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The SPR phenomenon results in an abrupt change in the optical phase such that one can measure the phase shift of the reflected light as a sensing parameter. Moreover, many studies have demonstrated that the phase changes more acutely than the intensity, leading to a higher sensitivity to the refractive index change. However, currently, the optical phase cannot be measured directly because of its high frequency; therefore, investigators usually have to use complicated techniques for the extraction of phase information. In this study, we propose a simple and effective strategy for measuring the SPR phase shift based on phase-shift interferometry. In this system, the polarization-dependent interference signals are recorded simultaneously by a pixelated polarization camera in a single snapshot. Subsequently, the phase information can be effortlessly acquired by a phase extraction algorithm. Experimentally, the proposed phase-sensitive SPR sensor was successfully applied for the detection of small molecules of glyphosate, which is the most frequently used herbicide worldwide. Additionally, the sensor exhibited a detection limit of 15 ng/mL (0.015 ppm). Regarding its simplicity and effectiveness, we believe that our phase-sensitive SPR system presents a prospective method for acquiring phase signals.

Cytomegalovirus (CMV) is the most frequent cause of congenital infection worldwide; congenital CMV may lead to significant mortality, morbidity, or long-term sequelae, such as sensorineural hearing loss. The current study presents a newly designed surface plasmon resonance (SPR) biosensor for CMV-specific microRNAs that does not involve extra care for receptor immobilization or treatment to prevent fouling on bare gold surfaces. The modification-free approach, which utilizes a poly-adenine [poly(A)]-Au interaction, exhibited a high affinity that was comparable to that of the gold-sulfur (Au-S) interaction. In addition, magnetic nanoparticles (MNPs) were used to separate the analyte from complex sample matrixes that significantly reduced nonspecific adsorption. Moreover, the MNPs also played an important role in SPR signal amplification due to the binding-induced change in the refractive index. Our SPR biosensing platform was used successfully for the multi-detection of the microRNAs, UL22A-5p, and UL112-3p, which were associated with CMV. Our SPR biosensor offered the detection limits of 108 fM and 24 fM for UL22A-5p and UL112-3p, respectively, with an R2 of 0.9661 and 0.9985, respectively. The precision of this biosensor has an acceptable CV (coefficient of variation) value of

Mycobacterium tuberculosis complex (MTBC) is the well-known causative agents of tuberculosis (TB). Transmission of bacteria via airborne routes makes infection control difficult. Hence, rapid and accurate identification of TB from clinical sputum samples is essential for minimizing the spread of the disease. However, traditional bacterial identification methods for TB are time consuming and labor intensive. The aim of this study is to propose a straightforward and rapid screening platform for MTBC using a portable organic light-emitting diode- (OLED-) based surface plasmon resonance (SPR) biosensor integrated with a nested PCR technique. Experimentally, the limit of detection (LOD) for MTBC PCR products measurement was estimated to be around 63 pg/mL. In addition, the biosensor can successfully differentiate MTBC from other nontuberculous mycobacterium strains. In 600 clinical sputum specimens, the sensitivity and specificity were 96.6% (86/89) and 98.4% (503/511), respectively. These results indicate that the portable OLED-based SPR biosensor may be taken into account as a suitable and convenient tool employed in the remote area and developing country for diagnosing TB diseases.

A white organic light-emitting diode (OLED) with enhanced sensitivity has been demonstrated as a novel light source in a portable surface plasmon resonance (SPR) optical biosensor. A disposable broad-spectral OLED was employed on the leg side of isosceles trapezoid prism for a fixed angle of incident light. Bimetallic Ag/Au composition layers were used as sensing layers and their structures evaluated such that the wavelength resonance occurred at the peak of the light spectrum. The SPR signal detection applied differential intensities at two reference wavelengths. We show that the integration of a white spectral OLED on an SPR sensor improved the sensor's sensitivity by ∼19.29% compared to an SPR sensor system using a green OLED for a bimetallic Ag/Au sensing layer. The limit of detection (LOD) of 2.4 × 10−6 refractive index units (RIU) has been established in the range of refractive index samples (Δn) around 3.6 × 10−3 RIU. This optical sensor demonstrated the capability of rapid, real-time monitoring operation. The activation of self-assembled monolayer (SAM), antibody immobilization, and biomolecular interaction detection of immunoglobulin G (IgG) protein are recorded successfully with a detection limit around 40.3 pg/mL.

In 2013 a new reassortant avian influenza A H7N9 virus emerged in China, causing human infection with high mortality. An accurate and timely diagnosis is crucial for controlling the outbreaks of the disease. We therefore propose a simple strategy for rapidly and sensitively detecting the H7N9 virus using an intensity-modulated surface plasmon resonance (IM-SPR) biosensor integrated with a new generated monoclonal antibody. The novel antibody exhibits significant specificity to recognize H7N9 virus compared with other clinical human influenza isolates (p0.01). Experimentally, the detection limit of the proposed approach for H7N9 virus detection is estimated to be 144 copies/mL, which is a 20-fold increase in sensitivity compared with homemade target-captured ELISA using the identical antibody. For the measurement of mimic clinical specimens containing the H7N9 virus mixed with nasal mucosa from flu-like syndrome patients, the detection limit is calculated to be 402 copies/mL, which is better than conventional influenza detection assays; quantitative reverse transcription polymerase chain reaction (qRT-PCR) and rapid influenza diagnostic test (RIDT). Most importantly, the assay time took less than 10 min. Combined, the results of this study indicate that the proposed simple strategy demonstrates high sensitivity and time-saving in H7N9 virus detection. By incorporating a high specific recognizer, the proposed technique has the potential to be used in applications and development of other emerging or re-emerging microbe detection platforms.

White-light scanning interferometry (WLSI) is often used to study the surface profiles and properties of thin films because the strength of the technique lies in its ability to provide fast and high resolution measurements. An innovative attempt is made in this paper to apply WLSI as a time-domain spectroscopic system for localized surface plasmon resonance (LSPR) sensing. A WLSI-based spectrometer is constructed with a breadboard of WLSI in combination with a spectral centroid algorithm for noise reduction and performance improvement. Experimentally, the WLSI-based spectrometer exhibits a limit of detection (LOD) of 1.2 × 10−3 refractive index units (RIU), which is better than that obtained with a conventional UV-Vis spectrometer, by resolving the LSPR peak shift. Finally, the bio-applicability of the proposed spectrometer was investigated using the rs242557 tau gene, an Alzheimer’s and Parkinson’s disease biomarker. The LOD was calculated as 15 pM. These results demonstrate that the proposed WLSI-based spectrometer could become a sensitive time-domain spectroscopic biosensing platform.

This study aims to improve the signal sensitivity of a portable surface plasmon resonance (SPR) sensor system. An organic light emitting diode (OLED) was integrated with a brightness enhancement film (BEF) and a giant birefringent optical (GBO) film as a light source to construct the SPR based on an OLED–BEF–GBO film. A method for calculating the SPR signal by summing the differences in optical intensity at two different wavelengths was used to minimize the effect of the noise error that particularly occurs in a portable SPR device. The experimental results indicated that the limit of detection (LOD) of the SPR using an Au sensing layer has an effective refractive index change of 7.8 × 10−6 RIU. Furthermore, for the SPR using Au/Ag sensing metal layers, an LOD of 3.2 × 10−6 RIU was achieved due to the improved sensitivity and resolution value compared with the use of an Au sensing layer. The use of the SPR device in a bio-affinity assay to test the interaction between goat anti-mouse immunoglobulin G (IgG) and mouse IgG protein achieved a LOD of approximately 40.6 pg/mL.

On the extraordinary journey cruising into the interdisciplinary field of molecular electronics by experimentalists, many of the proposed mechanisms for electron transporting across molecular junctions have been witnessed, such as hopping, direct tunneling, thermionic emission, and field emission. For a newcomer to this research field, the terms of the mechanisms can be confusing. This mini-review is intended to provide a very elementary introduction to the basics of the mechanisms with the help of selected literature examples to make the concept less abstract. In addition to the definition of terminologies used in molecular electronics, the correlation of experimental conditions with the pathways of electron transport is emphasized.

Handling the (AFM) tip: The duration of stable molecular junctions was prolonged using a tactile feedback method in which the operator can sense the force of the AFM tip on the sample surface. The movement of the tip is adjusted accordingly, maintaining a more consistent current (i) and voltage (V), instead of having the tip move at a constant preset speed, as in the conventional setup.

A multiplexed biosensor based on WLSI is capable to measure various gold nanoparticles accompanied by the LSPR extinction spectrum shift simultaneously. In this paper, the multiplex detection can be realized by the WLSI system.

A novel “degree of coherence paired surface plasma wave biosensor” (DOC-PSPWB) is proposed wherein the principle of detection involves the degree of coherence of highly correlated surface plasma waves when these are excited on a metal/dielectric interface within the DOC-PSPWB. Using the sensor, the concentration of total PSA (t-PSA) in a phosphate-buffered saline solution was measured, and a detection limit of 0.015pg/mL was determined experimentally. Finally, the dynamic range of the DOC-PSPWB when used on samples with ultralow molecular concentrations is discussed.

In this study, we applied the developed paired surface plasma waves biosensor (PSPWB) in a dual-channel biosensor for rapid and sensitive detection of swine-origin influenza A (H1N1) virus (S-OIV). In conjunction with the amplitude ratio of the signal and the reference channel, the stability of the PSPWB system is significantly improved experimentally. The theoretical limit of detection (LOD) of the dual-channel PSPWB for S-OIV is 30 PFU/mL (PFU, plaque-forming unit), which was calculated from the fitting curve of the surface plasmon resonance signal with a S-OIV clinical isolate concentration in phosphate-buffered saline (PBS) over a range of 18-1.8 × 10(6) PFU/mL. The LOD is 2 orders of magnitude more sensitive than the commercial rapid influenza diagnostic test at worst and an order of magnitude less sensitive than real-time quantitative polymerase chain reaction (PCR) whose LOD for S-OIV in PBS was determined to be 3.5 PFU/mL in this experiment. Furthermore, under in vivo conditions, this experiment demonstrates that the assay successfully measured S-OIV at a concentration of 1.8 × 10(2) PFU/mL in mimic solution, which contained PBS-diluted normal human nasal mucosa. Most importantly, the assay time took less than 20 min. From the results, the dual-channel PSPWB potentially offers great opportunity in developing an alternative PCR-free diagnostic method for rapid, sensitive, and accurate detection of viral pathogens with epidemiological relevance in clinical samples by using an appropriate pathogen-specific antibody.

In renal transplant patients, immunosuppressive therapy may result in the reactivation of polyomavirus BK (BKV), leading to polyomavirus-associated nephropathy (PVAN), which inevitably causes allograft failure. Since the treatment outcomes of PVAN remain unsatisfactory, early identification and continuous monitoring of BKV reactivation and reduction of immunosuppressants are essential to prevent PVAN development. The present study demonstrated that the developed dual-channel heterodyne-based surface plasmon resonance (SPR) biosensor is applicable for the rapid detection of urinary BKV. The use of a symmetrical reference channel integrated with the poly(ethylene glycol)-based low-fouling self-assembled monolayer to reduce the environmental variations and the nonspecific noise was proven to enhance the sensitivity in urinary BKV detection. Experimentally, the detection limit of the biosensor for BKV detection was estimated to be around 8500 copies/mL. In addition, urine samples from five renal transplant patients were tested to rapidly distinguish PVAN-positive and PVAN-negative renal transplant patients. By virtue of its simplicity, rapidity, and applicability, the SPR biosensor is a remarkable potential to be used for continuous clinical monitoring of BKV reactivation.

In this study, a novel high-throughput biosensor based on metal-enhanced fluorescence technique and harmonic intensity-modulated fluorescence technique was developed and demonstrated to be highly sensitive for the detection of a pancreatic cancer marker, UL16-binding protein 2 (ULBP2), in diluted serum. Experimentally, the biosensor is able to detect ULBP2 at 16-18 pg/mL in 1% BSA-PBS and in 10-fold-diluted human serum. Compared with the limit of detection (LOD) of the conventional enzyme-linked immunosorbent assay (ELISA) method, the LOD of the proposed biosensor for ULBP2 is significantly improved by 100-fold under the same conditions. In addition, the proposed method uses two identical polyclonal antibodies for the sandwich immunoassay, simplifying the experiment in terms of the reagents needed. Consequently, this biosensor is a cost-effective tool for clinical diagnosis. We believe that the proposed high-throughput biosensor has great potential to become a clinical diagnostic tool for the detection of a pancreatic cancer marker in the near future.

Diffuse scattering measurements to determine the changes of glucose concentration in a highly scattering medium are conducted by using an optical heterodyne technique. The heterodyne technique can increase the signal-to-noise ratio (SNR) of the detection amplitude and phase by coherence gating and narrow detection bandwidth. The experimental results showed that a good sensitivity of 0.1% scattering change per mM is observed.

Prostate-specific antigen (PSA) has been reported to be a potential biomarker of breast cancer. Serum PSA of normal women is around 1 pg/mL, which is usually undetectable by current assay methods; thus an ultrasensitive measurement of PSA expression in women's serum is necessary to distinguish normal from malignant breast diseases. To enhance the sensitivity of conventional immunoassay technology for the detection of PSA in sera, we adopted a localized surface plasmon coupled fluorescence fiber-optic biosensor, which combines a sandwich immunoassay with the localized surface plasmon technique. The concentration of total PSA (t-PSA) (from 0.1 to 1000 pg/mL) in phosphate-buffered saline solution and the normalized fluorescence signal exhibit a linear relationship where the correlation coefficient is 0.9574. In addition, the concentration of additional t-PSA in 10-fold-diluted healthly women's serum across a similar range was measured. The correlation coefficient for this measurement is 0.9142. In clinical serum samples, moreover, the experimental results of t-PSA detection show that both the mean value and median of normalized fluorescence signals in the breast cancer group (155.2 and 145.7, respectively) are higher than those in the noncancer group (46.6 and 37.1, respectively). We also examined the receiver operating characteristic curve for t-PSA, and the area under the curve (AUC) is estimated to be 0.9063, the AUC being used to measure the performance of a test to correctly identify diseased and nondiseased subjects.

Measuring the kinetic constants of protein-protein interactions at ultralow concentrations becomes critical in characterizing biospecific affinity, and exploring the feasibility of clinical diagnosis with respect to detection sensitivity, efficiency and accuracy. In this study, we propose a method that can calculate the binding constants of protein-protein interactions in sandwich assays at ultralow concentrations at the pg/mL level, using a localized surface plasmon coupled fluorescence fiber-optic biosensor (LSPCF-FOB). We discuss a two-compartment model to achieve reaction-limited kinetics under the stagnant conditions of the reaction chamber. The association rate constant, dissociation rate constant, and the equilibrium dissociation constant, that is, k(a), k(d), K(D), respectively, of the kinetics of binding between total prostate-specific antigen (t-PSA) and anti-t-PSA at concentrations from 0.1 pg/mL to 1 ng/mL, were measured either in PBS or in human serum. This is the first time that k(a), k(d), and K(D) have been measured at such a low concentration range in a complex sample such as human serum.

In this study, we describe a novel method for analyzing protein-protein binding kinetics at ultra-low concentration (1 pg/mL) using a localized surface plasmon coupled fluorescence fiber-optic biosensor (LSPCF-FOB). The association and dissociation rate constants, ka and kd, respectively, for the binding kinetics of the mouse IgG/ anti-mouse IgG interaction have been calculated to be ka = (5.9928±3.1540)x106 M-1s-1 and kd = (1.0587±0.5572)x10-3 s-1. The theoretical basis of this analytical approach is a rapid-mixing model integrated with a two-compartment model; has been experimentally verified in this study as well. The LSPCF-FOB provides a potentially alternative option for characterizing the interaction of biomolecules at ultra-low concentrations.

In order to enhance the sensitivity of conventional rapid test technique for the detection of swine-origin influenza A (H1N1) viruses (S-OIVs), we used a paired surface plasma waves biosensor (PSPWB) based on SPR in conjunction with an optical heterodyne technique. Experimentally, PSPWB showed a 125-fold improvement at least in the S-OIV detection as compared to conventional enzyme linked immunosorbent assay. Moreover, the detection limit of the PSPWB for the S-OIV detection was enhanced 250-fold in buffer at least in comparison with that of conventional rapid influenza diagnostic test.

In this study, we demonstrated that an amplitude-sensitive paired surface plasma wave biosensor (PSPWB) is capable of real-time detection of prostate-specific antigen (PSA) in diluted human serum without labeling. Experimentally, the detection limit of PSPWB was 8.4 x 10(-9) refractive index unit (RIU) and the PSPWB could measure PSA in a phosphate buffered saline solution from 10 fg/mL ( approximately 300 aM) to 100 pg/mL ( approximately 3 pM) successfully, with demonstration of a linear relationship between PSA concentrations and surface plasmon resonance (SPR) signals. Therefore, results were obtained over a wide dynamic range 5 orders of magnitude for analyte concentration. In addition, the PSPWB successfully detected PSA in diluted human serum as well. These experimental results indicate that the PSPWB is capable of detection with high sensitivity over a wide range by using SPR-based biosensors and has a capability of detecting biological analytes in clinical sample without complicated operating procedures.

Detection of severe acute respiratory syndrome (SARS) coronavirus nucleocapsid protein in human serum using localized surface plasmon coupled fluorescence (LSPCF) fiber-optic biosensor. The detection limit at 1pg/mL in human serum is successfully demonstrated.

Prostate-specific antigen (PSA) in diluted human serum was detected by using a novel amplitude-sensitive paired surface plasma waves biosensor (PSPWB). The detection limit on PSA concentration in diluted human serum at 61pg/mL (2pM) was demonstrated.

In this paper, a novel differential-phase-sensitive surface plasmon resonance biosensor (DP-SPRB) is proposed and developed, in which a two-frequency laser is integrated with a differential amplifier in order to analytically convert the phase modulation into amplitude modulation. With the use of the conventional envelope detection technique, the differential phase is precisely decoded in real time in terms of the demodulated amplitude. In order to verify high detection sensitivity of the DP-SPRB, a sucrose-water solution and glycerin-water solution at low concentrations were both tested, and the experimental results confirm that the detection sensitivity on wt % concentration of the sucrose solution is 0.00001%. Moreover, the real-time monitoring mouse IgG/antimouse IgG interaction shows the minimum concentration of mouse IgG to be at 10 fg/mL. To our knowledge, this is the highest sensitivity ever measured by a surface plasmon resonance biosensor. However, because of the limited dynamic range of DP-SPRB, it can only apply to biomolecule interactions at extremely low concentration.

In this study, we demonstrated that the fiber-optic biosensor based on localized surface plasmon coupled fluorescence (LSPCF) is capable of detecting alpha-fetoprotein (AFP) in human serum. The sensitivity of LSPCF fiber-optic biosensor is not only enhanced but also the specific selectivity is improved since the fluorophores are excited by the localized surface plasmon with high efficiency. Experimentally, this fiber-optic biosensor is able to detect AFP concentration in phosphate buffered saline (PBS) solution from 0.1ng/mL to 100ng/mL whereas the linear relationship between the AFP concentrations and the fluorescence signals is shown. Furthermore, a linear response between the fluorescence signals and the concentrations of AFP in human serum from 2.33ng/mL to 143.74ng/mL is also obtained. As a result, the detection limit of the LSPCF fiber-optic biosensor on AFP detection is comparable with the conventional enzyme-linked immunosorbent assay (ELISA). Additionally, the LSPCF fiber-optic biosensor benefits on inexpensive, disposable and simpler optical geometry that can become a high efficient immunoassay comparable with the conventional ELISA and radioimmunoassay (RIA) clinically.

Conventionally, the detection and characterization of an optical inhomogeneity embedded in turbid media is dependent on the perturbation of diffuse photon density wave (DPDW) and its noise level, which is defined as the signal-to-noise ratio (SNR). In this study, we calculate the limitation of detection and characterization by using diffuse photon-pairs density wave (DPPDW) which is a novel method in studying turbid media. DPPDW is produced by linear polarized photon-pairs (LPPPs) laser beam which experience multiple-scattering events in turbid media. Meanwhile, the fractional amplitude and phase noise in detecting heterodyne signal determine the detection and characterization of DPPDW in a multiple scattering medium. The amplitude attenuation and phase change of heterodyne signal of DPPDW and their SNR analysis are demonstrated and discussed. As a result, we anticipate that the properties of DPPDW depending upon the degree of spatial coherence (DOC) and the degree of polarization (DOP) of LPPPs in turbid media can result in an improvement on detection and then the perturbation of DPPDW produced by an inhomogeneity embedded in a multiple scattering medium is able to be measured.

In this study, a novel heterodyne linear polarization modulation ellipsometer (LPME) is developed. It is based on a linear polarization rotator and is integrated with a common path heterodyne interferometer for ellipsometric parameter measurement. LPME is an amplitude-sensitive interferometric ellipsometer that can not only provide a wider range for its polarization modulation frequency than that of a conventional photometric ellipsometer but also be used for measurement in real time. LPME is also insensitive to laser intensity fluctuations. The independence of the elliptical polarization to the incident laser beam induced by imperfections in the quarter-wave plate in LPME is analyzed.