Academic Laboratories Research Articles

Current Status of Solid Oxide Fuel Cell Technology Research and Development at National Energy Technology Laboratory

The DOE Office of Fossil Energy Solid Oxide Fuel Cell (SOFC) Program is interested in the near-term commercialization of high-temperature SOFC and solid oxide electrolyzer cell (SOEC) technologies that are robust, reliable, and resilient. A recent report delivered to the United States Congress highlighted several development recommendations including the design of pilot-scale units, continued early stage research and development, increased industrial engagement, and the exploration of reversible operation of SOFC technology.The National Energy Technology Laboratory (NETL) SOFC research group currently addresses most of these recommendations. NETL’s in-house research efforts focus on the characterization, simulation, and mitigation of high temperature degradation of fuel cell components. The capstone of these efforts is NETL’s SOFC degradation modeling framework, which uses NETL supercomputing facilities to simulate SOFC performance degradation of thousands of possible electrode configurations experiencing multiple simultaneous degradation modes under a broad array of relevant operating conditions. The models for the different degradation modes are based upon experimental data (1) generated in-house, (2) referenced from available scientific publications, and (3) shared from collaborations with other industrial, academic, and national laboratory partners within the SOFC Program. The team then employs techniques in data analytics to select optimal electrodes to maximize the SOFC performance for given operating conditions. These modeling efforts guide electrode engineering efforts in-house and through external collaborations by identifying (1) which degradation modes contribute the most to overall performance degradation for given operating conditions and (2) which electrode features will have the greatest impact on lowering cell degradation and system costs. Additionally, the development on non-invasive in situ high temperature fiber optic sensors for temperature and gas composition measurement provides valuable data for inclusion in degradation models as well as informing technology development at the commercial scale. Finally, the wealth of experience gained in development degradation models and materials for reducing the cost of SOFC technology is being readily applied to reducing the cost of SOEC technology.NETL will report on its most recent progress in the field of SOFC and SOEC development, including degradation modeling, in situ fiber optic sensor development, electrode engineering, and relevant systems-level analyses.

Generating Standard Operating Procedures for the Manipulation of Hazardous Chemicals in Academic Laboratories

Generating standard operating procedures (SOPs) for high-risk chemical processes where toxic, pyrophoric, self-reactive, or energetic materials are used is necessary for academic research safety. W...

Microfluidics for Biotechnology: Bridging Gaps to Foster Microfluidic Applications.

Microfluidics and novel lab-on-a-chip applications have the potential to boost biotechnological research in ways that are not possible using traditional methods. Although microfluidic tools were increasingly used for different applications within biotechnology in recent years, a systematic and routine use in academic and industrial labs is still not established. For many years, absent innovative, ground-breaking and “out-of-the-box” applications have been made responsible for the missing drive to integrate microfluidic technologies into fundamental and applied biotechnological research. In this review, we highlight microfluidics’ offers and compare them to the most important demands of the biotechnologists. Furthermore, a detailed analysis in the state-of-the-art use of microfluidics within biotechnology was conducted exemplarily for four emerging biotechnological fields that can substantially benefit from the application of microfluidic systems, namely the phenotypic screening of cells, the analysis of microbial population heterogeneity, organ-on-a-chip approaches and the characterisation of synthetic co-cultures. The analysis resulted in a discussion of potential “gaps” that can be responsible for the rare integration of microfluidics into biotechnological studies. Our analysis revealed six major gaps, concerning the lack of interdisciplinary communication, mutual knowledge and motivation, methodological compatibility, technological readiness and missing commercialisation, which need to be bridged in the future. We conclude that connecting microfluidics and biotechnology is not an impossible challenge and made seven suggestions to bridge the gaps between those disciplines. This lays the foundation for routine integration of microfluidic systems into biotechnology research procedures.

Automation in the Life Science Research Laboratory.

Protocols in the academic life science laboratory are heavily reliant on the manual manipulation of tools, reagents and instruments by a host of research staff and students. In contrast to industrial and clinical laboratory environments, the usage of automation to augment or replace manual tasks is limited. Causes of this ‘automation gap’ are unique to academic research, with rigid short-term funding structures, high levels of protocol variability and a benevolent culture of investment in people over equipment. Automation, however, can bestow multiple benefits through improvements in reproducibility, researcher efficiency, clinical translation, and safety. Less immediately obvious are the accompanying limitations, including obsolescence and an inhibitory effect on the freedom to innovate. Growing the range of automation options suitable for research laboratories will require more flexible, modular and cheaper designs. Academic and commercial developers of automation will increasingly need to design with an environmental awareness and an understanding that large high-tech robotic solutions may not be appropriate for laboratories with constrained financial and spatial resources. To fully exploit the potential of laboratory automation, future generations of scientists will require both engineering and biology skills. Automation in the research laboratory is likely to be an increasingly critical component of future research programs and will continue the trend of combining engineering and science expertise together to answer novel research questions.

Positive Behavior and Perceptions of Safety Culture in Academic Research Laboratories

In academic labs, organizational culture is an important consideration for safety compliance. This studyexamined perceptions of risk and safety behavior to target training improvement. College of Science lab person-nel (n = 1,066) were invited participate in a web-based survey with the number of respondents (n=97) and theresponse rate (9.1%). Analysis included descriptive statistics and thematic evaluation. The majority of respondentsrated safety as important and agreed training was sufficient, but believed there was room to improve safety culture.Encouraging use of lab-based safety and risk discussions related to new research procedures was identified as areafor improvement. Perceptions of safety among leadership is important to overall lab culture.

Circulating tumor DNA in advanced solid tumors: Clinical relevance and future directions.

The application of genomic profiling assays using plasma circulating tumor DNA (ctDNA) is rapidly evolving in the management of patients with advanced solid tumors. Diverse plasma ctDNA technologies in both commercial and academic laboratories are in routine or emerging use. The increasing integration of such testing to inform treatment decision making by oncology clinicians has complexities and challenges but holds significant potential to substantially improve patient outcomes. In this review, the authors discuss the current role of plasma ctDNA assays in oncology care and provide an overview of ongoing research that may inform real-world clinical applications in the near future.

Safety culture maturity in a civil engineering academic laboratory

Safety culture maturity is critical to the prevention of unsafe behaviors, especially in industries such as civil construction, with its high rates of injuries and fatalities. This concept is even more important when studying the academic environments in which professionals who will work in those industries are trained. The goal of this study was to evaluate (diagnose) the safety culture maturity and to identify and hierarchize its antecedent factors (organizational factors) in the laboratories at the Civil Engineering Department of the Federal University of Pará (UFPa), Brazil. Data were collected using questionnaires from 237 laboratories users. All respondents were students, a population that comprises the vast majority of users; thus, the results were based on these individuals’ perceptions. Descriptive statistics and regression modeling techniques were used to analyze the collected data. The results indicated that the laboratories are in “reactive” maturity stage. The main organizational factors directly affecting the maturity of that safety culture were “information”, “involvement” and “commitment”. The findings of this study may advance the theories of safety culture maturity by incorporating discussions related to the characteristics of functionalist versus interpretive approaches, as well as to the organizational structure influences. Idiosyncrasies related to a country's culture were also discussed.

Decoupling Protein Production from Cell Growth Enhances the Site-Specific Incorporation of Noncanonical Amino Acids in E.coli.

The site-specific incorporation of noncanonical amino acids (ncAAs) into proteins by amber stop codon suppression has become a routine method in academic laboratories. This approach requires an amber suppressor tRNACUA to read the amber codon and an aminoacyl-tRNA synthetase to charge the tRNACUA with the ncAA. However, a major drawback is the low yield of the mutant protein in comparison to the wild type. This effect primarily results from the competition of release factor 1 with the charged suppressor tRNACUA for the amber codon at the A-site of the ribosome. A number of laboratories have attempted to improve the incorporation efficiency of ncAAs with moderate results. We aimed at increasing the efficiency to produce high yields of ncAA-functionalized proteins in a scalable setting for industrial application. To do this, we inserted an ncAA into the enhanced green fluorescent protein and an antibody mimetic molecule using an industrial E.coli strain, which produces recombinant proteins independent of cell growth. The controlled decoupling of recombinant protein production from cell growth considerably increased the incorporation of the ncAA, producing substantially higher protein yields versus the reference E.coli strain BL21(DE3). The target proteins were expressed at high levels, and the ncAA was efficiently incorporated with excellent fidelity while the protein function was preserved.

A story of nimble knowledge production in an era of academic capitalism

A rise of academic capitalism over the past four decades has been well documented within many research-intensive universities. Largely missing, however, are in-depth studies of how particularly situated academic groups manage the uncertainties that come with intermittent and fickle commercial funding streams in their daily research practice and problem choice. To capture the strategies scientists adopt under these conditions, this article provides an ethnographically detailed (and true) story about how a single project in Artificial Intelligence grew over several years from a peripheral idea to the very center of an academic lab’s commercial portfolio. The analysis theorizes an epistemic form—nimble knowledge production—and documents three of its lab-level features: 1) rapid prototyping to keep sunk costs low, 2) shared search for “real world problems” rather than “theoretical” ones, and 3) nimble commitment to research problem choice. While similar forms of academic knowledge transfer have been lauded as “mode 2,” “innovative,” or “hybrid” for initiating cross-institutional collaboration and pushing science beyond disciplinary silos, this case suggests it can rely on fleeting attention to problems resistant to a quick fix.

A blueprint for academic laboratories to produce SARS-CoV-2 quantitative RT-PCR test kits

Widespread testing for the presence of the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals remains vital for controlling the COVID-19 pandemic prior to the advent of an effective treatment. Challenges in testing can be traced to an initial shortage of supplies, expertise, and/or instrumentation necessary to detect the virus by quantitative RT-PCR (RT-qPCR), the most robust, sensitive, and specific assay currently available. Here we show that academic biochemistry and molecular biology laboratories equipped with appropriate expertise and infrastructure can replicate commercially available SARS-CoV-2 RT-qPCR test kits and backfill pipeline shortages. The Georgia Tech COVID-19 Test Kit Support Group, composed of faculty, staff, and trainees across the biotechnology quad at Georgia Institute of Technology, synthesized multiplexed primers and probes and formulated a master mix composed of enzymes and proteins produced in-house. Our in-house kit compares favorably with a commercial product used for diagnostic testing. We also developed an environmental testing protocol to readily monitor surfaces for the presence of SARS-CoV-2. Our blueprint should be readily reproducible by research teams at other institutions, and our protocols may be modified and adapted to enable SARS-CoV-2 detection in more resource-limited settings.

Surveying the Safety Culture of Academic Laboratories

Surveying the Safety Culture of Academic Laboratories

Bringing Gene Therapies for HIV Disease to Resource-Limited Parts of the World.

Bringing Gene Therapies for HIV Disease to Resource-Limited Parts of the World.

The impact of online management systems: a qualitative assessment of staff perception at a clinical research laboratory

Good Clinical Laboratory Practices (GCLP) increase the quality and traceability of results in clinical research. However, high turnover of staff, insufficient resources, and lack of training in lab management may limit its implementation at Academic Health Centers (AHCs). This work aimed to qualitatively assess the staff perception of the implementation of a freeware Online Management System (OMS) on the workflow of an academic clinical research laboratory. A free online OMS (Quartzy, Quartzy Inc., USA) was selected and implemented from 2012-2016. After training interventions, a qualitative analysis was performed for the staff attitude towards the implementation, including a structured questionnaire (30 participants) and focus group assessments (16 participants). Indicators of management performance were also compared before and after the implementation. The results indicate that lab members perceive improvement in organization, communication, and commitment of staff, who reported the system as user-friendly and a facilitator for the autonomy of group members. On the other hand, there is a recognition of the need for constant training and engagement at the management level. These findings suggest that full-scope OMS may represent useful tools to assist in staff engagement in compliance with GCLP at AHC laboratories.

A blueprint for the implementation of a validated approach for the detection of SARS-Cov2 in clinical samples in academic facilities.

The COVID-19 pandemic is expanding at an unprecedented rate. As a result, diagnostic services are stretched to their limit, and there is a clear need for the provision of additional diagnostic capacity. Academic laboratories, many of which are closed due to governmental lockdowns, may be in a position to support local screening capacity by adapting their current laboratory practices. Here, we describe the process of developing a SARS-Cov2 diagnostic workflow in a conventional academic Containment Level 2 laboratory. Our outline includes simple SARS-Cov2 deactivation upon contact, the method for a quantitative real-time reverse transcriptase PCR detecting SARS-Cov2, a description of process establishment and validation, and some considerations for establishing a similar workflow elsewhere. This was achieved under challenging circumstances through the collaborative efforts of scientists, clinical staff, and diagnostic staff to mitigate to the ongoing crisis. Within 14 days, we created a validated COVID-19 diagnostics service for healthcare workers in our local hospital. The described methods are not exhaustive, but we hope may offer support to other academic groups aiming to set up something comparable in a short time frame.

Metabolomics Profiling of Critically Ill Coronavirus Disease 2019 Patients: Identification of Diagnostic and Prognostic Biomarkers.

Objectives:Coronavirus disease 2019 continues to spread rapidly with high mortality. We performed metabolomics profiling of critically ill coronavirus disease 2019 patients to understand better the underlying pathologic processes and pathways, and to identify potential diagnostic/prognostic biomarkers.Design:Blood was collected at predetermined ICU days to measure the plasma concentrations of 162 metabolites using both direct injection-liquid chromatography-tandem mass spectrometry and proton nuclear magnetic resonance.Setting:Tertiary-care ICU and academic laboratory.Subjects:Patients admitted to the ICU suspected of being infected with severe acute respiratory syndrome coronavirus 2, using standardized hospital screening methodologies, had blood samples collected until either testing was confirmed negative on ICU day 3 (coronavirus disease 2019 negative) or until ICU day 10 if the patient tested positive (coronavirus disease 2019 positive).Interventions:None.Measurements and Main Results:Age- and sex-matched healthy controls and ICU patients that were either coronavirus disease 2019 positive or coronavirus disease 2019 negative were enrolled. Cohorts were well balanced with the exception that coronavirus disease 2019 positive patients suffered bilateral pneumonia more frequently than coronavirus disease 2019 negative patients. Mortality rate for coronavirus disease 2019 positive ICU patients was 40%. Feature selection identified the top-performing metabolites for identifying coronavirus disease 2019 positive patients from healthy control subjects and was dominated by increased kynurenine and decreased arginine, sarcosine, and lysophosphatidylcholines. Arginine/kynurenine ratio alone provided 100% classification accuracy between coronavirus disease 2019 positive patients and healthy control subjects (p = 0.0002). When comparing the metabolomes between coronavirus disease 2019 positive and coronavirus disease 2019 negative patients, kynurenine was the dominant metabolite and the arginine/kynurenine ratio provided 98% classification accuracy (p = 0.005). Feature selection identified creatinine as the top metabolite for predicting coronavirus disease 2019-associated mortality on both ICU days 1 and 3, and both creatinine and creatinine/arginine ratio accurately predicted coronavirus disease 2019-associated death with 100% accuracy (p = 0.01).Conclusions:Metabolomics profiling with feature classification easily distinguished both healthy control subjects and coronavirus disease 2019 negative patients from coronavirus disease 2019 positive patients. Arginine/kynurenine ratio accurately identified coronavirus disease 2019 status, whereas creatinine/arginine ratio accurately predicted coronavirus disease 2019-associated death. Administration of tryptophan (kynurenine precursor), arginine, sarcosine, and/or lysophosphatidylcholines may be considered as potential adjunctive therapies.

TactViz: A VMD Plugin for Tactile Visualization of Protein Structures

Scientific disciplines spanning biology, biochemistry, and biophysics involve the study of proteins and their functions. Visualization of protein structures represents a barrier to education and research in these disciplines for students who are blind or visually impaired. Here, we present a software plugin for readily producing variable-height tactile graphics of proteins using the free biomolecular visualization software Visual Molecular Dynamics (VMD) and protein structure data that is publicly available through the Protein Data Bank. Our method also supports interactive tactile visualization of proteins with VMD on electronic refreshable tactile display devices. Employing our method in an academic laboratory has enabled an undergraduate student who is blind to carry out research alongside her sighted peers. By making the study of protein structures accessible to students who are blind or visually impaired, we aim to promote diversity and inclusion in STEM education and research.

Diagnosing the novel SARS-CoV-2 by quantitative RT-PCR: variations and opportunities.

The world is currently facing a novel viral pandemic (SARS-CoV-2), and large-scale testing is central to decision-making for the design of effective policies and control strategies to minimize its impact on the global population. However, testing for the presence of the virus is a major bottleneck in tracking the spreading of the disease. Given its adaptability regarding the nucleotide sequence of target regions, RT-qPCR is a strong ally to reveal the rapid geographical spreading of novel viruses. We assessed PCR variations in the SARS-CoV-2 diagnosis taking into account public genome sequences and diagnosis kits used by different countries. We analyzed 226 SARS-CoV-2 genome sequences from samples collected by March 22, 2020. Our work utilizes a phylogenetic approach that reveals the early evolution of the virus sequence as it spreads around the globe and informs the design of RT-qPCR primers and probes. The quick expansion of testing capabilities of a country during a pandemic is largely impaired by the availability of adequately trained personnel on RNA isolation and PCR analysis, as well as the availability of hardware (thermocyclers). We propose that rapid capacity development can circumvent these bottlenecks by training medical and non-medical personnel with some laboratory experience, such as biology-related graduate students. Furthermore, the use of thermocyclers available in academic and commercial labs can be promptly calibrated and certified to properly conduct testing during a pandemic. A decentralized, fast-acting training and testing certification pipeline will better prepare us to manage future pandemics.Electronic supplementary materialThe online version of this article (10.1007/s00109-020-01992-x) contains supplementary material, which is available to authorized users.

Can a Broad Molecular Screen Based on Circulating Tumor DNA Aid in Early Cancer Detection?

Early detection of cancer has been a major research focus for almost a century. Current methods for early cancer detection suffer from suboptimal sensitivity and specificity, especially when used for population screening. For most major cancers, including breast, prostate, lung, ovarian, and pancreatic cancer, population screening is still controversial or is not recommended by expert bodies. Circulating tumor DNA (ctDNA) is an exciting new cancer biomarker with potential applicability to all cancer types. Recent investigations have shown that genetic alterations or epigenetic modifications in ctDNA could be used for cancer detection with a liquid biopsy (i.e., a tube of blood). Tests based on ctDNA have attracted considerable attention for various applications, such as patient management, prognosis, early diagnosis, and population screening. Recently, new biotechnology companies were founded, with the goal of revolutionizing early cancer detection by using ctDNA. We previously examined this technology, as published by various academic laboratories and of one leading company, Grail, and drew attention to potential obstacles. After 3 years of intense development, this technology seems to have made some progress. Here, we will analyze the latest clinical data presented by Grail in October 2019, during the inaugural American Society of Clinical Oncology (ASCO) 2019 Breakthrough Conference. Despite considerable technical improvements, it seems that the sensitivity and specificity of the Grail test as a pan-cancer screening tool are still too low for clinical use. The prospects that this test could be further improved are also discussed.

Functional role of the long noncoding RNA X-inactive specific transcript in leiomyoma pathogenesis

To determine the expression and functional roles of a long noncoding RNA (lncRNA) X-inactive specific transcript (XIST) in leiomyoma. Experimental study. Academic research laboratory. Women undergoing hysterectomy for leiomyoma. Overexpression and underexpression of XIST; blockade of specific protein 1 (SP1). Expression of XIST in leiomyoma and its effects on microRNA 29c (miR-29c), miR-200c, and their targets. Leiomyoma expressed statistically significantly more XIST as compared with matched myometrium, independent of race/ethnicity and menstrual cycle phase. By use of a three-dimensional spheroid culture system, we found reduced XIST levels in leiomyoma smooth muscle cells (LSMC) after treatment with 17β-estradiol, progesterone, and their combination. The expression of XIST was down-regulated by treatment with the SP1-inhibitor mithramycin A and SP1 small interfering RNA. Knockdown of XIST resulted in inhibition of cell proliferation, up-regulation of miR-29c and miR-200c, and a concomitant inhibition of the target genes of these miRNAs, namely collagen type I (COL1A1), collagen type III (COL3A1), and fibronectin (FN1). By contrast, overexpression of XIST in myometrium smooth muscle cells repressed miR-29c and miR-200c, and induced COL1A1, COL3A1, and FN1 levels. By use of RNA immunoprecipitation analysis we confirmed XIST has sponge activity over miR-29c and miR-200c, which is more pronounced in leiomyoma as compared with myometrium. Our data demonstrate that increased expression of XIST in leiomyoma results in reduced expression of miR-29c and miR-200c with a consequent up-regulation of the genes targeted by these microRNAs including COL1A1, COL3A1, and FN1, which play key roles in extracellular matrix accumulation associated with fibroids.

Consensus Recommendations for the Safe Handling of Cytotoxic Agents in Cytotoxic Academic Research Laboratories (CARL).

Cytotoxic agents, also called antineoplastic agents, are used in cancer treatment due to their inherent activity to inhibit cell growth or proliferation, or DNA, RNA and protein synthesis. They are, therefore, hazardous by nature in a non-selective manner leading to disruption of cell growth and function of both diseased and healthy cells of treated patients.While the benefits of receiving cytotoxic agents may outweigh the incurred risks for patients, the same cannot be said for exposed healthcare practitioners involved in the transport, preparation, administration, and resulting waste disposal of these agents.Consequently, many professional bodies around the world have set standards of practice to prevent occupational exposure of healthcare workers to cytotoxic agents, and hospitals have been active in defining strict policies in this concern.However, due to the variability of the practice and infrastructure in academic settings, some activities performed within the cytotoxic academic research laboratory often do not adhere to recommendations published by guidelines.The present recommendations were therefore set forward by members of a working group who are experts on the subject matter representing academic, clinical, and research backgrounds in an attempt to promote safe cytotoxic handling in academic institutions.The document maps out the trajectory of cytotoxic agents being investigated in academic research laboratories while providing recommendations on the delivery, storage, use and disposal of cytotoxic agents in university settings.