Handheld ISFET Lab-on-Chip detection of TMPRSS2-ERG and AR mRNA for prostate cancer prognostics

Ion-sensitive field-effect transistors (ISFETs) in combination with unmodified complementary metal oxide semiconductors present a point-of-care platform for clinical diagnostics and prognostics. This work illustrates the sensitive and specific detection of two circulating mRNA markers for prostate cancer, the androgen receptor and the TMPRSS2-ERG fusion using a target-specific loop-mediated isothermal amplification method. TMPRSS2-ERG and androgen receptor RNA were detected down to 3x10 1 and 5x10 1 copies respectively in under 30 minutes. Administration of these assays onto the ISFET Lab-on-chip device was successful and the specificity of each marker was corroborated with mRNA extracted from prostate cancer cell lines

Production analysis applied to work improvement

This Note provides and introduction to the research being carried out in the Department of Civil Engineering at Loughborough University and funded by the Science and Engineering Research Council (SERC) into Work Study applied to construction work. The emphasis is directed towards ascertaining site efficiency factors and the methods of determining operation times. In subsequent notes the measuring techniques will be explained in detail and examples of typical data for us in estimating and cost control described

Classification of nucleic acid amplification on ISFET arrays using spectrogram-based neural networks.

The COVID-19 pandemic has highlighted a significant research gap in the field of molecular diagnostics. This has brought forth the need for AI-based edge solutions that can provide quick diagnostic results whilst maintaining data privacy, security and high standards of sensitivity and specificity. This paper presents a novel proof-of-concept method to detect nucleic acid amplification using ISFET sensors and deep learning. This enables the detection of DNA and RNA on a low-cost and portable lab-on-chip platform for identifying infectious diseases and cancer biomarkers. We show that by using spectrograms to transform the signal to the time-frequency domain, image processing techniques can be applied to achieve the reliable classification of the detected chemical signals. Transformation to spectrograms is beneficial as it makes the data compatible with 2D convolutional neural networks and helps gain significant performance improvement over neural networks trained on the time domain data. The trained network achieves an accuracy of 84% with a size of 30kB making it suitable for deployment on edge devices. This facilitates a new wave of intelligent lab-on-chip platforms that combine microfluidics, CMOS-based chemical sensing arrays and AI-based edge solutions for more intelligent and rapid molecular diagnostics

Detection of YAP1 and AR-V7 mRNA for Prostate Cancer prognosis using an ISFET Lab-On-Chip platform

AbstractProstate cancer (PCa) is the second most common cause of male cancer-related death worldwide. The gold standard of treatment for advanced PCa is androgen deprivation therapy (ADT). However, eventual failure of ADT is common and leads to lethal metastatic castration resistant PCa (mCRPC). As such, the detection of relevant biomarkers in the blood for drug resistance in mCRPC patients could lead to personalized treatment options. mRNA detection is often limited by the low specificity of qPCR assays which are restricted to specialised laboratories. Here, we present a novel reversetranscription loop-mediated isothermal amplification (RT-LAMP) assay and have demonstrated its capability for sensitive detection of AR-V7 and YAP1 RNA (3×101 RNA copies per reaction). This work presents a foundation for the detection of circulating mRNA in PCa on a non-invasive Lab-on-chip (LoC) device for use at point-of-care. This technique was implemented onto a Lab-on-Chip platform integrating an array of chemical sensors (ion-sensitive field-effect transistors - ISFETs) for real-time detection of RNA. Detection of RNA presence was achieved through the translation of chemical signals into electrical readouts. Validation of this technique was conducted with rapid detection (&lt;15 min) of extracted RNA from prostate cancer cell lines 22Rv1s and DU145s.</jats:p

The Physicist's Guide to the Orchestra

An experimental study of strings, woodwinds (organ pipe, flute, clarinet, saxophone and recorder), and the voice was undertaken to illustrate the basic principles of sound production in music instruments. The setup used is simple and consists of common laboratory equipment. Although the canonical examples (standing wave on a string, in an open and closed pipe) are easily reproduced, they fail to explain the majority of the measurements. The reasons for these deviations are outlined and discussed.Comment: 11 pages, 10 figures (jpg files). Submitted to European Journal of Physic

Using nominal group technique to advance power assisted exercise equipment for people with stroke

Background: Power assisted exercise is accessible and acceptable for people with stroke. The potential for technological advancement of the equipment to improve the user experience has been identified. Involvement of end users and service providers in the design of health technologies is essential in determining how said technology is perceived and adopted. This project invited people with stroke and service providers to influence design features and determine machine selection in the preliminary stages of a codesign research programme. Aims: To capture the perspectives of people with stroke and professionals working with people with stroke about proposed digitalisation of power assisted exercise equipment and select machines for prototype development. Methods: Nominal group technique was used to capture the perspectives, ideas, preferences and priorities of three stakeholder groups: people with stroke (n = 3, mean age 66 years), rehabilitation professionals (n = 3) and exercise scientists (n = 3). Two questions underpinned the structure of the events; ‘What does an assistive exercise machine need to do to allow the person with stroke to engage in exercise?’ and ‘Which machines would you prioritise for use with People with Stroke?’ Attendees were invited to cast votes to indicate their preferred machines. Findings: Synthesis of the data from the NGT identified four domains; software and interface, exercise programme, machine and accessories, setting and service. Three preferred machines from a range of nine were identified through vote counting. Conclusion: Nominal group technique directed the selection of machines to be included in the development of the proposed technology. The vision shared by users during the structured discussion shaped the subsequent steps in the design and testing of the new technology. Patient and service provider contribution: The opinions and preferences of people with stroke, rehabilitation professionals and exercise scientists were central to key decisions which will shape the digitalisation of power assisted equipment, influence future research and guide implementation of the new technologies

Creativity in public involvement: supporting authentic collaboration and inclusive research with seldom heard voices

Background The role of public involvement (PI) in healthcare research is growing in importance and it is imperative that researchers continuously reflect on how to promote the inclusion of patients and service users in the design and delivery of research. PI offers a mechanism for end-users to be involved planning, executing, and reporting research. Some patient groups, including people who have communication difficulties, may struggle to engage in the methods traditionally employed to promote PI engagement such as questionnaires and focus groups. Methods This article describes a longitudinal case-study of a PI group, consisting of people who have communication difficulties, for a patient-reported outcome development project. Creative methods, informed by the participatory design principles of enacting, seeing and doing, were introduced stepwise into seven PI meetings. Data from video and visual minutes were used to evaluate the impact of the methods, following each group. Feedback, in the form of verbal and visual outputs taken directly from group meeting minutes, along with vignettes evidenced the impact of the methods on the project and group members. Results Creative methods enabled the PI group members to successfully contribute in meetings, to interact dynamically and to engage with the aims and processes of the research project. Their involvement facilitated the development of accessible recruitment materials, informed data analysis and supported the dissemination of project outputs. Employing creative methods also enabled both PI group members and the academic team to reflect on their own roles within the research project and the impact that their active involvement in the PI group has had on their personal development and perspectives on research. Conclusion The impact of using creative methods in PI for this patient-reported outcome measure (PROM) development project improved collaboration and understanding between PI members and the academic team. The authentic engagement of people who have communication difficulties in PI generated a more accessible project in terms of both process and impact. Creativity has applicability beyond people whose communication is non-verbal; it should be harnessed by research teams to identify and breakdown barriers to involvement to develop outcome tools that reflect the diversity of our populations

UK informative inventory report (1990 to 2013)

This is the 10th Informative Inventory Report (IIR) from the UK National Atmospheric Emissions Inventory (NAEI) Programme. The report is compiled to accompany the UK’s 2015 data submission under the United Nations Economic Commission for Europe (UNECE) Convention on Long-Range Transboundary Air Pollution (CLRTAP) and contains detailed information on annual emission estimates of air quality pollutants by source in the UK from 1990 onwards

Practical guidance on use of TEARS-Q to diagnose post-stroke emotionalism

Objective: To evaluate, using a classification tree methodology, the ability of the Testing Emotionalism After Recent Stroke – Questionnaire (TEARS-Q) to determine the need for further assessment of post-stroke emotionalism and to identify those whose emotionalism is sufficiently clear that they need assessment for potential intervention. Setting: Acute stroke units of nine Scottish hospitals in the context of a longitudinal cohort study of post-stroke emotionalism. Subjects: A total of 228 stroke survivors recruited between October 1st 2015 and September 30th 2018, within two weeks of stroke. Measures: The measure was the self-report questionnaire TEARS-Q, constructed based on recognised diagnostic features of post-stroke tearful emotionalism. The reference standard was presence/absence of emotionalism on a diagnostic, semi-structured post-stroke emotionalism interview, administered at the same assessment point. Results: Nine of 159 subjects scoring 0 or 1 on TEARS-Q were diagnosed with post-stroke emotionalism on the reference standard, compared to 11 of 21 subjects scoring 2 to 5 on TEARS-Q and 42 of 48 participants scoring 6 and above. Adding age, sex, deprivation, stroke type, stroke severity, mood, cognition, daily functioning and education did not improve the prediction accuracy sufficiently to change the classification tree. Conclusion: TEARS-Q reliably identifies those who need no further post-stroke emotionalism assessment, those who need further assessment to clarify diagnosis, and those who almost certainly have post-stroke emotionalism and may benefit from intervention

The Long Journey from Ab Initio Calculations to Density Functional Theory for Nuclear Large Amplitude Collective Motion

At present there are two vastly different ab initio approaches to the description of the the many-body dynamics: the Density Functional Theory (DFT) and the functional integral (path integral) approaches. On one hand, if implemented exactly, the DFT approach can allow in principle the exact evaluation of arbitrary one-body observable. However, when applied to Large Amplitude Collective Motion (LACM) this approach needs to be extended in order to accommodate the phenomenon of surface-hoping, when adiabaticity is strongly violated and the description of a system using a single (generalized) Slater determinant is not valid anymore. The functional integral approach on the other hand does not appear to have such restrictions, but its implementation does not appear to be straightforward endeavor. However, within a functional integral approach one seems to be able to evaluate in principle any kind of observables, such as the fragment mass and energy distributions in nuclear fission. These two radically approaches can likely be brought brought together by formulating a stochastic time-dependent DFT approach to many-body dynamics.Comment: 9 page