Protein analysis using capillary electrophoresis coupled to mass spectrometry through vibrating sharp-edge spray ionization.

Capillary electrophoresis (CE) interfaced to mass spectrometry (MS) with electrospray ionization typically incorporates acidic additives or organic solvents to assist in ionization. Vibrating sharp-edge spray ionization (VSSI) is a voltage-free method to interface CE and MS that does not require these additives, making it appealing for protein analyses. CE-VSSI nanoflow sheath separations are performed with low ionic strength aqueous solutions in the sheath to reduce suppression. Serine is also included in the sheath to reduce analyte adduction. Proteins are detected in the 2.5-10 µM range, corresponding to an injected mass range of 0.1-1.2 ng. The anionic proteins ß-lactoglobulin and transferrin are resolved using an unmodified fused silica capillary because they do not exhibit nonspecific surface adsorption. Conversely, separations of cationic proteins cytochrome c, ribonuclease A, and α-chymotrypsinogen A in an unmodified capillary require acidic background electrolytes to overcome adsorption. Alternatively, a semipermanent coating comprised self-assembled lipids overcomes surface adsorption at a neutral pH. Separations with zwitterionic and hybrid cationic coatings are complete within 15 or 6 min, respectively. The dimeric form of triosephosphate isomerase was observed at a 60 µM, corresponding to a mass of 19 ng, by dropping the temperature of the MS inlet.

Long-term cardiovascular risks and the impact of statin treatment on socioeconomic inequalities: a microsimulation model.

BACKGROUND: UK cardiovascular disease (CVD) incidence and mortality have declined in recent decades but socioeconomic inequalities persist. AIM: To present a new CVD model, and project health outcomes and the impact of guideline-recommended statin treatment across quintiles of socioeconomic deprivation in the UK. DESIGN AND SETTING: A lifetime microsimulation model was developed using 117 896 participants in 16 statin trials, 501 854 UK Biobank (UKB) participants, and quality-of-life data from national health surveys. METHOD: A CVD microsimulation model was developed using risk equations for myocardial infarction, stroke, coronary revascularisation, cancer, and vascular and non-vascular death, estimated using trial data. The authors calibrated and further developed this model in the UKB cohort, including further characteristics and a diabetes risk equation, and validated the model in UKB and Whitehall II cohorts. The model was used to predict CVD incidence, life expectancy, quality-adjusted life years (QALYs), and the impact of UK guideline-recommended statin treatment across socioeconomic deprivation quintiles. RESULTS: Age, sex, socioeconomic deprivation, smoking, hypertension, diabetes, and cardiovascular events were key CVD risk determinants. Model-predicted event rates corresponded well to observed rates across participant categories. The model projected strong gradients in remaining life expectancy, with 4-5-year (5-8 QALYs) gaps between the least and most socioeconomically deprived quintiles. Guideline-recommended statin treatment was projected to increase QALYs, with larger gains in quintiles of higher deprivation. CONCLUSION: The study demonstrated the potential of guideline-recommended statin treatment to reduce socioeconomic inequalities. This CVD model is a novel resource for individualised long-term projections of health outcomes of CVD treatments.

Fluorescent parallel electrophoresis assay of enzyme inhibition.

BACKGROUND: Enzyme inhibitors comprise the largest class of pharmaceutical compounds. The discovery and development of new enzyme inhibitor drug candidates depends on sensitive tools to quantify inhibition constants, Ki, for the most promising candidates. A high throughput, automated, and miniaturized approach to measure inhibition is reported. In this technique enzyme inhibition occurs within a 16 nL nanogel reaction zone that is integrated into a capillary. The reaction and electrophoresis separation are completed in under 10 min. The nanoliter enzyme reaction zones are easily positioned inside a standard separation capillary by pseudo-immobilizing enzymes within a thermally reversible nanogel. RESULTS: This report optimizes and validates a capillary nanogel electrophoresis reaction and separation with a multi-capillary array instrument. Inhibitor constants are determined for the neuraminidase enzyme to quantify the effect of the transition state analog, 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DANA), as well as the inhibitor Siastatin B. With the multi-capillary array assay replicate Ki values are determined to be 5.7 ± 0.1 µM (n = 3) and 9.2 ± 0.2 µM (n = 3) for DANA and Siastatin B, respectively. The enzyme reaction in each separation capillary converts the substrate to a product in real time. The nanogel is used under suppressed electroosmotic flow, sustains enzyme function, and is easily filled and replaced by changing the capillary temperature. Using laser-induced fluorescence allows the determination to be achieved with substrate concentrations well below the Michaelis-Menten constant, making the method independent of the substrate concentration and therefore a more easily implemented assay. SIGNIFICANCE: A lower measurement cost is realized when the reaction volume is miniaturized because the amounts of enzyme, substrate and inhibitor are reduced. Fast enzyme reactions are possible because of the small reaction volume. With a multi-capillary array, the inhibition assay is achieved in a fraction of the time required for traditional methods. The separation-based assay can even be applied to labeled substrates not cleaned up following the labeling reaction.

A Cost-Effective Microfluidic Device to Teach the Principles of Electrophoresis and Electroosmosis.

Electrophoresis is integral to analytical and biochemistry experiences in undergraduate education; however, fundamental principles of the method are often taught in upper-level laboratories through hands-on experiences. A laboratory activity is reported that teaches the concepts of electrophoretic mobility and electroosmotic flow. A single reuseable instrument, called a mini-E, costs 37 USD and consists of a DC power supply, a voltmeter, platinum electrodes, and a chip cast in polydimethylsiloxane. This activity uses common reagents costing only 0.02 USD per student. Experiments are devised that allow students to investigate the properties of electrophoretic flow and electroosmotic flow by separating the two commonly used food dyeing agents Brilliant Blue FCF and Allura Red AC in vinegar and in a solution of ammonium hydroxide. A dark-purple mixture of these dyes is separated into red and blue bands that are easily visualized. The migration order of the dyes differs when the separation is performed under conditions of reversed polarity and suppressed electroosmotic flow (vinegar) compared to conditions of normal polarity and active electroosmotic flow (ammonium hydroxide). When delivered to chemistry majors, students had a significant gain in their ability to apply the concepts of electroosmosis and electrophoresis to predict analyte migration. Although this activity targets upper-level chemistry content, it can also be adapted for other laboratory experiences.

Gels in Microscale Electrophoresis.

Gel matrices are fundamental to electrophoresis analyses of biopolymers in microscale channels. Both capillary gel and microchannel gel electrophoresis systems have produced fundamental advances in the scientific community. These analytical techniques remain as foundational tools in bioanalytical chemistry and are indispensable in the field of biotherapeutics. This review summarizes the current state of gels in microscale channels and provides a brief description of electrophoretic transport in gels. In addition to the discussion of traditional polymers, several nontraditional gels are introduced. Advances in gel matrices highlighted include selective polymers modified to contain added functionality as well as thermally responsive gels formed through self-assembly. This review discusses cutting-edge applications to challenging areas of discovery in DNA, RNA, protein, and glycan analyses. Finally, emerging techniques that result in multifunctional assays for real-time biochemical processing in capillary and three-dimensional channels are identified.

Microscale Quantification of the Inhibition of Neuraminidase Using Capillary Nanogel Electrophoresis.

Neuraminidase inhibitors modulate infections that involve sialic acids, making quantitative analyses of this inhibitory effect important for selecting and designing potential therapeutics. An automated nanogel capillary electrophoresis system is developed that integrates a 5 nL enzyme inhibition reaction in line with a 5 min separation-based assay of the enzymatic product to quantify inhibition as the half maximal inhibitory concentration (IC50) and inhibitor constant (Ki). A neuraminidase enzyme from Clostridium perfringens is non-covalently immobilized in a thermally tunable nanogel positioned in the thermally controlled region of the capillary by increasing the capillary temperature to 37 °C. Aqueous inhibitor solutions are loaded into the capillary during the nanogel patterning step to surround the enzyme zone. The capillary electrophoresis separation provides a means to distinguish the de-sialylated product, enabling the use of sialyllactose which contains the trisaccharide motif observed on serine/threonine-linked (O-linked) glycans. A universal nanogel patterning scheme is developed that does not require pre-mixing of enzymes with inhibitors when an automated capillary electrophoresis instrument is used, thus reducing the consumption of enzymes and enabling adaption of the method to different inhibitors. The universal approach is successfully applied to two classical neuraminidase inhibitors with different electrophoretic mobilities. The IC50 and Ki values obtained for N-acetyl-2,3-dehydro-2-deoxyneuraminic acid (DANA) are 13 ± 3 and 5.0 ± 0.9 µM, respectively, and 28 ± 3 and 11 ± 1 µM, respectively, for Siastatin B. These values agree with literature reports and reflect the weaker inhibition anticipated for Siastatin B in comparison to DANA.

A Low-Cost and Simple Demonstration of Freezing Point Depression and Colligative Properties with Common Salts and Ice Cream.

A laboratory activity was developed to teach freezing point depression and colligative properties to introductory-level chemistry students. The laboratory uses food-grade reagents and is delivered in two units that can be taught in a single 2 hour session or two separate sessions. The total cost of the consumables is 1 USD. In the first part of this two-part activity, students perform measurements on the properties of five salt solutions to better know and understand freezing point depression. In the second part of the activity, students apply their knowledge and understanding of freezing point depression to make ice cream. The ice-cream-making experiment is delivered as a group activity to encourage reflection. Centering this experiment on ice cream allows students to connect properties described in chemistry to everyday life. The solutions used in the experiment are reusable and nonhazardous. The experiment can be implemented in a classroom, in a teaching laboratory, or at home.

Angiotensin receptor blockers and ß blockers in Marfan syndrome: an individual patient data meta-analysis of randomised trials.

BACKGROUND: Angiotensin receptor blockers (ARBs) and ß blockers are widely used in the treatment of Marfan syndrome to try to reduce the rate of progressive aortic root enlargement characteristic of this condition, but their separate and joint effects are uncertain. We aimed to determine these effects in a collaborative individual patient data meta-analysis of randomised trials of these treatments. METHODS: In this meta-analysis, we identified relevant trials of patients with Marfan syndrome by systematically searching MEDLINE, Embase, and CENTRAL from database inception to Nov 2, 2021. Trials were eligible if they involved a randomised comparison of an ARB versus control or an ARB versus ß blocker. We used individual patient data from patients with no prior aortic surgery to estimate the effects of: ARB versus control (placebo or open control); ARB versus ß blocker; and indirectly, ß blocker versus control. The primary endpoint was the annual rate of change of body surface area-adjusted aortic root dimension Z score, measured at the sinuses of Valsalva. FINDINGS: We identified ten potentially eligible trials including 1836 patients from our search, from which seven trials and 1442 patients were eligible for inclusion in our main analyses. Four trials involving 676 eligible participants compared ARB with control. During a median follow-up of 3 years, allocation to ARB approximately halved the annual rate of change in the aortic root Z score (mean annual increase 0·07 [SE 0·02] ARB vs 0·13 [SE 0·02] control; absolute difference -0·07 [95% CI -0·12 to -0·01]; p=0·012). Prespecified secondary subgroup analyses showed that the effects of ARB were particularly large in those with pathogenic variants in fibrillin-1, compared with those without such variants (heterogeneity p=0·0050), and there was no evidence to suggest that the effect of ARB varied with ß-blocker use (heterogeneity p=0·54). Three trials involving 766 eligible participants compared ARBs with ß blockers. During a median follow-up of 3 years, the annual change in the aortic root Z score was similar in the two groups (annual increase -0·08 [SE 0·03] in ARB groups vs -0·11 [SE 0·02] in ß-blocker groups; absolute difference 0·03 [95% CI -0·05 to 0·10]; p=0·48). Thus, indirectly, the difference in the annual change in the aortic root Z score between ß blockers and control was -0·09 (95% CI -0·18 to 0·00; p=0·042). INTERPRETATION: In people with Marfan syndrome and no previous aortic surgery, ARBs reduced the rate of increase of the aortic root Z score by about one half, including among those taking a ß blocker. The effects of ß blockers were similar to those of ARBs. Assuming additivity, combination therapy with both ARBs and ß blockers from the time of diagnosis would provide even greater reductions in the rate of aortic enlargement than either treatment alone, which, if maintained over a number of years, would be expected to lead to a delay in the need for aortic surgery. FUNDING: Marfan Foundation, the Oxford British Heart Foundation Centre for Research Excellence, and the UK Medical Research Council.

Nanoflow Sheath Voltage-Free Interfacing of Capillary Electrophoresis and Mass Spectrometry for the Detection of Small Molecules.

Coupling capillary electrophoresis (CE) to mass spectrometry (MS) is a powerful strategy to leverage a high separation efficiency with structural identification. Traditional CE-MS interfacing relies upon voltage to drive this process. Additionally, sheathless interfacing requires that the electrophoresis generates a sufficient volumetric flow to sustain the ionization process. Vibrating sharp-edge spray ionization (VSSI) is a new method to interface capillary electrophoresis to mass analyzers. In contrast to traditional interfacing, VSSI is voltage-free, making it straightforward for CE and MS. New nanoflow sheath CE-VSSI-MS is introduced in this work to reduce the reliance on the separation flow rate to facilitate the transfer of analyte to the MS. The nanoflow sheath VSSI spray ionization functions from 400 to 900 nL/min. Using the new nanoflow sheath reported here, volumetric flow rate through the separation capillary is less critical, allowing the use of a small (i.e., 20 to 25 µm) inner diameter separation capillary and enabling the use of higher separation voltages and faster analysis. Moreover, the use of a nanoflow sheath enables greater flexibility in the separation conditions. The nanoflow sheath is operated using aqueous solutions in the background electrolyte and in the sheath, demonstrating the separation can be performed under normal and reversed polarity in the presence or absence of electroosmotic flow. This includes the use of a wider pH range as well. The versatility of nanoflow sheath CE-VSSI-MS is demonstrated by separating cationic, anionic, and zwitterionic molecules under a variety of separation conditions. The detection sensitivity observed with nanoflow sheath CE-VSSI-MS is comparable to that obtained with sheathless CE-VSSI-MS as well as CE-MS separations with electrospray ionization interfacing. A bare fused silica capillary is used to separate cationic ß-blockers with a near-neutral background electrolyte at concentrations ranging from 1.0 nM to 1.0 µM. Under acidic conditions, 13 amino acids are separated with normal polarity at a concentration ranging from 0.25 to 5 µM. Finally, separations of anionic compounds are demonstrated using reversed polarity under conditions of suppressed electroosmotic flow through the use of a semipermanent surface coating. With a near-neutral separation electrolyte, anionic nonsteroidal anti-inflammatory drugs are detected over a concentration range of 0.1 to 5.0 µM.

Simple, rapid, and reproducible capillary gel electrophoresis separation and laser-induced fluorescence detection of DNA topoisomers with unmodified fused silica separation capillaries.

The topology of DNA is a critical quality attribute for plasmid-based pharmaceuticals, making quantification of trace levels of plasmid topoisomers an important analytical priority. An automated and cost-effective method based on capillary gel electrophoresis laser-induced fluorescence detection is described. The method outlined in this report is significant because it is easily implemented by any laboratory for which routine analyses of plasmid topology are critical for the development of new plasmid-based therapies as well as for quality control of gene therapies utilizing supercoiled DNA. Detection of topoisomers was achieved by incorporating ethidium bromide in the separation medium. The detector response was improved by 3 orders of magnitude by utilizing a 605-nm optical filter with a 15-nm bandwidth. Separations of linear, open circle, supercoiled, and multimer DNA plasmids ranging from 4.2 to 10.5 kbp were accomplished in under 6 min using an unmodified fused silica capillary (50-µm internal diameter). The background electrolyte was comprised of 0.5% gel, which was hydroxypropylmethyl cellulose, 1 mM ethylenediaminetetraacetic acid, and 50 mM N-(2-acetamido)-2-aminoethanesulfonic acid (pH of 6.25). The separations, which balanced the bulk electroosmotic flow, the electrophoretic mobility of the DNA, and gel sieving were dependent upon the pH of the electrolyte and the gel concentration. Reproducibility was dependent upon the procedure used to prepare the gel as well as other factors including the ethidium bromide concentration and capillary conditioning. A single unmodified capillary operated for more than 150 runs had an across-day migration time precision of 1% relative standard deviation and percent area precision of 10% relative standard deviation.

Capillary Nanogel Electrophoresis for the Determination of the ß1-4 Galactosyltransferase Michaelis-Menten Constant and Real-Time Addition of Galactose Residues to N-Glycans and Glycoprotein.

A thermally reversible nanogel is used in capillary electrophoresis to create discrete regions for a galactosyltransferase reaction and separation. The ß1-4 galactosyltransferase enzyme, donor, and co-factor were patterned in the capillary. The substrate was driven through these zones and converted to galactosylated products, which were separated and identified. Using this capillary electrophoresis method, the degree of glycosylation was discernible for a pentasaccharide and for biantennary N-glycans. With the ability to distinguish between reaction products for which either one or two galactose residues were transferred, the capillary nanogel electrophoresis system was used to determine the Michaelis-Menten value, KM. For the ß1-4 galactosyltransferase, the KM value obtained for a pentasaccharide substrate was 1.23 ± 0.08 mM. Once KM was established, the enzyme/substrate ratio was evaluated to add a single galactose residue or to fully galactosylate a biantennary N-glycan. Additionally, capillary nanogel electrophoresis was adapted to transfer galactose residues to protein. The applicability of the method for real-time online modification of whole protein was demonstrated with the Herceptin glycoprotein. Complete retardation by Erythrina cristagalli lectin after enzymatic modification confirmed the addition of galactose residues to the Herceptin. This demonstrated the potential of the method to be used for online modification of other glycoproteins.

Protein Sieving with Capillary Nanogel Electrophoresis.

Protein sieving, which is a fundamental tool in the biotechnology field, can be automated using capillary gel electrophoresis. The high-viscosity and biocompatible linear gels required for capillary sieving must be replaced for each run using high pressures. Thermally responsive gels are easier to renew in the capillary as they can be repetitively switched between low- and high-viscosity solutions. A thermally responsive sieving gel was recently demonstrated to separate DNA, which is a larger biomolecule than proteins. This material required no synthesis as it was self-assembled from common phospholipids. Nanogels composed of dimyristoyl-sn-glycero-2-phosphocholine and 1,2-dihexanoyl-sn-glycero-3-phosphocholine exhibit thermally reversible viscosity within a 10 °C temperature change, forming a sieving matrix above 24 °C. Additionally, these nanogels are nondenaturing and have been demonstrated to preserve the activity of enzymes. In this report, a phospholipid nanogel is used for the first time for capillary gel electrophoresis separations of proteins. The mobilities in buffer and nanogel demonstrated that 20-30% nanogel supports sieving of proteins ranging from 20 to 80 kDa. Capillary separations based on sieving rather than electrophoresis had similar precision in both area and migration time as well as similar separation efficiencies. However, the migration time increased with gel concentration. The nanogel was used for the analysis of proteins in human serum. Proteins in the sample were more effectively resolved and quantified with capillary sieving compared to free-solution capillary electrophoresis. This allowed for accurate quantification.

Low Flow Voltage Free Interface for Capillary Electrophoresis and Mass Spectrometry Driven by Vibrating Sharp-Edge Spray Ionization.

Capillary electrophoresis-mass spectrometry is a powerful technique for high-throughput and high efficiency separations combined with structural identification. Electrospray ionization is the primary interface used to couple capillary electrophoresis to mass analyzers; however, improved designs continue to be reported. A new interfacing method based on vibrating sharp-edge spray ionization is presented in this work to overcome the challenges of decoupling applied voltages and to enhance the compatibility with separations performed at near-neutral pH. The versatility and ease of use of this ionization source is demonstrated using ß-blockers, peptides, and proteins. The cationic ß-blocker pindolol was injected electrokinetically, and detected at concentrations ranging from 10 nM to 5 µM, with an estimated detection limit of 2 nM. The vibrating sharp-edge spray ionization functions with flow rates from 70 to 200 nL/min and did not perturb the capillary electrophoresis separation electroosmotic flow as evidenced by the observation that most migration times differed less than 7% (n = 3) across a lab-built system interfaced to mass spectrometry and a commercial system that utilizes absorbance detection. For cationic beta-blockers the theoretical plates achieved in the capillary electrophoresis-mass spectrometry setup were 80%-95% of that observed with a commercial capillary electrophoresis-UV absorbance detection system.

Quantification of the α2-6 Sialic Acid Linkage in Branched N-Glycan Structures with Capillary Nanogel Electrophoresis.

Sialylation and sialic acid linkage in N-glycans are markers of disease but are analytically challenging to quantify. A capillary electrophoresis method is reported that integrates a unique combination of enzymes and lectins to modify sialylated N-glycans in real time in the capillary so that N-glycan structures containing α2-6-linked sialic acid are easily separated, detected, and quantified. In this study, N-glycans were sequentially cleaved by enzymes at the head of the separation capillary so that the presence of α2-6-linked sialic acids corresponded to a shift in the analyte migration time in a manner that enabled interpretation of the N-glycan structure. Following injection, only afucosylated N-glycan structures were passed through enzyme zones that contained α2-3 sialidase, followed by ß1-3,4 galactosidase, which cleaved any terminal α2-3-linked sialic acid and underlying galactose yielding a terminal N-acetyl glucosamine. With this treatment complete, a third zone of α2-3,6,8 sialidase converted the remaining α2-6-linked sialic acid to terminal galactose. With these enzyme processing steps the α2-6-linked sialic acid residues on an N-glycan correlated directly to the number of terminal galactose residues that remained. The number of terminal galactose residues could be interpreted as a stepwise decrease in the migration time. Complex N-glycans from α-1-acid glycoprotein were analyzed using this approach, revealing that a limited number of α2-6-linked sialic acids were present with biantennary, triantennary, and tetraantennary N-glycans of α-1-acid glycoprotein generally containing 0 or 1 α2-6-linked sialic acid.

Profiling the N-Glycan Composition of IgG with Lectins and Capillary Nanogel Electrophoresis.

Glycosylated human IgG contains fucosylated biantennary N-glycans with different modifications including N-acetylglucosamine, which bisects the mannose core. Although only a limited number of IgG N-glycan structures are possible, human IgG N-glycans are predominantly biantennary and fucosylated and contain varying levels of α2-6-linked sialic acid, galactose, and bisected N-acetylglucosamine. Monitoring the relative abundance of bisecting N-acetylglucosamine is relevant to physiological processes. A rapid, inexpensive, and automated method is used to successfully profile N-linked IgG glycans and is suitable to distinguish differences in bisection, galactosylation, and sialylation in N-glycans derived from different sources of human IgG. The separation is facilitated with self-assembled nanogels that also contain a single stationary zone of lectin. When the lectin specificity matches the N-glycan, the peak disappears from the electropherogram, identifying the N-glycan structure. The nanogel electrophoresis generates separation efficiencies of 500 000 plates and resolves the positional isomers of monogalactosylated biantennary N-glycan and the monogalactosylated bisected N-glycan. Aleuria aurantia lectin, Erythrina cristagalli lectin (ECL), Sambucus nigra lectin, and Phaseolus vulgaris Erythroagglutinin (PHA-E) are used to identify fucose, galactose, α2-6-linked sialic acid, and bisected N-acetylglucosamine, respectively. Although PHA-E lectin has a strong binding affinity for bisected N-glycans that also contain a terminal galactose on the α1-6-linked mannose branch, this lectin has lower affinity for N-glycans containing terminal galactose and for agalactosylated bisected biantennary N-glycans. The lower affinity to these motifs is observed in the electropherograms as a change in peak width, which when used in conjunction with the results from the ECL lectin authenticates the composition of the agalactosylated bisected biantennary N-glycan. For runs performed at 17 °C, the precision in migration time and peak area was less than or equal to 0.08 and 4% relative standard deviation, respectively. The method is compatible with electrokinetic and hydrodynamic injections, with detection limits of 70 and 300 pM, respectively.

Student Integration into STEM Careers and Culture: A Longitudinal Examination of Summer Faculty Mentors and Project Ownership.

It is widely recognized that the United States needs to attract and retain more people in science, technology, engineering, and mathematics (STEM) careers. Intensive undergraduate research experiences (UREs) are one of the few strategies shown to improve longitudinal student interest and persistence in STEM-related career pathways; however, less is known about the underlying process linking activities to positive outcomes. The tripartite integration model of social influences (TIMSI) provides a framework for understanding the social influence processes by which students integrate into STEM careers and culture. The current study used a longitudinal design and latent growth curve modeling to examine and predict the development of scientific research career persistence intentions over the course of an intensive summer URE. The latent growth curve analysis showed that student persistence intentions declined and rebounded over the course of the summer. Furthermore, the positive impact of faculty mentor role modeling on growth trajectories was mediated through internalization of science community values. In addition, project ownership was found to buffer students from the typical trend of declining and rebounding persistence intentions. The TIMSI framework illuminates the contextual features and underlying psychological processes that link UREs to student integration into STEM careers and culture.

Enhancing research for undergraduates through a nanotechnology training program that utilizes analytical and bioanalytical tools.

Nanotechnology is a broad field combining traditional scientific disciplines; however, analytical chemistry plays an important role in material design, synthesis, characterization, and application. This article emphasizes the uniqueness of nanotechnology and the importance of providing high-quality undergraduate research experiences to both attract and retain talented individuals to the field of nanotechnology. In response to this need to develop a strong and sustainable nanotechnology work force, strategies to create authentic research experiences are considered within the framework of an interdisciplinary nanotechnology environment at West Virginia University. The program, named NanoSAFE Research Experiences for Undergraduates (REU), embeds students in different departments at West Virginia University and in research laboratories within the National Institute of Occupational Safety and Health. A large number of participants have little or no prior research experience and a strong effort is made to recruit applicants from under-represented populations. Components designed to foster research proficiency include frequent reporting, a strong peer-network, and training for secondary mentors. Evidence, which includes student publications and assessment findings demonstrating self-efficacy, is discussed to substantiate the viability of the strategies used in the 2016-2018 program. Graphical abstract ᅟ.