surface area provided by the iron powder. Finally, graphitization yield and thermal conductivity were stronger determinants (over graphite crystallinity) for accurate/precise/high-throughput biological, biomedical, and environmental14C-AMS applications such as absorption, distribution, metabolism, elimination (ADME), and physiologically based pharmacokinetics (PBPK) of nutrients, drugs, phytochemicals, and environmental chemicals

Expression of IL-23/Th17-related cytokines in basal cell carcinoma and in the response to medical treatments

Several immune-related markers have been implicated in basal cell carcinoma (BCC) pathogenesis. The BCC inflammatory infiltrate is dominated by Th2 cytokines, suggesting a specific state of immunosuppression. In contrast, regressing BCC are characterized by a Th1 immune response with IFN-γ promoting a tumor suppressive activity. IL-23/Th17-related cytokines, as interleukin (IL)-17, IL-23 and IL-22, play a significant role in cutaneous inflammatory diseases, but their involvement in skin carcinogenesis is controversial and is poorly investigated in BCC. In this study we investigated the expression of IFN-γ, IL-17, IL-23 and IL-22 cytokines in BCC at the protein and mRNA level and their modulation during imiquimod (IMQ) treatment or photodynamic therapy (PDT). IFN-γ, IL-17, IL-23 and IL-22 levels were evaluated by immunohistochemistry and quantitative Real Time PCR in 41 histopatho-logically-proven BCCs (28 superficial and 13 nodular) from 39 patients. All BCC samples were analyzed at baseline and 19 of 41 also during medical treatment (9 with IMQ 5% cream and 10 with MAL-PDT). Association between cytokines expression and clinico-pathological variables was evaluated. Higher levels of IFN-γ, IL-17, IL-23 and IL-22 were found in BCCs, mainly in the peritumoral infiltrate, compared to normal skin, with the expression being correlated to the severity of the inflammatory infiltrate. IFN-γ production was higher in superficial BCCs compared to nodular BCCs, while IL-17 was increased in nodular BCCs. A significant correlation was found between IFN-γ and IL-17 expression with both cytokines expressed by CD4+ and CD8+ T-cells. An increase of all cytokines occurred during the inflammatory phase induced by IMQ and at the early time point of PDT treatment, with significant evidence for IFN-γ, IL-23, and IL-22. Our results confirm the role of IFN-γ and support the involvement of IL-23/Th17-related cytokines in BCC pathogenesis and in the inflammatory response during IMQ and MAL-PDT treatments

Isolated limb perfusion for unresectable extremity cutaneous squamous cell carcinoma; an effective limb saving strategy

Background: A small minority of patients present with locally advanced cutaneous Squamous Cell Carcinoma (cSCC). The aim of this study was to evaluate the effectiveness of Tumour necrosis factor α (TNF) and melphalan based isolated limb perfusion (TM-ILP) as a limb saving strategy for locally advanced extremity cSCC. Methods: A retrospective search from prospectively maintained databases, at two tertiary referral centers, was performed to identify patients treated with TM-ILP for locally advanced cSSC of an extremity between 2000 and 2015. Results: A total of 30 patients treated with TM-ILP for cSCC were identified, with a median age of 71 years (36–92) and 50% female. Response could not be evaluated in 3 patients. After a median follow up of 25 months, the overall response rate was 81% (n = 22), with 16 patients having a complete response (CR, 59%). A total of 7 patients developed local recurrence, with a median time to recurrence of 9 months (Interquartile Range 7–10). Progressive disease was observed in 5 patients (19%). Limb salvage rate was 80%. The overall 2-year survival was 67%. Conclusions: TM-ILP should be considered as an option in patients with locally advanced cSCC in specialised centers, resulting in a high limb salvage rate

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

TRACE ELEMENT CHARACTERIZATION OF FORSTERITE CHONDRITES AND METEORITES OF SIMILAR REDOX STATE

From a systematic mineralogic/petrologic study of nine chondritic inclusions in the Cumberland Falls aubrite, Neal and Lipschutz (1981) reported that these inclusions constituted a new primitive chondritic suite--the forsterite (F) chondrites. The authors concluded that F chondrites acquired their chemical characteristics during nebular condensation and accretion into a parent body which later collided with the enstatite meteorite parent body, thereby being shocked and mixed. We report compositional data for volatile/mobile Ag, As, Au, Bi, Cd, Co, Cs, Ga, In, Rb, Sb, Se, Te, Tl, U, and Zn in: eight F chondrites studied by Neal and Lipschutz (1981) and another studied by Binns (1969); the Pontlyfni and Kakangari meteorites (putative forsterite chondrites of Graham et al., 1977); Acapulco and ALH A77081 (with similar redox state); and a chondritic inclusion from the aubrite ALH A78113. Our data show trace element contents of F chondrites to be unusually coherent (only Bi, Cd, In, and Tl vary \u3e10x) and distinct. Few elements in F chondrites vary with Fs content of low-Ca pyroxene or with the ferromagnesian silicate disequilibration parameter. Five elements (Cd, Rb, Sb, As, and Se) are present in F chondrites at ordinary chondrite levels; siderophiles are slightly lower while volatile/mobile chalcophiles are substantially lower. Lithophiles (U, Rb, and Cs) and Te are higher in F chondrites than in other type 3 material. The composition of F chondrites differs markedly from those of other meteorite populations considered, indicting \u3e2 parent populations of similar redox state. Compositionally, the chondritic inclusion from ALH A78113 is different from F chondrites, although interesting similarities exist; further mineralogic and chemical information should detail their relationship. These trace element data are consistent with the idea that F chondrites are a unique primitive chondrite group, affected negligibly by the considerable shock generated during the collision between their parent body and that of the enstatite meteorites. Therefore, these data provide the first compositional information for these primitive representatives from a hitherto-unknown portion of the early solar nebula