Triboelectric Nanogenerators for the Masses: A Low-Cost Do-It-Yourself Pulsed Ion Source for Sample-Limited Applications.

Triboelectric nanogenerators (TENG) are useful devices for converting mechanical motion into electric current using readily available materials. Though the applications for these devices span across many fields, TENG can be leveraged for mass spectrometry (MS) as inexpensive and effective power supplies for pulsed nanoelectrospray ionization (nESI). The inherently discontinuous spray provided by TENG is particularly useful in scenarios where high sample economy is imperative, as in the case of ultraprecious samples. Previous work has shown the utility of TENG MS as a highly sensitive technique capable of yielding quality spectra from only a few microliters of sample at low micromolar concentrations. As the field of miniaturized, fieldable mass spectrometers grows, it remains critical to develop advanced ion sources with similarly small power requirements and footprints. Here, we present a redesigned TENG ion source with a sub-1000 USD material cost, lower power consumption, reduced footprint, and improved capabilities. We validate the performance of this new device for a diverse set of applications, including lipid double bond localization and native protein analysis.

Triboelectric Nanogenerators: Low-Cost Power Supplies for Improved Electrospray Ionization.

Electrospray ionization (ESI) is one of the most popular methods to generate ions for mass spectrometry (MS). When compared with other ionization techniques, it can generate ions from liquid-phase samples without additives, retaining covalent and non-covalent interactions of the molecules of interest. When hyphenated to liquid chromatography, it greatly expands the versatility of MS analysis of complex mixtures. However, despite the extensive growth in the application of ESI, the technique still suffers from some drawbacks when powered by direct current (DC) power supplies. Triboelectric nanogenerators promise to be a new power source for the generation of ions by ESI, improving on the analytical capabilities of traditional DC ESI. In this review we highlight the fundamentals of ESI driven by DC power supplies, its contrasting qualities to triboelectric nanogenerator power supplies, and its applications to three distinct fields of research: forensics, metabolomics, and protein structure analysis.

Implementation of field detection devices for antimalarial quality screening in Lao PDR-A cost-effectiveness analysis.

Substandard and falsified (SF) antimalarials have devastating consequences including increased morbidity, mortality and economic losses. Portable medicine quality screening devices are increasingly available, but whether their use for the detection of SF antimalarials is cost-effective is not known. We evaluated the cost-effectiveness of introducing such devices in post-market surveillance in pharmacies in Laos, conservatively focusing on their outcome in detecting SF artemisinin-based combination therapies (ACTs). We simulated the deployment of six portable screening devices: two handheld near-infrared [MicroPHAZIR RX, NIR-S-G1], two handheld Raman [Progeny, TruScan RM]; one portable mid-infrared [4500a FTIR] spectrometers, and single-use disposable paper analytical devices [PADs]. We considered two scenarios with high and low levels of SF ACTs. Different sampling strategies in which medicine inspectors would test 1, 2, or 3 sample(s) of each brand of ACT were evaluated. Costs of inspection including device procurement, inspector time, reagents, reference testing, and replacement with genuine ACTs were estimated. Outcomes were measured as disability adjusted life years (DALYs) and incremental cost-effectiveness ratios were estimated for each device compared with a baseline of visual inspections alone. In the scenario with high levels of SF ACTs, all devices were cost-effective with a 1-sample strategy. In the scenario of low levels of SF ACTs, only four devices (MicroPHAZIR RX, 4500a FTIR, NIR-S-G1, and PADs) were cost-effective with a 1-sample strategy. In the multi-way comparative analysis, in both scenarios the NIR-S-G1 testing 2 samples was the most cost-effective option. Routine inspection of ACT quality using portable screening devices is likely to be cost-effective in the Laos context. This work should encourage policy-makers or regulators to further investigate investment in portable screening devices to detect SF medicines and reduce their associated undesired health and economic burdens.

Quality of Artemisinin-based Combination Therapy for malaria found in Ghanaian markets and public health implications of their use.

BACKGROUND: Ghana changed their antimalarial drug policy from monotherapies to Artemisinin-based Combination Therapies in 2004 in order to provide more efficacious medicines for treatment of malaria. The policy change can be eroded if poor quality Artemisinin-based Combination Therapies are allowed to remain on the Ghanaian market unchecked by regulatory bodies and law enforcement agencies. The presence and prevalence of substandard and counterfeit Artemisinin-based Combination Therapies need to be determined on open markets in Ghana; a review of the current policy; identifying any gaps and making recommendations on actions to be taken in addressing gaps identified are essential as the data provided and recommendations made will help in ensuring effective control of malaria in Ghana. METHODS: A field survey of antimalarial drugs was conducted in the central part of Ghana. The amount of active pharmaceutical ingredient in each Artemisinin-based Combination Therapy sample identified in the survey was measured using high performance liquid chromatographic analyses. Active pharmaceutical ingredient within the range of 85-115 % was considered as standard and active pharmaceutical ingredient results out of the range were considered as substandard. All samples were screened to confirm stated active pharmaceutical ingredient presence using mass spectrometry. RESULTS: A total of 256 Artemisinin-based Combination Therapies were purchased from known medicine outlets, including market stalls, hospitals/clinics, pharmacies, drug stores. Artemether lumefantrine (52.5 %) and artesunate amodiaquine (43.2 %) were the predominant Artemisinin-based Combination Therapies purchased. Of the 256 Artemisinin-based Combination Therapies purchased, 254 were tested, excluding two samples of Artesunate-SP. About 35 % of Artemisinin-based Combination Therapies were found to be substandard. Nine percent of Artemisinin-based Combination Therapies purchased were past their expiry date; no counterfeit (falsified) medicine samples were detected by either high performance liquid chromatographic or mass spectrometry. CONCLUSION: A high proportion of Artemisinin-based Combination Therapies sold in central Ghana were found to be substandard. Manufacturing of medicines that do not adhere to good manufacturing practices may have contributed to the poor quality of the Artemisinin-based Combination Therapies procured. A strict law enforcement and quality monitoring systems is recommended to ensure effective malaria case management as part of malaria control.

Quality of antimalarials at the epicenter of antimalarial drug resistance: results from an overt and mystery client survey in Cambodia.

Widespread availability of monotherapies and falsified antimalarials is thought to have contributed to the historical development of multidrug-resistant malaria in Cambodia. This study aimed to document the quality of artemisinin-containing antimalarials (ACAs) and to compare two methods of collecting antimalarials from drug outlets: through open surveyors and mystery clients (MCs). Few oral artemisinin-based monotherapies and no suspected falsified medicines were found. All 291 samples contained the stated active pharmaceutical ingredient (API) of which 69% were considered good quality by chemical analysis. Overall, medicine quality did not differ by collection method, although open surveyors were less likely to obtain oral artemisinin-based monotherapies than MCs. The results are an encouraging indication of the positive impact of the country's efforts to tackle falsified antimalarials and artemisinin-based monotherapies. However, poor-quality medicines remain an ongoing challenge that demands sustained political will and investment of human and financial resources.

Impact of poor-quality medicines in the 'developing' world.

Since our ancestors began trading several millennia ago, counterfeit and substandard medicines have been a recurring problem, with history punctuated by crises in the supply of anti-microbials, such as fake cinchona bark in the 1600s and fake quinine in the 1800s. Unfortunately this problem persists, in particular afflicting unsuspecting patients in 'developing' countries. Poor-quality drugs are a vital (but neglected) public health problem. They contribute to a 'crevasse' between the enormous effort in therapeutic research and policy decisions and implementation of good-quality medicines.

Optimization of a direct analysis in real time/time-of-flight mass spectrometry method for rapid serum metabolomic fingerprinting.

Metabolomic fingerprinting of bodily fluids can reveal the underlying causes of metabolic disorders associated with many diseases, and has thus been recognized as a potential tool for disease diagnosis and prognosis following therapy. Here we report a rapid approach in which direct analysis in real time (DART) coupled with time-of-flight (TOF) mass spectrometry (MS) and hybrid quadrupole TOF (Q-TOF) MS is used as a means for metabolomic fingerprinting of human serum. In this approach, serum samples are first treated to precipitate proteins, and the volatility of the remaining metabolites increased by derivatization, followed by DART MS analysis. Maximum DART MS performance was obtained by optimizing instrumental parameters such as ionizing gas temperature and flow rate for the analysis of identical aliquots of a healthy human serum samples. These variables were observed to have a significant effect on the overall mass range of the metabolites detected as well as the signal-to-noise ratios in DART mass spectra. Each DART run requires only 1.2 min, during which more than 1500 different spectral features are observed in a time-dependent fashion. A repeatability of 4.1% to 4.5% was obtained for the total ion signal using a manual sampling arm. With the appealing features of high-throughput, lack of memory effects, and simplicity, DART MS has shown potential to become an invaluable tool for metabolomic fingerprinting.

Assessment of hand-held Raman instrumentation for in situ screening for potentially counterfeit artesunate antimalarial tablets by FT-Raman spectroscopy and direct ionization mass spectrometry.

Pharmaceutical counterfeiting has become a significant public health problem worldwide and new, rapid, user-friendly, reliable and inexpensive methods for drug quality screening are needed. This work illustrates the chemical characterization of genuine and fake artesunate antimalarial tablets by portable Raman spectroscopy and validation by FT-Raman spectroscopy and ambient mass spectrometry. The applicability of a compact and robust portable Raman spectrometer (TruScan) for the in situ chemical identification of counterfeit tablets is reported.