Biomedical Diagnostic Devices Research Articles

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.

Self‐Cleaning Titanium Dioxide Metasurfaces with UV Irradiation

AbstractThe delicate nature of optical components requires very special handling and storage procedures to maximize their performance and lifetime. In the optical field, a long‐standing challenge is the cleaning of unavoidable contaminants during the daily use, especially for the coated elements and the biomedical diagnostic devices. Herein, the authors tackle this problem and experimentally demonstrate TiO2 based self‐cleaning optical meta‐devices with the illuminating of UV light. By arranging TiO2 nanopillars into different patterns, high‐efficiency TiO2 meta‐devices have been realized for the visible spectrum, for example, color nano‐printings, metalenses, and meta‐holograms. The TiO2 meta‐devices become hydrophilic and photoactive under UV irradiation. Consequently, the contaminants, such as, stearic acid or fingerprints have been completely cleaned. Owing to the stability of TiO2, the self‐cleaning effect and the internal nanostructures of meta‐devices are well preserved for many rounds of contamination. This research shall bring new opportunities to TiO2 metasurfaces for extreme applications.

Implementation of digital signal processing algorithms in biomedical electronics devices on the XILINX FPGA

The process of creating fully digital biomedical diagnostic devices involves deep knowledge in both digital electronics and digital biomedical signals processing [1-3]. The purpose of this paper is development of the engineering approach of hardware implementation of basic digital signal processing algorithms (DSP) applied in biomedical electronic devices based on programmable logic integrated circuits. The processes of hardware implementation of the basic algorithms for digital signal processing (DSP) can be divided into three main steps. At the first step, the amplitude values of the samples of discrete pulse characteristics of the low-pass filter and the Hilbert filter are calculated in the FDATool application of the Matlab. At the next step, the Simulink application performs simulation modeling based on the results of the first step, and at the hardware implementation step, the field programmable gate array Xilinx Spartan 6 is used to simulate DSP circuits in the Xilinx ISE design system, as well as directly measured measurements. The amplitude-modulated oscillations demodulator was chosen as an example of the full-scale implementation of basic DSP algorithms in biomedical devices. Experimental measurements were made of the nonlinear distortion coefficient of the detected (informational) signal for three variants of amplitude modulation demodulators: full-wave, using the square root function and synchronous with phase locked loop . During the experimental study, an optimal modulation factor of 60% was chosen from the point of view of energy efficiency. As the results of simulation and experimental studies show, the synchronous demodulator has turned out to be the best option.The obtained results of the experiment and simulation have confirmed the practical applicability of the proposed embodiment in DSP for use in biomedical electronic devices.

The influence of different pore forming agents on piezoelectric and dielectric properties of porous PZT-PCN ceramics

Abstract In this study, the researcher developed porous lead zirconate titanate-lead cobalt niobate 0.8Pb (Zr1/2Ti1/2)O3-0.2Pb(Co1/3Nb2/3)O3 (PZT-PCN) piezoelectric ceramics with varying porosity using PVC Stearic Acid (SA) and PMMA as pore forming agents (PFA) by burnable plastic sphere process (BURPS). The study investigated the effect of PFA on the microstructure, dielectric and piezoelectric properties pertaining to porous PZT-PCN ceramics. The density decreased as the content of pore formers increased. This resulted in increasing of the porosity. The values of both relative permittivity (Ɛr) and longitudinal piezoelectric coefficient (d33) were shown to have decreased by increasing the porosity. The results showed the hydrostatic of merit (dhgh) of PZT-PCN with density of about 4.4 g/cm3 reached 2732 × 10−15 m2/N, which demonstrates that porous PZT-PCN ceramic is a promising material for biomedical diagnostic devices.

Smartphone-Based Blood Lipid Data Acquisition for Cardiovascular Disease Management in Internet of Medical Things

With the ubiquitous deployment of smartphones worldwide recently, biomedical diagnostic devices based on smartphones are potential to be widely used for smart health management on the Internet of Medical Things (IoMT) applications under point-of-care (PoC) settings. Therefore, this paper introduces one smartphone-based blood lipid data acquisition dongle to monitor blood lipid level, including total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C), using only a fingertip blood drop for cardiovascular disease management. During detection, a thin photochemical test strip that consists of LEDs and detectors is plugged into the compact dongle, where changed color intensities will indicate the lipid determinant concentration from the measured reflection coefficient of the chromogenic product. Such smartphone-based photochemical blood lipid data acquisition dongle was validated by comparing with a clinical analyzer, and reached a correlation coefficient over 0.903 and averaged coefficient of variation (CV)% of 4.575% for blood lipid measurement of 115 patients. The photochemical dongle is, therefore, promising for the future chronic disease management in the IoMT.

Fluid pumping and cells separation by DC-biased traveling wave electroosmosis and dielectrophoresis

Fluid pumping in microchips using electrokinetic methods has been a hot area of research. This paper mainly investigates effects of DC offset imposed on traveling wave (TW) signal on electroosmotic flow above a spiral electrode array with 800 µm wavelength. The traveling wave voltage with different DC offsets was applied, and four cases were analyzed by superimposing consecutive images. Experiment results indicate that symmetric electrode array energized with DC-biased TW signal can not only generate a prominent improvement in flow rates, but also be capable of altering the flow direction by changing the polarity of electrical signal. Furthermore, such a device can also be used as an effective means to manipulate and separate PS microbeads and cells on their own for very small and non-flowing sample volumes in terms of the combination of the conventional dielectrophoresis (cDEP) forces and traveling wave DEP (twDEP) forces by properly choosing the parameters associated with the Clausius–Mossotti factor (K(w)). Through adjusting the applied frequencies, we successfully separated yeast cells from a mix containing PS microspheres based on the combination of cDEP and twDEP, providing new opportunities for integration with a charge-coupled device for various biomedical diagnostic devices.

Nature of radiative recombination processes in layered semiconductor PbCdI2 nanostructural scintillation material

We report on the efficient photoluminescence (PL) and radioluminescence (RL) of the PbI2 nanoclusters (NCLs), which are naturally formed in the nanostructured Pb1-XCdxI2 alloys (X=0.70). Here, we carried out the studies of the nature of radiative recombination processes in the NCLs of various sizes by measuring PL temperature evolution. Our results indicate that at low temperatures the PL is mainly caused by exciton emission and recombination of donor-acceptor pairs, generated in volume of large NCLs. The broad bands, which are associated with the deep intrinsic surface states, including self-trapped excitons (STEs), are dominant in the PL spectra at higher temperature (>100 K). Our work shows that the nature of emission, associated with RL bands is analogous to that for PL bands. It was shown that the investigated nanostructured material is strongly radiation-resistant. Thus, the Pb1-XCdXI2 alloys can be considered as new effective layered semiconductor nanostructured materials which can be suitable for the elaboration of perspective semiconductor scintillators. These nanomaterials have promising prospects for applications in new generations of devices for biomedical diagnostics and industrial imaging applications.

Laser-based Method for Sustainable Nanomanufacturing

Silicon nanowires are promising for being used as building blocks for high-performance electronics and biomedical diagnostic devices due to their ultra-small bodies and high surface-to-volume ratios. However, the commonly used methods for manufacturing silicon nanowires involve using high temperature furnaces and a large amount of toxic gases. In addition, nanowires are often manufactured in a manner that requires many additional manufacturing processes in order to make functional devices. Here we present a single-step laser manufacturing method to synthesize silicon nanowires. In this method, nanowires are produced using a laser-guided chemical vapor deposition process, allowing for in-situ doping, catalyst-free nanowire growth, and control of the position, orientation, and length of nanowires. Importantly, the process requires a minimum heating power, of the order of mW, and a minimum amount of gas flow, of the order of a few sccm, since the nanowires are synthesized within the focused laser spot which has a diameter of about 250nm. In addition, the direct manufacturing of semiconductor nanowires on an insulating surface provides a platform ready for subsequent device fabrication.

GS54 2層マイクロ流路を用いた3次元粒子集束法の開発

Particle focusing into a specific area in a microchannel is especially important for precise particle detection, separation and sorting in various microfluidic devices for biomedical diagnostics and cell biology. In recent years, although various particle focusing approaches in microchip have been reported, they have some problems such as complicated fabrication and peripherals. This study suggests an innovative three-dimensional (3D) hydrodynamic particle focusing technique applicable in wide Re with only two inlets. The performances of the particle focusing m under different flow rates and channel shapes were evaluated by numerical simulation. In addition, experimental evaluation of the focusing was performed by particle speed measurement. As a result, we confirmed the validity of the proposed particle focusing technique.

Conformational studies of common protein templates in macromolecularly imprinted polymers

Unlike the molecular imprinting of small molecule templates, molecularly imprinted polymers specific to large templates (>1,500 Da), have achieved limited success to date. Conformational stability of these labile macromolecules is one of the main factors that prevent the direct extension of successful procedures from the small molecule regime. We continue our systematic investigation of the effect of common components in macromolecular MIPs on the conformation of protein templates. Circular dichroism was used to show that frequently employed monomers and crosslinkers induce significant changes in the secondary structures of lysozyme and bovine hemoglobin. The extent to which this change occurs, at ligand concentrations far below what are typically used reported work, is cause for concern and provides as rational explanation for the lack of success in this arena. This is because a change in the template structure prior to polymerization would lead to the binding sites formed during polymerization to be specific to this alternate conformation. Subsequent studies with the macromolecule in its native state and the crosslinked network would not be successful. Using this information as a guide, we offer suggestions as to where work in macromolecular imprinted polymers should focus going forward in order for these antibody mimics to reach their vast potential as a new class of biomedical diagnostic devices.

Spintronic platforms for biomedical applications

Since the fundamental discovery of the giant magnetoresistance many spintronic devices have been developed and implemented in our daily life (e.g. information storage and automotive industry). Lately, advances in the sensors technology (higher sensitivity, smaller size) have potentiated other applications, namely in the biological area, leading to the emergence of novel biomedical platforms. In particular the investigation of spintronics and its application to the development of magnetoresistive (MR) biomolecular and biomedical platforms are giving rise to a new class of biomedical diagnostic devices, suitable for bench top bioassays as well as point-of-care and point-of-use devices. Herein, integrated spintronic biochip platforms for diagnostic and cytometric applications, hybrid systems incorporating magnetoresistive sensors applied to neuroelectronic studies and biomedical imaging, namely magneto-encephalography and magneto-cardiography, are reviewed. Also lab-on-a-chip MR-based platforms to perform biological studies at the single molecule level are discussed. Overall the potential and main characteristics of such MR-based biomedical devices, comparing to the existing technologies while giving particular examples of targeted applications, are addressed.

Highly flexible pseudocapacitor based on freestanding heterogeneous MnO2/conductive polymer nanowire arrays

Flexible electronics such as wearable electronic clothing, paper-like electronic devices, and flexible biomedical diagnostic devices are expected to be commercialized in the near future. Flexible energy storage will be needed to power these devices. Supercapacitor devices based on freestanding nanowire arrays are promising high power sources for these flexible electronics. Electrodes for these supercapacitor devices consisting of heterogeneous coaxial nanowires of poly (3,4-ethylenedioxythiophene) (PEDOT)-shell and MnO(2)-core materials have been shown in a half cell system to have improved capacitance and rate capabilities when compared to their pure nanomaterials; however, their performance in a full cell system has not been fully investigated. Herein, these coaxial nanowires are tested in both a symmetric and an asymmetric (utilizing a PEDOT nanowire anode) full cell configuration in the aspect of charge storage, charge rate, and flexibility without using any carbon additives and polymer binders. It is found that the asymmetric cell outperforms the symmetric cell in terms of energy density, rate capability, and cycle ability. The asymmetric device's electrode materials display an energy density of 9.8 Wh/kg even at a high power density of 850 W kg(-1). This device is highly flexible and shows fast charging and discharging while still maintaining 86% of its energy density even under a highly flexed state. The total device is shown to have a total capacitance of 0.26 F at a maximum voltage of 1.7 V, which is capable of providing enough energy to power small portable devices.

A comparison of mono and multivalent linkers and their effect on the colloidal stability of nanoparticle and immunoassays performance

When designing devices for biomedical diagnostics, increasing the signal to noise ratio is often critical for achieving clinically relevant sensitivity and limits of detection (LOD). In antibody-based assays, the measured signal can be amplified through the replacement of molecular fluorophores with doped nanoparticles (NP). However, the benefits of using NPs can only be realized if the NPs are coated efficiently with detection antibody, have good colloidal stability and the ratio of specific to non-specific binding (NSB) is high enough. The main focus of this paper is on the optimization of the bioconjugation protocol for antibody labeling of NPs leading to improved assay performance. Two types of linkers were used: monovalent linkers (glutaraldehyde; sulfo-SMCC; and sulfo-SIAB), and three generations of dendrimers endowed with multivalent carboxylic functionality. Overall, the NP-IgG conjugates prepared using multivalent linkers showed a significantly lower LOD and higher sensitivity than their homo- or hetero-functional counterparts. The multivalent dendrimers also improved NP stability and reduced aggregation. Moreover, the dendrimers showed a higher reactivity with biological material, a feature that could significantly reduce the cost of high-throughput biodiagnostics tests.

Clean data with dirty surfaces in electrokinetics

Experiments now quantitatively confirm the standard model of electrokinetics, in which electric fields drive the flow of electrolytes, potentially leading to better sensors and biomedical diagnostic devices.

High efficiency amine functionalization of cycloolefin polymer surfaces for biodiagnostics

Point-of-care (POC) diagnostics implementing microfluidic technology on single use disposable plastic chips has potential applications in personalized medicine, clinical diagnostics and global health. However, the challenges in commercializing POC devices must be addressed. Immobilization of biomolecules to plastic chips through appropriate surface functionalization is a key issue for the fabrication of new generation biomedical diagnostic devices. The most important requirements for a practicable surface functionalization process are speed, control and reliability. Plasma-based methods can meet these criteria. A single step, solventless, ecofriendly and high throughput nature of plasma processing makes them highly attractive. Here we demonstrate the efficient surface functionalization of a next-generation biosensor material, a chemically inert cycloolefin polymer (COP). The plasma formation of a surface-bound aminated siloxane network from mixed aminopropyltriethoxysilane and ethylenediamine precursors allowed us to form a well-adherent film with an exceptionally high degree of amine functionalization. We deduce that the siloxane was the critical component for radical insertion into the COP and for building a stable network to support the reactive amine functionalities. We present a full physical and chemical characterization of the films, including a detailed study of their swelling in water, using an array of surface analytical techniques: X-ray photoelectron spectroscopy, X-ray reflectivity, reflection infra-red spectroscopy, atomic force microscopy (AFM) and fluorophore binding reactions. We demonstrate an original approach for qualitatively analyzing the distribution of amine functionalities by counting surface-bound functionalized silica nanoparticles in the AFM. The relative contributions from covalent (specific) and non-covalent (non-specific) reaction chemistry assessed using 3′-fluorescein-labeled ssDNA attachment showed that the non-specific binding could be reduced significantly according to the particular feed gas mixture used to prepare the coating. A reaction mechanism has been proposed for the deposition of amine functionalities on COP plastic and also for enhancing the amine functionalities that affect the non-specific binding significantly.

Antibody immobilization to phospholipid polymer layer on gold substrate of quartz crystal microbalance immunosensor

To modify gold electrode for immunosensor to construct an artificial cell membrane structure, water-soluble amphiphilic phospholipid polymer, poly[2-methacryloyloxyehtyl phosphorylcholine-co-n-butyl methacrylate-co-p-nitrophenyloxycarbonyl poly(ethylene glycol) methacrylate (PMBN)] was applied. The polymer had active ester groups for immobilization of biomolecules and it was converted partially to thiol groups for binding to gold substrates. The partially thiolated PMBN was adsorbed on a gold electrode of quartz crystal microbalance (QCM). Surface characterization of adsorbed PMBN layers was thoroughly investigated with reflectance anisotropy spectroscopy, ellipsometry spectroscopy, dynamic contact angle and X-ray photoelectron spectroscopy measurements. Among several PMBN, having different degree of thiolation, it was concluded that 21.5% thiolated PMBN layer had the most well-ordered phosphorylcholine groups in its outer surface. The proteins adsorption test revealed that the phosphorylcholine group on the outer side of PMBN layers, which was substituted their active ester groups by glycine, showed suppress the non-specific adsorption of proteins, such as bovine serum albumin and γ-globulin. Also, through antigen–antibody binding evaluation, the anti-C-reactive protein antibody immobilized on the PMBN surface worked well and it was confirmed that denaturation of the antibody on the PMBN layers was hardly occurred in spite of 60 days storage at 4°C. The antibody conjugated phospholipid polymer layer with well-ordered phosphorylcholine group could be outstanding functional membrane for biomedical diagnostic devices without non-specific binding and reduction of immunologic activity of immobilized antibody.

Multiphase electrodes for microbead control applications: Integration of DEP and electrokinetics for bio-particle positioning

Advances in microfabrication have introduced new possibilities for automated, high-throughput biomedical investigations and analysis. Physical effects such as dielectrophoresis (DEP) and AC electrokinetics can be used to manipulate particles in solution to coordinate a sequence of bioanalytical processing steps. DEP is accomplished with non-uniform electric fields that can polarize particles (microbeads, cells, viruses, DNA, proteins, etc.) in suspension causing translational or rotational movement. AC electrokinetics is another phenomena involved with movement of particles in suspension with electric fields and is comprised of both electro-thermal and electro-osmotic effects. This paper investigates single layer electrodes that are effective for particle localization and clustering based on DEP and AC electrokinetic effects. We demonstrate a novel multi-electrode setup capable of clustering particles into an array of discrete bands using activated and electrically floating electrodes. These bands shift to adjacent regions on the electrode surface by altering the electrode activation scheme. The predictability of particle placement to specific locations provides new opportunities for integration and coordination with raster scanning lasers or a charge coupled device (CCD) for advanced biomedical diagnostic devices, and more sophisticated optical interrogation techniques.