167 results found
Nanopores in solid-state membranes are promising for a wide range of applications including DNA sequencing, ultra-dilute analyte detection, protein analysis, and polymer data storage. Techniques to fabricate solid-state nanopores have typically been time consuming or lacked the resolution to create pores with diameters down to a few nanometres, as required for the above applications. In recent years, several methods to fabricate nanopores in electrolyte environments have been demonstrated. These in situ methods include controlled breakdown (CBD), electrochemical reactions (ECR), laser etching and laser-assisted controlled breakdown (la-CBD). These techniques are democratising solid-state nanopores by providing the ability to fabricate pores with diameters down to a few nanometres (i.e. comparable to the size of many analytes) in a matter of minutes using relatively simple equipment. Here we review these in situ solid-state nanopore fabrication techniques and highlight the challenges and advantages of each method. Furthermore we compare these techniques by their desired application and provide insights into future research directions for in situ nanopore fabrication methods.
Zhao M, Yu J, Zhang X, et al., 2021, Tuning interfacial energy barriers in heterojunctions for anti‐interference sensing, Advanced Functional Materials, Vol: 31, ISSN: 1616-301X
Analytes with similar redox properties are normally difficult to distinguish through classic electrochemical methods. This becomes especially true for the on‐site detection in seawater where the high salinity and complex chemical components can impose severe interference. Hereby introducing numerous nanoscale heterojunctions in the Cu/CuO/reduced graphene oxide (rGO)/polypyrrole (PPy) and Cu/CuO/rGO/chitosan electrochemical sensors, tunable interfacial energy barriers to exponentially regulate the electrochemical signal can be constructed. Importantly, these energy barriers are independent to redox but closely related to the electrostatic interaction from absorbed charged analytes such as Hg2+ and Cu2+. Moreover, the similar sensing principle is also valid for the energy barriers in p‐n junctions as demonstrated in the Ni/NiO/ZnO/PPy sensor. The good anti‐interference properties and ultrahigh sensitivity of this sensing mode offers new opportunities in trace analyte detection in harsh environments such as seawater.
Tang L, Paulose Nadappuram B, Cadinu P, et al., 2021, Combined quantum tunnelling and dielectrophoretic trapping for molecular analysis at ultra-low analyte concentrations, Nature Communications, Vol: 12, Pages: 1-8, ISSN: 2041-1723
Quantum tunnelling offers a unique opportunity to study nanoscale objects with atomic resolution using electrical readout. However, practical implementation is impeded by the lack of simple, stable probes, that are required for successful operation. Existing platforms offer low throughput and operate in a limited range of analyte concentrations, as there is no active control to transport molecules to the sensor. We report on a standalone tunnelling probe based on double-barrelled capillary nanoelectrodes that do not require a conductive substrate to operate unlike other techniques, such as scanning tunnelling microscopy. These probes can be used to efficiently operate in solution environments and detect single molecules, including mononucleotides, oligonucleotides, and proteins. The probes are simple to fabricate, exhibit remarkable stability, and can be combined with dielectrophoretic trapping, enabling active analyte transport to the tunnelling sensor. The latter allows for up to 5-orders of magnitude increase in event detection rates and sub-femtomolar sensitivity.
Vilar Compte R, Summers P, Lewis B, et al., 2021, Visualising G-quadruplex DNA dynamics in live cells by fluorescence lifetime imaging microscopy, Nature Communications, Vol: 12, ISSN: 2041-1723
Guanine rich regions of oligonucleotides fold into quadruple-stranded structures called G-quadruplexes (G4s). Increasing evidence suggests that these G4 structures form in vivo and play a crucial role in cellular processes. However, their direct observation in live cells remains a challenge. Here we demonstrate that a fluorescent probe (DAOTA-M2) in conjunction with fluorescence lifetime imaging microscopy (FLIM) can identify G4s within nuclei of live and fixed cells. We present a FLIM-based cellular assay to study the interaction of non-fluorescent small molecules with G4s and apply it to a wide range of drug candidates. We also demonstrate that DAOTA-M2 can be used to study G4 stability in live cells. Reduction of FancJ and RTEL1 expression in mammalian cells increases the DAOTA-M2 lifetime and therefore suggests an increased number of G4s in these cells, implying that FancJ and RTEL1 play a role in resolving G4 structures in cellulo.
Ren R, Wang X, Cai S, et al., 2020, Selective sensing of proteins using aptamer functionalised nanopore extended field-effect transistors, Small Methods, Vol: 4, Pages: 1-8, ISSN: 2366-9608
The ability to sense proteins and protein‐related interactions at the single‐molecule level is becoming of increasing importance to understand biological processes and diseases better. Single‐molecule sensors, such as nanopores have shown substantial promise for the label‐free detection of proteins; however, challenges remain due to the lack of selectivity and the need for relatively high analyte concentrations. An aptamer‐functionalized nanopore extended field‐effect transistor (nexFET) sensor is reported here, where protein transport can be controlled via the gate voltage that in turn improves single‐molecule sensitivity and analyte capture rates. Importantly, these sensors allow for selective detection, based on the choice of aptamer chemistry, and can provide a valuable addition to the existing methods for the analysis of proteins and biomarkers in biological fluids.
Ma Y, Sikdar D, He Q, et al., 2020, Self-assembling two-dimensional nanophotonic arrays for reflectivity-based sensing, Chemical Science, Vol: 11, Pages: 9563-9570, ISSN: 2041-6520
We propose a nanoplasmonic platform that can be used for sensing trace levels of heavy metals in solutions via simple optical reflectivity measurements. The considered example is a lead sensor, which relies on the lead-mediated assembly of glutathione-functionalized gold nanoparticles (NPs) at a self-healing water/DCE liquid | liquid interface (LLI). Capillary forces tend to trap each NP at the LLI while the negatively charged ligands prevent the NPs settling too close to each other. In the presence of lead, due to chelation between the lead ion and glutathione ligand, the NPs assemble into a dense quasi-2D interfacial array. Such a dense assembly of plasmonic NPs can generate a remarkable broad-band reflectance signal, which is absent when NPs are adsorbed at the interface far apart from each other. The condensing effect of the LLI and the plasmonic coupling effect among the NP array gives rise to a dramatic enhancement of the reflectivity signals. Importantly, we show that our theory of the optical reflectivity from such an array of NPs works in perfect harmony with the physics and chemistry of the system with the key parameter being the interparticle distance at the interface. As a lead sensor, the system is fast, stable, and can achieve detection limits down to 14 ppb. Future alternative recognizing ligands can be used to build sister platforms for detecting other heavy metals.
Nanopore-based sensors have established themselves as a prominent tool for solution-based, single-molecule analysis of the key building blocks of life, including nucleic acids, proteins, glycans and a large pool of biomolecules that have an essential role in life and healthcare. The predominant molecular readout method is based on measuring the temporal fluctuations in the ionic current through the pore. Recent advances in materials science and surface chemistries have not only enabled more robust and sensitive devices but also facilitated alternative detection modalities based on field-effect transistors, quantum tunnelling and optical methods such as fluorescence and plasmonic sensing. In this Review, we discuss recent advances in nanopore fabrication and sensing strategies that endow nanopores not only with sensitivity but also with selectivity and high throughput, and highlight some of the challenges that still need to be addressed.
Clark R, Nawawi MA, Dobre A, et al., 2020, The effect of structural heterogeneity upon the microviscosity of ionic liquids, CHEMICAL SCIENCE, Vol: 11, Pages: 6121-6133, ISSN: 2041-6520
Cadinu P, Kang M, Paulose Nadappuram B, et al., 2020, Individually addressable multi-nanopores for single-molecule targeted operations, Nano Letters, Vol: 20, Pages: 2012-2019, ISSN: 1530-6984
The fine-tuning of molecular transport is a ubiquitous problem of single-molecule methods. The latter is evident even in powerful single-molecule methods such as nanopore sensing, where the quest for resolving more detailed biomolecular features is often limited by insufficient control of the dynamics of individual molecules within the detection volume of the nanopore. In this work, we introduce and characterize a reconfigurable multi-nanopore architecture that enables additional channels to manipulate the dynamics of DNA molecules in a nanopore. We show that the fabrication process of this device, consisting of four adjacent, individually addressable nanopores located at the tip of a quartz nanopipette, is fast and highly reproducible. By individually tuning the electric field across each nanopore, these devices can operate in several unique cooperative detection modes that allow moving, sensing, and trapping DNA molecules with high efficiency and increased temporal resolution.
Ma Y, Sikdar D, Fedosyuk A, et al., 2020, Electrotunable nanoplasmonics for amplified surface enhanced Raman spectroscopy, ACS Nano, Vol: 14, Pages: 328-336, ISSN: 1936-0851
Tuning the properties of optical metamaterials in real time is one of the grand challenges of photonics. Being able to do so will enable a new class of photonic materials for use in applications such as surface enhanced Raman spectroscopy and reflectors/absorbers. One strategy to achieving this goal is based on the electrovariable self-assembly and disassembly of two-dimensional nanoparticle arrays at a metal liquid interface. As expected the structure results in plasmonic coupling between NPs in the array but perhaps as importantly between the array and the metal surface. In such a system the density of the nanoparticle array can be controlled by the variation of electrode potential. Due to the additive effect, we show that less than 1 V variation of electrode potential can give rise to a dramatic simultaneous change in optical reflectivity from ~93 % to ~1 % and the amplification of the SERS signal by up to 5 orders of magnitude. The process allows for reversible tunability. These concepts are demonstrated in this manuscript, using a platform based on the voltage-controlled assembly of 40 nm Au-nanoparticle arrays at a TiN/Ag electrode in contact with an aqueous electrolyte. We show that all the physics underpinning the behaviour of this platform works precisely as suggested by the proposed theory, setting the electrochemical nanoplasmonics as a promising new direction in photonics research.
Wang X, Wilkinson MD, Lin X, et al., 2020, Single-molecule nanopore sensing of actin dynamics and drug binding, Chemical Science, Vol: 11, Pages: 970-979, ISSN: 2041-6520
Actin is a key protein in the dynamic processes within the eukaryotic cell. To date, methods exploring the molecular state of actin are limited to insights gained from structural approaches, providing a snapshot of protein folding, or methods that require chemical modifications compromising actin monomer thermostability. Nanopore sensing permits label-free investigation of native proteins and is ideally suited to study proteins such as actin that require specialised buffers and cofactors. Using nanopores, we determined the state of actin at the macromolecular level (filamentous or globular) and in its monomeric form bound to inhibitors. We revealed urea-dependent and voltage-dependent transitional states and observed unfolding process within which sub-populations of transient actin oligomers are visible. We detected, in real-time, filament-growth, and drug-binding at the single-molecule level demonstrating the promise of nanopores sensing for in-depth understanding of protein folding landscapes and for drug discovery.
Zhang Y, Takahashi Y, Hong SP, et al., 2019, High-resolution label-free 3D mapping of extracellular pH of single living cells, Nature Communications, Vol: 10, Pages: 1-9, ISSN: 2041-1723
Dynamic mapping of extracellular pH (pHe) at the single-cell level is critical for understanding the role of H+ in cellular and subcellular processes, with particular importance in cancer. While several pHe sensing techniques have been developed, accessing this information at the single-cell level requires improvement in sensitivity, spatial and temporal resolution. We report on a zwitterionic label-free pH nanoprobe that addresses these long-standing challenges. The probe has a sensitivity >0.01 units, 2 ms response time, and 50 nm spatial resolution. The technology was incorporated into a double-barrel nanoprobe integrating pH sensing with feedback-controlled distance sensing via Scanning Ion Conductance Microscopy. This allows for the simultaneous 3D topographical imaging and pHe monitoring of living cancer cells. These classes of nanoprobes were used for real-time high spatiotemporal resolution pHe mapping at the subcellular level and revealed tumour heterogeneity of the peri-cellular environments of melanoma and breast cancer cells.
Ma Y, Sikdar D, Fedosyuk A, et al., 2019, An auxetic thermo-responsive nanoplasmonic optical switch., ACS Applied Materials and Interfaces, ISSN: 1944-8244
Development and use of metamaterials have been gaining prominence in large part due to the possibility of creating platforms with 'disruptive' and unique optical properties. However, to date the majority of such systems produced using micro or nanotechnology, are static and can only perform certain target functions. Next-generation multifunctional smart optical metamaterials are expected to have tuneable elements with the possibility of controlling the optical properties in real time via variation in parameters such as pressure, mechanical stress, voltage, or through non-linear optical effects. Here, we address this challenge by developing a thermally controlled optical switch, based on the self-assembly of poly(N-isopropylacrylamide)-functionalised gold nanoparticles on a planar macroscale gold substrate. We show that such meta-surfaces can be tuned to exhibit substantial changes in the optical properties both in terms of wavelength and intensity, through the temperature-controlled variation of the interparticle distance within the nanoparticle monolayer as well as its separation from the substrate. This change is based on temperature induced auxetic expansion and contraction of the functional ligands. Such a system has potential for numerous applications, ranging from thermal sensors to regulated light harnessing.
Kubánková M, Lin X, Albrecht T, et al., 2019, Rapid fragmentation during seeded lysozyme aggregation revealed at the single molecule level, Analytical Chemistry, Vol: 91, Pages: 6880-6886, ISSN: 0003-2700
Protein aggregation is associated with neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. The poorly understood pathogenic mechanism of amyloid diseases makes early stage diagnostics or therapeutic intervention a challenge. Seeded polymerization that reduces the duration of the lag phase and accelerates fibril growth is a widespread model to study amyloid formation. Seeding effects are hypothesized to be important in the "infectivity" of amyloids and are linked to the development of systemic amyloidosis in vivo. The exact mechanism of seeding is unclear yet critical to illuminating the propagation of amyloids. Here we report on the lateral and axial fragmentation of seed fibrils in the presence of lysozyme monomers at short time scales, followed by the generation of oligomers and growth of fibrils.
Cai S, Sze YYJ, Ivanov A, et al., 2019, Small molecule electro-optical binding assay using nanopores, Nature Communications, Vol: 10, Pages: 1-9, ISSN: 2041-1723
The identification of short nucleic acids and proteins at the single molecule level is a major driving force for the development of novel detection strategies. Nanopore sensing has been gaining in prominence due to its label-free operation and single molecule sensitivity. However, it remains challenging to detect small molecules selectively. Here we propose to combine the electrical sensing modality of a nanopore with fluorescence-based detection. Selectivity is achieved by grafting either molecular beacons, complementary DNA, or proteins to a DNA molecular carrier. We show that the fraction of synchronised events between the electrical and optical channels, can be used to perform single molecule binding assays without the need to directly label the analyte. Such a strategy can be used to detect targets in complex biological fluids such as human serum and urine. Future optimisation of this technology may enable novel assays for quantitative protein detection as well as gene mutation analysis with applications in next-generation clinical sample analysis.
Much of the functionality of multi-cellular systems arises from the spatial organisation and dynamic behaviours within and between cells. Current single-cell genomic methods only provide a transcriptional “snapshot” of individual cells. The real-time analysis and perturbation of living cells would generate a step-change in single-cellanalysis. Here we describe minimally invasive nanotweezers that can be spatially controlled to extract samples from living cells with single-molecule precision. They consist of two closely spaced electrodes with gaps as small as 10-20 nm, which can be usedfor the dielectrophoretic trapping of DNA and proteins.Aside from trapping single molecules, we also extract nucleic acids for gene expression analysis from living cells, without affecting their viability. Finally, we report on the trapping, and extraction of a single mitochondrion. This work bridges the gap between single-molecule/organelle manipulation and cell biology and can ultimately enable a better understanding of living cells.
Ma Y, Zagar C, Klemme DJ, et al., 2018, A tunable nanoplasmonic mirror at an electrochemical interface, ACS Photonics, Vol: 5, Pages: 4604-4616, ISSN: 2330-4022
Designing tunable optical metamaterials is one of the great challenges in photonics. Strategies for reversible tuning of nanoengineered devices are currently being sought through electromagnetic or piezo effects. For example, bottom-up self-assembly of nanoparticles at solid | liquid or liquid | liquid interfaces can be used to tune optical responses by varying their structure either chemically or through applied voltage. Here, we report on a fully reversible tunable-color mirror based on a TiN-coated Ag substrate immersed in an aqueous solution of negatively charged Au-nanoparticles (NPs). Switching electrode potential can be used to fully control the assembly/disassembly of NPs at the electrode | electrolyte interface within a 0.6 V wide electrochemical window. The plasmon coupling between the electrode and the adsorbed NP array at high positive potentials produces a dip in the optical reflectance spectrum, creating the "absorber" state. Desorption of NPs at low potentials eliminates the dip, returning the system to the reflective "mirror" state. The intensity and wavelength of the dip can be finely tuned through electrode-potential and electrolyte concentration. The excellent match between the experimental data and the theory of optical response for such system allows us to extract valuable information on equilibrium and kinetic properties of NP-assembly/disassembly. Together with modeling of the latter, this study promotes optimization of such meta-surfaces for building electrotunable reflector devices.
Xue L, Cadinu P, Paulose Nadappuram B, et al., 2018, Gated single-molecule transport in double-barreled nanopores, ACS Applied Materials and Interfaces, Vol: 10, Pages: 38621-38629, ISSN: 1944-8244
Single-molecule methods have been rapidly developing with the appealing prospect of transforming conventional ensemble-averaged analytical techniques. However, challenges remain especially in improving detection sensitivity and controlling molecular transport. In this article, we present a direct method for the fabrication of analytical sensors that combine the advantages of nanopores and field-effect transistors for simultaneous label-free single-molecule detection and manipulation. We show that these hybrid sensors have perfectly aligned nanopores and field-effect transistor components making it possible to detect molecular events with up to near 100% synchronization. Furthermore, we show that the transport across the nanopore can be voltage-gated to switch on/off translocations in real time. Finally, surface functionalization of the gate electrode can also be used to fine tune transport properties enabling more active control over the translocation velocity and capture rates.
Al Sulaiman D, Cadinu P, Ivanov AP, et al., 2018, Chemically modified hydrogel-filled nanopores: a tunable platform for single-molecule sensing, Nano Letters: a journal dedicated to nanoscience and nanotechnology, Vol: 18, Pages: 6084-6093, ISSN: 1530-6984
Label-free, single-molecule sensing is an ideal candidate for biomedical applications that rely on the detection of low copy numbers in small volumes and potentially complex biofluids. Among them, solid-state nanopores can be engineered to detect single molecules of charged analytes when they are electrically driven through the nanometer-sized aperture. When successfully applied to nucleic acid sensing, fast transport in the range of 10–100 nucleotides per nanosecond often precludes the use of standard nanopores for the detection of the smallest fragments. Herein, hydrogel-filled nanopores (HFN) are reported that combine quartz nanopipettes with biocompatible chemical poly(vinyl) alcohol hydrogels engineered in-house. Hydrogels were modified physically or chemically to finely tune, in a predictable manner, the transport of specific molecules. Controlling the hydrogel mesh size and chemical composition allowed us to slow DNA transport by 4 orders of magnitude and to detect fragments as small as 100 base pairs (bp) with nanopores larger than 20 nm at an ionic strength comparable to physiological conditions. Considering the emergence of cell-free nucleic acids as blood biomarkers for cancer diagnostics or prenatal testing, the successful sensing and size profiling of DNA fragments ranging from 100 bp to >1 kbp long under physiological conditions demonstrates the potential of HFNs as a new generation of powerful and easily tunable molecular diagnostics tools.
Ivanov AP, Edel JB, 2018, Scissoring genes with light, NATURE CHEMISTRY, Vol: 10, Pages: 800-801, ISSN: 1755-4330
Rakers V, Cadinu P, Edel JB, et al., 2018, Development of microfluidic platforms for the synthesis of metal complexes and evaluation of their DNA affinity using online FRET melting assays, Chemical Science, Vol: 9, Pages: 3459-3469, ISSN: 2041-6520
Guanine-rich DNA sequences can fold into quadruple-stranded structures known as G-quadruplexes. These structures have been proposed to play important biological roles and have been identified as potential drug targets. As a result, there is increasing interest in developing small molecules that can bind to G-quadruplexes. So far, these efforts have been mostly limited to conventional batch synthesis. Furthermore, no quick on-line method to assess new G-quadruplex binders has been developed. Herein, we report on two new microfluidic platforms to: (a) readily prepare G-quadruplex binders (based on metal complexes) in flow, quantitatively and without the need for purification before testing; (b) a microfluidic platform (based on FRET melting assays of DNA) that enables the real-time and on-line assessment of G-quadruplex binders in continuous flow.
Cadinu P, Campolo G, Pud S, et al., 2018, Double barrel nanopores as a new tool for controlling single-molecule transport, Nano Letters, Vol: 18, Pages: 2738-2745, ISSN: 1530-6984
The ability to control the motion of single biomolecules is key to improving a wide range of biophysical and diagnostic applications. Solid-state nanopores are a promising tool capable of solving this task. However, molecular control and the possibility of slow readouts of long polymer molecules are still limited due to fast analyte transport and low signal-to-noise ratios. Here, we report on a novel approach of actively controlling analyte transport by using a double-nanopore architecture where two nanopores are separated by only a ∼ 20 nm gap. The nanopores can be addressed individually, allowing for two unique modes of operation: (i) pore-to-pore transfer, which can be controlled at near 100% efficiency, and (ii) DNA molecules bridging between the two nanopores, which enables detection with an enhanced temporal resolution (e.g., an increase of more than 2 orders of magnitude in the dwell time) without compromising the signal quality. The simplicity of fabrication and operation of the double-barrel architecture opens a wide range of applications for high-resolution readout of biological molecules.
Kornyshev AA, Sikdar D, Edel JB, et al., 2018, Towards Electrotuneable Nanoplasmonic Fabry–Perot Interferometer, Scientific Reports, Vol: 8, ISSN: 2045-2322
Directed voltage-controlled assembly and disassembly of plasmonic nanoparticles (NPs) at electrified solid–electrolyte interfaces (SEI) offer novel opportunities for the creation of tuneable optical devices. We apply this concept to propose a fast electrotuneable, NP-based Fabry–Perot (FP) interferometer, comprising two parallel transparent electrodes in aqueous electrolyte, which form the polarizable SEI for directed assembly–disassembly of negatively charged NPs. An FP cavity between two reflective NP-monolayers assembled at such interfaces can be formed or deconstructed under positive or negative polarization of the electrodes, respectively. The inter-NP spacing may be tuned via applied potential. Since the intensity, wavelength, and linewidth of the reflectivity peak depend on the NP packing density, the transmission spectrum of the system can thus be varied. A detailed theoretical model of the system’s optical response is presented, which shows excellent agreement with full-wave simulations. The tuning of the peak transmission wavelength and linewidth is investigated in detail. Design guidelines for such NP-based FP systems are established, where transmission characteristics can be electrotuned in-situ, without mechanically altering the cavity length.
Peveler WJ, Noimark S, Al-Azawi H, et al., 2018, Covalently attached antimicrobial surfaces using BODIPY: improving efficiency and effectiveness, ACS Applied Materials and Interfaces, Vol: 10, Pages: 98-104, ISSN: 1944-8244
The development of photoactivated antimicrobial surfaces that kill pathogens through the production of singlet oxygen has proved very effective in recent years, with applications in medical devices and hospital touch surfaces, to improve patient safety and well being. However, many of these surfaces require a swell-encapsulation-shrink strategy to incorporate the photoactive agents in a polymer matrix, and this is resource intensive, given that only the surface fraction of the agent is active against bacteria. Furthermore, there is a risk that the agent will leach from the polymer and thus raises issues of biocompatibility and patient safety. Here, we describe a more efficient method of fabricating a silicone material with a covalently attached monolayer of photoactivating agent that uses heavy-atom triplet sensitization for improved singlet oxygen generation and corresponding antimicrobial activity. We use boron-dipyrromethane with a reactive end group and incorporated Br atoms, covalently attached to poly(dimethylsiloxane). We demonstrate the efficacy of this material in producing singlet oxygen and killing Staphylococcus aureus and suggest how it might be easily modifiable for future antimicrobial surface development.
Aizpurua J, Arnolds H, Baumberg J, et al., 2017, Ultrasensitive and towards single molecule SERS: general discussion, FARADAY DISCUSSIONS, Vol: 205, Pages: 291-330, ISSN: 1359-6640
Barik A, Zhang Y, Grassi R, et al., 2017, Graphene-edge dielectrophoretic tweezers for trapping of biomolecules, Nature Communications, Vol: 8, Pages: 1-9, ISSN: 2041-1723
The many unique properties of graphene, such as the tunable optical, electrical, and plasmonic response make it ideally suited for applications such as biosensing. As with other surface-based biosensors, however, the performance is limited by the diffusive transport of target molecules to the surface. Here we show that atomically sharp edges of monolayer graphene can generate singular electrical field gradients for trapping biomolecules via dielectrophoresis. Graphene-edge dielectrophoresis pushes the physical limit of gradient-force-based trapping by creating atomically sharp tweezers. We have fabricated locally backgated devices with an 8-nm-thick HfO2 dielectric layer and chemical-vapor-deposited graphene to generate 10× higher gradient forces as compared to metal electrodes. We further demonstrate near-100% position-controlled particle trapping at voltages as low as 0.45 V with nanodiamonds, nanobeads, and DNA from bulk solution within seconds. This trapping scheme can be seamlessly integrated with sensors utilizing graphene as well as other two-dimensional materials.
Sze JYY, Ivanov AP, Cass AEG, et al., 2017, Single molecule multiplexed nanopore protein screening in human serum using aptamer modified DNA carriers, Nature Communications, Vol: 8, Pages: 1-10, ISSN: 2041-1723
The capability to screen a range of proteins at the single-molecule level with enhanced selectivity in biological fluids has been in part a driving force in developing future diagnostic and therapeutic strategies. The combination of nanopore sensing and nucleic acid aptamer recognition comes close to this ideal due to the ease of multiplexing, without the need for expensive labelling methods or extensive sample pre-treatment. Here, we demonstrate a fully flexible, scalable and low-cost detection platform to sense multiple protein targets simultaneously by grafting specific sequences along the backbone of a double-stranded DNA carrier. Protein bound to the aptamer produces unique ionic current signatures which facilitates accurate target recognition. This powerful approach allows us to differentiate individual protein sizes via characteristic changes in the sub-peak current. Furthermore, we show that by using DNA carriers it is possible to perform single-molecule screening in human serum at ultra-low protein concentrations.
Recently, there has been a drive to design and develop fully tunable metamaterials for applications ranging from new classes of sensors to superlenses among others. Although advances have been made, tuning and modulating the optical properties in real time remains a challenge. We report on the first realization of a reversible electrotunable liquid mirror based on voltage-controlled self-assembly/disassembly of 16 nm plasmonic nanoparticles at the interface between two immiscible electrolyte solutions. We show that optical properties such as reflectivity and spectral position of the absorption band can be varied in situ within ±0.5 V. This observed effect is in excellent agreement with theoretical calculations corresponding to the change in average interparticle spacing. This electrochemical fully tunable nanoplasmonic platform can be switched from a highly reflective 'mirror' to a transmissive 'window' and back again. This study opens a route towards realization of such platforms in future micro/nanoscale electrochemical cells, enabling the creation of tunable plasmonic metamaterials.
Crick CR, Albella P, Kim H-J, et al., 2017, Low-Noise Plasmonic Nanopore Biosensors for Single Molecule Detection at Elevated Temperatures, ACS Photonics, Vol: 4, Pages: 2835-2842, ISSN: 2330-4022
Advanced single molecular analysis is a key stepping stone for the rapid sensing and characterization of biomolecules. This will only be made possible through the implementation of versatile platforms, with high sensitivities and the precise control of experimental conditions. The presented work details an advancement of this technology, through the development of a low-noise Pyrex/silicon nitride/gold nanopore platform. The nanopore is surrounded by a plasmonic bullseye structure and provides targeted and controllable heating via laser irradiation, which is directed toward the center of the pore. The device architecture is investigated using multiwavelength laser heating experiments and 'individual DNA molecules are detected under controlled heating. The plasmonic features, optimized through numerical simulations, are tuned to the wavelength of incident light, ensuring a platform that provides substantial heating with high signal-to-noise.
Cadinu P, Paulose Nadappuram B, Lee DJ, et al., 2017, Single Molecule Trapping and Sensing Using Dual Nanopores Separated by a Zeptoliter Nanobridge., Nano letters, Vol: 17, Pages: 6376-6384, ISSN: 1530-6984
There is a growing realization, especially within the diagnostic and therapeutic community, that the amount of information enclosed in a single molecule can not only enable a better understanding of biophysical pathways, but also offer exceptional value for early stage biomarker detection of disease onset. To this end, numerous single molecule strategies have been proposed, and in terms of label-free routes, nanopore sensing has emerged as one of the most promising methods. However, being able to finely control molecular transport in terms of transport rate, resolution, and signal-to-noise ratio (SNR) is essential to take full advantage of the technology benefits. Here we propose a novel solution to these challenges based on a method that allows biomolecules to be individually confined into a zeptoliter nanoscale droplet bridging two adjacent nanopores (nanobridge) with a 20 nm separation. Molecules that undergo confinement in the nanobridge are slowed down by up to 3 orders of magnitude compared to conventional nanopores. This leads to a dramatic improvement in the SNR, resolution, sensitivity, and limit of detection. The strategy implemented is universal and as highlighted in this manuscript can be used for the detection of dsDNA, RNA, ssDNA, and proteins.
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