Biomedical Testing Research Articles

Gray Zone Identity: An Autoethnographic Journey of Chronic Illness, Diagnostic Uncertainty, and Autoimmunity

The author explores what it means to live in a liminal space of medical uncertainty as a person with an autoimmune disease. Autoethnography enables the author to examine the emotional, cognitive, and physical response to being told that her ill body and identity exist in a clinical gray zone. The author coins the term “gray zone identity” to capture the uncertainty and anxiety that accompanied years of symptoms without a diagnosis. Traveling in and out of health care facilities in search of answers, the author learns that not all bodies can be clinically explained by medical language or biomedical tests. It is in the liminal space of diagnostic uncertainty where the author endeavors to understand how to embrace her gray zone identity.

Patients’ effective doses assessment during low-dose computed tomography

Computed tomography has become increasingly common for diagnosing socially significant diseases in recent years. In foreign practice, screening schemes for lung cancer in people belonging to risk categories have been developed and implemented. These schemes have been successfully used over the past 10 years. In this case, “low-dose” scanning protocols are used, which make it possible to perform examination with patient effective dose several times lower compared to standard protocols. Lung cancer screening methods using low-dose computed tomography are beginning to be introduced in the Russian Federation. To ensure the radiation safety of those individuals eligible for inclusion in screening programs or participating in biomedical research testing lung cancer screening, it is necessary to evaluate effective doses from low-dose computed tomography and compare these doses to established radiation dose limits. This study assessed the patients’ effective doses who underwent different types of low-dose computed tomography of chest at two medical organizations. The results of the study show that it is possible to achieve non-exceedance of the current annual effective dose limit of 1 mSv only for patients weighing less than 90 kg. For patients with higher body weight, the minimum effective dose will be in the range of 1.2 – 1.4 mSv. The results of the study indicate the need to make changes to the current regulatory and methodological documents of Rospotrebnadzor to ensure the possibility of using low-dose computed tomography as part of screening for all categories of people.

Reproducible, Accurate, and Sensitive Food Toxin On-Site Detection with Carbon Nanotube Transistor Biosensors.

Field-effect transistor (FET) biosensors based on nanomaterials are promising in the areas of food safety and early disease diagnosis due to their ultrahigh sensitivity and rapid response. However, most academically developed FET biosensors lack real-world reproducibility and comprehensive methodological validation to meet the standards of regulatory bodies. Here, highly uniform and well-packaged semiconducting carbon nanotube (CNT) FET biosensor chips were developed and assessed for the plug-and-play sensing for the rapid and highly sensitive detection of aflatoxin B1 (AFB1) in real food samples to meet international standards. In order to meet the requirements for reproducibility and stability, a scalable residual-free passivation and packaging process was developed for CNT FET biosensors. Portable detection systems were then constructed for on-site detection. The resulting packaged chips were functionalized with nucleic aptamers to enable highly selective detection of AFB1 in food samples with a detection limit (LOD) of 0.55 fg/mL (standard) for AFB1 and cross-reactivity coefficients to interferences as low as 1.8 × 10-7 in simulated solutions. Utilizing the portable detection system, on-site real food detection was achieved with a rapid response time less than 60 s, and LOD of 0.25 pg/kg (standard) in complex corn sample matrices. Single-blind tests demonstrated the ability of the chips to detect AFB1-positive food with 100% accuracy, using a set of 30 peanut samples. Validation experiments confirmed that the detection range, stability, and repeatability met international standards. This study showcased the accuracy, reliability, and potential practical applications of CNT FET biosensor chips in areas such as food safety and rapid biomedical testing.

Molecularly Imprinted Polypyrrole-Modified Screen-Printed Electrode for Dopamine Determination.

This paper introduces a quantitative method for dopamine determination. The method is based on a molecularly imprinted polypyrrole (e-MIP)-modified screen-printed electrode, with differential pulse voltammetry (DPV) as the chosen measurement technique. The dopamine molecules are efficiently entrapped in the polymeric film, creating recognition cavities. A comparison with bare and non-imprinted polypyrrole-modified electrodes clearly demonstrates the superior sensitivity, selectivity, and reproducibility of the e-MIP-based one; indeed, a sensitivity of 0.078 µA µM-1, a detection limit (LOD) of 0.8 µM, a linear range between 0.8 and 45 µM and a dynamic range of up to 350 µM are achieved. The method was successfully tested on fortified synthetic and human urine samples to underline its applicability as a screening method for biomedical tests.

Phenylalanine: Amino Acid Metal Non-Enzymatic Electrochemical Voltammetric Sensors

This study presents a comparative analysis of non-enzymatic electrochemical voltammetric sensors, utilizing phenylalanine amino acid metal complexes (M: Ni, Zn, and Co) Polyaniline (PANI) nanocomposites (NCs). The PANI: Zn(Phala)2 NCs-based sensor detected dopamine (DA) with a sensitivity of 101.18 μAμM−1 cm−2. The limit of detection (LOD) for the PANI: Zn(Phala)2 NCs-based sensor was calculated as 0.391 μM. This exceptional sensitivity makes the PANI: Zn(Phala)2 NCs-based sensor highly promising for potential integration into biomedical test kits. To gain deeper insights into the structural properties of the PANI NCs, scanning electron microscopy (SEM), artificial-intelligence-based SEM, and Fourier transform infrared spectroscopy (FTIR) were employed for characterization. FTIR characterization provided insights into the functional groups of the NCs. The results of this comparative investigation a significant advancement in the field of PANI-based electrochemical sensors designed for DA sensing. The PANI: Zn(Phala)2 NCs-based sensor show great promise for a range of advanced sensing applications. The Z value of the PANI: Zn(Phala)2 NCs-based sensor is the lowest among the tested materials, indicating that the conductivity of the PANI: Zn(Phala)2 layer is higher than that of other active layers. Consequently, the PANI: Zn(Phala)2 NCs-based sensor achieved higher sensitivity in DA detection.

P20-16 The unwritten expectations from FDA on biomedical device testing

P20-16 The unwritten expectations from FDA on biomedical device testing

Research on Data Processing and Pattern Recognition Algorithms of Intelligent Biosensors in Biomedical Testing

Intelligent biosensors are increasingly used in biomedical testing, especially in the field of medical testing, showing great potential. This study mainly discusses the data processing and pattern recognition algorithms of intelligent biosensors in medical testing. In the system design, a power spectral density-based analysis method is proposed for human posture recognition and signal processing to optimize data filtering and feature extraction in the signal processing process. By combining pattern recognition and data processing algorithms, the system realizes efficient human posture detection and diagnosis functions. In the process of system simulation, multiple signal processing techniques along with diverse model simulation approaches are employed to guarantee the precision and resilience of the simulation outcomes. The findings from the study indicate that the suggested algorithm offers substantial benefits in enhancing detection precision and real-time efficiency. Detailed analysis of the system architecture and simulation outputs further corroborates the effectiveness and practicality of the algorithm.

Microfluidic Lab-on-CMOS Packaging Using Wafer-Level Molding and 3D-Printed Interconnects.

Lab-on-a-chip (LoC) technologies continue to promise lower cost and more accessible platforms for performing biomedical testing in low-cost and disposable form factors. Lab-on-CMOS or lab-on-microchip methods extend this paradigm by merging passive LoC systems with active complementary metal-oxide semiconductor (CMOS) integrated circuits (IC) to enable front-end signal conditioning and digitization immediately next to sensors in fluid channels. However, integrating ICs with microfluidics remains a challenge due to size mismatch and geometric constraints, such as non-planar wirebonds or flip-chip approaches in conflict with planar microfluidics. In this work, we present a hybrid packaging solution for IC-enabled microfluidic sensor systems. Our approach uses a combination of wafer-level molding and direct-write 3D printed interconnects, which are compatible with post-fabrication of planar dielectric and microfluidic layers. In addition, high-resolution direct-write printing can be used to rapidly fabricate electrical interconnects at a scale compatible with IC packaging without the need for fixed tooling. Two demonstration sensor-in-package systems with integrated microfluidics are shown, including measurement of electrical impedance and optical scattering to detect and size particles flowing through microfluidic channels over or adjacent to CMOS sensor and read-out ICs. The approach enables fabrication of impedance measurement electrodes less than 1 mm from the readout IC, directly on package surface. As shown, direct fluid contact with the IC surface is prevented by passivation, but long-term this approach can also enable fluid access to IC-integrated electrodes or other top-level IC features, making it broadly enabling for lab-on-CMOS applications.

Integration Of Acoustophoresis and Dielectrophoresis on A Single Chip Platform: A Numerical Study

Passive or active manipulation forces would be needed for the microfluidic system for chemical and biological analysis in order to regulate, trap, separate, sort, and discriminate between particles and cells. The primary goals of passive manipulation are consistency and repeatability to attain high levels of control with exact trajectories. In the meantime, by introducing external forces like hydrodynamic, dielectrophoretic, magnetophoretic, acoustophoretic, and optical tweezing, the active manipulations allow to control particle displacement in a highly predictable and consistent fashion. These methods are much more promising for the development of a small and compact biomedical diagnostic rapid test. Since most biological particles are suspended in different biological fluids like blood and urine, dielectrophoresis (DEP) and acoustophoresis (ACP) have been demonstrated to be promising among these external forces because of their ability to apply forces on the particles in a liquid environment. Additionally, both techniques are fast, inexpensive to fabricate, label-free, and incredibly selective. In this study, we introduce a novel method that combines these two forces into a single chip, improving the separation process for ACP and DEP based on the intrinsic dielectric and acoustic properties of the particles, respectively. It is anticipated that this research would shed light on why particular manipulative factors predominate more or less in particular situations.

Conversion of flat to cylindrical hydrogel structures by asymmetric crosslinking and ionic exchange

The similarity of hydrogels with human soft tissues serves a two-fold purpose: they are convenient, humane tissue substitutes for biomedical testing, while they are also a reliable platform for the development of biocompatible implantable devices and organoids. However, these assets come with challenges with reproducible processing of stable hollow structures that are common transducers of liquids in living organisms, from two-dimensional polymeric precursors. Here, we describe a protocol for film-to-tube transformation that is devoid of templates, catalysts, 3D printing, heating, and light, and can be used to prepare hollow hydrogel structures. The resulting hydrogel tubes have tensile strength of up to 45 MPa, turning these materials into the most robust hydrogel materials reported to date. The flexibility and elasticity favor the resulting hydrogel tubes for catheterization of artificial intestinal demonstrating the potential for medical applications. The approach can be applied to prepare structure/function-mimetic organoids such as branched blood vessels and nephrons with higher resolution than additive manufacturing. Then hollow structures are degradable in alkaline solution, and the solution can be recycled to recover the tubular structures. The convenience of the approach described overcomes some of the most challenging aspects of preparation of hollow hydrogel elements.

Optofluidic chip with directly printed polymer optical waveguide Mach-Zehnder interferometer sensors for label-free biodetection

Optofluidic devices hold great promise in biomedical diagnostics and testing because of their advantages of miniaturization, high sensitivity, high throughput, and high scalability. However, conventional silicon-based photonic chips suffer from complicated fabrication processes and less flexibility in functionalization, thus hindering their development of cost-effective biomedical diagnostic devices for daily tests and massive applications in responding to public health crises. In this paper, we present an optofluidic chip based on directly printed polymer optical waveguide Mach-Zehnder interferometer (MZI) sensors for label-free biomarker detection. With digital ultraviolet lithography technology, high-sensitivity asymmetric MZI microsensors based on a width-tailored optical waveguide are directly printed and vertically integrated with a microfluidic layer to make an optofluidic chip. Experimental results show that the sensitivity of the directly printed polymer optical waveguide MZI sensor is about 1695.95 nm/RIU. After being modified with capture molecules, i.e., goat anti-human immunoglobulin G (IgG), the polymer optical waveguide MZI sensors can on-chip detect human IgG at the concentration level of 1.78 pM. Such a polymer optical waveguide-based optofluidic chip has the advantages of miniaturization, cost-effectiveness, high sensitivity, and ease in functionalization and thus has great potential in the development of daily available point-of-care diagnostic and testing devices.

Observation of magnetic amplification using dark spins

Quantum amplification enables the enhancement of weak signals and is of great importance for precision measurements, such as biomedical science and tests of fundamental symmetries. Here, we observe a previously unexplored magnetic amplification using dark noble-gas nuclear spins in the absence of pump light. Such dark spins exhibit remarkable coherence lasting up to 6 min and the resilience against the perturbations caused by overlapping alkali-metal gas. We demonstrate that the observed phenomenon, referred to as "dark spin amplification," significantly magnifies magnetic field signals by at least three orders of magnitude. As an immediate application, we showcase an ultrasensitive magnetometer capable of measuring subfemtotesla fields in a single 500-s measurement. Our approach is generic and can be applied to a wide range of noble-gas isotopes, and we discuss promising optimizations that could further improve the current signal amplification up to [Formula: see text] with [Formula: see text]Ne, [Formula: see text] with [Formula: see text]Xe, and [Formula: see text] with [Formula: see text]He. This work unlocks opportunities in precision measurements, including searches for ultralight dark matter with sensitivity well beyond the supernova-observation constraints.

Confronting the bias towards animal experimentation (animal methods bias)

Laws and policies are in place around the world to promote the replacement and reduction of nonhuman animals in science. These principles are rooted not just in ethical considerations for animals, but also in scientific considerations regarding the limitations of using nonhuman animals to model human biology, health, and disease. New nonanimal research approaches that use human biology, cells, and data to mimic complex human physiological states and therapeutic responses have become increasingly effective and accessible, replacing the use of animals in several applications, and becoming a crucial tool for biomedical research and drug development. Despite many advantages, acceptance of these new nonanimal methods has been slow, and barriers to their broader uptake remain. One such barrier is animal methods bias, the preference for animal-based methods where they are not necessary or where animal-free methods are suitable. This bias can impact research assessments and can discourage researchers from using novel nonanimal approaches. This article provides an introductory overview of animal methods bias for the general public, reviewing evidence, exploring consequences, and discussing ongoing mitigation efforts aimed at reducing barriers in the shift away from animal use in biomedical research and testing.

Label-free and selective heparin detection by surface functionalized fiber Fabry-Perot interferometer biosensor

Heparin (Hep) is the most commonly used anticoagulant drug in clinical settings, and precise dosage control is crucial. To enable rapid and accurate quantification of Hep concentration in clinical practice, a label-free and selective fiber-optic Fabry-Perot interferometric (FPI) biosensor detection method based on graphene oxide (GO) was proposed. This method utilizes protamine (PRTM) sulfate as the modified layer and achieves Hep detection through layer-by-layer (LBL) assembly. In this study, we developed a label-free and selective fiber optic FPI biosensor for the detection of Hep using GO. The GO on the surface layer of the fiber optic FPI biosensor was treated with specific functionalization, it enables specific interaction with Hep. The binding of Hep to the functionalized surface induces a change in the luminal light signal, which can be monitored within the cavity for rapid and accurate detection of Hep. The results demonstrate that this biosensor exhibits good sensitivity, with a value of 10.82 nm/mM in the low-concentration control group, and an average limit of detection (LOD) calculated as 31μg/mL in the low-concentration group. This study presents a label-free, selective and efficient method for biomedical science testing that holds great potential for widespread application in clinical medicine.

Two-phase Porous Media Flow Model Based on the Incompressible Navier-Stokes Equation.

Two-phase porous media flow is important in many applications from drug delivery to groundwater diffusion and oil recovery and is of particular interest to biomedical diagnostic test developers using cellulose and nitrocellulose membranes with limited fluid sample volumes. This work presents a new two-phase porous media flow model based on the incompressible Navier-Stokes equation. The model aims to address the limitations of existing methods by incorporating a partial saturation distribution in porous media to account for limited fluid volumes. The basic parameters of the model are the pore size distribution and the contact angle. To validate the model, we solved five analytical solutions and compared them to corresponding experimental data. The experimentally measured penetration length data agreed with the model predictions, demonstrating model accuracy. Our findings suggest that this new two-phase porous media flow model can provide a valuable tool for researchers developing fluidic assays in paper and other porous media.

Efficient broadband NIR garnet phosphor Ca2LuScGa2Si2O12:Cr3+,Yb3+ for NIR pc-LED applications

Near-infrared phosphor-converted light emitting diodes (NIR pc-LEDs) have broad application prospects in the fields of solar cells, spectroscopic analysis, fluorescent labeling and biomedical testing. The current research faces challenges in enhancing the thermal stability and efficiency of near-infrared (NIR) emitting phosphors. Herein, a broadband NIR phosphor Ca2LuScGa2Si2O12:Cr3+ (CLSGS:Cr3+) was successfully synthesized. CLSGS:Cr3+ phosphor displays a broadband emission in the range (650–900 nm) with a full width at half maximum (FWHM) of 150 nm, a good luminescent thermal stability (I373K/I298K = 73%), and a high internal quantum efficiency (IQE = 70.3%). Moreover, the introducing Yb3+ into CLSGS:Cr3+ significantly improves thermal stability (I373K/I298K = 93%) and enhances internal quantum efficiency (IQE = 90.5%). By combining CLSGS:Cr3+,Yb3+ with a 460 nm commercial LED chip, the fabricated NIR pc-LED devices demonstrates potential applicability in night vision and bio-imaging.

Synthesis and characterization of n-isopropylacrylamide based copolymers with silver nanoparticles

In recent years, the so-called "smart" polymers, which can systematically respond to small environmental changes, such as pH, temperature and electric field, are widely used in many fields. Researchers are particularly interested in using drugs to transport to the right place in the human body. One of the types of these smart polymers are thermosensitive polymers. Among the thermosensitive polymers, the most well-known are homo- and copolymers based on N-isopropylacrylamide. In the research work, in order to improve the properties of thermosensitive polymers, silver nanoparticles were added to the hydrogel composition. Hydrogels based on N-isopropylacrylamide and 2-hydroxyethylacrylate monomers were synthesized by radical polymerization in solution (in H2O and AgNO3 solution). While the production of silver nanoparticles is based on the redox (by NaBH4 solution) mechanism, the formation of these nanoparticles in the gel was carried out by diffusion. While the introduction of silver nanoparticles into the gel was controlled by ultraviolet spectroscopy, its inclusion in the gel was confirmed using a scanning electron microscope (SEM). Meanwhile, a hydrogel containing silver nanoparticles exhibits antibacterial properties, it was investigated using biomedical tests. It has been shown here that a hydrogel containing silver has good antibacterial properties, whereas a hydrogel without silver does not have the ability to destroy bacteria.

Image testing based on biomedical drug loading in cardiovascular drug care simulation for coronary heart disease

Coronary heart disease is a common cardiovascular disease, and its therapeutic effect is affected by the distribution and absorption of drugs in the body. Biomedical drug-carrying image testing technology can provide a quantitative assessment of drug distribution and absorption in the body. This study aims to explore the application of biomedical drug-carrying image testing technology in the simulation of cardiovascular drug care in coronary heart disease, so as to provide reference for the optimization of drug treatment plan and individualized treatment. The study collected clinical data and medication regiments of patients with coronary heart disease. Then, the imaging examination of patients was carried out by selecting appropriate drug loading markers using the biomedical drug loading image examination technology. Then quantitative analysis was used to process the image data to quantitatively evaluate the distribution and absorption of drugs in the cardiovascular system. The quantitative data of drug distribution and absorption in patients with coronary heart disease have been obtained successfully by means of biomedical imaging. These data reveal the dynamic changes of drugs in the cardiovascular system, and help doctors optimize drug therapy, improve treatment effectiveness, and achieve personalized treatment.

NFTest: automated testing of Nextflow pipelines.

The ongoing expansion in the volume of biomedical data has contributed to a growing complexity in the tools and technologies used in research with an increased reliance on complex workflows written in orchestration languages such as Nextflow to integrate algorithms into processing pipelines. The growing use of workflows involving various tools and algorithms has led to increased scrutiny of software development practices to avoid errors in individual tools and in the connections between them. To facilitate test-driven development of Nextflow pipelines, we created NFTest, a framework for automated pipeline testing and validation with customizability options for Nextflow features. It is open-source, easy to initialize and use, and customizable to allow for testing of complex workflows with test success configurable through a broad range of assertions. NFTest simplifies the testing burden on developers by automating tests once defined and providing a flexible interface for running tests to validate workflows. This reduces the barrier to rigorous biomedical workflow testing and paves the way toward reducing computational errors in biomedicine. NFTest is an open-source Python framework under the GPLv2 license and is freely available at https://github.com/uclahs-cds/tool-NFTest. The call-sSNV Nextflow pipeline is available at: https://github.com/uclahs-cds/pipeline-call-sSNV.

Hybrid manipulation of inkjet-printing deposition pattern of high particle concentration droplet by means of thermal and binary solvent effects

Inkjet-printing of functional material is a well-known drop-on-demand technology used in a wide range of modern applications, such as flexible electronics, biomedical testing, etc. It enables to deliver small amount of materials as ink to the specific location on target substrates. However, it is challenging to precisely manipulate the particle deposition characteristics which is crucial to the quality of the fabricated device. Unlike the traditional passive methods by manipulating the nanoparticle, solvent or substrate surface condition, we propose a passive-active hybrid manipulation method by employing a binary mixture solvent and heating substrate. In this paper, the effects of the solvent mixing ratio, the substrate temperature, the substrate thermal properties on the deposition characteristics of high concentration ITO nano-ink were investigated. Interestingly, we have observed a transition of the classic slim coffee-ring to a fat coffee-ring with a large ring width. A dimensionless number was developed to predict the transition boundary from fat-ring pattern to slim-ring pattern. Finally, the phase diagrams of deposition patterns on three substrates were developed, which were convenient for deposition pattern manipulation in real applications.