Diagnostic Medical Devices Research Articles

Size effects of mechanical properties of nanohoneycomb with multiple surface orientations

Nanostructures and nanomaterials have been studied thoroughly due to their remarkable properties. With various sizes and shapes, they serve as highly functional sensors in nanoelectromechanical systems (NEMS), noninvasive medical diagnostic devices or drug delivers. Although the importance of surfaces has been recognized when it comes to the nanoscale, few researchers investigate nanostructures with multiple surface orientations. In this work, we propose a two-surface theoretical model for nanohoneycombs and verify the model by conducting molecular dynamics (MD) simulations on regular hexagonal Al nanohoneycombs with cell-wall thickness ranging from 5 nm to 30 nm. These numerical examples show excellent agreement with the proposed theory, proving the applicability of the two-surface model. The Al nanohoneycomb exhibits significant “positive” size dependence – it is 2.4 times stiffer compared with its large counterpart when the cell-wall thickness is 5.7 nm. In sum, this study improves the accuracy of the predicted in-plane Young's moduli of nanohoneycombs by taking differently oriented surfaces into account and considering more comprehensive deformation mechanisms. By investigating nanosized honeycomb structure in-depth and providing a more general theoretical model, we aim to improve the accuracy of predicted mechanical properties and provide a guide for the applicability of various models for honeycombs. Furthermore, this study can help exploit the full potential of various nanoporous structures, not restricted to nanohoneycombs.

Changes and Related Reflections on the European Union's in Vitro Diagnostic Medical Device Classification Supervision System

By analyzing and comparing the IVD product classification supervision system in the EU's new IVDR, old IVDD and related guidance documents, concepts of related regulatory reforms were analyzed and explored, to provide references for industrial personnel to understand and master the new EU IVD classification system, and for China's ongoing classification management reform.

Biomarker and Companion Diagnostics-A Review of Medicinal Products Approved by the European Medicines Agency.

Background: An increasing number of medicines authorised in Europe recommend or require biomarker-based patient selection. For some of these the use of a companion diagnostic (CDx), a subset of in vitro diagnostics (IVDs), to identify patient populations eligible for a specific medicinal product may be required. The information and recommendations of use of a medicinal product for which a CDx is required is particularly important to healthcare professionals for correct patient identification.Methods: We reviewed the existing information in SmPCs and European Public Assessment Reports (EPARs) of EU medicinal products approved via the centralised procedure at EMA where reference was made to biomarker testing, including by CDx, for patient selection.Results: The results show that varying levels of detail are provided for the biomarker and the diagnostic test, including variability in where the information was presented. The overall results demonstrate transparent but sometimes heterogeneous reporting of CDx in the SmPC and EPAR.Conclusions: With the introduction of the new Regulation (EU) 2017/746 on in vitro diagnostic medical devices, medicines regulatory authorities' will be required to be consulted during the review of CDx conformity assessment and so, there is opportunity for more consistent and transparent information on CDx to be provided in the SmPC and EPAR.

Legal and Normative Requirements Related to Medical Devices for Individual Supply in Clinical Practice.

This article has the form of a communication presenting recent legal changes in relation to medical devices. Until 26 May 2021, three medical directives were in force, namely Directive 98/79 / EC, Council Directive 93/42/ EEC and Council Directive 90/385 / EEC. They have been replaced by two regulations: Regulation (EU) 2017/745 on medical devices and Regulation (EU) 2017/746 on in vitro diagnostic medical devices. The article presents the reasons for introducing the changes and the new obligations that these changes bring for manufacturers of medical devices, in particular, products manufactured individually on a special order as necessary for the implementation of personalized therapies in clinical practice. There are also forecasts for the industry and end users of medical devices manufactured to order and used individually at medical centers.

Sweet diagnostics and smartphone spiders

Conductive candy Some people don’t like Tootsie Roll candy, Newscripts has learned. Regardless of the validity of that opinion, researchers have come up with an alternate use for the little chocolate logs: shaping them into electrodes that diagnose kidney disease or track ovulation ( ACS Appl. Mater. Interfaces 2021, DOI: 10.1021/acsami.1c11306 ). Beelee Chua of Korea University has worked for years developing medical diagnostic devices. He says he noticed that single-use tests—which help ensure equipment remains sterile between uses—are both expensive and generate a lot of waste. So Chua and his former student Donghyun Lee, now of Pusan National University, have looked for ways to repurpose other materials to potentially reduce the cost and waste of diagnostics. They previously described using gummy bears to measure bite force ( Sens. Actuators, A 2019, DOI: 10.1016/j.sna.2019.03.013 ). Now they’ve shown that Tootsie Roll candies molded with a grid pattern can trap saliva

Recent advances in electrocatalysts, mechanism, and cell architecture for direct formic acid fuel cells

AbstractDirect formic acid fuel cells (DFAFCs) are potential candidates as power sources for various applications, especially in portable electronics and medical diagnostic devices. Though they have been the subject of considerable research, commercial prototypes of DFAFCs are rudimentary compared to other liquid fuel cells, particularly the widespread methanol‐based direct methanol fuel cells. Various strategies for rationally engineering the electrocatalysts for enhancing DFAFC performance have been explored in the last few years, such as alloying noble metals with earth‐abundant transition metals, designing specific morphological and structural arrangements, decorating the surface with corrosion‐tolerant cocatalysts, and providing better catalyst support for effective catalyst dispersion. An overall approach may be necessary and should include (i) understanding the underlying mechanism, which will guide the direction of catalyst engineering, (ii) employing morphological, compositional, and structural control of the electrocatalysts to improve catalyst utilization and enhance the intrinsic activity for real‐world applications, and (iii) integrating these in a proficiently designed cell architecture suitable for targeted applications. In this review, we focus on the recent advances in electrocatalysts, formic acid electrooxidation mechanisms, and DFAFC cell architectures, which could help address the opportunities and challenges of commercializing DFAFC as a prospective alternative power source for portable applications.This article is categorized under: Fuel Cells and Hydrogen > Science and Materials Energy Research & Innovation > Science and Materials

Brief Introduction about New Regulation of EU on IVDR

There are five-year transitional period for manufacturers after the issue of regulation(EU) 2017/746 on in vitro diagnostic medical devices(IVDR) in May, 2017. The article introduces the background, major change, the impact of new regulation and the coping strategies of enterprises, the main preparation work should be taken etc, to provide reference or help for the domestic manufacturers when they prepare the CE marking according to IVDR.

Numerical and experimental studies of acoustic streaming effects on microparticles/droplets in microchannel flow

Exploiting acoustic streaming effects for microfluidic devices has been proven to be important for cell, microparticle and fluid manipulation in many fields such as, biomedical engineering, medical diagnostic devices, cell studies and chemistry. Acoustic streaming is used in acoustofluidic systems for directing and sorting microparticles as well as mixing and pumping fluids. To understand the underlying physics of such acoustofluidic systems and thus use them more efficiently in practical setups, computational modelling is critically needed. Although some work has been done to numerically model acoustofluidic systems, there are few studies to evaluate the capability and accuracy of different numerical schemes for analysing this complex multi-physics problem and to be directly validated by experiments. This paper aims to investigate the acoustic streaming effects caused by surface acoustic waves in a microchannel flow by using two different computational approaches to model the acoustic effects in three dimensions. In the first approach, we model the whole acoustic field caused by the oscillating lower wall. Here, the acoustic streaming effects were directly calculated from the density and velocity fields caused by the acoustic field. In the second approach, a low fidelity model is employed to capture the effects of acoustic streaming without modelling the acoustic field itself. In this approach, we substituted the velocity of a one-dimensional attenuating wave in the acoustic streaming force formula, and calculated the acoustic streaming force without using the density and velocity caused by the acoustic field. Both the computational methods are then validated by the results obtained from microflow experiments. The results from the second approach are in reasonable agreement with experiments while being more efficient in terms of computational cost. On the contrary, the first approach, while being computationally more expensive, allows to estimate the pressure field resulting from acoustic waves and thus predicts the dynamic behaviour of microparticles more accurately. Results suggest that the first approach is best to use for analysing the mechanism of microparticle and fluid manipulation in microfluidic devices.

Oral Carcinoma and Therapeutic Approaches of Nanotechnology: From Fundamental Concepts, Incidence, Molecular Mechanism to Emerging Treatment Techniques

Oral carcinoma is the most general, with a large fatality rate and aggressive cancer that can cause metastasis as it attacks other tissues. The prevalence of carcinoma is a multistep method, requiring the collection of many hereditary changes influenced by a patient's hereditary predisposition and environmental effects, including nicotine, alcoholic beverages, chronic infection, and viral contamination. The data were searched using focal keywords, including oral cancer, molecular mechanisms, treatments, and nanotechnology, through various search engines and the Pubmed database. There are two major types of carcinogenesis genetic manipulation, i.e., tumor suppressor genes and oncogenes. Tumor suppression genes can be inactivated throughout genetic phenomena, such as mutations, loss of heterozygosity, deletion, or epigenetic alterations such as methylation of DNA or dynamic modification of chromatin. Oncogenes can be activated through overexpression due to gene amplification, enhanced transcription, or a variation in structure due to mutation, leading to enhanced transforming activity. The current review focused on enhancing cancer therapy techniques using nanomedicines, including nanoscale medicine transfer systems' design, characterization, production, and utilization. Instruments for diagnostic investigations and medical devices are for nanotechnologies-based therapies are polymeric nanoparticles, nanostructured lipid carriers, gold nanoparticles, and cyclodextrin complexes, which are promising apparatuses for symptomatic tests and helpful treatment gadgets. The present investigation's keen interest was the molecular mechanisms of oral carcinogenesis and the application of biologic therapies to target altered molecules in oral carcinoma and nano-based drug delivery system.

Laboratory-Developed Tests: Design of a Regulatory Strategy in Compliance with the International State-of-the-Art and the Regulation (EU) 2017/746 (EU IVDR [In Vitro Diagnostic Medical Device Regulation

PurposeThis study aimed at the development of a regulatory strategy for compliance of laboratory-developed tests (LDTs) with requirements of the Regulation (EU) 2017/746 (“EU-IVDR”) under consideration of international requirements for LDTs as established in major regulatory regions. Furthermore, it was analysed in how far elements of current LDT regulation could qualify for an internationally harmonised concept ensuring quality, safety and performance of LDTs.MethodsA review of regulatory literature including legislation as well as guidance documents was performed. The regulatory strategy was adapted from international guidance concepts used for commercially marketed IVD. It was then applied to the example of a large medical laboratory in the EU. A high-level comparison was conducted to identify gaps and matches between the different international regulatory requirements for LDTs.ResultsA four-step strategy for compliance of LDTs with the EU IVDR was implemented in an exemplary medical laboratory. On the basis of an internationally used LDT definition, LDTs constitute nearly 50% of the total IVD devices used in the laboratory. While an ISO 15189-compliant QMS is a major component, it should be accompanied by the application of appropriate processes for risk management, performance evaluation and continuous monitoring of LDTs. At least six criteria represent common characteristics of a potential, internationally convergent concept for the regulation/standardization of LDTs.ConclusionsThis study confirms the impact of LDTs for individualized and innovative medical laboratory testing. Prerequisites for LDT use as especially given by the IVDR and missing interpretation in the EU with regard to the scope of LDT definition, the application of standards and the extent of documentation for LDTs currently lead to uncertainties for both laboratories and regulatory bodies responsible for LDT oversight. The characteristics identified as common criteria for ensuring quality, safety and performance of LDTs may be considered as central elements of future international consensus guidance.

Current Insights into Oral Cancer Diagnostics.

Oral cancer is one of the most common head and neck malignancies and has an overall 5-year survival rate that remains below 50%. Oral cancer is generally preceded by oral potentially malignant disorders (OPMDs) but determining the risk of OPMD progressing to cancer remains a difficult task. Several diagnostic technologies have been developed to facilitate the detection of OPMD and oral cancer, and some of these have been translated into regulatory-approved in vitro diagnostic systems or medical devices. Furthermore, the rapid development of novel biomarkers, electronic systems, and artificial intelligence may help to develop a new era where OPMD and oral cancer are detected at an early stage. To date, a visual oral examination remains the routine first-line method of identifying oral lesions; however, this method has certain limitations and as a result, patients are either diagnosed when their cancer reaches a severe stage or a high-risk patient with OPMD is misdiagnosed and left untreated. The purpose of this article is to review the currently available diagnostic methods for oral cancer as well as possible future applications of novel promising technologies to oral cancer diagnosis. This will potentially increase diagnostic options and improve our ability to effectively diagnose and treat oral cancerous-related lesions.

Features of the technology for producing multicomponent ferropiezoelectric materials

A technological method has been developed for the manufacture of multicomponent ferroelectric piezoelectric materials based on lead titanate, including those modified by oxides of rare-earth elements, of the Pb(Ti, Zr)O3 binary system, and alkali metal niobates. The method is considered step by step on the example of the composition Pb0.88Nd0.1Ti0.92Mn0.02In0.06O3 and consists in additional heat treatment of the synthesized product at a temperature corresponding to the termination of the change in the unit cell parameters. It is shown that the materials obtained by using the proposed method have improved characteristics in comparison with similar ones realized in materials manufactured by the traditional method. The developed materials are promising for the creation of high-frequency electroacoustic transducers, ultrasonic flaw detectors, and medical diagnostic devices.

Genetic Diagnostic Approaches in Familial Hypercholesterolemia Evaluation

Abstract Familial hypercholesterolemia (FH) manifested as atherosclerosis is a major cause of coronary heart disease. Different scoring systems based on clinical and paraclinical data are currently used, but the FH diagnosis should be made only in the presence of the causative genetic defect. In the present study, 12 symptomatic (previously diagnosed with atherosclerosis) and asymptomatic family members were investigated. Serum lipids were measured using commercial reagents. A genetic investigation was performed by Sanger sequencing using commercial reagents and custom primers, while copy number variations and a selected set of 40 point mutations were evaluated using in vitro diagnostic medical devices. For the investigated patients, serum lipids were within the reference range, due to the fact that the subjects were following lipid-lowering therapy, and smoking was the only identifiable additional risk factor. Four benign exon variants and three intron variants situated within the low-density lipoprotein cholesterol receptor gene were identified by Sanger sequencing. No copy number variations and none of the 40 investigated point mutations were determined. Although independently considered benign, the combined effect of the identified genetic conditions could be pathogenic under the influence of additional risk factors. Even in the presence of a diagnosis made using clinical scores, the molecular diagnosis is often challenging, attesting to the complexity of FH genetic etiology.

Advisory opinion of the AWMF Ad hoc Commission In-vitro Diagnostic Medical Devices regarding in-vitro diagnostic medical devices manufactured and used only within health institutions established in the Union according to Regulation (EU) 2017/746 (IVDR).

In view of the approaching application date of Regulation (EU) 2017/746 („IVDR“) and the resulting EU-wide, harmonized requirements for in-vitro diagnostic medical devices (IVD) manufactured and used within European health institutions, the Ad hoc Commission IVD of the German Association of the Scientific Medical Societies (AWMF) takes a national position on the details of the requirements and conditions related to the use of these IVD products.The Ad hoc Commission IVD emphasizes the relevance of examination procedures developed in medical laboratories, especially in the field of orphan diseases and new diagnostic markers. The IVDR sets an adequate regulatory framework for IVD manufactured and used within health institutions as long as these requirements are fulfilled with reliability and in accordance with the current state of the art in medical laboratory sciences. At the same time, the IVDR requirements have to be regarded under a pragmatic view and in accordance with the quality management systems approved within the different EU Member States. On the one hand, the mandatory requirements of the RiLiBÄK play an essential role in Germany. On the other hand, elements of voluntarily applicable international standards may support the fulfilment of product requirements for safety and performance according to Annex I of the IVDR. Both the complexity and possible solutions for the implementation of the IVDR requirements are discussed on the basis of examples such as the required documentation, performance evaluation and software validation.The Ad hoc Commission IVD recommends that, while aiming at a preferably EU-wide harmonized interpretation of the IVDR requirements, the flexibility in medical laboratory diagnostics necessary for patient care, including the use of IVD from in-house production, should be emphasized.

Postmarketing Surveillance of In-vitro Diagnostic System in the European Union

Advances in medical device technology and regulatory authorization adapt to changing requirements and market conditions. The assessment of safety and performance in the real-world scenario will help us understand clinical benefits and help in the evolution of the medical device and in-vitro diagnostic devices. The paradigm shift in the evaluation of medical devices and in vitro diagnostic devices will ensure that the device delivers intended benefits. This article discusses the new approach of the post-marketing surveillance in the context of new in vitro diagnostic regulation in the European Union.

How the European in vitro diagnostic regulation could negatively impact the European response to the next pandemic: an urgent call for action before May 2022

Abstract The Corona Virus Disease 2019 (COVID-19) pandemic has demonstrated that the ability for laboratories to quickly set up and implement labdeveloped tests (LDTs) is essential to respond to an emerging health crisis. The Regulation on in vitro diagnostic medical devices (IVDR) could, however, profoundly impact our ability to respond to a future pandemic since the IVDR could significant restrict the use of LDTs. We address using the example of the current pandemic a number of LDT implementing issues problems which should be addressed. We conclude that the COVID-19 pandemic illustrates that commercial tests cannot cover all patient needs under any given circumstance and that sufficient degrees of freedom for laboratories to ensure their expertise to develop and implement LDTs ultimately benefit European citizens.

Silicon Nitride, a Close to Ideal Ceramic Material for Medical Application

This topical review describes the salient results of recent research on silicon nitride, a ceramic material with unique properties. The outcome of this ongoing research strongly encourages the use of monolithic silicon nitride and coatings as contemporary and future biomaterial for a variety of medical applications. Crystallographic structure, the synthesis and processing of monolithic structures and coatings, as well as examples of their medical applications that relate to spinal, orthopedic and dental implants, bone grafts and scaffolds, platforms for intelligent synthetic neural circuits, antibacterial and antiviral particles and coatings, optical biosensors, and nano-photonic waveguides for sophisticated medical diagnostic devices are all covered in the research reviewed herein. The examples provided convincingly show that silicon nitride is destined to become a leader to replace titanium and other entrenched biomaterials in many fields of medicine.

Deformation and rupture of microcapsules flowing through constricted capillary

The dynamics of deformable microcapsules flowing through constricted channels is relevant in target delivery of chemicals in physiological systems, porous media, microfluidic medical diagnostic devices and many other applications. In some situations, the microcapsules need to sustain the stress they are subjected to as they flow through constricted channels and in others, the stress may be the rupture trigger used to release the internal content. We experimentally investigate the flow of monodispersed gellan gum microcapsules through a constricted capillary tube by measuring the evolution of the pressure difference and flow visualization. The maximum pressure difference and capsule deformation is obtained for capsules with different diameter and shell thickness. We map the conditions, e.g. diameter and shell thickness, at which the capsule membrane ruptures during the flow, releasing its internal phase.

Hybrid Medical Data Mining Model for Identifying Tumor Severity in Breast Cancer Diagnosis

Purpose: This study proposes a methodology for detecting tumor severity using data mining of databases relating to breast imaging modalities. In doing so, it proposes creating a software application that can serve as an efficient decision-making support system for medical practitioners, especially those in areas where there is a shortage of modern medical diagnostic devices or specialized practitioners, such as in developing countries.Method: we investigated the data of approximately 3754 screened women by using “BI-RADS” categories as a quality assessment tool to screening, measure, and identify the size and location of lesions, determine the number of lymph nodes, collect biopsy samples, determine final diagnoses, prognoses, and age which were all available from the screening registry. Result: The application of each algorithm on BI-RADS values 4 and 5 for Invasive Ductal Carcinoma lesions was assessed, and the following accuracy was acquired: CART: 84.71%. In order to get the best result, four optimum clusters based on tumor size were applied to constructing simple rules with significant confidence. Conclusion: This study presents a hybrid approach - a combination of k-means with GRI and CART decision tree - to better assess breast cancer data sets.

Abstract PR-06: Utilizing biological domain knowledge and machine learning methods to improve cellular segmentation on multiplex fluorescence and imaging mass cytometry datasets improves the quality of single-cell data obtained

Abstract Currently, many existing multi-modality image analysis methods rely heavily on manual annotations for the extraction of quantitative readouts. This limits both the analytical throughput and the complexity to which one can analyze the data – for every hour of imaging time, several additional hours of tedious manual labor are require to extract even rudimentary metrics. Recent advances in computer vision-based techniques, including the use of machine and deep learning methods, have shown tremendous promise for solving previously intractable image segmentation and classification problems. This presents an opportunity for the development of image analysis pipelines that utilize these technical advances to solve known biomedical imaging challenges. We have developed a series of image analysis pipelines for multiplex image segmentation that draws from several interdisciplinary collaborations between biological scientists, pathologists, and biomedical image analysis specialists. For example, we have recently utilized biomedical domain knowledge to develop a customized cellular segmentation methodology for Imaging Mass Cytometry, to identify invading immune cells of various biomarker-identified types, and measure their density and proximity to blood vessels (a marker of active invasion) in multiple sclerosis lesions in the brain. A robust image segmentation and classification pipeline permits us to move these complex datasets from the format of “pixels embedded in spatial coordinates” towards the format of a “single-cell proteomic” dataset, that also permits spatial relationships between markers or tissue regions to be queried. Likewise, we have illustrated a number of methods for single-cell and per-vessel analysis of hypoxia and proliferation gradients within solid tumor tissue sections. Development of single-cell “tissue cytometric” methods permits the in-depth study of spatial relationships that would be difficult or impossible to quantify with more rudimentary whole-tissue analysis approaches. The spatial relationships between tissue components are tightly integrated with tissue metabolism and biomedical transport phenomena, so the study of these relationships permits us to better model tissue physiology in silico, through more accurate measurement of relevant physiological parameters. Clinical validation and deployment of analytical methodologies developed in the laboratory, along with robust methods for quality control and validation of the analytical outputs, allows us to move these promising research tools towards the ultimate goal of clinically approved diagnostic algorithms and medical devices. Such efforts hold the promise to deliver a profound positive impact on the healthcare system, reducing tedious manual steps like counting cells or reviewing scans, through an optimal combination of the advantages of validated automated methods with clinical wisdom and experience. Citation Format: Trevor D. McKee, Mark Zaidi, Veronica Cojocari. Utilizing biological domain knowledge and machine learning methods to improve cellular segmentation on multiplex fluorescence and imaging mass cytometry datasets improves the quality of single-cell data obtained [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr PR-06.