Single Nanoparticle Detection Research Articles

Design of nanoslotted photonic crystal waveguide cavities for single nanoparticle trapping and detection

We design and numerically simulate an on-chip photonic device that integrates both optical manipulation and detection functionalities for a single nanoparticle or macromolecule. A unique combination of a photonic crystal waveguide cavity and a nanoslot structure leads to a approximately 1300 times enhancement of the optical gradient trapping force compared with a conventional waveguide trapping device. Numerical simulations indicate that the designed device is capable of stably trapping a single nanoparticle inside the nanoslot cavity, and thus provides an ideal platform for single particle detection and analysis using cavity-enhanced spectroscopic technologies.

Single Particle Quantum Dot Imaging Achieves Ultrasensitive Detection Capabilities for Western Immunoblot Analysis

Substantially improved detection methods are needed to detect fractionated protein samples present at trace concentrations in complex, heterogeneous tissue and biofluid samples. Here we describe a modification of traditional Western immunoblotting using a technique to count quantum-dot-tagged proteins on optically transparent PVDF membranes. Counts of quantum-dot-tagged proteins on immunoblots achieved optimal detection sensitivity of 0.2 pg and a sample size of 100 cells. This translates to a 10(3)-fold improvement in detection sensitivity and a 10(2)-fold reduction in required cell sample, compared to traditional Westerns processed using the same membrane immunoblots. Quantum dot fluorescent blinking analysis showed that detection of single QD-tagged proteins is possible and that detected points of fluorescence consist of one or a few (<9) QDs. The application of single nanoparticle detection capabilities to Western blotting technologies may provide a new solution to a broad range of applications currently limited by insufficient detection sensitivity and/or sample availability.

Qualitative detection of single submicron and nanoparticles in human skin by scanning transmission x-ray microscopy

First results on single particle detection in human skin samples by x-ray microscopy are reported. 94+/-6 and 161+/-13 nm gold core particles with silica shells and 298+/-11 nm silica particles coated with a gold shell on ultramicrotome sections of human skin were determined. The particles were applied on fresh intact skin samples, which were sectioned prior to imaging. After screening the sections by conventional microscopy techniques, defined areas of interest were qualitatively investigated by scanning transmission x-ray microscopy at the Swiss Light Source. In studies on the percutaneous penetration of 161+/-13 nm particles on human skin samples, x-ray microscopy yielded high-resolution images of single particles spreading on the superficial layer of the stratum corneum and on the epithelium in superficial parts of hair follicles. No deeper penetration was observed. The present work using x-ray microscopy provides the unique opportunity to study qualitative penetration processes and membrane-particle interactions on the level of single particles. This goes beyond present approaches using optical microscopy. Further improvement of this approach will allow one to study particles with different physicochemical properties and surface modifications, including responses of the exposed tissue.

Detection of Single Photoluminescent Diamond Nanoparticles in Cells and Study of the Internalization Pathway

Diamond nanoparticles are promising photoluminescent probes for tracking intracellular processes, due to embedded, perfectly photostable color centers. In this work, the spontaneous internalization of such nanoparticles (diameter 25 nm) in HeLa cancer cells is investigated by confocal microscopy and time-resolved techniques. Nanoparticles are observed inside the cell cytoplasm at the single-particle and single-color-center level, assessed by time-correlation intensity measurements. Improvement of the nanoparticle signal-to-noise ratio inside the cell is achieved using a pulsed-excitation laser and time-resolved detection taking advantage of the long radiative lifetime of the color-center excited state as compared to cell autofluorescence. The internalization pathways are also investigated, with endosomal marking and colocalization analyses. The low colocalization ratio observed proves that nanodiamonds are not trapped in endosomes, a promising result in prospect of drug delivery by these nanoparticles. Low cytotoxicity of these nanoparticles in this cell line is also shown.

Optical response of a single gold nanoparticle

Optical detection and spectroscopy of single gold nanoparticles using the spatial-modulation spectroscopy technique is described, focusing on the connection between the nanoparticle and environment parameters with the measured linear optical extinction spectrum. Characterisation of the size, shape and orientation on the substrate of a nanoparticle through quantitative determination of its optical extinction cross-section spectrum is illustrated in the case of gold nanospheres and nanorods. Extension of this technique to ultrafast nonlinear spectroscopy of a single gold nanoparticle is also discussed.

Noise Characteristics and Particle Detection Limits in Diode$+$MTJ Matrix Elements for Biochip Applications

A fully scalable matrix-based magnetoresistive biochip has been recently introduced for the detection of biomolecular recognition events. This work reports results for a 3times3 cells matrix comprising hydrogenated amorphous silicon diodes (PIN and Schottky) and aluminum oxide magnetic tunnel junctions (MTJ). The noise characteristics of the individual thin film diodes (TFD) and the MTJ were analyzed for measuring frequencies from DC to 1 kHz, allowing the detection of single magnetic nanoparticles with 250 nm and 130 nm diameters. For 50 nm particles, and at 1 kHz, minimum number of detectable labels ranges from 20 (Schottky diodes) to 50 (PIN diodes).

Submicrometer Hall Sensors for Superparamagnetic Nanoparticle Detection

Submicrometer Hall sensors, with Hall cross width of ~250 nm, were fabricated from InAs/AlSb quantum well semiconductor heterostructures. The room-temperature device characteristics were examined by experimental Hall effect and electronic noise measurements combined with analytical calculations. The noise-equivalent magnetic moment resolution of the order of 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sup> mu <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">B</sub> /radicHz was obtained at frequencies above ~1 kHz. We show that the devices can achieve single superparamagnetic nanoparticle detection and thus be employed in experiments involving single magnetically labeled biomolecule detection.

Thermally Assisted Magnetic Tunneling Junction for Biosensing Applications

We present a concept of the thermally assisted magnetic tunneling junction (MTJ)-based biosensor. The sensor consists of an MTJ, an isolation layer, and a gold coating layer right underneath a biocoating layer. During the sensing phase, a current pulse heats the top free ferromagnet of the MTJ stack above its blocking temperature. The top magnet loses its magnetization at this point. During the cool down period, the top free magnet picks up its magnetization orientation based on the external magnetic field. A vertical excitation field is applied to excite the superparamagnetic biolabels during the sensing phase. If there is no magnetic biolabel captured by the sensing cell, the magnetization in MTJ top free magnetic layer will be programmed by the fringe field from the bottom pinned magnet and will be anti-parallel to the latter. If there are one or more magnetic labels captured by the sensing cell, the superparamagnetic nanoparticle(s) will generate fringe field. The top magnet follows the orientation of the in-plane fringe field component, which is parallel to the pinned bottom magnet. The sensing result can be read out by measuring the tunneling resistance of the MTJ cell. The proposed biosensor design can achieve high sensitivity in three different ways: 1) the magnetic sensing and electronic read-out operations are decoupled in time domain; 2) the binary readout increases the signal to noise ratio significantly; and 3) thermally assisted magnetic sensing decouples the sensor sensitivity from the magnetic stiffness of the sensing layer. Our simulation results demonstrate sensitivity sufficient for single nanoparticle detection. The thermal analysis indicates that the temperature on the top surface of gold layer can be maintained below 50 degC in order to avoid damage to the biocoating layer.

Nanoparticle-Induced Fluorescence Lifetime Modification as Nanoscopic Ruler: Demonstration at the Single Molecule Level

We combine interferometric detection of single gold nanoparticles, single molecule microscopy, and fluorescence lifetime measurement to study the modification of the fluorescence decay rate of an emitter close to a nanoparticle. In our experiment, gold particles with a diameter of 15 nm were attached to single dye molecules via double-stranded DNA of different lengths. Nanoparticle-induced lifetime modification (NPILM) has promise in serving as a nanoscopic ruler for the distance range well beyond 10 nm, which is the upper limit of fluorescence resonant energy transfer (FRET). Furthermore, the simultaneous detection of single nanoparticles and fluorescent molecules presented in this work provides new opportunities for single molecule biophysical studies.

A common-path interferometer for time-resolved and shot-noise-limited detection of single nanoparticles

We give a detailed description of a novel method for timeresolved experiments on single non-luminescent nanoparticles. The method is based on the combination of pump-probe spectroscopy and a commonpath interferometer. In our interferometer, probe and reference arms are separated in time and polarization by a birefringent crystal. The interferometer, fully described by an analytical model, allows us to separately detect the real and imaginary contributions to the signal. We demonstrate the possibilities of the setup by time-resolved detection of single gold nanoparticles as small as 10 nm in diameter, and of acoustic oscillations of particles larger than 40 nm in diameter.

Optical Detection of Single Nanoparticles and Viruses

We have developed two different optical techniques for the detection of nanoscale particles. One of the methods is based on measuring the optical gradient force exerted on a nanoparticle as it passes through a confined optical field, and the other method uses a background-free interferometric scheme to detect the scattered field amplitude from a laser-irradiated particle. In both cases, the measured signal depends on the third power of the particle size (R <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> ) as opposed to the R <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">6</sup> dependence inherent to traditional scattering-based detection methods. The weaker size dependence in our schemes leads to a better signal-to-noise ratio (SNR) for small particles. Similar to mass spectrometry, the first detection method influences the trajectory of a particle as it passes through a tightly focused laser beam. On the other hand, the second detection method combines an interferometer with a split detector that yields no signal in the absence of a particle. For both systems, we demonstrate real-time (1 ms) detection of single nanoparticles in a microfluidic system and discuss the limits of each detection approach

Quantitative Detection and Fixation of Single and Multiple Gold Nanoparticles on a Microfluidic Chip by Thermal Lens Microscope

A detection and fixation method of single and multiple gold nanoparticles on the wall of a microfluidic channel is demonstrated. A thermal lens microscope (TLM) with continuous-wave excitation (wavelength, 532 nm) and probe (wavelength, 670 nm) laser beams was used to realize the sensitive detection of heat generated by light absorption of individual gold nanoparticles (50 nm in diameter); fixation of the individual nanoparticles was realized simultaneously. The fixation mechanism was investigated and attributed to an absorption-based optical force. In addition to single nanoparticle detection, multiple-nanoparticle detection and fixation was demonstrated. An acceleration of fixation was observed when the number of fixed particles was increased. TLM is expected to be a powerful tool for both the quantitative detection and precise fixation of individual nanoparticles.

Modeling Electrochemical Deposition inside Nanotubes to Obtain Metal−Semiconductor Multiscale Nanocables or Conical Nanopores

Nanocables with a radial metal-semiconductor heterostructure have recently been prepared by electrochemical deposition inside metal nanotubes. First, a bare nanoporous polycarbonate track-etched membrane is coated uniformly with a metal film by electroless deposition. The film forms a working electrode for further deposition of a semiconductor layer that grows radially inside the nanopore when the deposition rate is slow. We propose a new physical model for the nanocable synthesis and study the effects of the deposited species concentration, potential-dependent reaction rate, and nanopore dimensions on the electrochemical deposition. The problem involves both axial diffusion through the nanopore and radial transport to the nanopore surface, with a surface reaction rate that depends on the axial position and the time. This is so because the radial potential drop across the deposited semiconductor layer changes with the layer thickness through the nanopore. Since axially uniform nanocables are needed for most applications, we consider the relative role of reaction and axial diffusion rates on the deposition process. However, in those cases where partial, empty-core deposition should be desirable (e.g., for producing conical nanopores to be used in single nanoparticle detection), we give conditions where asymmetric geometries can be experimentally realized.

Detection of single micron-sized magnetic bead and magnetic nanoparticles using spin valve sensors for biological applications

We have fabricated a series of highly sensitive spin valve sensors on a micron scale that successfully detected the presence of a single superparamagnetic bead (Dynabeads M-280, 2.8 μm in diameter), and thus showed suitability for identifying biomolecules labeled by such magnetic beads. By polarizing the magnetic microbead on a spin valve sensor with a dc magnetic field and modulating its magnetization with an orthogonal ac magnetic field, we observed a magnetoresistance (MR) signal reduction caused by the magnetic dipole field from the bead that partially cancelled the applied fields to the spin valve. A lock-in technique was used to measure a voltage signal due to the MR reduction. A signal of 1.2 mV rms or 5.2 mΩ of resistance reduction was obtained from a 3 μm wide sensor and a signal of 3.8 mV rms or 11.9 mΩ from a 2.5 μm wide sensor. Micromagnetic simulations were also performed for the spin valve sensors with a single bead and gave results consistent with experiments. Further experiments and simulations suggested that these sensors or their variations can detect 1–10 Co nanoparticles with a diameter of ∼11 nm, and are suitable for DNA fragment detection.

Nanofluidic networks based on surfactant membrane technology.

We explore possibilities to construct nanoscale analytical devices based on lipid membrane technology. As a step toward this goal, we present nanotube-vesicle networks with fluidic control, where the nanotube segments reside at, or very close (<2 microm) to optically transparent surfaces. These nanofluidic systems allow controlled transport as well as LIF detection of single nanoparticles. In the weak-adhesion regime, immobilized vesicles can be approximated as perfect spheres with nanotubes attached at half the height of the vesicle in the axial (z) dimension. In the strong-adhesion regime (relative contact area, Sr* approximately 0.3), nanotubes can be adsorbed to the surface with a distance to the interior of the nanotubes defined by the membrane thickness of approximately 5 nm. Strong surface adsorption restricts nanotube self-organization, enabling networks of nanotubes with arbitrary geometries. We demonstrate LIF detection of single nanoparticles (30-nm-diameter fluorescent beads) inside single nanotubes. Transport of nanoparticles was induced by a surface tension differential applied across nanotubes using a hydrodynamic injection protocol. Controlled transport in nanotubes together with LIF detection enables construction of nanoscale fluidic devices with potential to operate with single molecules. This opens up possibilities to construct analytical platforms with characteristic length scales and volume orders of magnitudes smaller than employed in traditional microfluidic devices.

Probing Single Molecules and Single Nanoparticles by Surface-Enhanced Raman Scattering

Optical detection and spectroscopy of single molecules and single nanoparticles have been achieved at room temperature with the use of surface-enhanced Raman scattering. Individual silver colloidal nanoparticles were screened from a large heterogeneous population for special size-dependent properties and were then used to amplify the spectroscopic signatures of adsorbed molecules. For single rhodamine 6G molecules adsorbed on the selected nanoparticles, the intrinsic Raman enhancement factors were on the order of 10(14) to 10(15), much larger than the ensemble-averaged values derived from conventional measurements. This enormous enhancement leads to vibrational Raman signals that are more intense and more stable than single-molecule fluorescence.