Polydopamine-modified konjac glucomannan scaffold with sustained release of vascular endothelial growth factor to promote angiogenesis.

The fabrication of scaffolds capable of the sustained release of the vascular endothelial growth factor (VEGF) to promote angiogenesis for a long time remains a challenge in tissue engineering. Here, we report a facile approach for effectively fabricating a bioactive scaffold that gradually releases VEGF to promote angiogenesis. The scaffold was fabricated by coating polydopamine (PDA) on a konjac glucomannan (KGM) scaffold, followed by the surface immobilization of VEGF with PDA. The resulting VEGF-PDA/KGM scaffold, with a porous and interconnected microstructure (392 µm pore size with 84.80 porosity), combined the features of long-term biodegradability (10 weeks with 51 % degradation rate), excellent biocompatibility, and sustained VEGF release for up to 21 days. The bioactive VEGF-PDA/KGM scaffold exhibited multiple angiogenic activities over time, as confirmed by in vivo and in vitro experiments. For example, the scaffold significantly promoted the attachment and proliferation of human umbilical vein endothelial cells and the formation of vascular tubes in vitro. Moreover, the in vivo results demonstrated the formation and maturation of blood vessels after subcutaneous implantation in rats for four weeks. This promising strategy is a feasible approach for producing bioactive materials that can induce angiogenesis in vivo. These findings provide a new avenue for designing and fabricating biocompatible and long-term biodegradable scaffolds for sustained VEGF release to facilitate angiogenesis.

Brain Image Segmentation for Ultrascale Neuron Reconstruction via an Adaptive Dual-Task Learning Network.

Accurate morphological reconstruction of neurons in whole brain images is critical for brain science research. However, due to the wide range of whole brain imaging, uneven staining, and optical system fluctuations, there are significant differences in image properties between different regions of the ultrascale brain image, such as dramatically varying voxel intensities and inhomogeneous distribution of background noise, posing an enormous challenge to neuron reconstruction from whole brain images. In this paper, we propose an adaptive dual-task learning network (ADTL-Net) to quickly and accurately extract neuronal structures from ultrascale brain images. Specifically, this framework includes an External Features Classifier (EFC) and a Parameter Adaptive Segmentation Decoder (PASD), which share the same Multi-Scale Feature Encoder (MSFE). MSFE introduces an attention module named Channel Space Fusion Module (CSFM) to extract structure and intensity distribution features of neurons at different scales for addressing the problem of anisotropy in 3D space. Then, EFC is designed to classify these feature maps based on external features, such as foreground intensity distributions and image smoothness, and select specific PASD parameters to decode them of different classes to obtain accurate segmentation results. PASD contains multiple sets of parameters trained by different representative complex signal-to-noise distribution image blocks to handle various images more robustly. Experimental results prove that compared with other advanced segmentation methods for neuron reconstruction, the proposed method achieves state-of-the-art results in the task of neuron reconstruction from ultrascale brain images, with an improvement of about 49% in speed and 12% in F1 score.

Who can benefit from postmastectomy radiotherapy among HR+/HER2- T1-2 N1M0 breast cancer patients? An explainable machine learning mortality prediction based approach.

Objective: The necessity of postmastectomy radiotherapy(PMRT) for patients with HR+/HER2 T1-2 N1M0 breast cancer remains controversial. We want to use explainable machine learning to learn the feature importance of the patients and identify the subgroup of the patients who may benefit from the PMRT. Additionally, develop tools to provide guidance to the doctors. Methods: In this study, we trained and validated 2 machine learning survival models: deep learning neural network and Cox proportional hazard model. The training dataset consisted of 35,347 patients with HR+/HER2- T1-2 N1M0 breast cancer who received mastectomies from the SEER database from 2013 to 2018. The performance of survival models were assessed using a concordance index (c-index).Then we did subgroup analysis to identify the subgroup who could benefit from PMRT. We also analyzed the global feature importance for the model and individual feature importance for individual survival prediction. Finally, we developed a Cloud-based recommendation system for PMRT to visualize the survival curve of each treatment plan and deployed it on the Internet. Results: A total of 35,347 patients were included in this study. We identified that radiotherapy improved the OS in patients with tumor size >14mm and age older than 54: 5-year OS rates of 91.9 versus 87.2% (radio vs. nonradio, P <0.001) and cohort with tumor size >14mm and grade worse than well-differentiated, 5-year OS rates of 90.8 versus 82.3% (radio vs. nonradio, P <0.001).The deep learning network performed more stably and accurately in predicting patients survival than the random survival forest and Cox proportional hazard model on the internal test dataset (C-index=0.776 vs 0.641) and in the external validation(C-index=0.769 vs 0.650).Besides, the deep learning model identified several key factors that significantly influence patient survival, including tumor size, examined regional nodes, age at 45-49 years old and positive regional nodes (PRN). Conclusion: Patients with tumor size >14mm and age older than 54 and cohort with tumor size >14mm and grade worse than well-differentiated could benefit from the PMRT. The deep learning network performed more stably and accurately in predicting patients survival than Cox proportional hazard model on the internal test. Besides, tumor size, examined regional nodes, age at 45-49 years old and PRN are the most significant factors to the overall survival (OS).

Co-existing pericardial and pleural malignant mesothelioma responding well to nedaplatin and pemetrexed: a case report.

Background: Malignant mesothelioma (MM) is a rare cancer with poor prognosis. It is less common that two serosal cavities are involved when the patient seeks medical attention firstly. The current first-line chemotherapy for advanced MM is a combination with cisplatin and pemetrexed. However, nedaplatin, a second-generation platinum-based antitumor agent, has the similar therapeutic effects as cisplatin but lower toxicity and higher water solubility. To our knowledge, this is the first case of co-existing pericardial and pleural MM treated with nedaplatin and pemetrexed and responding well. Case Description: A 33-year-old woman, who had worked in a kiln for more than 10 years, suffered from dyspnea and chest tightness for 6 days. Chest computed tomography (CT) showed a massive pericardial effusion. She was diagnosed tuberculous pericarditis and received 6 months antituberculosis treatment (rifampicin, isoniazide, pyrazinamide, ethambutol). But it was ineffective and she was re hospitalized again due to massive pleural effusion and pericardial effusion. She was diagnosed with co-existing pericardial and pleural MM finally based on pleural biopsy and cytology of pericardial effusion. She was responding well excitedly to chemotherapy with nedaplatin and pemetrexed with high tolerance. Bone marrow toxicity or recurrent massive pericardial or pleural effusion were not observed during chemotherapy. However, she gave up chemotherapy and has survived for 22 months, from the onset symptoms. Conclusions: In terms of clinical tolerance and less adverse reactions, we suggest that chemotherapy of nedaplatin with pemetrexed may be a more appropriate treatment in advanced MM. Further clinical trials are warrant.

Association between anticholinergic medication uses and the risk of pneumonia in elderly adults: a meta-analysis and systematic review.

OBJECTIVE: To conduct a meta-analysis and systematic review on the association between anticholinergic medication uses and the risk of pneumonia in elderly adults. MATERIALS AND METHODS: Medical databases were searched included PubMed, Web of Science, EBSCO and Google Scholar (up to December 7, 2022). Studies evaluating association between anticholinergic medication uses and the risk of pneumonia in elderly adults were included. Studies without available data were excluded. We made meta-analysis by using adjusted odds ratio (aOR) with 95% confidence intervals (CIs) from random-effects model. The risk of bias was assessed using ROBINS-I tool and statistical heterogeneity using the I2 statistic. Registration: INPLASY202330070. RESULTS: A total of six studies with 107,012 participants were included. Meta-analysis results showed that anticholinergic medication uses was related with an increased risk of pneumonia (aOR = 1.59; 95%CI, 1.32-1.92) and stroke-associated pneumonia (aOR = 2.02; 95%CI, 1.76-2.33). Moreover, risk estimates of pneumonia for high-potency anticholinergics (aOR = 1.96; 95%CI, 1.22-3.14) were higher than those for low-potency anticholinergics (aOR = 1.58; 95%CI, 1.27-1.97). And increased risk of pneumonia was associated with the anticholinergic medication uses within 30 days (aOR = 2.13; 95%CI, 1.33-3.43), within 90 days (aOR = 2.03; 95%CI, 1.26-3.26) and chronic use (aOR = 1.65; 95%CI, 1.09-2.51). CONCLUSIONS: The risk of pneumonia is increased in elderly adults with anticholinergic medication, especially with higher-potency anticholinergic drugs and in the initiation phase of anticholinergic medication. Clinicians should monitor their use in older patients carefully, especially when the pneumonia-related signs and symptoms are identified.

Anticholinergic medication could increase the risk of pneumonia in elderly adults.The risk of pneumonia was higher in the initiation phase of anticholinergic medication and when the older patients was medicated with higher-potency anticholinergic drugs.Clinicians should monitor anticholinergic drugs use in older patients carefully, especially when the pneumonia-related signs and symptoms are identified.

Calcium alginate gels-functionalized polyurethane foam decorated with silver nanoparticles as an antibacterial agent for point-of-use water disinfection.

This paper reports the preparation of calcium alginate gels-functionalized PUF decorated with AgNPs (CA/PUF@Ag) by in situ reduction of Ag+ ions to form AgNPs with weakly reducing glycerol in CA/PUF composite. The water-adsorbing capacity, chemical structure, crystalline nature, elemental composition and morphologies of the composite were characterized. The Ag release behavior of CA/PUF@Ag was investigated. The inhibition zone test, time-dependent co-culture assay, test tube test, and antibacterial filtration experiment with Escherichia coli as an indicator of bacterial contamination were conducted to explore the antimicrobial efficacy. Results indicated that the CA/PUF@Ag prepared at 0.25 % w/v of SA could absorb more water with a higher swelling ratio of 8.0 g/g than that of PUF@Ag (6.0 g/g), which was subsequently squeezed by minimal pressure stimuli. The CA/PUF@Ag had a larger initial AgNPs loading amount (8.48 mg/g), lower Ag release concentration (44.35 µg/L) and lower Ag release rate (0.27 %) after 14 days tests than those of PUF@Ag (7.93 mg/g, 80.87 µg/L and 0.60 % respectively). The CA/PUF@Ag was highly reusable because bacterial cells in the squeezed water recovered from the composite were completely inactivated over five cycles of operation, and exhibited good antibacterial efficacy as an antibacterial filter in a flow test.

Biological Application of Novel Biodegradable Cellulose Composite as a Hemostatic Material.

Degradable hemostatic materials have unique advantages in reducing the amount of bleeding, shortening the surgical operation time, and improving patient prognosis. However, none of the current hemostatic materials are ideal and have disadvantages. Therefore, a novel biodegradable cellulose-based composite hemostatic material was prepared by crosslinking sodium carboxymethyl cellulose (CCNa) and hydroxyethyl cellulose (HEC), following an improved vacuum freeze-drying method. The resulting cellulose composite material was neutral in pH and spongy with a density of 0.042 g/cm3, a porosity of 77.68%, and an average pore size of 13.45 µm. The composite's compressive and tensile strengths were 0.1 MPa and 15.2 MPa, respectively. Under in vitro conditions, the composites were degraded gradually through petite molecule stripping and dissolution, reaching 96.8% after 14 days and 100% degradation rate at 21 days. When implanted into rats, the degradation rate of the composite was slightly faster, reaching 99.7% in 14 days and 100% in 21 days. Histology showed a stable inflammatory response and no evidence of cell degeneration, necrosis, or abnormal hyperplasia in the tissues around the embedded material, indicating good biocompatibility. In the hemorrhagic liver model, the time to hemostasis and the total blood loss in the cellulose composite group was significantly lower than in the medical gauze group and the blank control group (P < 0.05). These data indicate that the novel cellulose composite is a promising implantable hemostatic material in clinical settings.

Mesenchymal Stem Cells (MSCs) in Targeted Drug Delivery: Literature Review and Exploratory Data on Migrating and Differentiation Capacities of Bone MSCs into Hepatic Progenitor Cells.

BACKGROUND AND OBJECTIVE: Mesenchymal stem cells (MSCs), particularly bone MSCs (BMSCs) offer great potentials for targeted therapeutic applications owing to their migratory and differentiation capacities. Significant advances have been achieved in the differentiation of hepatocyte or hepatocyte-like cells both in vitro and in vivo. However, there is limited knowledge on the differentiation of BMSCs into bipotential hepatic progenitor cells or cholangiocyte. This study reviews the potentials and advances in using MSCs as vehicles for targeted drug delivery and proposes a new method for the induction of differentiation in rat BMSCs into hepatic progenitor cells in vitro and assesses the differential and migratory capacities. METHODS: The BMSCs of Sprague Dawley (SD) rats were harvested from the femur and the tibiae of the rats. After isolation and culturing, BMSCs from Passage 1 were used for the study. The in vitro differentiation of the hepatic progenitor cells was performed using a 2-step induction approach after 5-day serum deprivation from the BMSCs and culturing in Dulbecco's modified eagle medium. Spontaneous in vitro differentiation of BMSCs was examined in the absence of growth factors for 15 days as control treatment. Hepatocytes differentiation was achieved by exposing the culture to collagen type I-coated plates. Cholangiocytes differentiation was achieved with replating the BMC-HepPCs on a layer of Matrigel. Immunofluorescence was conducted on twelve-well plates to determine cell differentiations. Real-Time Quantitative Reverse Transcription PCR (qRTPCR) was used to determine the total RNA extracted using the Trizol LS reagent. In the hepatocyte differentiation group, after periodic acid-schiff (PAS) staining for glycogen, inverted microscope was used to determine differentiations and undifferentiated BMC-HepPCs served as controls. The amount of low-density lipoprotein (LDL) uptake by the BMSCs-derived hepatocytes was assessed using fluorescence microscopy. The secretion of rat albumin was quantified using a quantitative ELISA kit. RESULTS: Differentiation induction is indicative of the sequential supplementation of sodium butyrate and cytokines, which are involved in the embryonic development of the mammalian liver. Hepatic progenitor cells, derived from bone marrow, can be differentiated bidirectionally in vitro into both hepatocyte and cholangiocyte cell-lines. The differentiated cells, including hepatic progenitor cells, hepatocytes, and bile duct-like cells, were identified and analyzed at mRNA and protein levels. CONCLUSION: Our findings show that BMSCs can be utilized as novel bipotential hepatic progenitor cells and thereby for hepatobiliary disease treatment or hepatobiliary tissue-engineering.

[Effects and significance of methacholine bronchial provocation tests and salbutamol bronchial dilation test on measurements of fractional exhaled nitric oxide in patients with asthma].

OBJECTIVE: To study the effects and significance of methacholine (Mch) bronchial provocation tests and salbutamol bronchial dilation test on measurements of fractional exhaled nitric oxide (FeNO) in patients with asthma. METHODS: This was a prospective study conducted between November 2014 and August 2015. A total of 135 patients with asthma visiting the respiratory clinic of Zhujiang Hospital were enrolled. The patients received either Mch bronchial provocation test or salbutamol bronchial dilation test based on their FEV1/FVC values and cooperative degree. Mch bronchial provocation test was performed by using Astograph Jupiter-21 (Astograh group) or APS-Pro airway reaction testing apparatus (APS group), and salbutamol bronchial dilation test was performed by using Jaeger spirometer (Dilation group). We compared the differences between FeNO values measured before examinations (Pre-FeNO) and 5 min after completion of these examinations (Post-FeNO). RESULTS: The geometric mean of Pre-FeNO and Post-FeNO was 28.07 ppb and 24.08 ppb respectively in the Astograh group, with a significant decrease of the FeNO value after the examination (Z=-3.093, P=0.002). A significant difference between Pre-FeNO and Post-FeNO was found in patients who had positive provocation results in the Astograh group (Z=-2.787, P=0.005), but not in the patients with negative results (Z=-1.355, P=0.176). The geometric mean of FeNO in the APS group decreased significantly from 27.95 ppb to 23.15 ppb after the examination was completed (Z=-5.170, P=0.000); both in patients with positive saline or Mch provocation results and in patients with negative provocation results, the differences between Pre-FeNO and Post-FeNO in the APS group being significant (Z=-2.705, -3.709, -2.371, P=0.002, 0.000, 0.018). No difference of FeNO change(ΔFeNO) was observed between the 2 Mch bronchial provocation test groups (U<918.000, P=0.117). The geometric mean of Pre-FeNO was 36.74 ppb and that of Post-FeNO was 34.79 ppb in the Dilation group; the difference being not significant (Z=-1.281, P=0.200). CONCLUSIONS: Our results confirm that salbutamol bronchial dilation test has minor effect on the measurement of FeNO, but Mch bronchial provocation tests can significantly decrease measured FeNO value in patients with asthma, and therefore Post-FeNO values should be interpreted with caution.

The interaction affinity between vascular cell adhesion molecule-1 (VCAM-1) and very late antigen-4 (VLA-4) analyzed by quantitative FRET.

Very late antigen-4 (VLA-4), a member of integrin superfamily, interacts with its major counter ligand vascular cell adhesion molecule-1 (VCAM-1) and plays an important role in leukocyte adhesion to vascular endothelium and immunological synapse formation. However, irregular expressions of these proteins may also lead to several autoimmune diseases and metastasis cancer. Thus, quantifying the interaction affinity of the VCAM-1/VLA-4 interaction is of fundamental importance in further understanding the nature of this interaction and drug discovery. In this study, we report an 'in solution' steady state organic fluorophore based quantitative fluorescence resonance energy transfer (FRET) assay to quantify this interaction in terms of the dissociation constant (Kd). We have used, in our FRET assay, the Alexa Fluor 488-VLA-4 conjugate as the donor, and Alexa Fluor 546-VCAM-1 as the acceptor. From the FRET signal analysis, Kd of this interaction was determined to be 41.82 ± 2.36 nM. To further confirm our estimation, we have employed surface plasmon resonance (SPR) technique to obtain Kd = 39.60 ± 1.78 nM, which is in good agreement with the result obtained by FRET. This is the first reported work which applies organic fluorophore based 'in solution' simple quantitative FRET assay to obtain the dissociation constant of the VCAM-1/VLA-4 interaction, and is also the first quantification of this interaction. Moreover, the value of Kd can serve as an indicator of abnormal protein-protein interactions; hence, this assay can potentially be further developed into a drug screening platform of VLA-4/VCAM-1 as well as other protein-ligand interactions.

Ultrasensitive biosensors using enhanced Fano resonances in capped gold nanoslit arrays.

Nanostructure-based sensors are capable of sensitive and label-free detection for biomedical applications. However, plasmonic sensors capable of highly sensitive detection with high-throughput and low-cost fabrication techniques are desirable. We show that capped gold nanoslit arrays made by thermal-embossing nanoimprint method on a polymer film can produce extremely sharp asymmetric resonances for a transverse magnetic-polarized wave. An ultrasmall linewidth is formed due to the enhanced Fano coupling between the cavity resonance mode in nanoslits and surface plasmon resonance mode on periodic metallic surface. With an optimal slit length and width, the full width at half-maximum bandwidth of the Fano mode is only 3.68 nm. The wavelength sensitivity is 926 nm/RIU for 60-nm-width and 1,000-nm-period nanoslits. The figure of merit is up to 252. The obtained value is higher than the theoretically estimated upper limits of the prism-coupling SPR sensors and the previously reported record high figure-of-merit in array sensors. In addition, the structure has an ultrahigh intensity sensitivity up to 48,117%/RIU.

Dynamic monitoring of mechano-sensing of cells by gold nanoslit surface plasmon resonance sensor.

We demonstrated a real-time monitoring of live cells upon laminar shear stress stimulation via surface plasmon resonance (SPR) in gold nanoslit array. A large-area gold nanostructure consisted of 500-nm-period nanoslits was fabricated on a plastic film using the thermal-annealed template-stripping method. The SPR in the gold nanoslit array provides high surface sensitivity to monitor cell adhesion changes near the sensor surface. The human non-small cell lung cancer (CL1-0), human lung fibroblast (MRC-5), and human dermal fibroblast (Hs68) were cultured on the gold nanoslits and their dynamic responses to laminar shear stress were measured under different stress magnitudes from 0 to 30 dyne/cm(2). Cell adhesion was increased in CL1-0 under shear flow stimulation. No adhesion recovery was observed after stopping the flow. On the other hand, MRC-5 and Hs68 decreased adhesion and recovered from the shear stress. The degree of recovery was around 70% for MRC-5. This device provides dynamic study and early detection of cell adhesion changes under shear flow conditions.

The effect of acidic pH on the inhibitory efficacy of peptides against the interaction ICAM-1/LFA-1 studied by surface plasmon resonance (SPR).

Synthetic peptides have been developed for therapeutic applications for decades. The therapeutic efficacy often depends not only on the stabilization of the peptides but also on their binding specificity and affinity to the target molecules to interfere with designated molecular interaction. In this study, the binding affinity of human intercellular adhesion molecule 1 (ICAM-1) chimera and leukocyte function-associated antigen-1 (LFA-1) derived peptides was measured by surface plasmon resonance (SPR) detection, and the results were compared with that of the interaction (of ICAM-1) with the LFA-1 whole protein. To mimic diverse pathological situations in vivo where a low pH has been reported, we studied pH regulated binding affinity of ICAM-1/LFA-1 at pH 7.4, 6.5, and 4.0 without and with magnesium ion. We have found that the binding affinity of LFA-1 whole protein and ICAM-1 increases significantly as the environmental pH decreases, regardless of the absence or the presence of magnesium ion. The affinity of different (LFA-1) derived peptides also depends on the pH, although in all cases the peptides retain its ability to inhibit ICAM-1/LFA-1 interaction. The biomedical relevance of these data has been confirmed using a cell aggregation assay, suggesting that LFA-1 derived peptides show great potential for peptide drug development with a wide functional window of pH range for potential applications in LFA-1 related tumor therapy and autoimmune disease treatment.

Optofluidic platform for real-time monitoring of live cell secretory activities using Fano resonance in gold nanoslits.

An optofluidic platform for real-time monitoring of live cell secretory activities is constructed via Fano resonance in a gold nanoslit array. Large-area and highly sensitive gold nanoslits with a period of 500 nm are fabricated on polycarbonate films using the thermal-annealed template-stripping method. The coupling between gap plasmon resonance in the slits and surface plasmon polariton Bloch waves forms a sharp Fano resonance with intensity sensitivity greater than 11 000% per refractive index unit. The nanoslit array is integrated with a cell-trapping microfluidic device to monitor dynamic secretion of matrix metalloproteinase 9 (MMP-9) from human acute monocytic leukemia cells in situ. Upon continuous lipopolysaccharide (LPS) stimulation, MMP-9 secretion is detected within 2 h due to ultrahigh surface sensitivity and close proximity of the sensor to the target cells. In addition to the advantage of detecting early cell responses, the sensor also allows interrogation of cell secretion dynamics. Furthermore, the average secretion per cell measured using our system well matches previous reports while it requires orders of magnitude less cells. The optofluidic platform may find applications in fundamental studies of cell functions and diagnostics based on secretion signals.

Magnetic nanoparticle-enhanced SPR on gold nanoslits for ultra-sensitive, label-free detection of nucleic acid biomarkers.

We have demonstrated a detection method for the ultra-sensitive detection of an mRNA biomarker. The method utilizes functionalized magnetic nanoparticles (MNPs) for signal enhancement in conjunction with surface plasmon resonance (SPR) on gold nanoslits. The approach for detection includes double hybridization at two different specific locations in two steps. First, the biomarker target molecule is captured with MNPs, and second, MNPs carrying the target molecule are introduced to the SPR chip to hybridize with probes immobilized on the gold nanoslits. In this work, MNPs were applied for a dual purpose: to isolate the target molecule from the sample matrix to prevent non-specific binding and to enhance the SPR response. Gold nanoslits that provide SPR sensing were fabricated by nanoimprinting lithography on polycarbonate (PC) film. The film was integrated with a microliter volume microfluidic chip to form the SPR detection chip. This detection method was used to detect mRNA heterogeneous nuclear ribonucleoproteins (hnRNP B1) in two cancer cell lines, CL1-0 and CL1-5. hnRNP B1 is an mRNA biomarker that is overexpressed in lung cancer tissue in the early stage of cancer and can be found in the serum and plasma of lung cancer patients. A synthetic target molecule and extracted total RNA from the cell lines were used as samples. Without amplification and labeling of the target molecule, the SPR results demonstrate a specific and sensitive method for the detection of hnRNP B1 mRNA in extracted RNA from the two selected cell lines. The method is capable of measuring down to 30 fM of the target molecule in a 7 µl sample (corresponding to 1.26 × 10(5) molecules) without amplification and labeling of the target molecule.

Enhancing surface plasmon detection using template-stripped gold nanoslit arrays on plastic films.

Nanostructure-based sensors are capable of sensitive and label-free detection for biomedical applications. However, high-throughput and low-cost fabrication techniques are the main issues which should be addressed. In this study, chip-based nanostructures for intensity-sensitive detection were fabricated and tested using a thermal-annealing-assisted template-stripping method. Large-area uniform nanoslit arrays with a 500 nm period and various slit widths, from 30 to 165 nm, were made on plastic films. A transverse magnetic-polarized wave in these gold nanostructures generated sharp and asymmetric Fano resonances in transmission spectra. The full width at half-maximum bandwidth decreased with the decrease of the slit width. The narrowest bandwidth was smaller than 10 nm. Compared to nanoslit arrays on glass substrates using electron-beam lithography, the proposed chip has a higher intensity sensitivity up to 10367%/RIU (refractive index unit) and reaches a figure of merit up to 55. The higher intensity sensitivity for the template-stripped nanostructure is attributed to a smoother gold surface and larger grain sizes on the plastic film, which reduces the surface plasmon propagation loss.

Sensitive biosensors using Fano resonance in single gold nanoslit with periodic grooves.

Chip-based biosensors for sensitive label-free detection were fabricated and tested by using Fano-type resonant nanostructures. The sensor was composed of a 190 nm-thick gold nanoslit surrounded by 600-nm-period grooves. Transverse-magnetic polarized wave in these gold nanostructures generated asymmetrical resonant spectra due to the interference of broad-band cavity resonance in the single slit and narrow-band surface plasmon resonance on the periodic grooves. Compared to nanoslit arrays, such Fano-type sensor has a sharper resonance which yields a figure of merit up to 48. In addition, the crossed talk between sensing elements is reduced due to the Bragg reflection of the periodic grooves. A smaller detection separation down to 10 µm width was achieved. An antigen-antibody interaction experiment in aqueous environment verified the detection sensitivity in surface binding event.

Intensity sensitivity of gold nanostructures and its application for high-throughput biosensing.

A new microarray for dynamical studies of surface biomolecular interactions without fluorescent labeling is proposed. We employed gold nanostructures to excite surface plasmons on the microarray surface and detected the intensity changes in the extraordinary transmission. The calculation and measurement results indicate that the nanoslit array has an intensity sensitivity much higher than the nanohole array due to its narrower resonant bandwidth. In addition, the sensitivity is increased as the slit width decreases. For 35 nm slit width, the intensity sensitivity reaches to approximately 4000%/RIU, two times larger than the slit width larger than 150 nm. Using the intensity changes, we demonstrate a 10 x 10 microarray for real-time measurements of antigen-antibody and DNA-DNA interactions.