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Many common amphiphiles self-assemble in water to produce heterogeneous populations of discrete and symmetric but polydisperse and multilamellar vesicles isolating the encapsulated aqueous core from the surrounding bulk. But when mixtures of amphiphiles of vastly different elastic properties co-assemble, their non-uniform molecular organization can stabilize lower symmetries and produce novel shapes. Here, using high resolution electron cryomicroscopy and tomography, we identify the spontaneous formation of a membrane morphology consisting of unilamellar tubular vesicles in dilute aqueous solutions of binary mixtures of two different amphiphiles of vastly different origins. Our results show that aqueous phase mixtures of a fluid-phase phospholipid and an amphiphilic block copolymer spontaneously assume a bimodal polymorphic character in a composition dependent manner: over a broad range of compositions (15–85 mol% polymer component), a tubular morphology co-exists with spherical vesicles. Strikingly, in the vicinity of equimolar compositions, an exclusively tubular morphology (Lt; diameter, ∼15 nm; length, >1 μm; core, ∼2.0 nm; wall, ∼5–6 nm) emerges in an apparent steady state. Theory suggests that the spontaneous stabilization of cylindrical vesicles, unaided by extraneous forces, requires a significant spontaneous bilayer curvature, which in turn necessitates a strongly asymmetric membrane composition. We confirm that such dramatic compositional asymmetry is indeed produced spontaneously in aqueous mixtures of a lipid and polymer through two independent biochemical assays – (1) reduction in the quenching of fluorophore-labeled lipids and (2) inhibition in the activity of externally added lipid-hydrolyzing phospholipase A2, resulting in a significant enrichment of the polymer component in the outer leaflet. Taken together, these results illustrate the coupling of the membrane shape with local composition through spontaneous curvature generation under conditions of asymmetric distribution of mixtures of disparate amphiphiles.

The only nonthermal method of depositing a bioceramic-based coating on polymeric substrates is by incubation in liquid, e.g., simulated body fluid to form an apatite-like layer. The drawbacks of this method include the long processing time, the production of low scratch resistant coating, and an end product that does not resemble the intended bioceramic composition. Techniques, such as plasma spraying and magnetron sputtering, involving high processing temperature are unsuitable for polymers, e.g., PMMA. Here, we introduce a nonthermal coating method to immobilize hydroxyapatite (HAp) and TiO2 nanoparticles on PMMA via a simple and fast dip coating method. Cavities that formed on the PMMA, induced by chloroform, appeared to trap the nanoparticles which accumulated to form layers of bioceramic coating only after 60 s. The resulting coating was hydrophilic and highly resistant to delamination. In the context of our research and to address the current clinical need, we demonstrate that the HAp-coated PMMA, which is intended to be used as a visual optic of a corneal prosthetic device, improves its bonding and biointegration with collagen, the main component of a corneal stroma. The HAp-coated PMMA resulted in better adhesion with the collagen than untreated PMMA in artificial tear fluid over 28 days. Human corneal stromal fibroblasts showed better attachment, viability, and proliferation rate on the HAp-coated PMMA than on untreated PMMA. This coating method is an innovative solution to immobilize various bioceramic nanoparticles on polymers and may be used in other biomedical implants. NMRC (Natl Medical Research Council, S’pore) Accepted version

Peptide-functionalized gold nanoparticles (AuNPs) are extensively utilized in colorimetric assays for rapid and sensitive detection of various biomedical and environmental targets. Although extensively used as colorimetric reporting systems, the role of the size and concentration of the AuNPs has not been thoroughly investigated. In this study, a 12-mer cardiac troponin I (cTnI)-specific peptide CALNN-Peg4-FYSHSFHENWPS was immobilized on AuNPs of different size and concentration via the CALNN anchoring sequence. A relationship was established between the total surface area of the AuNPs (binding availability) and response (centroid shift). Moreover, a colorimetric assay for cTnI operating under optimized conditions (36 nm AuNPs) yielded a limit of detection of 0.2 ng/mL (8.4 pM) when tested in diluted serum samples with an assay time of 10 min. This encouraging result opens up for further development of AuNP assays in early diagnosis of cardiac injury.

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. Refereed/Peer-reviewed

Using single-particle tracking, we investigate the interaction of small unilamellar vesicles (SUVs) that are electrostatically tethered to the freestanding membrane of a giant unilamellar vesicle (GUV). We find that the surface mobility of the GUV-riding SUVs is Brownian, insensitive to the bulk viscosity, vesicle size, and vesicle fluidity but strongly altered by the viscosity of the underlying membrane. Analyzing the diffusional behavior of SUVs within the Saffman-Delbrück model for the dynamics of membrane inclusions supports the notion that the mobility of the small vesicles is coupled to that of dynamically induced lipid clusters within the target GUV membrane. The reversible binding also offers a nonperturbative means for measuring the viscosity of biomembranes, which is an important parameter in cell physiology and function.

A colorimetric Al3+ sensor based on fluorescence recovery of a conjugated copolymer-ATP complex is proposed. An optimized ratio of two polythiophene (PT) monomers is utilized to synthesize copolymer (CP) that yielded maximized colorimetric response for Al3+ in deionized (DI) and tap water. The electrostatic disassembly of CP-ATP upon addition of Al3+ led to an evident visual color change. The lowest concentration of Al3+ for naked eye observation is around 4 μM, which is below the threshold levels in drinking water according to European Economic Community (EEC) standard. Besides, the proposed assay showed a similar response to Al3+ in tap water. The proposed methodology showed selective and sensitive detection for Al3+ in analytically relevant concentration ranges without involving sophisticated instrumentation, illustrating the applicability for on-site drinking water monitoring., MOE (RG 82/12); Provost Office Nanyang Technological University, Singapore

Gold nanoparticles (AuNPs) have been extensively used for decades in biosensing-related development due to outstanding optical properties. Peptides, as newly realized functional biomolecules, are promising candidates of replacing antibodies, receptors, and substrates for specific molecular interactions. Both peptides and AuNPs are robust and easily synthesized at relatively low cost. Hence, peptide-AuNP-based bio-nano-technological approaches have drawn increasing interest, especially in the field of molecular targeting, cell imaging, drug delivery, and therapy. Many excellent works in these areas have been reported: demonstrating novel ideas, exploring new targets, and facilitating advanced diagnostic and therapeutic technologies. Importantly, some of them also have been employed to address real practical problems, especially in remote and less privileged areas. This contribution focuses on the application of peptide-gold hybrid nanomaterials for various molecular interactions, especially in biosensing/diagnostics and cell targeting/imaging, as well as for the development of highly active antimicrobial/antifouling coating strategies. Rationally designed peptide-gold nanomaterials with functional properties are discussed along with future challenges and opportunities.

A novel conjugated oligoelectrolyte (COE) material, named S6, is designed to have a lipid-bilayer stabilizing topology afforded by an extended oligophenylenevinylene backbone. S6 intercalates biological membranes acting as a hydrophobic support for glycerophospholipid acyl chains. Indeed, Escherichia coli treated with S6 exhibits a twofold improvement in butanol tolerance, a relevant feature to achieve within the general context of modifying microorganisms used in biofuel production. Filamentous growth, a morphological stress response to butanol toxicity in E. coli, is observed in untreated cells after incubation with 0.9% butanol (v/v), but is mitigated by S6 treatment. Real-time fluorescence imaging using giant unilamellar vesicles reveals the extent to which S6 counters membrane instability. Moreover, S6 also reduces butanol-induced lipopolysaccharide release from the outer membrane to further maintain cell integrity. These findings highlight a deliberate effort in the molecular design of a chain-elongated COE to stabilize microbial membranes against environmental challenges. Ministry of Education (MOE) Nanyang Technological University C.Z. and G.W.N.C. contributed equally to this work. G.C.B. thanks the NTU start up grant M4081984.120. Work at SCELSE was supported by the Singapore Ministry of Education through grant M4360005. Work at UCSB was supported by the Institute for Collaborative Biotechnologies through grant W911NF-09-D-0001.

Biobutanol production by fermentation is potentially a sustainable alternative to butanol production from fossil fuels. However, the toxicity of butanol to fermentative bacteria, resulting largely from cell membrane fluidization, limits production titers and is a major factor limiting the uptake of the technology. Here, studies were undertaken, in vitro and in silico, on the butanol effects on a representative bacterial (i.e. Escherichia coli) inner cell membrane. A critical butanol : lipid ratio for stability of 2 : 1 was observed, computationally, consistent with complete interdigitation. However, at this ratio the bilayer was ∼20% thicker than for full interdigitation. Furthermore, butanol intercalation induced acyl chain bending and increased disorder, measured as a 27% lateral diffusivity increase experimentally in a supported lipid bilayer. There was also a monophasic Tm reduction in butanol-treated large unilamellar vesicles. Both behaviours are inconsistent with an interdigitated gel. Butanol thus causes only partial interdigitation at physiological temperatures, due to butanol accumulating at the phospholipid headgroups. Acyl tail disordering (i.e. splaying and bending) fills the subsequent voids. Finally, butanol short-circuits the bilayer and creates a coupled system where interdigitated and splayed phospholipids coexist. These findings will inform the design of strategies targeting bilayer stability for increasing biobutanol production titers. Ministry of Education (MOE) Nanyang Technological University National Research Foundation (NRF) Accepted version The computational work for this article was performed on resources of the National Supercomputing Centre, Singapore (https://www.nscc.sg). This work was supported by the Ministry of Education, Singapore (MOE) Grants M4360005 and Tier 1 RG146/17. SCELSE is funded by Singapore’s Ministry of Education, National Research Federation, Nanyang Technological University (NTU), and National University of Singapore (NUS) and hosted by NTU in partnership with NUS.

Early detection of toxic proteases in food matrices plays a major role in preventing the occurrence of diseases as well as outbreaks. However, on-site detection of proteases, for instance, botulinum, anthrax and cholera in food matrices remains challenging due to their extremely low lethal dose levels. Here, we report a lateral flow assay (LFA) in a dipstick format for on-site visual detection of proteases in food matrices. The light chain of BoNT serotype A (BoNT/A LC) is used as a model system for validation of the proposed assay using magnetic beads conjugated to a synthetic peptide that provide a specific cleavage site for BoNT/A LC. Magnetic beads serve as both reporters for visual detection and as facilitators for sample clean-up, owing to the efficient magnetic separation protocol adopted. Digestion of the peptide substrate by BoNT/A LC for 5 h followed by the dipstick assay yields a reduction in color intensity of the test line on the dipstick compared to the control line obtained using an un-cleaved peptide substrate. Concentration dependent responses for the assay in carrot juice were obtained with a limit of detection (LOD) of 1 nM/2.5 nM (with/without amplification), also supported by RGB (ΔE) analysis, indicating the potential of the proposed methodology for on-site assaying of proteases in food matrices. Unlike typical affinity-based assays that yield a collective response for the active and inactive forms of the proteases, the proposed functional LFA targets only the active form, thereby enabling a more precise analysis for preventing potential false-positives. The proposed approach could be extended for detection of BoNT serotypes and other proteases in food matrices, upon utilizing appropriate substrates with specific cleavage sites.

International audience; It is of paramount importance to be able to accurately quantify surface coverage of antibodies on gold nanoparticles (AuNP) so as to optimise the sensitivity of AuNP-based immunosensors. Herein, we developed a fluorescence-based method to directly quantify rabbit immunoglobulin G (IgG) used as antibody model bound to AuNP. Rabbit IgG was first labelled with fluorescein-5-isothiocyanate (FITC) prior to conjugation to AuNP via either physisorption or chemisorption. IgG-conjugated AuNP were treated with NaCN to dissolve the AuNP and restore the fluorescence emission that was quenched in the presence of the metallic colloids, followed by quantification of fluorescein by spectrofluorimetry. This direct assay gave about 4 IgG bound to each 15-nm diameter AuNP for both immobilization strategies. This surface coverage value was in good agreement with that determined from the theoretical value calculated from the Localized Surface Plasmon Resonance (LSPR) band shift. For comparison, we also applied two indirect methods based on the quantitation of excess IgG remaining in the supernatant using fluorescence assay or enzyme-linked immunosorbent assay (ELISA). The indirect assays, either fluorescence or ELISA, commonly used to assess the antibody coverage on AuNP, overestimated the IgG surface coverage to a large extent, since up to 3 to 4 times higher coverages were measured. Therefore, the direct fluorescence method reported in this paper appears as a valuable method for quantification of surface coverage of antibody on AuNP.

Conjugated polyelectrolytes (CPEs) have been widely used as reporters in colorimetric assays targeting nucleic acids. CPEs provide naked eye detection possibility by their superior optical properties however, as concentration of target analytes decrease, trace amounts of nucleic acid typically yield colorimetric responses that are not readily perceivable by naked eye. Herein, we report a pixelated analysis approach for correlating colorimetric responses of CPE with nucleic acid concentrations down to 1 nM, in plasma samples, utilizing a smart phone with an algorithm that can perform analytical testing and data processing. The detection strategy employed relies on conformational transitions between single stranded nucleic acid-cationic CPE duplexes and double stranded nucleic acid-CPE triplexes that yield distinct colorimetric responses for enabling naked eye detection of nucleic acids. Cationic poly[N,N,N-triethyl-3-((4-methylthiophen-3-yl)oxy)propan-1-aminium bromide] is utilized as the CPE reporter deposited on a polyvinylidene fluoride (PVDF) membrane for nucleic acid assay. A smart phone application is developed to capture and digitize the colorimetric response of the individual pixels of the digital images of CPE on the PVDF membrane, followed by an analysis using the algorithm. The proposed pixelated approach enables precise quantification of nucleic acid assay concentrations, thereby eliminating the margin of error involved in conventional methodologies adopted for interpretation of colorimetric responses, for instance, RGB analysis. The obtained results illustrate that a ubiquitous smart phone could be utilized for point of care colorimetric nucleic acids assays in complex matrices without requiring sophisticated software or instrumentation., Graphical abstract Image 1, Highlights • A cost effective sensory cartridge and an algorithm compatible with smart phone are developed. • Conjugated polyelectrolyte impregnated paper for detection of nucleic acid. • A pixelated assay to visualize nucleic acid down to concentration of 1 nM.

Targeting enzymes, proteases in particular, using various assay formats has attracted considerable interest for early disease diagnosis. While affinity-based assays that report the presence of proteases in samples have been widely explored, it is of utmost importance to develop functional assays that provide information on the activity of proteases for a more precise indication of the disease state and progression. Herein, we report a paper-based functional assay that yields naked eye observable and concentration dependent responses for the active form of proteases. The paper-based assay involves a facile single step fabrication process of depositing protease specific peptide functionalized gold nanoparticles on paper membranes. Matrilysin is used as a model protease to validate the proposed methodology. The proteolysis-driven aggregation of nanoparticles on the membrane yields a colorimetric response that has limit of detection that is ∼4 times lower (3.1 μg/mL) than for the same assay performed in homogeneous solution (12.5 μg/mL). To the best of our knowledge, this is the first report on heterogeneous protease assay on paper relying on aggregation of peptide-functionalized nanoparticles. The approach easily can be extended to assay other enzymes by functionalizing the gold nanoparticles using specific peptides.

We describe herein a series of self-assembled monolayers (SAMs) on gold designed for adjustable tethering of model lipid membrane phases. The SAMs consist of deuterated aliphatic anchors, HS(CH2)15CONH(CH2CH2O)6CH2CONH-X, where X is either −(CD2)7CD3 or −(CD2)15CD3, dispersed in a stable matrix of protein-repellent molecules, HS(CH2)15CONHCH2CH2OH. The mixed SAMs with variable surface densities of the anchors are thoroughly characterized before and after adsorption of phospholipids by means of ellipsometry, contact angle goniometry, and infrared reflection–absorption spectroscopy (IRRAS). In all cases, the bottom portions of the mixed SAMs (i.e., the h-alkyl thiol segments of the molecules) are arranged in a highly ordered all-trans conformation stabilized by a network of lateral hydrogen bonds. The terminal portions of the anchors (the oligo(ethylene glycol) spacer and deuterated alkyl segments, respectively), however, possess less ordered conformations in the mixed composition regime. For the SAMs conta...

Liedberg, Bo/0000-0003-2883-6953, WOS: 000427204100023, PubMed: 29430928, A luminescent paper-based device for the visual detection of oxidative stress biomarkers is reported. The device consists of a polyvinylidene fluoride membrane impregnated with poly(3-alkoxy-4-methylthiophene) (PT) for colorimetric detection. 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker associated with oxidative stress, is used as a model system for validating the proposed methodology. The detection strategy is based on monitoring the changes in optical properties of PT associated with its conformational changes upon interaction with an aptamer in the presence and in the absence of 8-OHdG. Fluorometric and colorimetric monitoring revealed linear responses for 8-OHdG concentrations between 50 pM and 500 nM (similar to 14 pg/mL to 140 ng/mL), with limits of detection of 300 pM and 350 pM, respectively for (n = 3). Colorimetric responses in artificial urine ascertained rapid, sensitive, and selective detection of 8-OHdG at clinically relevant (pM to nM) concentration levels. Furthermore, the proposed methodology enables point-of-care diagnostics for oxidative stress without requiring sophisticated instrumentation.

A volatile organic compounds (VOC) sensor built on SOI-based photonic platform is presented in this paper. The sensor consists of a high-Q factor ring-resonator. It is tested with acetone vapor, achieving a detection limit of 200 ppm. The sensor obtained relative high sensitivity (1.7 pm/1000 ppm), fast response time (∼20 s) and the stability of

In this review, recent advances in the development of electronic detection methodologies based on non-antibody recognition elements such as functional liposomes, aptamers and synthetic peptides are discussed. Particularly, we highlight the progress of field effect transistor (FET) sensing platforms where possible as the number of publications on FET-based platforms has increased rapidly. Biosensors involving antibody-antigen interactions have been widely applied in diagnostics and healthcare in virtue of their superior selectivity and sensitivity, which can be attributed to their high binding affinity and extraordinary specificity, respectively. However, antibodies typically suffer from fragile and complicated functional structures, large molecular size and sophisticated preparation approaches (resource-intensive and time-consuming), resulting in limitations such as short shelf-life, insufficient stability and poor reproducibility. Recently, bio-sensing approaches based on synthetic elements have been intensively explored. In contrast to existing reports, this review provides a comprehensive overview of recent advances in the development of biosensors utilizing synthetic recognition elements and a detailed comparison of their assay performances. Therefore, this review would serve as a good summary of the efforts for the development of electronic bio-sensing approaches involving synthetic recognition elements.

We investigated the simultaneous excitation of localized surface plasmons (LSPs) and propagating surface plasmons (PSPs) on a thin metallic film with an array of nanoholes for the enhancement of fluorescence intensity in heterogeneous bioassays. Experiments supported by simulations reveal that the co-excitation of PSP and LSP modes on the nanohole array in a Kretschmann configuration allows for fluorescence enhancement of about 10(2) as compared to a flat Au surface irradiated off-resonance. Moreover, this fluorescence signal was about 3-fold higher on the substrate supporting both PSPs and LSPs than that on a flat surface where only PSPs were resonantly excited. Simulations also indicated the highly directional fluorescence emission as well as the high fluorescence collection efficiency on the nanohole array substrate. Our contribution attempts to de-convolute the origin of this enhancement and identify further ways to maximize the efficiency of surface plasmon-enhanced fluorescence spectroscopy for implementation in ultra-sensitive bioassays.

A facile, sensitive, and label-free assay for detection of interleukin-6 (IL-6) using liquid-gated field-effect transistor (FET) sensors based on horizontally aligned single-walled carbon nanotubes (SWCNT) is proposed. This approach relies on the drain current (Id) responses of the transistor upon interactions of IL-6 with its corresponding antibody (IL-6R) immobilized on SWCNT. The proposed immunosensor exhibits superior sensitivity (limit-of-detection = 1.37 pg/mL) in virtue of the reduced tube-to-tube contact resistance, good selectivity (no responses to bovine serum albumin and cysteine were observed and detection of target molecules in serum was achieved) as a result of the highly specific interaction between IL-6 and IL-6R, and excellent stability (no significant degradation in the electronic performance after storage under ambient conditions for up to 3 months) in virtue of the strong adhesion of CNT to the quartz substrate and good horizontal alignment of these tubes. Therefore, the proposed immunosensor is a promising platform for early diagnosis of various diseases (including some cancers) that can be indicated by the circulating level of IL-6. Keywords: Interleukin-6, Field-effect transistor, Horizontally aligned single-walled carbon nanotubes

Patients with advanced corneal disease do poorly with conventional corneal transplantation and require a keratoprosthesis (KPro) for visual rehabilitation. The most widely used KPro is constructed using poly(methyl methacrylate) (PMMA) in the central optical core and a donor cornea as skirt material. In many cases, poor adherence between the PMMA and the soft corneal tissue is responsible for device "extrusion" and bacterial infiltration. The interfacial adhesion between the tissue and the PMMA was therefore critical to successful implantation and device longevity. In our approach, we modified the PMMA surface using oxygen plasma (plasma group); plasma followed by calcium phosphate (CaP) coating (p-CaP); dopamine followed by CaP coating (d-CaP); or plasma followed by coating with (3-aminopropyl)triethoxysilane (3-APTES). To create a synthetic KPro model, we constructed and attached 500 μm thick collagen type I hydrogel on the modified PMMA surfaces. Surface modifications produced significantly improved interfacial adhesion strength compared to untreated PMMA (p < 0.001). The p-CaP group yielded the best interfacial adhesion with the hydrogel (177 ± 27 mN/cm(2)) followed by d-CaP (168 ± 31 mN/cm(2)), 3-APTES (145 ± 12 mN/cm(2)), and plasma (119 ± 10 mN/cm(2)). Longer-term stability of the adhesion was achieved by d-CaP, which, after 14 and 28 days of incubation in phosphate buffered saline, yielded 164 ± 25 mN/cm(2) (p = 0.906 compared to adhesion at day 1) and 131 ± 20 mN/cm(2) (p = 0.053), respectively. In contrast, significant reduction of adhesion strength was observed in p-CaP group over time (p < 0.001). All surface coatings were biocompatible to human corneal stromal fibroblasts, except for the 3-APTES group, which showed no live cells at 72 h of culture. In contrast, cells on d-CaP surface showed good anchorage, evidenced by the expression of focal adhesion complex (paxillin and vinculin), and prominent filopodia protrusions. In conclusion, d-CaP can not only enhance and provide stability to the adhesion of collagen hydrogel on the PMMA surface but also promote biointegration.

At the nano-bio interface, human plasma differentially interacts with engineered nanomaterials through the creation of protein coronas, which in turn become primary determinants of both the pharmacokinetics and pharmacodynamics of circulating nanoparticles. Here, for the first time, the specific binding kinetics of the four major corona forming proteins (human serum albumin, fibrinogen, ApoA1, and polyclonal IgG) are determined for gold nanoparticles (AuNPs). Using a multiplexed surface plasmonic assay, highly reproducible measurements of on rate (k(on)), off rate (k(off)), and disassociation constant (K(D)), in addition to relative amounts of protein binding, are obtained. Dramatic differences in k(on) for individual components are shown as primary determinants of protein affinities, with k(on) ranging over nearly two orders of magnitude for the proteins studied, while k(off) remains within a factor of two for the set. The effect of polyethylene glycol (PEG) modification on plasma component binding is also studied and the effect of PEG length on human serum interaction is characterized through systematic screening of PEG molecular weight (2-30k). The effect of nanoparticle modification on particle targeting is also characterized through study of a hybrid AuNP system.

Lipopolysaccharide (LPS) is a toxic inflammatory stimulator released from the outer cell membrane of Gram-negative bacteria, known to be directly related to, for example, septic shock, that causes millions of casualties annually. This number could potentially be lowered significantly if specific, sensitive, and more simply applicable LPS biosensors existed. In this work, we present a facile, sensitive and selective LPS sensor, developed by assembling tetramethylrhodamine-labeled LPS-binding peptides on graphene oxide (GO). The fluorescence of the dye-labeled peptide is quenched upon interaction with GO. Specific binding to LPS triggers the release of the peptide-LPS complex from GO, resulting in fluorescence recovery. This fluorescent turn-on sensor offers an estimated limit of detection of 130 pM, which is the lowest ever reported among all synthetic LPS sensors to date. Importantly, this sensor is applicable for detection of LPS in commonly used clinical injectable fluids, and it enables selective detection of LPS from different bacterial strains as well as LPS on the membrane of living E. coli.

Particle trapping and binding in optical potential wells provide a versatile platform for various biomedical applications. However, implementation systems to study multi-particle contact interactions in an optical lattice remain rare. By configuring an optofluidic lattice, we demonstrate the precise control of particle interactions and functions such as controlling aggregation and multi-hopping. The mean residence time of a single particle is found considerably reduced from 7 s, as predicted by Kramer’s theory, to 0.6 s, owing to the mechanical interactions among aggregated particles. The optofluidic lattice also enables single-bacteria-level screening of biological binding agents such as antibodies through particle-enabled bacteria hopping. The binding efficiency of antibodies could be determined directly, selectively, quantitatively and efficiently. This work enriches the fundamental mechanisms of particle kinetics and offers new possibilities for probing and utilising unprecedented biomolecule interactions at single-bacteria level., Optical trapping is a versatile tool for biomedical applications. Here, the authors use an optofluidic lattice to achieve controllable multi-particle hopping and demonstrate single-bacteria-level screening and measurement of binding efficiency of biological binding agents through particle-enabled bacteria hopping.

Researchers explore loosely overdamped system with extreme low stiffness for nanoparticle sorting with nanometer precision., The past two decades have witnessed the revolutionary development of optical trapping of nanoparticles, most of which deal with trapping stiffness larger than 10−8 N/m. In this conventional regime, however, it remains a formidable challenge to sort out sub–50-nm nanoparticles with single-nanometer precision, isolating us from a rich flatland with advanced applications of micromanipulation. With an insightfully established roadmap of damping, the synchronization between optical force and flow drag force can be coordinated to attempt the loosely overdamped realm (stiffness, 10−10 to 10−8 N/m), which has been challenging. This paper intuitively demonstrates the remarkable functionality to sort out single gold nanoparticles with radii ranging from 30 to 50 nm, as well as 100- and 150-nm polystyrene nanoparticles, with single nanometer precision. The quasi-Bessel optical profile and the loosely overdamped potential wells in the microchannel enable those aforementioned nanoparticles to be separated, positioned, and microscopically oscillated. This work reveals an unprecedentedly meaningful damping scenario that enriches our fundamental understanding of particle kinetics in intriguing optical systems, and offers new opportunities for tumor targeting, intracellular imaging, and sorting small particles such as viruses and DNA.

Hizal, Gurkan/0000-0003-1238-362X; Liedberg, Bo/0000-0003-2883-6953, WOS: 000430512200028, PubMed: 29557164, This study reports on a hand-held volatilome analyzer for selective determination of clinically relevant bio-markers in exhaled breath. The sensing platform is based on electrospun polymer nanofiber-multiwalled carbon nanotube (MWCNT) sensing microchannels. Polymer nanofibers of poly(vinylidene fluoride) (PVDF), polystyrene (PS), and poly(methyl methacrylate) (PMMA) incorporated with MWCNT exhibits a stable response to interferences of humidity and CO2 and provides selective deformations upon exposure of exhaled breath target volatilomes acetone and toluene, exhibiting correlation to diabetes and lung cancer, respectively. The sensing microchannels "P1" (PVDF-MWCNT), "P2" (PS-MWCNT), and "P3" (PMMA-MWCNT) are integrated with a microfluidic cartridge (mu-card) that facilitates collection and concentration of exhaled breath. The volatilome analyzer consists of a conductivity monitoring unit, signal conditioning circuitries and a low energy display module. A combinatorial operation algorithm was developed for analyzing normalized resistivity changes of the sensing microchannels upon exposure to breath in the concentration ranges between 35 ppb and 3.0 ppm for acetone and 1 ppb and 10 ppm for toluene. Subsequently, responses of volatilomes from individuals in the different risk groups of diabetes were evaluated for validation of the proposed methodology. We foresee that proposed methodology provides an avenue for rapid detection of volatilomes thereby enabling point of care diagnosis in high-risk group individuals.

This article reports on carbon nanotube/manganese dioxide (CNT-MnO2) composites as electrochemical tags for non-enzymatic signal amplification in immunosensing. The synthesized CNT-MnO2 composites showed good electrochemical activity, electrical conductivity and stability. The electrochemical signal of CNT-MnO2 composites coated glassy carbon electrode (GCE) increased by nearly two orders of magnitude compared to bare GCE in hydrogen peroxide (H2O2) environment. CNT-MnO2 composite was subsequently validated as electrochemical tags for sensitive detection of α-fetoprotein (AFP), a tumor marker for diagnosing hepatocellular carcinoma. The electrochemical immunosensor demonstrated a linear response on a log-scale for AFP concentrations ranging from 0.2 to 100 ng mL(-1). The limit of detection (LOD) was estimated to be 40 pg mL(-1) (S/N=3) in PBS buffer. Further measurements using AFP spiked plasma samples revealed the applicability of fabricated CNT-MnO2 composites for clinical and diagnostic applications.

Graphene Oxide (GO) is analogous to graphene with oxygen moieties. It offers several advantages over graphene, such as a tunable band-gap, facile synthesis and no use of metal catalysts. Due to the monolayer configuration of GO, all of its carbon atoms are readily exposed to the atmosphere and are sensitive to surface perturbations, thus making GO very suitable for liquid-gated field effect transistor (FET) type sensing applications. However, there are two main limitations preventing GO usage in practical FET sensors. It displays (1) variable coverage between fabricated chips and (2) high electrical resistance. In this paper, we overcome these two limitations by using a facile atmospheric-pressure ethanol Chemical Vapor Deposition treatment on top of pre-coated GO (ECVDGO) which decreases the electrical resistivity from 1.99 × 106 Ω square−1 to 4.68 × 103 Ω square−1, and resistivity variation from 1.60 × 106 to 7.72 × 102 Ω square−1; whilst enlarging the surface GO coverage up to 100%. We then demonstrate the ability of the post-treated ECVDGO liquid-gated FET transducer to detect Interleukin-6 which is a multi-functional cytokine involved in regulating the immune function and the acute phase response. The sensing window of the fabricated biosensor to Interleukin-6 is within the physiologically-relevant range, from 4.7 to 300 pg ml−1. The LOD of the sensor based on 3σ is 2.9 pA or 1.53 pg ml−1. This study demonstrates the emerging potential of GO with high manufacturability in liquid-gated FET biosensors for sensitive and label-free detection of bio-molecules.

A novel thymine-based surface chemistry suitable for label-free electrochemical DNA detection is described. It involves a simple two-step sequential process: immobilization of 9-mer thymine-terminated probe DNAs followed by backfilling with 9-mer thymine-based spacers (T9). As compared to commonly used organic spacer groups like 2-mercaptoethanol, 3-mercapto-1-propanol and 6-mercapto-1-hexanol, the 9-mer thymine-based spacers offer a 10-fold improvement in discriminating between complementary and non-complementary target hybridization, which is due mainly to facilitated transport of the redox probes through the probe-DNA/T9 layers. Electrochemical measurements, complemented with Surface Plasmon Resonance (SPR) and Quartz Crystal Microbalance (QCM-D) binding analyses, reveal that optimum selectivity between complementary and non-complementary hybridization is obtained for a sensing surface prepared using probe-DNA and backfiller T9 at equimolar concentration (1:1). At this particular ratio, the probe-DNAs are preferentially oriented and easily accessible to yield a sensing surface with favorable hybridization and electron transfer characteristics. Our findings suggest that oligonucleotide-based spacer groups offer an attractive alternative to short organic thiol spacers in the design of future DNA biochips.

Surface plasmon field-enhanced fluorescence energy transfer is employed for sensitive optical readout of a reversible hairpin aptamer assay that is suitable for continuous monitoring of low-molecular-weight chemical analytes. A hairpin aptamer specific to adenosine and adenosine triphosphate with Alexa Fluor 647 fluorophore attached to its 5′ end was anchored via 3′ end thiol to a gold thin film. Molecular spacers were used to control the distance of the fluorophore from the surface in the aptamer “off” and “on” states. The specific binding of the target analyte changes the aptamer conformation, which alters the distance of the fluorophore from the gold surface and translates to variations in the detected fluorescence intensity. The plasmonically mediated fluorescence signal increases the measured signal-to-noise ratio and allows for real-time observation of the analyte binding. Theoretical as well as experimental study of the optical signal dependence on fluorophore orientation, design of spacers, and angular distribution of collected light is presented for rational design of the assay. The detected sensor signal increased by a factor as large as 23 upon switching the aptamer from the “off” to “on” state due to the hairpin opening associated with the specific capture of target analyte.

Surface plasmon field-enhanced fluorescence is reported for the readout of a heterogeneous assay that utilizes low affinity split aptamer ligands. Weak affinity ligands that reversibly interact with target analytes hold potential for facile implementation in continuous monitoring biosensor systems. This functionality is not possible without the regeneration of more commonly used assays relying on high affinity ligands and end-point measurement. In fluorescence-based sensors, the use of low affinity ligands allows avoiding this step but it imposes a challenge associated with the weak optical response to the specific capture of the target analyte which is also often masked by a strong background. The coupling of fluorophore labels with a confined field of surface plasmons is reported for strong amplification of the fluorescence signal emitted from the sensor surface and its efficient discrimination from the background. This optical scheme is demonstrated for time-resolved analysis of chosen model analytes – adenoside and adenosine triphosphate – with a split aptamer that exhibits an equilibrium affinity binding constant between 0.73 and 1.35 mM. The developed biosensor enables rapid and specific discrimination of target analyte concentration changes from low μM to mM in buffer as well as in 10% serum.

The shift of the localized surface plasmon resonance (LSPR) spectrum is widely used in bio- and chemical sensing. Traditionally, the shift is monitored at the peak maximum of the extinction spectrum. We demonstrate that the inflection point at the long wavelength side of the peak maximum shows better refractive index sensitivity than the peak maximum. A consistent improvement in bulk refractive index sensitivity of 18-55% is observed for six different nanoparticles such as spherical particles of different sizes, nanostar and nanorods with different aspect ratios. Local refractive index changes induced by molecular adsorption confirm the superior performance of the method. We contribute this improvement in sensitivity to the change in shape of the LSPR peak in response to an increase of the local refractive index. We further illustrate the advantage of using the inflection point method for analyzing DNA adsorption on U-shaped metamaterials, and for using 17 nm spherical gold nanoparticles for detection of matrix metalloprotease 7 (MMP-7), a biomarker that is heavily up-regulated during certain cancers. With the inflection point, the limit of detection (LOD) for MMP-7 is improved to 0.094 μg/mL from 0.22 μg/mL. This improvement may facilitate early diagnosis of salivary and colorectal cancers. We also envision that this generic method can be employed to track minute optical responses in other analytical areas.

© 2017 Biophysical Society The response of lipid bilayers to osmotic stress is an important part of cellular function. Recent experimental studies showed that when cell-sized giant unilamellar vesicles (GUVs) are exposed to hypotonic media, they respond to the osmotic assault by undergoing a cyclical sequence of swelling and bursting events, coupled to the membrane's compositional degrees of freedom. Here, we establish a fundamental and quantitative understanding of the essential pulsatile behavior of GUVs under hypotonic conditions by advancing a comprehensive theoretical model of vesicle dynamics. The model quantitatively captures the experimentally measured swell-burst parameters for single-component GUVs, and reveals that thermal fluctuations enable rate-dependent pore nucleation, driving the dynamics of the swell-burst cycles. We further extract constitutional scaling relationships between the pulsatile dynamics and GUV properties over multiple timescales. Our findings provide a fundamental framework that has the potential to guide future investigations on the nonequilibrium dynamics of vesicles under osmotic stress.

We report a smartphone label-free biosensor platform based on grating-coupled surface plasmon resonance (GC-SPR). The sensor system relies on the smartphone's built-in flash light source and camera, a disposable sensor chip with Au diffraction grating and a compact disk (CD) as the spectra dispersive unit. The Au grating sensor chip was modified with a synthetic peptide receptor and employed on the GC-SPR detection of lipopolysaccharides (known as endotoxins) with detection limit of 32.5ng/mL in water. Upon incubation of various small and macro-molecules with the synthetic peptide modified sensor chips, we concluded the good selectivity of the sensor for LPS detection. In addition, the sensor shows feasibility for the detection of LPS in commonly used clinical injectable fluids, such as clinical-grade 0.9% sodium chloride intravenous infusion, compound sodium lactate intravenous infusion and insulin aspart. The developed sensor platform offers the advantage of portability and simplicity, which is attractive for point-of-care and remote detection of biomedical and environmental targets. ASTAR (Agency for Sci., Tech. and Research, S’pore)

We describe the engineering of stable gold nanoparticle (AuNP) bioconjugates for the detection of staphylococcal enterotoxin A (SEA) using localized surface plasmon resonance (LSPR). Two types of AuNP bioconjugates were prepared by covalently attaching anti-SEA antibody (Ab) or SEA to AuNPs. This was achieved by reacting Traut's reagent with lysine residues of both proteins to generate thiol groups that bind to gold atoms on the AuNP surface. These bioconjugates were characterized in-depth by absorption spectroscopy, cryo-transmission electron microscopy, dynamic light scattering, and zeta potential measurements. Their stability over time was assessed after 1 year storage in the refrigerator at 4 °C. Two formats of homogeneous binding assays were set up on the basis of monitoring of LSPR peak shifts resulting from the immunological reaction between the (i) immobilized antibody and free SEA, the direct assay, or (ii) immobilized SEA and free antibody, the competitive assay. In both formats, a correlation between the LSPR band shift and SEA concentration could be established. Though the competitive format did not meet the expected analytical performance, the direct format, the implementation of which was very simple, afforded a specific and sensitive response within a broad dynamic range-nanogram per milliliter to microgram per milliliter. The limit of detection (LOD) of SEA was estimated to equal 5 ng/mL, which was substantially lower than the LOD obtained using a quartz crystal microbalance. Moreover, the analytical performance of AuNP-Ab bioconjugate was preserved after 1 year of storage at 4 °C. Finally, the LSPR biosensor was successfully applied to the detection of SEA in milk samples. The homogeneous nanoplasmonic immunosensor described herein provides an attractive alternative for stable and reliable detection of SEA in the nanogram per milliliter range and offers a promising avenue for rapid, easy to implement, and sensitive biotoxin detection. Sensitive LSPR Biosensing of SEA in buffer and milk using stable AuNP-Antibody bioconjugates Graphical abstract.

Visualization of phase coexistence in the β region of cholesterol–phospholipid mixtures consisting of high cholesterol concentrations has proved elusive in lipid bilayers. Here, using the solvent-assisted lipid bilayer approach to prepare supported membranes with high cholesterol fractions close to the cholesterol solubility limit, we report the observation of coexisting liquid phases using fluorescence microscopy. At ∼63 mol % cholesterol, supported membranes consisting of mixtures of DOPC and cholesterol exhibit large-area striping reminiscent of the stripe superstructures that characterize the proximity of the second critical point in the miscibility phase diagram. The properties of the two phases are consistent with condensed complex-rich and cholesterol-rich liquids. Both phases exhibit long-range lateral mobility, and diffusion through a given phase is favored over hopping across the phase boundary, producing an “archipelago effect” and a complex percolation path. NMRC (Natl Medical Research Council, S’pore)

A novel water-compatible macroporous molecularly imprinted film (MIF) has been developed for rapid, sensitive, and label-free detection of small molecule testosterone in urine. The MIF was synthesized by photo copolymerization of monomers (methacrylic acid [MAA] and 2-hydroxyethyl methacrylate [HEMA]), cross-linker (ethylene glycol dimethacrylate, EGDMA), and polystyrene nanoparticles (PS NPs) in combination with template testosterone molecules. The PS NPs and template molecules were subsequently removed to form an MIF with macroporous structures and the specific recognition sites of testosterone. Incubation of artificial urine and human urine on the MIF and the non-imprinted film (NIF), respectively, indicated undetectable nonspecific adsorption. Accordingly, the MIF was applied on a surface plasmon resonance (SPR) sensor for the detection of testosterone in phosphate-buffered saline (PBS) and artificial urine with a limit of detection (LOD) down to 10(-15)g/ml. To the best of our knowledge, the LOD is considered as one of the lowest among the SPR sensors for the detection of small molecules. The control experiments performed with analogue molecules such as progesterone and estradiol demonstrated the good selectivity of this MIF for sensing testosterone. Furthermore, this MIF-based SPR sensor shows high stability and reproducibility over 8months of storage at room temperature, which is more robust than protein-based biosensors.

The myocardium is unable to regenerate itself after infarct, resulting in scarring and thinning of the heart wall. Our objective was to develop a patch to buttress and bypass the scarred area, whil ...

Stretchable conductors are the basic units of advanced flexible electronic devices, such as skin‐like sensors, stretchable batteries and soft actuators. Current fabrication strategies are mainly focused on the stretchability of the conductor with less emphasis on the huge mismatch of the conductive material and polymeric substrate, which results in stability issues during long‐term use. Thermal‐radiation‐assisted metal encapsulation is reported to construct an interlocking layer between polydimethylsiloxane (PDMS) and gold by employing a semipolymerized PDMS substrate to encapsulate the gold clusters/atoms during thermal deposition. The stability of the stretchable conductor is significantly enhanced based on the interlocking effect of metal and polymer, with high interfacial adhesion (>2 MPa) and cyclic stability (>10 000 cycles). Also, the conductor exhibits superior properties such as high stretchability (>130%) and large active surface area (>5:1 effective surface area/geometrical area). It is noted that this method can be easily used to fabricate such a stretchable conductor in a wafer‐scale format through a one‐step process. As a proof of concept, both long‐term implantation in an animal model to monitor intramuscular electric signals and on human skin for detection of biosignals are demonstrated. This design approach brings about a new perspective on the exploration of stretchable conductors for biomedical applications. NRF (Natl Research Foundation, S’pore) ASTAR (Agency for Sci., Tech. and Research, S’pore) Accepted version

The original version of this Article omitted the author Kuan Wang, who is from the ‘College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan’ and ‘Nanyang Environment & Water Research Institute, Nanyang Technological University, Singapore 637141, Singapore.’Also, the author S.H. Lim was incorrectly given as L.S. Hoi and A. Larsson was incorrectly given as A. Larson.The “Author contributions” was amended to reflect the authorship changes. It previously read ‘Y.Z.S., C.-W.Q., and A.Q.L. jointly conceived the idea. Y.Z.S., S.X., Y.Z., J.B.Z., W.S., J.H.W., T.N.C., Z.C.Y., Y.L.H., B.L., P.H.Y., D.P.T., and C.-W.Q. performed the numerical simulations and theoretical analysis. Y.Z.S., S.X., and L.K.C. did the fabrication and experiments of particle hopping, biomolecule binding and flow cytometry. A.L. and L.S.H. did the SPR experiments. S.X., Y.Z.S., Y.Z., C.-W.Q., Y.-Y.C., L.K.C., T.H.Z., and A.Q.L. prepared the manuscript. S.X., Y.Z., C.-W.Q., and A.Q.L. supervised and coordinated all the work. All authors commented on the manuscript.’ The correct version states ‘B.L., K. W., P.H.Y.’ instead of ‘B.L., P.H.Y.’ and ‘S.H.L.’ in place of ‘L.S.H.’This has been corrected in both the PDF and HTML versions of the Article.

Bulk and surface refractive index sensitivity for localized surface plasmon resonance (LSPR) sensing based on edge gold-coated silver nanoprisms (GSNPs) and gold nanospheres was investigated and compared with conventional surface plasmon resonance (SPR) sensing based on propagating surface plasmons. The hybrid GSNPs benefit from an improved stability since the gold frame protecting the unstable silver facets located at the silver nanoprisms (SNPs) edges and tips prevents truncation or rounding of their sharp tips or edges, maintaining a high refractive index sensitivity even under harsh conditions. By using layer-by-layer deposition of polyelectrolytes and protein adsorption, we found that GSNPs exhibit 4-fold higher local refractive index sensitivity in close proximity (

A simple strategy based on the synergistic modulation of inter-particle and substrate-particle interaction is applied for the large-scale fabrication of two-dimensional (2D) Au and Ag nanoparticle arrays. The surface charge of the substrate is used to redistribute the double layer electric charges on the particles and to modulate the inter-particle distance within the 2D nanoparticle arrays on the substrate. The resultant arrays, with a wide range of inter-particle distances, display tunable plasmonic properties. It can be foreseen that such 2D nanoparticle arrays possess potential applications as multiplexed colorimetric sensors, integrated devices and antennas. Herein, it is demonstrated that these arrays can be employed as wavelength-selective substrates for multiplexed acquisition of surface-enhanced Raman scattering (SERS) spectra. This simple one step process provides an attractive and low cost strategy to produce high quality and large area 2D ordered arrays with tunable properties.

We theoretically and experimentally investigate the influence of the incident angle of illumination on the fluorescence enhancement for two kinds of gold nanohole arrays – a gold nanohole array on glass substrate (Au-hole array), and a gold coated photoresist nanohole array (Au/PR-hole array). Our simulations show that the absorption spectra for the Au/PR-hole array vary substantially with angle of incidence, whereas the corresponding spectra for the Au-hole array are marginally affected. The experimental results reveal fluorescence enhancement up to 14 and 12 times for the Au-hole array at an incident angle of 70° and the Au/PR-hole array at an incident angle of 20°, respectively. Moreover, a model sandwich immunoassay for the detection of prostate specific antigen (PSA) shows about 3-fold higher sensitivity on Au/PR-hole array as compared to planar gold at 70°. To the best of our knowledge this is the first investigation reporting on the relationship between the incident angle and the fluorescence enhancement on gold nanohole arrays. Our findings provide a solid foundation for designing a highly efficient fluorescence detection system with oblique angular illumination.

A simple and efficient principle for nanopatterning with wide applicability in the sub-50 nanometer regime is chemisorption of nanoparticles; at homogeneous substrates, particles carrying surface charge may spontaneously self-organize due to the electrostatic repulsion between adjacent particles. Guided by this principle, a method is presented to design, self-assemble, and chemically functionalize gradient nanopatterns where the size of molecular domains can be tuned to match the level corresponding to single protein binding events. To modulate the binding of negatively charged gold nanoparticles both locally ( 100 μm) onto a single modified gold substrate, ion diffusion is used to achieve spatial control of the particles' mutual electrostatic interactions. By subsequent tailoring of different molecules to surface-immobilized particles and the void areas surrounding them, nanopatterns are obtained with variable chemical domains along the gradient surface. Fimbriated Escherichia coli bacteria are bound to gradient nanopatterns with similar molecular composition and macroscopic contact angle, but different sizes of nanoscopic presentation of adhesive (hydrophobic) and repellent poly(ethylene) glycol (PEG) domains. It is shown that small hydrophobic domains, similar in size to the diameter of the bacterial fimbriae, supported firmly attached bacteria resembling catch-bond binding, whereas a high number of loosely adhered bacteria are observed on larger hydrophobic domains. Chemical gradients with the resolution needed to address complex biological binding events at the single protein level are prepared using surface-deposited gold nanoparticles as a versatile template for orthogonal chemical modifications. The effect of hydrophobic domain arrangement on the sub-50 nm scale is shown to influence binding of fimbriae carrying E. coli bacteria. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The heme protein cytochrome c adsorbed to a two-layer gold surface modified with a self-assembled monolayer of 2-mercaptoethanol was analyzed using a two-dimensional (2D) heterospectral correlation analysis that combined surface-enhanced infrared absorption spectroscopy (SEIRAS) and surface-enhanced Raman spectroscopy (SERS). Stepwise increasing electric potentials were applied to alter the redox state of the protein and to induce conformational changes within the protein backbone. We demonstrate herein that 2D heterospectral correlation analysis is a particularly suitable and useful technique for the study of heme-containing proteins as the two spectroscopies address different portions of the protein. Thus, by correlating SERS and SEIRAS data in a 2D plot, we can obtain a deeper understanding of the conformational changes occurring at the redox center and in the supporting protein backbone during the electron transfer process. The correlation analyses are complemented by molecular dynamics calculations to explore the intramolecular interactions. ASTAR (Agency for Sci., Tech. and Research, S’pore) Accepted version

The solvatochromic response of polydiacetylene (PDA) in the vapor phase is enabled upon incorporation with matrix polymers such as polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), polyacrylic acid (PAA), and poly-4-vinylpyridine (P4VP). The matrix polymers provide a soft/gel-like framework for accommodating photopolymerized PDA, while facilitating its conformational alternations upon interaction with preconcentrated volatile organic compounds (VOCs). The matrix polymers enabled the differentiation of VOCs owing to their varying morphology, chemical affinity and solubility in VOCs. The ratios between PDA and the matrix polymers are optimized according to the obtained solvatochromic responses evaluated in varying temperature, humidity and storage conditions. As a proof of concept, a finger-print array for differentiation of 7 VOCs is demonstrated using matrix polymer-embedded PDA. The obtained results indicate that the response time and sensitivity of the proposed methodology supersedes previous reports on solvatochromic VOC assays. Furthermore, the proposed methodology would enable differentiation of a wide range of VOCs upon incorporation of additional matrix polymers with varying sorption properties., Nanyang Technological University (NTU); MOE-Tier 1 (2014-T1-001-133-01)

An optofluidic chip is demonstrated in experiments for high-resolution and multi-range particle separation through the optically-induced microscopic vibration effect, where nanoparticles are trapped in loosely overdamped optical potential wells created with combined optical and fluidic constraints. It is the first demonstration of separating single nanoparticles with diameters ranging from 60 to 100 nm with a resolution of 10 nm. Nanoparticles vibrate with an amplitude of 3-7 μm in the loosely overdamped potential wells in the microchannel. The proposed optofluidic device is capable of high-resolution particle separation at both nanoscale and microscale without reconfiguring the device. The separation of bacteria from other larger cells is accomplished using the same chip and operation conditions. The unique trapping mechanism and the superb performance in high-resolution and multi-range particle separation of the proposed optofluidic chip promise great potential for a diverse range of biomedical applications. NRF (Natl Research Foundation, S’pore) Accepted version