Biomedical Detection Research Articles

Nano-Biosensors Based on Noble Metal and Semiconductor Materials: Emerging Trends and Future Prospects

The aim of this review is to gather current researches into sensors based on noble metal and semiconductor nanomaterials in biomedical detection and elucidate the basic principle and applications of different sorts of semiconductor nanomaterials, i.e., metal oxide NPs, transition metal dichalcogenides (TMDs), metal-organic frameworks (MOFs) and magnetic metal oxide (MMO) NPs. Based on the classifications of nano-biosensors, they can be summarized as electrochemical nano-biosensors, optical nano-biosensors, calorimetric nano-biosensors, and piezoelectric nano-biosensors, wherein, electrochemical and optical nano-biosensors acting as most popular study objects are focused on to excavate the great improvements in excellent sensitivity, selectivity and stability based on fabrication techniques.

Fiber-Fed 3D Printing of Germanate Glass Optics

In recent years, 3D printing glass optics has gained massive attention in industry and academia since glass could be an ideal material to make optical elements, including the lens. However, the limitation of materials and printing methods has prevented 3D printing glass optics progress. Therefore, we have developed a novel printing strategy for germanate glass printing instead of pure silica. Moreover, compared with traditional multi-component quartz glass, germanate glass has unmatched advantages for its mid-infrared (MIR) transparency and outstanding visible light imaging performance. Furthermore, compared with non-oxide glass (fluoride glass and chalcogenide glass), germanate glass has much better mechanical, physical, and chemical properties and a high refractive index. Germanate glass has been widely applied in remote sensing, ranging, environmental detection, and biomedical detection. However, it is difficult to shape, cast, polish, and grind for optical and photonics applications such as imaging optics and laser-collimation optics. These drawbacks have made germanate glass inaccessible to complex optical elements and greatly increased their cost. In this report, we use germanate glass fibers with a diameter of 125 µm based on fiber-fed laser heating technology to fabricate an mm-size optical application. In this paper, we combine the fiber-fed laser heating technology with an optimized temperature control process to manufacture high-precision optical elements. Germanate glass optics can be printed with excellent visible light and IR transparency and a smooth surface with roughness under 4 nm. By optimizing the layer-by-layer 3D printing process and the thermal feedback in the printing process, we avoid cracks and minimize surface deformation. This work shows the possibility of the mm-size glass optical elements 3D printing and widens its application for IR optics.

Enhanced Terahertz Fingerprint Sensing Mechanism Study of Tiny Molecules Based on Tunable Spoof Surface Plasmon Polaritons on Composite Periodic Groove Structures

Highly sensitive detection of enhanced terahertz (THz) fingerprint absorption spectrum of trace-amount tiny molecules is essential for biosensing. THz surface plasmon resonance (SPR) sensors based on Otto prism-coupled attenuated total reflection (OPC-ATR) configuration have been recognized as a promising technology in biomedical detection applications. However, THz-SPR sensors based on the traditional OPC-ATR configuration have long been associated with low sensitivity, poor tunability, low refractive index resolution, large sample consumption, and lack of fingerprint analysis. Here, we propose an enhanced tunable high-sensitivity and trace-amount THz-SPR biosensor based on a composite periodic groove structure (CPGS). The elaborate geometric design of the spoof surface plasmon polaritons (SSPPs) metasurface increases the number of electromagnetic hot spots on the surface of the CPGS, improves the near-field enhancement effect of SSPPs, and enhances the interaction between THz wave and the sample. The results show that the sensitivity (S), figure of merit (FOM) and Q-factor (Q) can be increased to 6.55 THz/RIU, 4234.06 1/RIU and 629.28, respectively, when the refractive index range of the sample to measure is between 1 and 1.05 with the resolution 1.54×10-5 RIU. Moreover, by making use of the high structural tunability of CPGS, the best sensitivity (SPR frequency shift) can be obtained when the resonant frequency of the metamaterial approaches the biological molecule oscillation. These advantages make CPGS a strong candidate for the high-sensitivity detection of trace-amount biochemical samples.

Green Synthesis of Iron Oxide nanoparticles using Neem leaf (Azadirachta indica) extract & it’s Characterisation via UV-Vis Spectroscopy

Nanotechnology has come into limelight few years back and is following the same trend by the virtue of its opportune and multifarious diligence that it shows in the field of Biomedical (Biomarker Mapping, Targeted Therapy, Detection and Diagnosis etc.) etc. Azadirachta indica aka Neem Plant is highly rich in antioxidant and phytochemical properties which ultimately fabricate it to be a good way for synthesising remarkably stable Iron Oxide nanoparticles (Fe3 O4 -NP’s). This review approaches to the procedure and characterisation via UV-Vis Spectrometer of Fe3 O4 -NP’s. The nanoparticles were chosen for research because of its more antimicrobial and antioxidant properties comparatively to the normal plant extract. At last the comparison can be made on the basis of the results which come after the synthesis using UV-Vis Spectroscopy.

Highly Sensitive Biosensor Based on Metamaterial Absorber With an All-Metal Structure

In this article, an all-metal metamaterial absorber as a sensitive biosensor is proposed in the terahertz regime for biomolecular detection, such as protein, bacillus bacteria, and cancer cells. Here, the highly sensitive characteristic of the proposed absorber is implemented by the enhanced electromagnetic loss of symmetry-broken metal structures, where two discontinuous hollow rectangular metal arms are arranged orthogonally above the metal ground plane in geometry. Finite integral theory (FIT)-based software is utilized for modeling and full-wave numerical simulation. The results show that a near-perfect absorption of 100% at 1.99 THz is achieved with a quality factor value of 87, which could be an excellent performance in the terahertz regime below 2 THz. The electric and magnetic field distribution analysis is performed to reveal the mechanism, which is the significant confinement of electromagnetic field in the specially designed metal structure. The sensing performance of a refractive index is also investigated, and the resonance frequency and peak absorption of the spectra will get shift due to the variation of biological samples. The maximum sensitivity and figure of merit reach 540 GHz/RIU and 23.5 RIU−1, respectively. In addition, the effect of polarization angles and performance under different incident angles is also discussed. The presented biosensor with high sensitivity and feasible fabrication is a good candidate for biomedical detection in the terahertz regime.

Multiple-Droplet Selective Manipulation Enabled by Laser-Textured Hydrophobic Magnetism-Responsive Slanted Micropillar Arrays with an Ultrafast Reconfiguration Rate.

Biomimetic structures based on the magnetic response have attracted ever-increasing attention in droplet manipulation. Till now, most methods for droplet manipulation by a magnetic response are only applicable to a single droplet. It is still a challenge to achieve on-demand and precise control of multiple droplets (≥2). In this paper, a strategy for on-demand manipulation of multiple droplets based on magnetism-responsive slanted micropillar arrays (MSMAs) is proposed. The Glaco-modified superhydrophobic surface is the basis of multiple-droplet manipulation. The droplet's motion mode (pinned, unidirectional, and bidirectional) can be readily fine-tuned by changing the volume of droplets and the speed of the magnetic field. The rapid movement of droplets (10-80 mm/s) in the horizontal direction is realized by the unidirectional waves of the micropillar array driven by a specific magnetic field. The bending angle of micropillars can be rapidly and reversibly adjusted from 0 to 90° under the action of a magnetic field. Meanwhile, the liquid-involved light, electric switch, and biomedical detection can be designed by manipulating the droplets on demand. The superiority of MSMAs in multiple-droplet programmable manipulation opens up an avenue for applications in microfluidic and biomedical engineering.

Detection of biomarkers using terahertz metasurface sensors and machine learning.

To achieve classification and concentration detection of cancer biomarkers, we propose a method that combines terahertz (THz) spectroscopy, metasurface sensors, and machine learning. A metasurface sensor suitable for biomarker detection was designed and fabricated with five resonance frequencies in the range of 0.3-0.9THz. We collected biomarkers of five types and nine concentrations at 100 sets of time-domain spectra per concentration. The spectrum is processed by noise reduction and fast Fourier transform to obtain the frequency-domain spectrum. Five machine learning algorithms are used to analyze time- and frequency-domain spectra and ascertain which algorithm is more suitable for the classification of the biomarker THz spectrum. Experimental results show that random forest can better distinguish five biomarkers with an accuracy of 0.984 for the time-domain spectrum. For the frequency-domain spectrum, the support vector machine performs better, with an accuracy of 0.989. For biomarkers at different concentrations, we used linear regression to fit the relationship between biomarker concentration and frequency shift. Experimental results show that machine learning can distinguish different biomarker species and their concentrations by the THz spectrum. This work provides an idea and data processing method for the application of THz technology in biomedical detection.

Fabrication of ultrahigh aspect ratio Si nanopillar and nanocone arrays

High aspect ratio (HAR) structures have many promising applications such as biomedical detection, optical spectroscopy, and material characterization. Bottom-up self-assembly is a low-cost method to fabricate HAR structures, but it remains challenging to control the structure dimension, shape, density, and location. In this paper, an optimized top-down method using a combination of pseudo-Bosch etching and wet isotropic thinning/sharpening is presented to fabricate HAR silicon (Si) nanopillar and nanocone arrays. To achieve these structure profiles, electron beam lithography and reactive ion etching were carried out to fabricate silicon pillars having a nearly vertical sidewall, followed by thinning or sharpening by wet etching with a mixture of hydrofluoric (HF) acid and nitric acid (HNO3). For the dry etching step using the pseudo-Bosch process, the sidewall angle is largely dependent on the SF6/C4F8 gas flow ratio, and it was found that a vertical profile can be attained with a ratio of 22/38. For the wet etching process, a very large HNO3/HF volume ratio is shown to give smooth etching with a slow and controllable etching rate. The final structure profile also depends on the pattern density/array periodicity. When the array period is large, silicon nanopillar is thinned down, and its aspect ratio can reach 1:135 with a sub-100 nm apex. When the pillar array becomes very dense (periodicity much smaller than height), a very sharp nanocone structure is obtained after wet etching with an apex diameter under 20 nm.

Biophysical Properties of Bifunctional Phage-Biosensor.

Biosensor research is a swiftly growing field for developing rapid and precise analytical devices for biomedical, pharmaceutical, and industrial use and beyond. Herein, we propose a phage-based biosensor method to develop a sensitive and specific system for biomedical detection. Our method is based on in vitro selected phages and their interaction with the targeted analytes as well as on optical properties that change according to the concentration of the model analyte. The green fluorescent protein (GFP) was chosen as our model analyte as it has its own well-known optical properties. Brilliant green was used as a reporter component for the sensor. Its presence enables a color intensity (absorbance) change when the analyte is present in the solution. Furthermore, the reporter dye functioned as a quencher for an additional lanthanide label in our assay. It mediated the specific phage-derived interference in the signal measured with the time-resolved luminescence. Most importantly, our results confirmed that the presented bifunctional phage with its liquid crystal properties enabled the measurement of GFP in a concentration-dependent, quantitative manner with a limit of detection of 0.24 µg/mL. In the future, our novel method to develop phage-based biosensors may provide highly sensitive and specific biosensors for biomedical or otherwise-relevant targets.

Application of SERS in In-Vitro Biomedical Detection.

Surface-enhanced Raman scattering (SERS), as a rapid and nondestructive biological detection method, holds great promise for clinical on spot and early diagnosis. In order to address the challenging demands of on spot detection of biomedical samples, a variety of strategies has been developed. These strategies include substrate structural and component engineering, data processing techniques, as well as combination with other analytical methods. This report summarizes the recent SERS developments for biomedical detection, and their promising applications in cancer detection, virus or bacterial infection detection, miscarriage spotting, neurological disease screening et al. The first part discusses the frequently used SERS substrate component and structures, the second part reports on the detection strategies for nucleic acids, proteins, bacteria, and virus, the third part summarizes their promising applications in clinical detection in a variety of illnesses, and the forth part reports on recent development of SERS in combination with other analytical techniques. The special merits, challenges, and perspectives are discussed in both introduction and conclusion sections.

Enrichment of Aggregation-Induced Emission Aggregates Using Acoustic Streaming Tweezers in Microfluidics for Trace Human Serum Albumin Detection.

Aggregation-dependent brightness (ADB) indirectly limits the in vitro performance of a pure aggregation-induced emission (AIE) probe in many ways; thus, controlling the aggregation state of the AIE probe is helpful for detecting an object of interest. Many studies are focused on the molecule design of the AIE probes, while less efforts have been made for the control of the aggregation of the AIEs. Here, an acoustic streaming tweezer (AST) generated using a gigahertz bulk acoustic wave resonator was applied to manipulate the aggregation status of the AIE probe and further enhance their performance for human serum albumin (HSA) detection. As the trapping size of the AST matches the working size of the AIE probe, the streaming can enrich and accumulate AIE nanoparticles, which then further trigger larger aggregates. Due to the ADB effect, the fluorescence intensity strongly increased, and thus, the detection limit of HSA was reduced to 0.5 μg/mL, which is low enough for kidney disease detection. Such an AST-assisted ADB strategy is potentially applicable to other AIE probes and can work as a portable choice for the biomedical detection.

Copper-based biological alloys and nanocomposites for enzymatic catalysis and sensing applications.

Copper (Cu) is an inexpensive transition metal on Earth, exhibiting high catalytic activity due to its rich d-electron configuration and variable oxidation states. Cu-based biological alloys and nanocomposites have emerged as a prominent research area. Under specific synthesis conditions, alloys or nanocomposites formed by Cu with other metals demonstrate excellent enzyme-like and sensing activities. These advanced materials offer significant advantages over artificial enzymes in enzymatic applications, including high stability, simple synthesis, flexible catalytic performance, and ease of preservation. In addition, various types of sensors have been designed based on the unique electrochemical properties exhibited by these alloys and nanocomposites as well as their specific reactions with the target substances. These sensors possess advantages such as stability, high efficiency, a broad detection range, low detection limits, and high sensitivity. In this review, we summarize the current research status of Cu-based biological alloys and nanocomposites in enzyme-like applications and sensing applications. Based on this, we introduce the diverse enzyme-like activities exhibited by Cu-based nanozymes prepared under different synthesis conditions and their applications in areas such as biosensing, cancer treatment, and antibacterial therapy. Furthermore, we provide an overview of the applications of Cu-based alloys and nanocomposites in the field of sensing based on their enzyme-like activity or chemical activities. These sensors have been widely employed in biomedical detection, environmental hazardous substance monitoring, and food safety testing. Challenges and prospects faced by Cu-based alloys and nanocomposites are also highlighted for future works.

Increasing charge transfer of SERS by the combination of amorphous Al2O3-Al thin film and ZnO nanorods decorated with Ag nanoparticles for trace detection of metronidazole.

In this work, we study the charge transfer improvement by the combination of two semiconductors of SERS. The energy levels of the semiconductor, when combined, become intermediate energy levels that support the charge transfer from the HOMO to the LUMO level, amplifying the Raman signal of the organic molecules. The SERS substrates of Ag/a-Al2O3-Al/ZnO nanorods with high sensitivity are prepared for detecting dye rhodamine 6G (R6G) and metronidazole (MNZ) standard. The highly ordered vertically grown ZnO nanorods (NRs) are first developed on a glass substrate by a wet chemical bath deposition method. Then, ZnO NRs are covered with an amorphous oxidized aluminum thin film by a vacuum thermal evaporation method to produce a platform with a large surface area and high charge transfer performance. Finally, silver nanoparticles (NPs) are decorated onto this platform to form an active SERS substrate. The structure, surface morphology, optical properties, and elements in the sample are investigated by Raman spectroscopy, X-ray diffractometry, field-emission scanning electron microscopy (FE-SEM), ultraviolet-visible spectroscopy (UV-vis), reflectance spectroscopy, and energy dispersion X-ray spectroscopy (EDS). Rhodamine 6G is used as a reagent to evaluate the SERS substrates with an analytical enhancement factor (EF) of ∼1.85 × 1010 at the limit of detection (LOD) of 10-11 M. These SERS substrates are used to detect metronidazole standard at a LOD of 0.01 ppm and an EF of 2.2 × 106. The SERS substrate exhibits high sensitivity and stability for promising wide application in chemical, biomedical, and pharmaceutical detection.

Epidemic Analysis and Prediction of Novel Coronavirus based on XGBoost Algorithm

The sudden outbreak of COVID-19 poses a great threat to the health and safety of people all over the world. Since the outbreak of the epidemic, the number of suspected and confirmed infections in the world has continued to rise. During the period of epidemic prevention and control, it is very important to carry out scientific research quickly, such as finding the source of the virus, controlling the spread of the virus, studying the pathogenic mechanism, collecting data, looking for scientific treatment and prevention and control programs, screening and developing effective drugs, and so on. At the same time, according to the data collected and published by the World Health Organization, it can reflect the response measures in different regions and the number of people found to be affected by COVID. The epidemic situation in COVID-19 is a critical period for major scientific research projects to tackle key problems, and an important stage to win time and save lives. Today, Covid is still rampant, and there are still different varieties. Based on the existing data, the COVID infection model can be calculated to predict the infectivity of new varieties, and different measures can be taken for countries with high mortality or infection rates. The experimental results show that, compared with three traditional machine learning algorithms, the model built based on the integrated algorithm XGBoost has the highest prediction accuracy rate for whether human beings are infected with novel coronavirus, and the accuracy rate reaches 95.6%, providing a non-destructive auxiliary method for biomedical detection of COVID-19.

Dynamically Switchable Sub-THz Absorber Using VO2 Metamaterial Suitable in Optoelectronic Applications

Temperature-sensitive materials are known as phase change materials (PCMs) which has transition between two different states. Dynamically tunable devices can be designed utilizing these materials. Vanadium dioxide (VO2) considered as a PCM material which transits from the insulator state to the metal one by increasing the temperature. VO2 has recently been utilized to design tunable absorbers. In this article, we presented a dual-band absorber structure design which consist of double arrays of VO2 ring-based placed on top of a dielectric buffer/spacer terminated with a conducting layer acting as a back reflector. Each ring acts as a resonator producing a surface plasmon resonance (SPR). Having a proper unit cell design with an appropriate dimension, a dual-band absorber with an absorption amplitude above 95% (ON state) can be achieved at terahertz (THz) frequency range in the metallic state; whereas the absorption value is 0.6% (OFF state) in the insulator state of VO2. Therefore, the proposed structure design has the possibility to switch between these two ON/OFF states by changing the material’s temperature. The interference theory and the equivalent circuit model are investigated to verify the achieved result using high-frequency structure simulator (HFSS) software which works based on finite element method (FEM). This structure has the potential optoelectronic applications such as refractive index (RI) optical sensing and biomedical detection, photonics detectors, and optical storage applications.

Electrochemical detection of tyrosine with casting electrode with carbon black and graphene oxide co-doped

This study investigated the performance of carbon-based carbon black (CB) and graphene oxide (GO) co-doped electrodes for electrochemical testing and analyzed their respective contributions to electrochemical performance. In this study, a CB–GO/CP two-layer electrode system was constructed on the surface of a hydrophilic carbon paper (CP) for the electrochemical detection of tyrosine (Tyr). The fabricated electrochemical electrode significantly increases the active area, and as a convenient and low-cost method of electrode fabrication, it significantly simplifies the electrode manufacturing process, eliminating the steps of electrode pretreatment, in situ modification, and post-treatment. Electrochemical test results demonstrate that the sensitivity to Tyr is [1.07 × 10−1 µA/µM cm2], Limit of detection (LOD) [100 µM], and linear ranges [0.1–2 mM]. It also has one-week electrode stability and good repeatability. Scanning electron microscopy and Raman spectra of the CB–GO/CP electrodes show that GO and CB form a solid structure through the combination of van der Waals force, adsorption force, and CP substrate. A convenient CB–GO co-doped electrochemical electrode for Tyr detection will play a significant role in biomedical and civilian detection fields.

Designing a Fano-resonance-based temperature sensor by side-coupling double cavities to waveguide in photonic crystals.

Optical sensors are widely used for temperature measurement in chemistry, biomedical detection, and food processing industries. In this paper, we present a highly sensitive temperature sensor based on the Fano resonance in two-dimensional photonic crystals. A carefully designed double cavity is used within the photonic crystals to symmetrically side-couple to a line-defect waveguide. Due to the direct and indirect coupling between two cavities, we found an asymmetric Fano-like line shape in the transmission spectrum. The optimized quality factor of the Fano resonance and the modulation depth are improved to a maximum of 10672 and above 90%, respectively. Furthermore, the sensitivity of the temperature sensor can reach as high as 91.9pm/°C, which is direct evidence for its high sensing capability. Thus, our proposed temperature sensor has comparable quality factor and sensitivity with other reported sensors, indicating its high application potential in the sensing field.

Ultrawideband metamaterial absorber for oblique incidence using characteristic mode analysis

An ultrawideband, polarization-insensitive, metamaterial absorber for oblique angle of incidence is presented using characteristic mode analysis. The absorber consists of conductive meander square loops and symmetric bent metallic strips, which are embedded with lumped resistors. With the aid of modal currents and modal weighting coefficients, the positions of the lumped resistors are determined. After that, the equivalent circuit (EC) model and admittance formula are proposed and analyzed to further understand the working principle and ultrawide bandwidth. The proposed absorber measures an absorption bandwidth of 4.3–26.5 GHz (144.1% in fractional bandwidth) for 90% absorptivity under normal incidence. At the oblique angle of incidence of 45°, the bandwidth of 90% absorptivity is still 5.1–21.3 GHz (122.72%) for transverse electric (TE) polarization, and 6.8–29.5 GHz (125.07%) for transverse magnetic (TM) polarization. The good agreement among simulation, measurement, and EC calculation demonstrates the validity of the proposed method and indicates that the method can be applied to other microwave and optical frequency bands. The proposed metamaterial absorber can be widely applied in electromagnetic compatibility, electromagnetic interference, radar stealth, and biomedical detection.

A flexible surface-enhanced Raman Spectroscopy chip integrated with microlens

A novel flexible Surface-enhanced Raman Spectroscopy (SERS) chip integrated with microlens was proposed and designed, which consisted of PDMS film, planoconvex microlens, and silver nanoparticles (AgNPs) monolayer, and was of high signal collection efficiency. The flexible PDMS film integrated with microlens was designed by optical simulation, and fabricated by optimized micromachining process. AgNPs monolayer were uniformly assembled on the other side of the PDMS film through a liquid–liquid interface self-assembly method to form SERS chip. The prepared chip revealed excellent SERS performance with a Raman enhancement factor of about 107 and a signal variation of <11.5 %. The SERS chip was successfully utilized for in-situ detection of thiram residues on tomato skins, and its characteristic peaks could still be clearly distinguished when the concentration was down to 2.5 μM. It was shown that the proposed SERS chip was suitable for in-situ detection of a real sample on complex surface morphology and shown potential prospect in the fields of chemical and biomedical detections.

Preparation Methods and Functional Characteristics of Regenerated Keratin-Based Biofilms.

The recycling, development, and application of keratin-containing waste (e.g., hair, wool, feather, and so on) provide an important means to address related environmental pollution and energy shortage issues. The extraction of keratin and the development of keratin-based functional materials are key to solving keratin-containing waste pollution. Keratin-based biofilms are gaining substantial interest due to their excellent characteristics, such as good biocompatibility, high biodegradability, appropriate adsorption, and rich renewable sources, among others. At present, keratin-based biofilms are a good option for various applications, and the development of keratin-based biofilms from keratin-containing waste is considered crucial for sustainable development. In this paper, in order to achieve clean production while maintaining the functional characteristics of natural keratin as much as possible, four important keratin extraction methods-thermal hydrolysis, ultrasonic technology, eco-friendly solvent system, and microbial decomposition-are described, and the characteristics of these four extraction methods are analysed. Next, methods for the preparation of keratin-based biofilms are introduced, including solvent casting, electrospinning, template self-assembly, freeze-drying, and soft lithography methods. Then, the functional properties and application prospects of keratin-based biofilms are discussed. Finally, future research directions related to keratin-based biofilms are proposed. Overall, it can be concluded that the high-value conversion of keratin-containing waste into regenerated keratin-based biofilms has great importance for sustainable development and is highly suggested due to their great potential for use in biomedical materials, optoelectronic devices, and metal ion detection applications. It is hoped that this paper can provide some basic information for the development and application of keratin-based biofilms.