Integrated LSPR Biosensing Signal Processing Strategy and Visualization Implementation.

The LSPR biosensor chip is a groundbreaking tool popular in laboratory settings for identifying disease markers. However, its use in clinical environments is not as widespread. One notable gap is the lack of a universal signal processing tool for LSPR biosensing. To escalate its precision, there is an emerging need for software that not only optimizes signal processing but also incorporates self-verification functionalities within LSPR biochemical sensors. Enter the visual LSPR sensor software-an innovative platform that processes real-time transmission or reflection spectra. This advanced software adeptly captures the nuanced structural changes at the nanostructure interface prompted by environmental fluctuations. It diligently records and computes a suite of parameters, including the resonance wavelength shift, full width at half maximum, sensitivity, and quality factor. These features empower users to tailor processing algorithms for each data capture session. Transcending traditional instruments, this method accommodates a multitude of parameters and ensures robust result validation while tactfully navigating nanostructure morphology complexities. Forsaking third-party tool dependencies, the software tackles challenges of precision and cost-effectiveness head-on, heralding a significant leap forward in nanophotonics, especially for high-throughput LSPR biosensing applications. This user-centric innovation marks substantial progress in biochemical detection. It is designed to serve both researchers and practitioners in the field of nanophotonic sensing technology, simplifying complexity while enhancing reliability and efficiency.

Sensitivity-enhanced nanoplasmonic biosensor using direct immobilization of two engineered nanobodies for SARS-CoV-2 spike receptor-binding domain detection.

Sensitive, rapid, and easy-to-implement biosensors are critical in responding to highly contagious and fast-spreading severe acute respiratory syndrome coronavirus (SARS-CoV-2) mutations, enabling early infection screening for appropriate isolation and treatment measures to prevent the spread of the virus. Based on the sensing principle of localized surface plasmon resonance (LSPR) and nanobody immunological techniques, an enhanced sensitivity nanoplasmonic biosensor was developed to quantify the SARS-CoV-2 spike receptor-binding domain (RBD) in serum within 30 min. The lowest concentration in the linear range can be detected down to 0.01 ng/mL by direct immobilization of two engineered nanobodies. Both the sensor fabrication process and immune strategy are facile and inexpensive, with the potential for large-scale application. The designed nanoplasmonic biosensor achieved excellent specificity and sensitivity for SARS-CoV-2 spike RBD, providing a potential option for accurate early screening of the novel coronavirus disease 2019 (COVID-19).

Route to flexible metamaterial terahertz biosensor based on multi-resonance dips.

A flexible terahertz (THz) metamaterial biosensor is theoretically and experimentally investigated. The metamaterial unit cell of the periodic structure array was simply composed of three non-overlapping cut wires with different length parameters on a flexible thin-film (parylene-C) to improve sensitivity. The biosensor sample was fabricated using a lithography process and characterized by a THz time-domain spectroscopy (TDS) system. The metamaterial exhibited multi-resonance dips in transmission spectrum at 0.6-2.0 THz, which can self-correct errors in biosensing. Numerical results show that the Q-factor, figure of merit (FOM) and sensitivity can change in dynamic ranges with the geometric parameters (space and width) of three-cut-wire metamaterial. When space distance was 40 µm and other parameters were default, the sensitivity, FOM and Q-factor reached 710 GHz/RIU (Refractive Index Unit), 9, and 20, respectively. Therefore, through proper design and preparation, the metamaterial can be applied to biochemical detection.

Flexible terahertz metamaterial biosensor for label-free sensing of serum tumor marker modified on a non-metal area.

Terahertz (THz) metamaterials for rapid label-free sensing show application potential for the detection of cancer biomarkers. A novel flexible THz metamaterial biosensor based on a low refraction index parylene-C substrate is proposed. The biomarkers are modified on non-metal areas by a three-step modification method that simplifies the modification steps and improves the modified effectivity. Simulation results for non-metal modification illustrate that a bulk refractive index sensitivity of 325 GHz/RIU is achieved, which is larger than that obtained for the traditional metal modification (147 GHz/RIU). Meanwhile, several fluorescence experiments proved the uniform modification effect and selective adsorption capacity of the non-metal modification method. The concentration of the carcinoembryonic antigen (CEA) biomarkers for breast cancer patients tested using this THz biosensor is found to be consistent with results obtained from traditional clinical tests. The limit of detection reaches 2.97 ng/mL. These findings demonstrate that the flexible THz metamaterial biosensor can be extensively used for the rapid detection of cancer biomarkers in the future.

Gold Nanostrip Array-Mediated Wireless Electrical Stimulation for Accelerating Functional Neuronal Differentiation.

Neural stem cell (NSC)-based therapy holds great promise for the treatment of neurodegenerative diseases. Presently, however, it is hindered by poor functional neuronal differentiation. Electrical stimulation is considered one of the most effective ways to promote neuronal differentiation of NSCs. In addition to surgically implanted electrodes, traditional electrical stimulation includes wires connected to the external power supply, and an additional surgery is required to remove the electrodes or wires following stimulation, which may cause secondary injuries and infections. Herein, a novel method is reported for generation of wireless electrical signals on an Au nanostrip array by leveraging the effect of electromagnetic induction under a rotating magnetic field. The intensity of the generated electrical signals depends on the rotation speed and magnetic field strength. The Au nanostrip array-mediated electric stimulation promotes NSC differentiation into mature neurons within 5 days, at the mRNA, protein, and function levels. The rate of differentiation is faster by at least 5 days than that in cells without treatment. The Au nanostrip array-based wireless device also accelerates neuronal differentiation of NSCs in vivo. The novel method to accelerate the neuronal differentiation of NSCs has the advantages of wireless, timely, localized and precise controllability, and noninvasive power supplementation.

A Flexible Terahertz Metamaterial Biosensor for Cancer Cell Growth and Migration Detection.

Metamaterial biosensors have been extensively used to identify cell types and detect concentrations of tumor biomarkers. However, the methods for in situ and non-destruction measurement of cell migration, which plays a key role in tumor progression and metastasis, are highly desirable. Therefore, a flexible terahertz metamaterial biosensor based on parylene C substrate was proposed for label-free and non-destructive detection of breast cancer cell growth and migration. The maximum resonance peak frequency shift achieved 183.2 GHz when breast cancer cell MDA-MB-231 was cultured onto the surface of the metamaterial biosensor for 72 h. A designed polydimethylsiloxane (PDMS) barrier sheet was applied to detect the cell growth rate which was quantified as 14.9 µm/h. The experimental peak shift expressed a linear relationship with the covered area and a quadratic relationship with the distance, which was consistent with simulation results. Additionally, the cell migration indicated that the transform growth factor-ß (TGF-ß) promoted the cancer cell migration. The terahertz metamaterial biosensor shows great potential for the investigation of cell biology in the future.

Route to Cost-Effective Fabrication of Wafer-Scale Nanostructure through Self-Priming Nanoimprint.

Nanoimprint technology is powerful for fabricating nanostructures in a large area. However, expensive equipment, high cost, and complex process conditions hinder the application of nano-imprinting technology. Therefore, double-layer self-priming nanoimprint technology was proposed to fabricate ordered metal nanostructures uniformly on 4-inch soft and hard substrates without the aid of expensive instruments. Different nanostructure (gratings, nanoholes and nanoparticles) and different materials (metal and MoS2) were patterned, which shows wide application of double-layer self-priming nanoimprint technology. Moreover, by a double-layer system, the width and the height of metal can be adjusted through the photoresist thickness and developing condition, which provide a programmable way to fabricate different nanostructures using a single mold. The double-layer self-priming nanoimprint method can be applied in poor condition without equipment and be programmable in nanostructure parameters using a single mold, which reduces the cost of instruments and molds.

A Potential Plasmonic Biosensor Based Asymmetric Metal Ring Cavity with Extremely Narrow Linewidth and High Sensitivity.

To achieve high sensitivity and multi-mode sensing characteristics based on the plasmon effect, we explored a high-sensitivity refractive index sensor structure with narrow linewidth and high absorption characteristics based on theoretical analysis. The sensor structure is composed of periodic asymmetric ring cavity array, spacer layer and metal thin-film layer. The reflection spectrum of this structure shows six resonance modes in the wavelength range from visible to near-infrared. The sensor performance was optimized based on the change of the sensor structure parameters combining the simulation data, and the results shown that this kind of asymmetric laminated structure sensor has good sensing performance. In theory, it can be combined with microfluidic technology to achieve sensing detection of diverse test samples, multi-mode and multi-component, which has great potential in the field of biosensing.

Strategies to improve performances of LSPR biosensing: Structure, materials, and interface modification.

Due to the unique nature of localized surface plasmon resonance (LSPR), LSPR has attracted extensive attention in the field of biochemical sensing. However, compared with other sensors, the LSPR biosensor has lower sensitivity which has the limitation of insufficient repeatability and greatly limits its application and further promotion. Many researchers have invested a lot of energy in various ways to investigate different methods to improve sensitivity. This review summarizes these methods from the three aspects of structure, material, and interface modification. Meanwhile, it can be predicted that the strategies to improve the performance of LSPR biosensing will extend its application.

Exploring performance of THz metamaterial biosensor based on flexible thin-film.

To extend the application of flexible metamaterial in the biosensor field, a metamaterial biosensor, which consisted of metal elliptical split-ring resonator array with a subwavelength structure based on flexible thin-film (parylene-c), was presented. The structure parameters (ring width, period ratio of structure, gap width, axial ratio) of the elliptical split-ring resonator and polarization direction of incident light were investigated as to how to affect the performances of the flexible metamaterial biosensor. Meanwhile, the permittivity (ε) of the tested sample on the surface of metamaterials biosensor also affected the shift of transmission spectra. The results showed that the sensitivity, quality (Q) factor, and figure of merit (FOM) of the flexible metamaterial biosensor could reach 243 GHz/RIU, 14.2, and 3.3, respectively. Moreover, the full-width-half-maximum (FWHM) was only 82 GHz. Therefore, these results provided an improved direction to design metamaterial biosensors with high Q-factor, low FOM, and high sensitivity, which could meet the need for sample detection in the terahertz regime.

Nanoparticles Enhanced Self-driven Microfludic Biosensor.

C-reactive protein (CRP) plays an important role in inflammation detection and disease monitoring. The optical biosensor is a highly sensitive and easy detection tool. The microfluidic self-driving optical sensors were fabricated with transparent glass material and used for the enhanced surface plasmon resonance (SPR) optical detection of the model protein CRP using Au nanoparticles (AuNPs) and a sandwich immune reaction. The 3D design of the chip was devised to improve the optical coupling efficiency and enable integration with a microfluidic control and rapid detection. The array of pre-fixed antibody modified by Au nanoparticles was used to achieve rapid antigen capture and improve the optical sensitivity. The Au nanoparticle amplification approach was introduced for the SPR detection of a target protein. CRP was used as a model target protein as part of a sandwich assay. The use of Au NP measurements to detect the target signal is a threefold improvement compared to single SPR detection methods.

Luminescent ruthenium(II)-containing metallopolymers with different ligands: synthesis and application as oxygen nanosensor for hypoxia imaging.

A series of Ru(II)-containing metallopolymers with different polypyridyl complexes, namely [Ru(N^N)2(L)](PF6)2 (L = bipyridine-branched polymer; N^N = bpy: 2,2'-bipyridine (Ru 1); phen: 1,10-phenanthroline (Ru 2); dpp: 4,7-diphenyl-1,10-phenanthroline (Ru 3)), were synthesized with the motive that adjusting π-conjugation length of ligands might produce competent luminescent oxygen probes. The three hydrophobic metallopolymers were studied with 1H NMR, UV-Vis absorption, and emission spectroscopy, and then were utilized to prepare biocompatible nanoparticles (NPs) via a nanoprecipitation method. Luminescent properties of the NPs were investigated against dissolved oxygen by steady-state and time-resolved spectroscopy respectively. Luminescence quenching of the three NPs all followed a linear behavior in the range of 0-43 ppm (oxygen concentration), but Ru 3-NPs exhibited the highest oxygen sensitivity (82%) and longest emission wavelength (λex = 460 nm; λem = 617 nm). In addition, external interferons from cellular environments (e.g., pH, temperature, and proteins) had been studied on Ru 3-NPs. Finally, dissolved oxygen in monolayer cells under normoxic/hypoxic conditions was clearly differentiated by using Ru 3-NPs as the luminescent sensor, and, more importantly, hypoxia within multicellular tumor spheroids was vividly imaged. These results suggest that such Ru(II)-containing metallopolymers are strong candidates for luminescent nanosensors towards hypoxia. Graphical abstract.

Smartphone Biosensor System with Multi-Testing Unit Based on Localized Surface Plasmon Resonance Integrated with Microfluidics Chip.

Detecting biomarkers is an efficient method to diagnose and monitor patients' stages. For more accurate diagnoses, continuously detecting and monitoring multiple biomarkers are needed. To achieve point-of-care testing (POCT) of multiple biomarkers, a smartphone biosensor system with the multi-testing-unit (SBSM) based on localized surface plasmon resonance (LSPR) integrated multi-channel microfluidics was presented. The SBSM could simultaneously record nine sensor units to achieve the detection of multiple biomarkers. Additional 72 sensor units were fabricated for further verification. Well-designed modularized attachments consist of a light source, lenses, a grating, a case, and a smartphone shell. The attachments can be well assembled and attached to a smartphone. The sensitivity of the SBSM was 161.0 nm/RIU, and the limit of detection (LoD) reached 4.2 U/mL for CA125 and 0.87 U/mL for CA15-3 through several clinical serum specimens testing on the SBSM. The testing results indicated that the SBSM was a useful tool for detecting multi-biomarkers. Comparing with the enzyme-linked immunosorbent assays (ELISA) results, the results from the SBSM were correlated and reliable. Meanwhile, the SBSM was convenient to operate without much professional skill. Therefore, the SBSM could become useful equipment for point-of-care testing due to its small size, multi-testing unit, usability, and customizable design.

Facile synthesis of multifunctional nanoparticles encoded with quantum dots and magnetic nanoparticles: cell tagging and MRI.

In this study, fluorescence-encoded magnetic biocompatible nanoparticles (NPs) were constructed from CdSe@ZnS quantum dots (QDs) and Fe3O4 nanoparticles with a one-step reprecipitation-encapsulation method. The resultant hybrid NPs exhibit small size (∼130 nm in diameter), highly bright QDs, two-color emissions (green and red) under single-wavelength excitation, easy separation with a magnet and efficient cellular internalization. Energy transfer between the incorporated QDs was studied to better tailor the encoded fluorescence, and 11 barcodes were obtained by adjusting the ratio of green and red QDs. We used four sets of the barcodes to tag specific cancer cells (HepG2) as a proof-of-concept, and distinguished each set according to respective overlayed fluorescence images using laser confocal microscopy. Moreover, the incorporated Fe3O4 NPs endowed as-constructed optical barcode superparamagnetic property by T 2-enhanced magnetic resonance effect with an r 2 value of 145.25 s-1 mM-1 at 3 T. These results suggest that the multifunctional NPs are very promising for discriminating different cells and dual-modality imaging.

Selective transverse mode operation of a fiber laser based on few-mode FBG for rotation sensing.

A fiber laser with selective transverse mode operation based on few-mode FBG was designed, and rotation sensing via hybrid mode operation was successfully demonstrated. The mode selection was achieved by a few-mode FBG inscribed in homemade elliptical multilayer-core fiber (EMCF). The particular designed EMCF only supports LP01 and LP11 even mode groups, and the resonance of a few-mode FBG could be adjusted through mode excitation. Therefore, selective transverse mode operation was realized by switching the resonance wavelengths corresponding to the self-coupling mode or cross-coupling mode. Besides, rotation sensing was achieved in the hybrid mode operation due to the asymmetric multilayer-core design. A sensitivity of 0.074 mW/° was preliminarily demonstrated. The measured angle of the rotation sensing system is within ± 2° in the temperature range of 10-90 °C, showing that this system was inherently insensitive to temperature, eliminating the requirement for temperature compensation.

Label-Free Exosome Detection Based on a Low-Cost Plasmonic Biosensor Array Integrated with Microfluidics.

Localized surface plasmon resonance-based plasmonic biosensors are interesting candidates for the design of portable optical biosensor platforms owing to their integration, miniaturization, multiparameter, real-time, and label-free detection characteristics. Plasmonic biosensor arrays that have been combined with microfluidics have been developed herein to detect exosomes label-free. Gold nano-ellipsoid arrays were fabricated with low-cost anodic aluminum oxide thin films that act as shadow masks for evaporation of Au. The nano-ellipsoid arrays were integrated with a microfluidic chip to achieve multiparameter detection. The anti-CD63 antibody that is specific to the exosome transmembrane protein CD63 is modified on the surface of the nano-ellipsoids. Exosome samples were injected into the biosensor platform at different concentrations and detected successfully. The detection limit was 1 ng/mL. The proposed plasmonic biosensor array can be universally applicable for the detection of other biomarkers by simply changing the antibody on the surface of the Au nano-ellipsoids. Moreover, this biosensor platform is envisaged to be potentially useful in the development of low-cost plasmonic-based biosensors for biomarker detection and for the investigation of exosomes for noninvasive disease diagnoses.

Exploring surface sensitivity of Rayleigh anomaly in metal/dielectric multilayer gratings.

Biosensors based on Rayleigh anomaly (RA) in metal gratings exhibit impressive bulk refractive index (RI) sensitivity and narrow linewidth. However, the electric field enhancement extends far away from surface of the gratings, which limits the application on biosensor where the RI changes are restricted at the sensor interface. To overcome this shortcoming, a novel grating composed of a 8-layer Au/Al2O3 stack was optimized by numerical simulation. The electric field is limited in several hundreds of nanometers from surface. The surface sensitivity increases 10 times than that of Au gratings at the detection depth of less than 400 nm. The surface index sensitivity can be improved 5 times under oblique incidence than that under normal incidence when the thickness of cover media is 20 nm.

Facile synthesis of fluorinated nanophotosensitizers with self-supplied oxygen for efficient photodynamic therapy.

Tumor hypoxia severely reduces the efficiency of photodynamic therapy (PDT) through the insufficient supply of oxygen. In this work, we reported on a design of fluorinated nanophotosensitizers (NPSs) prepared by a facile reprecipitation-encapsulation method, with the aim of addressing the issue of hypoxia. The fluorinated NPSs consisted of a hybrid particle core of perfluorosiloxane-polystyrene, doped with a fluorinated photosensitizer, and a biocompatible poly-l-lysine shell. Compared with non-fluorinated counterpart NPSs that are similarly prepared except for the replacement of perfluorosiloxane with alkoxysilane, the fluorinated NPSs saturated with O2 exhibit approximately 3.5 fold higher singlet oxygen production yield and higher in vitro PDT efficiency due to the O2-carrying capability of intra-particle 'F-C' bonds.

Highly Stable and Luminescent Oxygen Nanosensor Based on Ruthenium-Containing Metallopolymer for Real-Time Imaging of Intracellular Oxygenation.

Metal complex-based luminescent oxygen nanosensors have been intensively studied for biomedical applications. In terms of monitoring dynamics of intracellular oxygen, however, high-quality nanosensors are still badly needed, because of stringent requirements on stability, biocompatibility and luminescence intensity, aside from oxygen sensitivity. In this paper, we reported a type of highly luminescent and stable oxygen nanosensors prepared from metallopolymer. First, a novel ruthenium(II)-containing metallopolymer was synthesized by chelating the oxygen probe [Ru(bpy)3]2+ with a bipyridine-branched hydrophobic copolymer, which was then doped into polymeric nanoparticles (NPs) by a reprecipitation method, followed by further conjugation to selectively target mitochondria (Mito-NPs). The resultant Mtio-NPs possessed a small hydrodynamic size of ∼85 nm, good biocompatibility and high stability resulting from PEGylation and stable nature of Ru-complex. Because the complexed [Ru(bpy)3]2+ homogeneously resided on particle surface, Mito-NPs exhibited strong luminescence at 608 nm that was free of aggregation-caused-quenching, the utmost oxygen sensitivity of free [Ru(bpy)3]2+ probe ( Q = 75%), and linear Stern-Volmer oxygen luminescence quenching plots. Taking advantage of the mitochondria-specific nanosensors, intracellular oxygenation and deoxygenation processes were real-time monitored for 10 min by confocal luminescence imaging, visualized by the gradual weakening (by more than 90%) and enhancing (by 50%) of the red emission, respectively.

Point-of-care testing based on smartphone: The current state-of-the-art (2017-2018).

Smartphone-based point-of-care testing (POCT) is rapidly emerging as a potential alternative to the traditional laboratory-based diagnostic testing owing to economic considerations and availability of medical equipment especially in resource-limited areas. A smartphone, combined with a biosensor and other related accessories, can offer high accuracy and sensitivity for medical testing. Moreover, the ubiquity of smartphone has propelled the development considerably, and accordingly research in recent years has shown promising progress in POCT. Here, we used samples (blood, urine, sweat, saliva and tears) of liquid biopsy as the standard for classification of smartphone-based POCT devices, considering that these samples contain multiple biomarkers of serious diseases. The colorimetric, fluorescent, brightfield, and electrochemical methods were utilized to examine these samples. We performed a comprehensive review of the development of smartphone-based POCT devices over the past two years (2017-2018) and assessed their relative merits and drawbacks. Based on the progress of POCT development, it illustrates that the various technological and economical requirements are urgent and tremendous. The tendency of high-quality, low-cost smartphone-based POCT devices, feature of biosensors (paper-based sensor, flexible device, microfluidic chip, et al.) currently widely used in POCT and recommendations of future works were summarized.