2D TiS2-Nanosheet-Coated Concave Gold Arrays with Triple-Coupled Resonances as Sensitive SERS Substrates.

Herein, a hybrid substrate for surface-enhanced Raman scattering (SERS) is fabricated, which couples localized surface plasmon resonance (LSPR), charge transfer (CT) resonance, and molecular resonance. Exfoliated 2D TiS2 nanosheets with semimetallic properties accelerate the CT with the tested analytes, inducing a remarkable chemical mechanism enhancement. In addition, the LSPR effect is coupled with a concave gold array located underneath the thin TiS2 nanosheet, providing a strong electromagnetic enhancement. The concave gold array is prepared by etching silicone nanospheres assembled on larger polystyrene nanospheres, followed by depositing a gold layer. The LSPR intensity near the gold layer can be adjusted by changing the layer thickness to couple the molecular and CT resonances, in order to maximize the SERS enhancement. The best SERS performance is recorded on TiS2-nanosheet-coated plasmonic substrates, with a detectable methylene blue concentration down to 10-13 m and an enhancement factor of 2.1 × 109 and this concentration is several orders of magnitude lower than that of the TiS2 nanosheet (10-11 m) and plasmonic substrates (10-9 m). The present hybrid substrate with triple-coupled resonance further shows significant advantages in the label-free monitoring of curcumin (a widely applied drug for treating multiple cancers and inflammations) in serum and urine.

Clinical Insights into Structure, Regulation, and Targeting of ABL Kinases in Human Leukemia.

Chronic myeloid leukemia is a multistep, multi-lineage myeloproliferative disease that originates from a translocation event between chromosome 9 and chromosome 22 within the hematopoietic stem cell compartment. The resultant fusion protein BCR::ABL1 is a constitutively active tyrosine kinase that can phosphorylate multiple downstream signaling molecules to promote cellular survival and inhibit apoptosis. Currently, tyrosine kinase inhibitors (TKIs), which impair ABL1 kinase activity by preventing ATP entry, are widely used as a successful therapeutic in CML treatment. However, disease relapses and the emergence of resistant clones have become a critical issue for CML therapeutics. Two main reasons behind the persisting obstacles to treatment are the acquired mutations in the ABL1 kinase domain and the presence of quiescent CML leukemia stem cells (LSCs) in the bone marrow, both of which can confer resistance to TKI therapy. In this article, we systemically review the structural and molecular properties of the critical domains of BCR::ABL1 and how understanding the essential role of BCR::ABL1 kinase activity has provided a solid foundation for the successful development of molecularly targeted therapy in CML. Comparison of responses and resistance to multiple BCR::ABL1 TKIs in clinical studies and current combination treatment strategies are also extensively discussed in this article.

Tensile-Strained Cu Penetration Electrode Boosts Asymmetric C-C Coupling for Ampere-Level CO2-to-C2+ Reduction in Acid.

The synthesis of multicarbon (C2+) products remains a substantial challenge in sustainable CO2 electroreduction owing to the need for sufficient current density and faradaic efficiency alongside carbon efficiency. Herein, we demonstrate ampere-level high-efficiency CO2 electroreduction to C2+ products in both neutral and strongly acidic (pH = 1) electrolytes using a hierarchical Cu hollow-fiber penetration electrode (HPE). High concentration of K+ could concurrently suppress hydrogen evolution reaction and facilitate C-C coupling, thereby promoting C2+ production in strong acid. By optimizing the K+ and H+ concentration and CO2 flow rate, a faradaic efficiency of 84.5% and a partial current density as high as 3.1 A cm-2 for C2+ products, alongside a single-pass carbon efficiency of 81.5% and stable electrolysis for 240 h were demonstrated in a strong acidic solution of H2SO4 and KCl (pH = 1). Experimental measurements and density functional theory simulations suggested that tensile-strained Cu HPE enhances the asymmetric C-C coupling to steer the selectivity and activity of C2+ products.

Rapidly Blocking the Calcium Overload/ROS Production Feedback Loop to Alleviate Acute Kidney Injury via Microenvironment-Responsive BAPTA-AM/BAC Co-Delivery Nanosystem.

Calcium overload and ROS overproduction, two major triggers of acute kidney injury (AKI), are self-amplifying and mutually reinforcing, forming a complicated cascading feedback loop that induces kidney cell "suicide" and ultimately renal failure. There are currently no clinically effective drugs for the treatment of AKI, excluding adjuvant therapy. In this study, a porous silicon-based nanocarrier rich in disulfide bond skeleton (<50 nm) is developed that enables efficient co-loading of the hydrophilic drug borane amino complex and the hydrophobic drug BAPTA-AM, with its outer layer sealed by the renal tubule-targeting peptide PEG-LTH. Once targeted to the kidney injured site, the nanocarrier structure collapses in the high glutathione environment of the early stage of AKI, releasing the drugs. Under the action of the slightly acidic inflammatory environment and intracellular esterase, the released drugs produce hydrogen and BAPTA, which can rapidly eliminate the excess ROS and overloaded Ca2+ , blocking endoplasmic reticulum/mitochondrial apoptosis pathway (ATF4-CHOP-Bax axis, Casp-12-Casp-3 axis, Cyt-C-Casp-3 axis) and inflammatory pathway (TNF-α-NF-κB axis) from the source, thus rescuing the renal cells in the "critical survival" state and further restoring the kidney function. Overall, this nanoparticle shows substantial clinical promise as a potential therapeutic strategy for I/R injury-related diseases.

Highly Efficient CO2 Reduction at Steady 2 A cm-2 by Surface Reconstruction of Silver Penetration Electrode.

Electroreduction of CO2 to CO is a promising route for greenhouse gas resource utilization, but it still suffers from impractical current density and poor durability. Here, a nanosheet shell (NS) vertically standing on the Ag hollow fiber (NS@Ag HF) surface formed by electrochemical surface reconstruction is reported. As-prepared NS@Ag HF as a gas penetration electrode exhibited a high CO faradaic efficiency of 97% at an ultra-high current density of 2.0 A cm-2 with a sustained performance for continuous >200 h operation. The experimental and theoretical studies reveal that promoted surface electronic structures of NS@Ag HF by the nanosheets not only suppress the competitive hydrogen evolution reaction but also facilitate the CO2 reduction kinetics. This work provides a feasible strategy for fabricating robust catalysts for highly efficient and stable CO2 reduction.

Dielectrophoresis-electrophoresis transition during the photovoltaic manipulation of water microdroplets on LiNbO3:Fe platform.

The abrupt behaviors of microdroplets during the LN-based photovoltaic manipulation may cause the transient instability and even failure of the microfluidic manipulation. In this paper, we perform a systematical analysis on the responses of water microdroplets to laser illumination on both naked and PTFE-coated LN:Fe surface, and find that the abrupt repulsive behaviors of the microdroplets are due to the electrostatic transition from the dielectrophoresis (DEP) to electrophoresis (EP) mechanism. Charging of the water microdroplets through the Rayleigh jetting from electrified water/oil interface is suggested as the cause of the DEP-EP transition. Fitting the kinetic data of the microdroplets to the models describing the motion of the microdroplets under the photovoltaic field yields the charging amount depending on the substrate configuration (∼1.7 × 10-11 and 3.9 × 10-12 C on the naked and PTFE-coated LN:Fe substrates), and also reveals the dominance of the EP mechanism in the co-existence of the DEP and EP mechanisms. The outcome of this paper will be quite important to the practicalization of the photovoltaic manipulation in LN-based optofluidic chips.

Synergetic Theory of Information Entropy Based on Failure Approach Index for Stability Analysis of Surrounding Rock System.

It is generally acknowledged that the stability evaluation of surrounding rock denotes nonlinear complex system engineering. In order to accurately and quantitatively assess the safety states of surrounding rock and provide a scientific basis for the prevention and control of surrounding rock stability, the analysis method of the synergetic theory of information entropy using the failure approach index has been proposed. By means of deriving the general relationship between the total two-dimensional plastic shear strain and the total three-dimensional plastic shear strain and obtaining the numerical limit analysis step of the plastic shear strain, the threshold value of the ultimate plastic shear strain can be determined, which has provided the key criterion for the calculation of the information entropy based on the failure approach index. In addition, combining with the synergetic theory of the principle of maximum information entropy, the evolution equation of the excavation step and information entropy based on the failure approach index of the surrounding rock system in underground mining space are established, and the equations of the general solution and particular solution as well as the expression of the destabilizing excavation step are given. To account for this, the method is applied to analyze the failure states of the floor surrounding rock after the mining of the 71 coal seam in Xutuan Coal Mine and involve the disturbance effect and stability control method of the underlying 72 coal seam roof from the macroscopic and microscopic aspects. Consequently, the validity of the analysis method of synergetic theory of information entropy based on the failure approach index has been verified, which presents an updated approach for the stability evaluation of surrounding rock systems that is of satisfactory capability and value in engineering applications.

Atomically Thin TaSe2 Film as a High-Performance Substrate for Surface-Enhanced Raman Scattering.

An atomically thin TaSe2 sample, approximately containing two to three layers of TaSe2 nanosheets with a diameter of 2.5 cm is prepared here for the first time and applied on the detection of various Raman-active molecules. It achieves a limit of detection of 10-10  m for rhodamine 6G molecules. The excellent surface-enhanced Raman scattering (SERS) performance and underlying mechanism of TaSe2 are revealed using spectrum analysis and density functional theory. The large adsorption energy and the abundance of filled electrons close to the Fermi level are found to play important roles in the chemical enhancement mechanism. Moreover, the TaSe2 film enables highly sensitive detection of bilirubin in serum and urine samples, highlighting the potential of using 2D SERS substrates for applications in clinical diagnosis, for example, in the diagnosis of jaundice caused by excess bilirubin in newborn children.

Modeling the dynamic growth and branching of actin filaments.

As an essential component of the cytoskeleton, actin filaments play a key role in a variety of cellular physiological activities. To better understand the function of actin filaments, which are a special kind of polymer chain, researchers have started to focus on the Brownian dynamics of polymers. Currently, to study the dynamics of polymers, classical explicit bead-spring models and finite-element methods (FEMs) have both been broadly used. However, compared to bead-spring models, FEMs can address the mechanical properties of actin filaments and actin networks with more detail and better accuracy. However, current FEMs do not consider the dynamic assembly of actin into an actin filament network. Here, we extend the traditional FEM and present a new framework of the FEM based on the co-rotational grid method, which allows us to simulate the dynamic growth and branching of actin filaments. Several examples are studied. The proposed numerical model is capable of capturing the dynamic assembly of actin filaments.

Novel chlorpromazine derivatives as anti-endometrial carcinoma agents with reduced extrapyramidal side effects.

As the traditional conservative remedy for endometrial carcinoma (EC), progesterone has great limitations due to its poor performance, and a new strategy is urgently needed. Our previous work revealed that the antipsychotic drug chlorpromazine (CPZ) has stronger antitumor activity on EC than progesterone does, which may provide a promising conservative alternative for EC patients. Unfortunately, the severe extrapyramidal symptoms (EPSs) at concentrations (>5 mg/kg) that are required for anticarcinoma activity limited its repurposing. Therefore, a series of novel CPZ derivatives were designed and synthesized to avoid EPS and retain its antitumor activity. Among them, 11·2HCl and 18 displayed greater inhibitory activity by modulating SOS1. Notably, even at a dose of 100 mg/kg, 11·2HCl/18 had little effect on the extrapyramidal system. In conclusion, 11·2HCl and 18 greatly repressed the malignant features of endometrial carcinoma and decreased extrapyramidal side effects compared with the original drug CPZ.

Preparation and characterisation of ecdysterone/hydroxypropyl-Β-cyclodextrin inclusion complex with enhanced oral and transdermal bioavailability.

To prepare ecdysterone (ES)/hydroxypropyl-ß-cyclodextrin (HP-ß-CD) inclusion complex, thus improving the water solubility and bioavailability of ES. Phase-solubility study was performed to study the mass ratio of ES and HP-ß-CD. Then, the ES/HP-ß-CD inclusion complex was prepared by the solvent evaporation method, and its physicochemical properties were characterised using the SEM, DSC, XRD, 1HNMR and FT-IR. In addition, in vitro dissolution and bioavailability (oral and transdermal) experiments were also conducted. The inclusion complex was formed with ES and HP-ß-CD at the mass ratio of 1:1. ES existed in an amorphous form in the inclusion complex. The equilibrium solubility of ES/HP-ß-CD inclusion complex in SGF (simulated gastric fluid) and SIF (simulated intestinal fluid) was 50.6 ± 0.11 mg/mL and 75.9 ± 0.38 mg/mL in SGF and SIF, which was 5.93 and 9.96 times higher than that of free ES, respectively. The ES/HP-ß-CD inclusion complex had better dissolution ability and transdermal permeability than the free ES. The oral bioavailability and the transdermal bioavailability were respectively increased by 2.97 times and 1.92 times compared with the free ES. These data suggest that the ES/HP-ß-CD inclusion complex can be developed as potential pharmaceutical product for future clinical applications.

Dopamine Imaging in Living Cells and Retina by Surface-Enhanced Raman Scattering Based on Functionalized Gold Nanoparticles.

Retinal dopamine is believed to be involved in the development of myopia, which is projected to affect almost half of the world population's visual health by 2050. Direct visualization of dopamine in the retina with high spatial precision is essential for understanding the biochemical mechanism during the development of myopia. However, there are very few approaches for the direct detection of dopamine in the visual system, particularly in the retina. Here, we report surface-enhanced Raman scattering (SERS)-based dopamine imaging in cells and retinal tissues with high spatial precision. The surface of gold nanoparticles is modified with N-butylboronic acid-2-mercaptoethylamine and 3,3'-dithiodipropionic acid di(N-hydroxysuccinimide ester), which shows excellent specific reaction with dopamine. The existence of dopamine triggers the aggregation of gold nanoparticles that subsequently form plasmonic hot spots to dramatically increase the Raman signal of dopamine. The as-synthesized SERS nanoprobes have been evaluated and applied for dopamine imaging in living cells and retinal tissues in form-deprivation (FD) myopia guinea pigs, followed by further investigation on localized dopamine levels in the FD-treated mice. The results suggest a declined dopamine level in mice retina after 2-week FD treatment, which is associated with the development of myopia. Our approach will greatly contribute to better understanding the localized dopamine level associated with myopia and its possible treatments. Furthermore, the imaging platform can be utilized to sensing other important small molecules within the biological samples.

Hydrophobic-substrate based water-microdroplet manipulation through the long-range photovoltaic interaction from a distant LiNbO3:Fe crystal.

Development of photovoltaic water-microdroplet manipulation using LN:Fe crystals has to meet the requirement of the hybrid and heating-avoided design of biological lab-on-chips. To fulfill this, we demonstrate a successful manipulation of a water microdroplet on a hydrophobic substrate by utilizing the long-range photovoltaic interaction from a distant LN:Fe crystal (see Visualization 1). The maximal manipulation distance (MMD) is found to be dependent on the laser-illumination intensity at the LN:Fe crystal and it can be tuned up to a sub-centimeter level (∼4 mm). Basing on the two-center model of light-induced charge transport in the LN:Fe crystal, we establish an analytic model to describe the force balance during the microdroplet manipulation under a long-range photovoltaic interaction. Either shortening the manipulation distance or increasing the illumination intensity can enhance the photovoltaic interaction and increase the velocity of the microdroplet being manipulated. An abrupt shape change followed by a fast repelling movement of the water microdroplet is observed under a strong photovoltaic interaction (see Visualization 2).

Sustained Release Systems for Delivery of Therapeutic Peptide/Protein.

Peptide/protein therapeutics have been significantly applied in the clinical treatment of various diseases such as cancer, diabetes, etc. owing to their high biocompatibility, specificity, and therapeutic efficacy. However, due to their immunogenicity, instability stemming from its complex tertiary and quaternary structure, vulnerability to enzyme degradation, and rapid renal clearance, the clinical application of protein/peptide therapeutics is significantly confined. Though nanotechnology has been demonstrated to prevent enzyme degradation of the protein therapeutics and thus enhance the half-life, issues such as initial burst release and uncontrollable release kinetics are still unsolved. Moreover, the traditional administration method results in poor patient compliance, limiting the clinical application of protein/peptide therapeutics. Exploiting the sustained-release formulations for more controllable delivery of protein/peptide therapeutics to decrease the frequency of injection and enhance patient compliance is thus greatly meaningful. In this review, we comprehensively summarize the substantial advancements of protein/peptide sustained-release systems in the past decades. In addition, the advantages and disadvantages of all these sustained-release systems in clinical application together with their future challenges are also discussed in this review.

Infrared thermography for assessment of thoracic paravertebral block: a prospective observational study.

BACKGROUND: There was no "gold standard" to assess the success or failure of thoracic paravertebral block (TPVB). Measurement of skin temperature with infrared thermography (IT) would be a reliable method to evaluate the effectiveness of regional blocks. This study aimed to explore the feasibility of using skin temperature difference (Td) determined by IT between the blocked and unblocked side to predict the spread of TPVB. METHODS: Sixty-one patients undergoing elective unilateral breast or thoracoscopic surgery were enrolled in this prospective observational study. TPVB was performed at T4 and T5 under real-time ultrasound guidance with 10 mL of 0.4% ropivacaine for each patient, respectively. Td between the blocked and unblocked side were measured with IT from T2 to T10 at the anterior chest wall before TPVB and 5 min, 10 min, 15 min and 20 min after TPVB. Pinprick test was performed at 20 min after TPVB. Successful TPVB was defined as no sensation to pinprick in 3 or more adjacent dermatomes corresponding to the site of injection at 20 min after TPVB. Td was compared to pinprick test for evaluating its effectiveness in predicting the success of TPVB. The sensitivity, specificity, and cut-off value of Td for predicting successful TPVB were determined by receiver operator characteristic (ROC) curve analysis. RESULTS: Compared with the baseline value before block, Td from T2 to T10 were significantly increased at each time point in successful blocks. In failed blocks, Td was not increased in any dermatome. The increase of Td at T4-T7 was more than 1 °C 20 min after successful TPVB. Fifteen minutes after block, Td increase at T4 had the greatest potential to predict block success. The area under the ROC curve was 0.960 at a cut-off value of 0.63 °C with a sensitivity of 83.3% and a specificity of 100.0%. CONCLUSIONS: This study suggested that the increase of Td at T4 dermatome determined by IT between the blocked and unblocked side is an early, quantitative, and reliable predictor of successful TPVB. TRIAL REGISTRATION: Clinical trial registration: NCT04078347 .

Photovoltaic splitting of water microdroplets on a y-cut LiNbO3:Fe crystal coated with oil-infused hydrophobic insulating layers.

We demonstrate the successful photovoltaic splitting of water microdroplets on a $y$y-cut ${{\rm LiNbO}_3}:{\rm Fe}$LiNbO3:Fe substrate coated with an oil-infused hydrophobic layer. The temporal evolution of the microdroplet contact angle upon a central illumination and the distinct behaviors of two sub-droplets during a following boundary illumination reveal that both electrowetting and electroosmotic effects induced by the dipolar photovoltaic potential on the substrate contribute to the water microdroplet splitting. The reciprocal relationship between the splitting time and the illumination intensity verifies the inherent photovoltaic nature of the water microdroplet splitting. The splitting time is found to be linearly dependent on the initial microdroplet size. These points are quite important to the practicalization of lithium niobate (LN)-based microfluidic chips in the biological field.

[Effect of ginsenoside Rg_1 in delaying premature ovarian failure induced by D-gal in mice through PI3K/Akt/mTOR autophagy pathway].

The aim of this paper was to study the role of phosphoinositide 3-kinase(PI3 K), protein kinase B(Akt) and mamma-lian target of rapamycin(mTOR) in the inhibition of premature ovarian failure induced by D-galactose(D-gal) in mice model by ginsenoside Rg_1(Rg_1). Fifty-four female SPF BALB/c mice were randomly divided into PBS group, D-gal group, and Rg_1 group. In the D-gal group, D-galactose(200 mg·kg~(-1)·d~(-1)) was injected subcutaneously into the neck and back for 42 days. In the PBS group, an equal amount of phosphate buffered saline(PBS) was injected into the neck and back for 42 days. In addition to the therapy of D-gal group, Rg_1 group was given Rg_1(20 mg·kg~(-1)·d~(-1)) through intraperitoneal injection since the 15 th day for 28 days, at the same time, the D-gal group and the PBS group were also given an equal amount of PBS through intraperitoneal injection since the 15 th day for 28 days. After the treatment, the estrous cycle changes of the mice were detected, and the ovarian SA-ß-Gal staining was used to detect the changes of ovarian aging. Western blot was used to detect the changes in protein expressions of PI3 K, Akt, mTOR, S6 k, LC3-Ⅱ and P16~(INK4 a). Fluorescence quantitative PCR was used to detect the changes in mRNA expressions of PI3 K, Akt, mTOR, S6 k, LC3-Ⅱ and P16~(INK4 a). According to the findings, compared with the PBS group, the D-gal group began to show estrous cycle disorder in the 3 rd week,the ovarian SA-ß-Gal staining positive granulosa cells increased in the D-gal group, the expression of senescence marker P16~(INK4 a) increased, while the expression of autophagy signaling molecule LC3-Ⅱ decreased. After treatment with Rg_1, the positive rate of ovarian SA-ß-Gal staining in Rg_1 group decreased, the expression level of autophagy signaling molecule LC3-Ⅱ in Rg_1 group was higher than that in D-gal group, while the expression level of senescence marker P16~(INK4 a) was lower than that in D-gal group. Compared with the PBS group, the protein and mRNA expressions of PI3 K, Akt, mTOR and S6 k in the D-gal group were up-regulated, the protein expressions of Akt, mTOR and S6 k in the Rg_1 group were up-regulated, and the mRNA expressions of PI3 K and mTOR were up-regulated. After treatment with Rg_1, the protein expressions of PI3 K, Akt, mTOR and S6 k in the Rg_1 group were lower than those in the D-gal group, while the mRNA expressions of Akt, mTOR and S6 k in the Rg_1 group were lower than those in the D-gal group. The finding ssuggested that Rg_1 has the effect in delaying ovarian premature failure in D-gal-induced mouse models, and PI3 K/Akt/mTOR autophagy signaling pathways play an important role.

Prioritizing disease genes with an improved dual label propagation framework.

BACKGROUND: Prioritizing disease genes is trying to identify potential disease causing genes for a given phenotype, which can be applied to reveal the inherited basis of human diseases and facilitate drug development. Our motivation is inspired by label propagation algorithm and the false positive protein-protein interactions that exist in the dataset. To the best of our knowledge, the false positive protein-protein interactions have not been considered before in disease gene prioritization. Label propagation has been successfully applied to prioritize disease causing genes in previous network-based methods. These network-based methods use basic label propagation, i.e. random walk, on networks to prioritize disease genes in different ways. However, all these methods can not deal with the situation in which plenty false positive protein-protein interactions exist in the dataset, because the PPI network is used as a fixed input in previous methods. This important characteristic of data source may cause a large deviation in results. RESULTS: A novel network-based framework IDLP is proposed to prioritize candidate disease genes. IDLP effectively propagates labels throughout the PPI network and the phenotype similarity network. It avoids the method falling when few disease genes are known. Meanwhile, IDLP models the bias caused by false positive protein interactions and other potential factors by treating the PPI network matrix and the phenotype similarity matrix as the matrices to be learnt. By amending the noises in training matrices, it improves the performance results significantly. We conduct extensive experiments over OMIM datasets, and IDLP has demonstrated its effectiveness compared with eight state-of-the-art approaches. The robustness of IDLP is also validated by doing experiments with disturbed PPI network. Furthermore, We search the literatures to verify the predicted new genes got by IDLP are associated with the given diseases, the high prediction accuracy shows IDLP can be a powerful tool to help biologists discover new disease genes. CONCLUSIONS: IDLP model is an effective method for disease gene prioritization, particularly for querying phenotypes without known associated genes, which would be greatly helpful for identifying disease genes for less studied phenotypes. AVAILABILITY: https://github.com/nkiip/IDLP.

Nanoplasmonic Sensing from the Human Vision Perspective.

Localized surface plasmon resonance (LSPR) constitutes a versatile technique for biodetection, exploiting the sensitivity of plasmonic nanostructures to small changes in refractive index. The optical shift in the LSPR band caused by molecular interactions in the vicinity of the nanostructures are typically <5 nm and can readily be detected by a spectrophotometer. Widespread use of LSPR-based sensors require cost-effective devices and would benefit from sensing schemes that enables use of very simple spectrophotometers or even naked-eye detection. This paper describes a new strategy facilitating visualization of minute optical responses in nanoplasmonic bioassays by taking into account the physiology of human color vision. We demonstrate, using a set of nine different plasmonic nanoparticles, that the cyan to green transition zone at ∼500 nm is optimal for naked-eye detection of color changes. In this wavelength range, it is possible to detect a color change corresponding to a wavelength shift of ∼2-3 nm induced by refractive index changes in the medium or by molecular binding to the surface of the nanoparticles. This strategy also can be utilized to improve the performance of aggregation-based nanoplasmonic colorimetric assays, which enables semiquantitative naked-eye detection of matrix metalloproteinase 7 (MMP7) activity at concentrations that are at least 5 times lower than previously reported assays using spherical gold nanoparticles. We foresee significant potential of this strategy in medical diagnostic and environmental monitoring, especially in situations where basic laboratory infrastructure is sparse or even nonexistent. Finally, we demonstrate that the developed concept can be used in combination with cell phone technology and red-green-blue (RGB) analysis for sensitive and quantitative detection of MMP7.

Exploiting Surface-Plasmon-Enhanced Light Scattering for the Design of Ultrasensitive Biosensing Modality.

Development of new detection methodologies and amplification schemes is indispensable for plasmonic biosensors to improve the sensitivity for the detection of trace amounts of analytes. Herein, an ultrasensitive scheme for signal enhancement based on the concept of surface-plasmon-resonance-enhanced light scattering (SP-LS) was validated experimentally and theoretically. The SP-LS of gold nanoparticles' (AuNPs) tags was employed in a sandwich assay for the detection of cardiac troponin I and provided up to 2 orders of magnitude improved sensitivity over conventional AuNPs-enhanced refractometric measurements and 3 orders of magnitude improvement over label-free SPR. Simulations were also performed to provide insights into the physical mechanisms.