Seasonal variation of patulous Eustachian tube diagnoses using climatic and national health insurance data.

OBJECTIVES: This study aimed to analyse if there were any associations between patulous Eustachian tube occurrence and climatic factors and seasonality. METHODS: The correlation between the monthly average number of patients diagnosed with patulous Eustachian tube and climatic factors in Seoul, Korea, from January 2010 to December 2016, was statistically analysed using national data sets. RESULTS: The relative risk for patulous Eustachian tube occurrence according to season was significantly higher in summer and autumn, and lower in winter than in spring (relative risk (95 per cent confidence interval): 1.334 (1.267-1.404), 1.219 (1.157-1.285) and 0.889 (0.840-0.941) for summer, autumn and winter, respectively). Temperature, atmospheric pressure and relative humidity had a moderate positive (r = 0.648), negative (r = -0.601) and positive (r = 0.492) correlation with the number of patulous Eustachian tube cases, respectively. CONCLUSION: The number of patulous Eustachian tube cases was highest in summer and increased in proportion to changes in temperature and humidity, which could be due to physiological changes caused by climatic factors or diet trends.

Comparison of patulous Eustachian tube patients with and without a concave defect in the anterolateral wall of the tubal valve.

OBJECTIVE: Patulous Eustachian tube appears to be caused by a concave defect in the anterolateral wall of the tubal valve of the Eustachian tube. This study aimed to compare the clinical features of patulous Eustachian tube patients with or without a defect in the anterolateral wall of the tubal valve. METHODS: Sixty-six patients with a patulous Eustachian tube completed a questionnaire, which was evaluated alongside endoscopic findings of the tympanic membrane, nasal cavity and Eustachian tube orifice. RESULTS: Females were more frequently diagnosed with a patulous Eustachian tube, but the valve defect was more common in males (p = 0.007). The ratio of patulous Eustachian tube patients with or without defects in the anterolateral wall of the tubal valve was 1.6:1. Weight loss in the previous six months and being refractory to conservative management were significantly associated with the defect (p = 0.035 and 0.037, respectively). Symptom severity was significantly higher in patients with the defect. CONCLUSION: Patulous Eustachian tube patients without a defect in the anterolateral wall of the tubal valve can be non-surgically treated more often than those with the defect. Identification of the defect could assist in making treatment decisions for patulous Eustachian tube patients.

Automated real-time detection of drug-resistant Mycobacterium tuberculosis on a lab-on-a-disc by Recombinase Polymerase Amplification.

With the emergence of multi- and extensive-drug (MDR/XDR) resistant Mycobacterium tuberculosis (M. tb), tuberculosis (TB) persists as one of the world's leading causes of death. Recently, isothermal DNA amplification methods received much attention due to their ease of translation onto portable point-of-care (POC) devices for TB diagnosis. In this study, we aimed to devise a simple yet robust detection method for M. tb. Amongst the numerous up-and-coming isothermal techniques, Recombinase Polymerase Amplification (RPA) was chosen for a real-time detection of TB with or without MDR. In our platform, real-time RPA (RT-RPA) was integrated on a lab-on-a-disc (LOAD) with on-board power to maintain temperature for DNA amplification. Sputa collected from healthy volunteers were spiked with respective target M. tb samples for testing. A limit of detection of 102 colony-forming unit per millilitre in 15 min was achieved, making early detection and differentiation of M. tb strains highly feasible in extreme POC settings. Our RT-RPA LOAD platform has also been successfully applied in the differentiation of MDR-TB from H37Ra, an attenuated TB strain. In summary, a quantitative RT-RPA on LOAD assay with a high level of sensitivity was developed as a foundation for further developments in medical bedside and POC diagnostics.

Sample-to-answer on molecular diagnosis of bacterial infection using integrated lab--on--a--disc.

Sepsis by bacterial infection causes high mortality in patients in intensive care unit (ICU). Rapid identification of bacterial infection is essential to ensure early appropriate administration of antibiotics to save lives of patients, yet the present benchtop molecular diagnosis is time-consuming and labor-intensive, which limits the treatment efficiency especially when the number of samples to be tested is extensive. Therefore, we hereby report a microfluidic platform lab-on-a-disc (LOAD) to provide a sample-to-answer solution. Our LOAD customized design of microfluidic channels allows automation to mimic sequential analytical steps in benchtop environment. It relies on a simple but controllable centrifugation force for the actuation of samples and reagents. Our LOAD system performs three major functions, namely DNA extraction, isothermal DNA amplification and real-time signal detection, in a predefined sequence. The disc is self-contained for conducting sample heating with chemical lysis buffer and silica microbeads are employed for DNA extraction from clinical specimens. Molecular diagnosis of specific target bacteria DNA sequences is then performed using a real-time loop-mediated isothermal amplification (RT-LAMP) with SYTO-9 as the signal reporter. Our LOAD system capable of bacterial identification of Mycobacterium tuberculosis (TB) and Acinetobacter baumanii (Ab) with the detection limits 103cfu/mL TB in sputum and 102cfu/mL Ab in blood within 2h after sample loading. The reported LOAD based on an integrated approach should address the growing needs for rapid point-of-care medical diagnosis in ICU.

Dysregulated Serum MiRNA Profile and Promising Biomarkers in Dengue-infected Patients.

OBJECTIVES: Pathological biomarkers and mechanisms of dengue infection are poorly understood. We investigated a new serum biomarker using miRNAs and performed further correlation analysis in dengue-infected patients. METHODS: Expression levels of broad-spectrum miRNAs in serum samples from three patients with dengue virus type 1 (DENV-1) and three healthy volunteers were separately analyzed using miRNA PCR arrays. The expressions of the five selected miRNAs were verified by qRT-PCR in the sera of 40 DENV-1 patients and compared with those from 32 healthy controls. Receiver operating characteristic (ROC) curve and correlation analyses were performed to evaluate the potential of these miRNAs for the diagnosis of dengue infection. RESULTS: MiRNA PCR arrays revealed that 41 miRNAs were upregulated, whereas 12 miRNAs were down-regulated in the sera of DENV-1 patients compared with those in healthy controls. Among these miRNAs, qRT-PCR validation showed that serum hsa-miR-21-5p, hsa-miR-590-5p, hsa-miR-188-5p, and hsa-miR-152-3p were upregulated, whereas hsa-miR-146a-5p was down-regulated in dengue-infected patients compared with healthy controls. ROC curves showed serum hsa-miR-21-5p and hsa-miR-146a-5p could distinguish dengue-infected patients with preferable sensitivity and specificity. Correlation analysis indicated that expression levels of serum hsa-miR-21-5p and hsa-miR-146a-5p were negative and positively correlated with the number of white blood cells and neutrophils, respectively. Functional analysis of target proteins of these miRNAs in silico indicated their involvement in inflammation and cell proliferation. CONCLUSION: Dengue-infected patients have a broad "fingerprint" profile with dysregulated serum miRNAs. Among these miRNAs, serum hsa-miR-21-5p, hsa-miR-146a-5p, hsa-miR-590-5p, hsa-miR-188-5p, and hsa-miR-152-3p were identified as promising serum indicators for dengue infection.

Dysregulated Serum MicroRNA Expression Profile and Potential Biomarkers in Hepatitis C Virus-infected Patients.

OBJECTIVES: Circulating microRNAs (miRNAs) play critical roles in pathogen-host interactions. Aberrant miRNA expression profiles might have specific characteristics for virus strains, and could serve as noninvasive biomarkers for screening and diagnosing infectious diseases. In this study, we aimed to find new potential miRNA biomarkers of hepatitis C virus (HCV) infection. METHODS: Expression levels of broad-spectrum miRNAs in serum samples from 10 patients with HCV viremia and 10 healthy volunteers were analyzed using miRNA PCR arrays. Subsequently, the differential expression of four selected miRNAs (miR-122, miR-134, miR-424-3p, and miR-629-5p) was verified by qRT-PCR in the serum of 39 patients compared with that in 29 healthy controls. Receiver operating characteristic (ROC) curve analysis was performed to evaluate their potential for the diagnosis of HCV infection. RESULTS: miRNA PCR array assays revealed differential expression of 106 miRNAs in sera of HCV patients compared with that in healthy controls. Serum hsa-miR-122, miR-134, miR-424-3p, and miR-629-5p were well identified. The ROC curves showed that miR-122, miR-134, miR-424-3p, and miR-629-5p could distinguish HCV patients with preferable sensitivity and specificity. In addition, Correlation analysis indicated serum miR-122 expression was positive correlation with ALT/AST levels. Functional analysis of target proteins of these miRNAs indicated the involvement of viral replication, inflammation, and cell proliferation. CONCLUSION: HCV patients have a broad 'fingerprint' profile with dysregulated serum miRNAs compared with that in healthy controls. Among these, serum hsa-miR-122, miR-134, miR-424-3p, and miR-629-5p are identified as promising indication factors of the serum miRNA profile of HCV infection. Particularly, miR-122 could be one of serum biomarkers for early pathological process of HCV. However, more miRNA biomarkers and biological functions of these miRNAs require further investigation.

A non-PCR SPR platform using RNase H to detect MicroRNA 29a-3p from throat swabs of human subjects with influenza A virus H1N1 infection.

As in all RNA viruses, influenza viruses change and mutate constantly because their RNA polymerase has no proofreading ability. This poses a serious threat to public health nowadays. In addition, traditional pathogen-based detection methods may not be able to report an infection from an unknown type or a subtype of virus if its nucleotide sequence is not known. Because of these factors, targeting host microRNA signatures may be an alternative to classify infections and distinguish types of pathogens as microRNAs are produced in humans shortly after infection. Although this approach is in its infant stage, there is an urgent need to develop a rapid reporter assay for microRNA for disease control and prevention. As a proof of concept, we report herein for the first time a non-PCR MARS (MicroRNA-RNase-SPR) assay to detect the microRNA miR-29a-3p from human subjects infected with influenza virus H1N1 by surface plasmon resonance (SPR). In our MARS assay, RNase H is employed to specifically hydrolyze the RNA probes immobilized on the gold surface where they hybridize with its cognate target cDNAs miR-29a-3p, where it was formed from reverse transcription with mature miR-29a-3p specific stem-looped primers. After the digestion of the RNA probe by RNase H, the intact cDNA was released from the RNA-DNA hybrid and bound to a new RNA probe for another enzymatic reaction cycle to amplify signals. With assay optimization, the detection limit of our MARS assay for miR-29a-3p was found to be 1 nM, and this new assay could be completed within 1 hour without thermal cycling. This non-PCR assay with high selectivity for mature microRNA provides a new platform for rapid disease diagnosis, quarantine and disease control.

Quantitative detection of eryptosis in human erythrocytes using tunable resistive pulse sensing and annexin-V-beads.

Toxicological assessments of human red blood cells (RBCs) are important in human health because RBCs are the most abundant cell type in our body. Erythrotoxicology testing guidelines using hemolysis have been established as a standard (e.g. by the ASTM International). However, many xenobiotics promote eryptosis (apoptosis in human RBCs) without causing hemolysis. Based on the major features of eryptosis, i.e. cell shrinkage and translocation of phosphatidylserine (PS) to the outer lipid bilayer of the plasma membrane, we report here a novel approach utilizing the quantitative tunable resistive pulse sensing (TRPS) technology, a widely adopted technique for characterizing nanoparticles in the field of nanotechnology, to measure the degree of eryptosis in a non-optical manner. With the TRPS system, we were able to determine PS externalization with microbeads functionalized with annexin-V for PS binding, cell swelling and shrinkage in physiological buffers (cell volume: 86 ± 12 fL) and solutions of different osmolarities with or without apoptotic trigger. After setting these standards, we then evaluated the toxicity of Polyphyllin D (PD), a potential anti-cancer drug that kills more liver cancer cells with multi-drug resistance, in erythrocytes to prove our concept. Data revealed that PD induced PS externalization and shrinkage in RBCs in a dose-dependent manner. Moreover, another feature of eryptosis, as small as 5 fL, was detected thus showing the PD-induced erythrotoxicity in human cells. Taken together, our results indicate that our approach using annexin-V-beads and TRPS is simple, safe and convenient, using only a small volume (35 µL) to evaluate the erythrotoxicity of xenobiotics.

The Essential Component in DNA-Based Information Storage System: Robust Error-Tolerating Module.

The size of digital data is ever increasing and is expected to grow to 40,000 EB by 2020, yet the estimated global information storage capacity in 2011 is <300 EB, indicating that most of the data are transient. DNA, as a very stable nano-molecule, is an ideal massive storage device for long-term data archive. The two most notable illustrations are from Church et al. and Goldman et al., whose approaches are well-optimized for most sequencing platforms - short synthesized DNA fragments without homopolymer. Here, we suggested improvements on error handling methodology that could enable the integration of DNA-based computational process, e.g., algorithms based on self-assembly of DNA. As a proof of concept, a picture of size 438 bytes was encoded to DNA with low-density parity-check error-correction code. We salvaged a significant portion of sequencing reads with mutations generated during DNA synthesis and sequencing and successfully reconstructed the entire picture. A modular-based programing framework - DNAcodec with an eXtensible Markup Language-based data format was also introduced. Our experiments demonstrated the practicability of long DNA message recovery with high error tolerance, which opens the field to biocomputing and synthetic biology.

Monitoring bacterial growth using tunable resistive pulse sensing with a pore-based technique.

A novel bacterial growth monitoring method using a tunable resistive pulse sensor (TRPS) system is introduced in this study for accurate and sensitive measurement of cell size and cell concentration simultaneously. Two model bacterial strains, Bacillus subtilis str.168 (BSU168) and Escherichia coli str.DH5α (DH5α), were chosen for benchmarking the growth-monitoring performance of the system. Results showed that the technique of TRPS is sensitive and accurate relative to widely used methods, with a lower detection limit of cell concentration measurement of 5 × 105 cells/ml; at the same time, the mean coefficient of variation from TRPS was within 2 %. The growth of BSU168 and DH5α in liquid cultures was studied by TRPS, optical density (OD), and colony plating. Compared to OD measurement, TRPS-measured concentration correlates better with colony plating (R = 0.85 vs. R = 0.72), which is often regarded as the gold standard of cell concentration determination. General agreement was also observed by comparing TRPS-derived cell volume measurements and those determined from microscopy. We have demonstrated that TRPS is a reliable method for bacterial growth monitoring, where the study of both cell volume and cell concentration are needed to provide further details about the physical aspects of cell dynamics in real time.

Mitochondrial toxin betulinic acid induces in vitro eryptosis in human red blood cells through membrane permeabilization.

Betulinic acid (BA), a compound isolated from the bark of white birch (Betula pubescens), was reported to induce apoptosis in many types of cancer through mitochondrial dysfunction with low side effects in normal cells. Because of these features, BA is regarded as a potential anti-cancer agent. However, the effect of BA on the induction of cell death in human erythrocytes remains unknown. Given that BA is a mitochondrial toxin and mitochondria are the central cell death regulator, we hypothesized that BA is unable to elicit apoptosis (also known as eryptosis or erythroptosis) in human erythrocytes devoid of mitochondria. This study therefore tried to determine the in vitro effect of BA on the induction of eryptosis/erythroptosis. Contrary to our prediction, BA caused phosphatidylserine externalization, increase in cellular Ca(2+) ion concentration ([Ca(2+)]i) and eryptosis/erythroptosis in human erythrocytes with a lethal dose larger than that in cancer lines. Mechanistically, the rise of [Ca(2+)]i seems not to be the only key mediator in the BA-mediated eryptosis/erythroptosis because depletion of external Ca(2+) and use of Ca(2+) channels blockers could not eliminate the BA's effect. Also, BA was able to elicit discocyte-echinocyte transformation and release calcein from the RBC ghosts in a way similar to digitonin through membrane permeabilization. Collectively, we report here for the first time that BA induced eryptosis/erythroptosis in human erythrocytes through Ca(2+) loading and membrane permeabilization.

An aptamer-based bio-barcode assay with isothermal recombinase polymerase amplification for cytochrome-c detection and anti-cancer drug screening.

Based on a recently reported ultra-sensitive bio-barcode (BBC) assay, we have developed an aptamer-based bio-barcode (ABC) alternative to detect a cell death marker cytochrome-c (Cyto-c) and its subsequent application to screen anti-cancer drugs. Aptamer is a short single-stranded DNA selected from a synthetic DNA library by virtue of its high binding affinity and specificity to its target based on its unique 3D structure from the nucleotide sequence after folding. In the BBC assay, an antigen (Ag) in analytes is captured by a micro-magnetic particle (MMP) coated with capturing antibodies (Abs). Gold nanoparticles (NPs) with another recognition Ab against the same target and hundreds of identical DNA molecules of known sequence are subsequently added to allow the formation of sandwich structures ([MMP-Ab1]-Ag-[Ab2-NP-DNA]). After isolating the sandwiches by a magnetic field, the DNAs hybridized to their complementary DNAs covalently bound on the NPs are released from the sandwiches after heating. Acting as an Ag identification tag, these bio-barcode DNAs with known DNA sequence are then amplified by polymerase chain reaction (PCR) and detected by fluorescence. In our ABC assay, we employed a Cyto-c-specific aptamer to substitute both the recognition Ab and barcode DNAs on the NPs in the BBC assay; and a novel isothermal recombinase polymerase amplification for the time-consuming PCR. The detection limit of our ABC assay for the Cyto-c was found to be 10 ng/mL and this new assay can be completed within 3h. Several potential anti-cancer drugs have been tested in vitro for their efficacy to kill liver cancer with or without multi-drug resistance.

An integrated lab-on-a-disc for automated cell-based allergen screening bioassays.

We have utilized various valving scheme to leverage purely rotation-regulated flow control to enable comprehensive cell-based bioassays (CBBs) on centrifuge-based lab-on-a-disc (LOAD). A LOAD has been developed to examine allergic degranulation from live basophils for allergens screening for the first time, which can also be adjusted to suit a wide range of CBBs. In this system, controlled allergic reaction together with mediator separation from basophils using siphon valving and centrifugal sedimentation are realized inside microstructured network. The entire degranulation analysis process including on-demand release of samples, reaction and degranulation, allergic mediator separation and detection is executed in an automatic sequence within a single run. To validate our cell-based approach, detection of degranulation mediated by known secretagagues, ionomycin or chemotatic peptide formyl-methionine-leucine-pheylalanine (fMLP), is first demonstrated. Further experiments using real allergens house dust mite protein (Der p1) and its corresponding human serum IgE also show positive results. The overall efficiency of the assay is 80.6%, which is comparable to other conventional methods. With 4 identical units on a disc running in a parallel format, the device offers the possibility of single-step, multiplexed allergens screening. The device is capable of reporting a result within 30 min. It has many desirable merits including fast and multiplexed analysis, low cost, single-step operation, minimal sample volume, less discomfort and most importantly increased safety as patients are no longer susceptible to possible anaphylactic shock reactions induced by the common skin-prick-test. The flexibility of the flow control within the device makes it suitable to a wide range of CBBs.

Polyphyllin D induces apoptosis in human erythrocytes through Ca²âº rise and membrane permeabilization.

Polyphyllin D (PD) is a potent anticancer agent isolated from a traditional medicinal herb Paris polyphylla that has been used in China for many years to treat cancer. PD is not a substrate of p-glycoprotein, and it can bypass the multi-drug resistance in cancer cell line R-HepG2. However, the effect of PD on the induction of cell death in human erythrocytes remains unknown. Given that PD is a small molecule that can depolarize the mitochondrial membrane potential and release apoptosis-inducing factor (AIF) in isolated mitochondria, we hypothesized that the apoptogenic effect of PD in human erythrocytes devoid of mitochondria would be minimal. This study therefore tried to evaluate the in vitro effect of PD on hemolysis and apoptosis in human erythrocytes. Apoptosis in human red blood cells (RBCs), also known as eryptosis or erythroptosis, after PD treatment was determined by flow cytometry and confocal microscopy for the phosphatidyl-serine externalization and other apoptosis feature events. False to our prediction, PD caused hemolysis and eryptosis/erythroptosis in human RBCs. Mechanistically, elevation in the cytosolic Ca²âº ion level seems to be a key but not the only mediator in the PD-mediated eryptosis/erythroptosis because depletion of the external Ca²âº could not eliminate the PD effect. Also, PD was able to permeabilize the membrane of RBC ghosts in a way similar to digitonin. Taken together, we report here for the first time the toxicity of PD in human RBCs as well as its underlying mechanism for the hemolysis and eryptosis/erythroptosis.

Phase sensitive SPR sensor for wide dynamic range detection.

Phase detection has been utilized to enhance the sensitivity of surface plasmon resonance (SPR) sensors for a long time. However, an inherent drawback for phase sensitive SPR sensors are their limited dynamic range, which has greatly hindered wide applications of such sensors. In this Letter, a design combining phase detection and angular interrogation has been proposed to provide an SPR sensor with both high sensitivity and wide dynamic range. As a result, a resolution of 2.2×10-7 RIU with a dynamic range of over 0.06 RIU has been achieved simultaneously. An added advantage of this design is the flexibility for sensitivity and dynamic range adjustment.

Differential spectral phase interferometry for wide dynamic range surface plasmon resonance biosensing.

We introduce a novel wide dynamic range phase-sensitive surface plasmon resonance (SPR) biosensor based on differential spectral interferometry. Superseding conventional spectroscopic approach where only the SPR dip is monitored, our system acquires the spectral phase information of the entire electromagnetic field that undergoes SPR transformation. Since the SPR-induced phase change is highly wavelength specific with fixed incident angle, ultra-high sensitivity achievable through phase-sensitive detection, as reported herein, is maintained continuously across the spectral domain in response to refractive index changes. Our system has demonstrated a detection limit of 2.2×10(-7) in terms of refractive index unit (RIU) using standard single-layer gold surface. In terms of biosensing performance, the estimated detection sensitivity obtained from bovine serum albumin (BSA) antibody-antigen binding experiments is 0.5 ng ml(-1).

Aptamer-based bio-barcode assay for the detection of cytochrome-c released from apoptotic cells.

The recently developed bio-barcode (BBC) assay using polymerase chain reaction (PCR) to generate signals has been shown to be an extraordinarily sensitive method to detect protein targets. The BBC assay involves a magnetic microparticle (with antibody to capture the target of interest) and gold nanoparticle (with recognition antibody and thiolated single-stranded barcode DNAs) to form a sandwich around the target. The concentration of target is determined by the amount of barcode DNA released from the nanoparticles. Here we describe a modification using aptamers to substitute the gold nanoparticles for the BBC assay. In this study, we isolated a 76-mer monoclonal aptamer against cytochrome-c (cyto-c) and this single-stranded DNA in defined 3D structure for cyto-c was used in the BBC assay for both recognition and readout reporting. After magnetic separation, the aptamer was amplified by PCR and this aptamer-based barcode (ABC) assay was sensitive enough to detect the cyto-c in culture medium released from the apoptotic cells after drug treatment at the picomolar level. When compared to the conventional cyto-c detection by Western blot analysis, our ABC assay is sensitive, and time for the detection and quantification with ready-made probes was only 3 h.

Real-time protein biosensor arrays based on surface plasmon resonance differential phase imaging.

This paper reports the application of differential phase surface plasmon resonance (SPR) imaging in two-dimensional (2D) protein biosensor arrays. Our phase imaging approach offers a distinct advantage over the conventional angular SPR technique in terms of utilization efficiency of optical sensor elements in the imaging device. In the angular approach, each biosensor site in the biosensor array requires a linear array of optical detector elements to locate the SPR angular dip. The maximum biosensor density that a two-dimensional imaging device can offer is a one-dimensional SPR biosensor array. On the other hand, the phase-sensitive SPR approach captures data in the time domain instead of the spatial domain. It is possible that each pixel in the captured interferogram represents one sensor site, thus offering high-density two-dimensional biosensor arrays. In addition, our differential phase approach improves detection resolution through removing common-mode disturbances. Experimental results demonstrate a system resolution of 8.8 x 10(-7)RIU (refractive index unit). Real-time monitoring of bovine serum albumin (BSA)/anti-BSA binding interactions at various concentration levels was achieved using a biosensor array. The detection limit was 0.77 microg/ml. The reported two-dimensional SPR biosensor array offers a real-time and non-labeling detection tool for high-throughput protein array analysis. It may find promising applications in protein therapeutics, drug screening and clinical diagnostics.

Polyphyllin D induces mitochondrial fragmentation and acts directly on the mitochondria to induce apoptosis in drug-resistant HepG2 cells.

We previously showed that polyphyllin D (PD) produced a stronger apoptotic effect in R-HepG2 with multi-drug resistance (MDR) than that in its parent HepG2 cells without MDR. In this study, PD was found to elicit mitochondrial fragmentation in live cells by using total internal reflection fluorescence microscopy (TIRFM). When mitochondria were isolated and treated directly with PD, a stronger swelling, deeper transmembrane depolarization, and more apoptosis-inducing factor (AIF) release were observed from the mitochondria of R-HepG2 than that of HepG2. These observations suggest that PD is a potent anti-cancer agent that bypasses MDR and elicits apoptosis via mitochondrial injury.

Improving the sensitivity limit of surface plasmon resonance biosensors by detecting mixed interference signals.

We demonstrate that the sensitivity limit of intensity-based surface plasmon resonance (SPR) biosensors can be enhanced when we combine the effects of the phase and amplitude contributions instead of detecting the amplitude variation only. Experimental results indicate that an enhancement factor of as much as 20 times is achievable, yet with no compromise in measurement dynamic range. While existing SPR biosensor systems are predominantly based on the angular scheme, which relies on detecting intensity variations associated with amplitude changes only, the proposed scheme may serve as a direct system upgrade approach for these systems. The new measurement scheme may therefore lead to a strong impact in the design of SPR biosensors.