Single Particle Detection Research Articles

Single particle detection in CMOS compatible photonic crystal nanobeam cavities

We report the label-free detection of single particles using photonic crystal nanobeam cavities fabricated in silicon-on-insulator platform, and embedded inside microfluidic channels fabricated in poly-dimethylsiloxane (PDMS). Our system operates in the telecommunication wavelength band, thus leveraging the widely available, robust and tunable telecom laser sources. Using this approach, we demonstrated the detection of polystyrene nanoparticles with dimensions down to 12.5nm in radius. Furthermore, binding events of a single streptavidin molecule have been observed.

Reduced blinking behavior of single 2-mercapto ethanol capped CdTe quantum dots

Water soluble small size CdTe QDs were synthesized by using 2-mercapto ethanol (2ME) as stabilizer. The optimum size of QDs was obtained after certain time of reflux. Synthesized 2ME capped CdTe QDs show large Stokes shifted photoluminescence. At the single particle detection level, 2ME capped CdTe QDs showed reduced blinking behavior compared to that of TGA capped CdTe QDs. These results indicate that the thiol moiety of 2ME, which is a strong electron donor, saturated the surface traps with electrons, preventing the traps from accepting the Auger ionized electrons from the core of CdTe QD.

Development of a single-particle detector for the dielectronic recombination experiment on HIRFL-CSRm

A single-particle detector, which is designed to detect ions with energies of more than 2MeV/u, has been built and tested. The detector is operated based on the secondary-electron emission, which are produced by the incident ions impacting on a molybdenum foil with a thickness of about 5μm. The secondary electrons are deflected and focused onto two microchannel plates with chevron assembly. We simulated the trajectories of the secondary electrons in the electrostatic field and obtained the theoretical detection efficiency, which is greater than 90% and depends on electron yields and diameter of area of the electron emission. The detector was tested by an alpha radioactive source offline and by 86Kr26+ ions (25MeV/u) from accelerator. The detector can be used under the counting rate up to about 1×107s−1, which satisfies the requirements of the dielectronic recombination experiment on storage ring CSRm.

Development of Au-coated THGEM for single photon, charged particle, and neutron detection

We report the successful development of Au-coated Thick Gas Electron Multipliers (THGEMs) based totally on homemade industrial PCB technology in China. THGEMs with various dimensions and substrates have been produced and tested. Production achievements include sensitive areas up to 500×1000mm2, hole diameters down to 200μm, thicknesses down to 150μm, rims from 20 to 120μm, and feasibility of mass production. In addition, effective techniques have been applied to improve the quality and performance of THGEMs. The effective gain, gain stability, gain uniformity, and energy resolution in Ar-based and Ne-based gas mixtures were studied. Test results of X-rays, VUV&UV lights, cosmic ray muons, and alpha particles show that these kinds of THGEMs are promising.

Optimizing the Acquisition and Analysis of Confocal Images for Quantitative Single‐Mobile‐Particle Detection

Quantification of the fluorescence properties of diffusing particles in solution is an invaluable source of information for characterizing the interactions, stoichiometry, or conformation of molecules directly in their native environment. In the case of heterogeneous populations, single-particle detection should be the method of choice and it can, in principle, be achieved by using confocal imaging. However, the detection of single mobile particles in confocal images presents specific challenges. In particular, it requires an adapted set of imaging parameters for capturing the confocal images and an adapted event-detection scheme for analyzing the image. Herein, we report a theoretical framework that allows a prediction of the properties of a homogenous particle population. This model assumes that the particles have linear trajectories with reference to the confocal volume, which holds true for particles with moderate mobility. We compare the predictions of our model to the results as obtained by analyzing the confocal images of solutions of fluorescently labeled liposomes. Based on this comparison, we propose improvements to the simple line-by-line thresholding event-detection scheme, which is commonly used for single-mobile-particle detection. We show that an optimal combination of imaging and analysis parameters allows the reliable detection of fluorescent liposomes for concentrations between 1 and 100 pM. This result confirms the importance of confocal single-particle detection as a complementary technique to ensemble fluorescence-correlation techniques for the studies of mobile particle.

Single Particle Detection by Area Amplification: Single Wall Carbon Nanotube Attachment to a Nanoelectrode

We describe the electrochemical detection of single nanoparticle (NP) attachment on a nanoelectrode by the increase in the active electrode area. The attachment of gold NP-decorated single wall carbon nanotubes (Au-SWCNTs) was observed by their current-time transients for ferrocenemethanol (FcMeOH) oxidation. Since the attached Au-SWCNT increases the electroactive area available for FcMeOH oxidation, the current increases after attachment of the particle. The "staircase" shape of the current response establishes that the particles do not become deactivated for the outer-sphere electron transfer reaction after attachment. Au-SWCNTs migrate to and are held at the nanoelectrode by an electric field. However, SWCNTs that are not decorated with a gold NP produce only a sharp transient ("blip") response.

A pixel detector system for laser-accelerated ion detection

Laser ion acceleration is an unique acceleration process that creates ultra-short ion pulses of high intensity ( > 107 ions/cm2/ns), which makes online detection an ambitious task. Non-electronic detectors such as radio-chromic films (RCF), imaging plates (IP) or nuclear track detectors (e.g. CR39) are broadly used at present. Only offline information on ion pulse intensity and position are available by these detectors, as minutes to hours of processing time are required after their exposure. With increasing pulse repetition rate of the laser system, there is a growing need for detection of laser accelerated ions in real-time.Therefore, we have investigated a commercial pixel detector system for online detection of laser-accelerated proton pulses. The CMOS imager RadEye1 was chosen, which is based on a photodiode array, 512 × 1024 pixels with 48 μm pixel pitch, thus offering a large sensitive area of approximately 25 × 50 mm2. First detection tests were accomplished at the conventional electrostatic 14 MV Tandem accelerator in Munich as well as Atlas laser accelerator. Detector response measurements at the conventional accelerator have been accomplished in a proton beam in dc (15 MeV) and pulsed (20 MeV) irradiation mode, the latter providing comparable particle flux as under laser acceleration conditions. Radiation hardness of the device was studied using protons (20 MeV) and C-ions (77 MeV), additionally. The detector system shows a linear response up to a maximum pulse flux of about 107 protons/cm2/ns. Single particle detection is possible in a low flux beam (104 protons/cm2/s) for all investigated energies. The radiation hardness has shown to give reasonable lifetime for an application at the laser accelerator. The results from the irradiation at a conventional accelerator are confirmed by a cross-calibration with CR39 in a laser-accelerated proton beam at the MPQ Atlas Laser in Garching, showing no problems of detector operation in presence of electro-magnetic pulse (EMP). The calibrated detector system was finally used for online detection of laser-accelerated proton and carbon ions at the Astra-Gemini laser.

Liposome–Quantum Dot Complexes Enable Multiplexed Detection of Attomolar DNAs without Target Amplification

Sensitive detection of DNA usually relies on target amplification approaches such as polymerase chain reaction and rolling circle amplification. Here we describe a new approach for sensitive detection of low-abundance DNA using liposome-quantum dot (QD) complexes and single-particle detection techniques. This assay allows for detection of single-stranded DNA at attomolar concentrations without the involvement of target amplification. Importantly, this strategy can be employed for simultaneous detection of multiple DNA targets.

Influence of gold coating and interplate voltage on the performance of chevron micro-channel plates for temporally and spatially resolved single particle detection

We present a study of two different sets of Micro-Channel Plates used for time and space resolved single particle detection. We investigate the effects of the gold coating and that of introducing an interplate voltage between the spatially separated plates. We find that the gold coating increases the count rate of the detector and the pulse amplitude as previously reported for non-spatially resolved setups. The interplate voltage also increases count rates. In addition, we find that a non-zero interplate voltage improves the spatial accuracy in determining the arrival position of incoming single particles (by ~20%) while the gold coating has a negative effect (by ~30%).

The Role of Pore Geometry in Single Particle Detection

Single pores prepared in thin membranes have demonstrated great potential as platforms for next generation, high-throughput single particle biosensors. The realization of readily accessible solid-state devices applicable to virion-sized particles has yet to come due to an inadequate understanding of particle detection mechanics in pores whose diameters are comparable to their length. Successful detection experiments involving nanoparticles have largely relied on high-aspect-ratio pores prepared in glass or polymers and, most recently, low-aspect-ratio solid-state pores. We present a systematic study of pores bridging the gap between these regimes and evaluating their detection parameters as they relate to pore geometry.In pore-based detection, a particle occludes current-carrying electrolyte as it translocates the pore. This creates a transient pulse of diminished ionic current which can be characterized by its depth and duration. Integrating recent findings with low-aspect-ratio pores and long-standing high-aspect-ratio pore considerations with our experiments, we formulate an approximation for event depth which, for the first time, depends explicitly on geometric parameters. Further, we develop an approximation for the electric field which allows us to characterize particle zeta potentials with our pores. This approximation is utilized to quantify capture rates in terms of known electric potentials and geometric factors, revealing higher-than-anticipated rates, potentially reducing amount the time an experiment needs to run for successful analysis. Although our results yield refined approximations, these findings represent a step toward realizing practical detection devices.This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344. Portions of this work were performed as a User project at the Molecular Foundry, Lawrence Berkeley National Laboratory, which is supported by the Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy under Contract DE-AC02-05CH11231. LLNL-ABS-588174

Single particle detection, manipulation and analysis with resonant optical trapping in photonic crystals

We demonstrate a resonant optical trapping mechanism based on two-dimensional hollow photonic crystal cavities. This approach benefits simultaneously from the resonant nature and unprecedented field overlap with the trapped specimen. The photonic crystal structures are implemented in a 30 mm × 12 mm optofluidic chip consisting of a patterned silicon substrate and an ultrathin microfluidic membrane for particle injection and control. Firstly, we demonstrate permanent trapping of single 250 and 500 nm-sized particles with sub-mW powers. Secondly, the particle induces a large resonance shift of the cavity mode amounting up to several linewidths. This shift is exploited to detect the presence of a particle within the trap and to retrieve information on the trapped particle. The individual addressability of multiple cavities on a single photonic crystal device is also demonstrated.

Hybrid optofluidic integration.

Complete integration of microfluidic and optical functions in a single lab-on-chip device is one goal of optofluidics. Here, we demonstrate the hybrid integration of a PDMS-based fluid handling layer with a silicon-based optical detection layer in a single optofluidic system. The optical layer consists of a liquid-core antiresonant reflecting optical waveguide (ARROW) chip that is capable of single particle detection and interfacing with optical fiber. Integrated devices are reconfigurable and able to sustain high pressures despite the small dimensions of the liquid-core waveguide channels. We show the combination of salient sample preparation capabilities-particle mixing, distribution, and filtering-with single particle fluorescence detection. Specifically, we demonstrate fluorescent labelling of λ-DNA, followed by flow-based single-molecule detection on a single device. This points the way towards amplification-free detection of nucleic acids with low-complexity biological sample preparation on a chip.

Heterogeneities of individual catalyst particles in space and time as monitored by spectroscopy

Recent years have witnessed the introduction of spatiotemporal spectroscopy for the characterization of catalysts at work at previously unattainable resolution and sensitivity. They have revealed that heterogeneous catalysts are more heterogeneous than often expected. Dynamic changes in the nature of active sites, such as their distribution and accessibility, occur both between and within particles. Scientists now have micro- and nanospectroscopic methods at hand to improve the understanding of catalyst heterogeneities and exploit them in catalyst design. Here we review the latest developments within this lively field. The trends include detection of single particles or molecules, super-resolution imaging, the transition from two- to three-dimensional imaging, selective staining, integration of spectroscopy with electron microscopy or scanning probe methods, and measuring under realistic reaction conditions. Such experimental approaches change the hitherto somewhat static picture of heterogeneous catalysis into one that acknowledges that catalysts behave almost like living objects--explaining why many characterization methods from the life sciences are being incorporated into catalysis research.

Velocity map photoelectron-photoion coincidence imaging on a single detector

Here we report on a new simplified setup for velocity map photoelectron-photoion coincidence imaging using only a single particle detector. We show that both photoelectrons and photoions can be extracted toward the same micro-channel-plate delay line detector by fast switching of the high voltages on the ion optics. This single detector setup retains essentially all the features of a standard two-detector coincidence imaging setup, viz., the high spatial resolution for electron and ion imaging, while only slightly decreasing the ion time-of-flight mass resolution. The new setup paves the way to a significant cost reduction in building a coincidence imaging setup for experiments aiming to obtain the complete correlated three-dimensional momentum distribution of electrons and ions.

Efficient single particle detection with a superconducting nanowire

Detection of α- and β-particles is of paramount importance in a wide range of applications. Current particle detectors are all macroscopic and have limited time resolution. We demonstrate a nanoscale particle detector with a small detection volume, high detection efficiency, short dead times and low dark count levels. We measure α- and β-particle detection efficiencies close to unity using different sources and also demonstrate blindness towards γ-rays. Our nanoscale detector offers particle detection measurements with unprecendented spatial resolution.

Optical single-particle detection in nanoholes towards simple parallel detection of molecular binding events

A novel scheme for the optical detection of a few or even single gold nanoparticle labels is introduced. It utilizes sub-wavelength holes in a chromium layer on a glass substrate, where a bioaffinity reaction could take place and the outcome (regarding particle label binding) can be monitored using optical means. Experiments in combination with simulations demonstrate that the presence of particles in such a chromium hole can be simply detected by using the color information of images by a charge couple device (CCD) camera without the need for additional spectroscopy setups. The presence of gold nanoparticles leads to a detectable red-shift in the images of the respective nanohole, which is the sensing principle of the sensor.

Circular depolarization ratios of single water droplets and finite ice circular cylinders: a modeling study

Abstract. Computations of the phase matrix elements for single water droplets and ice crystals in fixed orientations are presented to determine if circular depolarization δC is more accurate than linear depolarization for phase discrimination. T-matrix simulations were performed to calculate right-handed and left-handed circular depolarization ratios δ+C, respectively δ−C and to compare them with linear ones. Ice crystals are assumed to have a circular cylindrical shape where their surface-equivalent diameters range up to 5 μm. The circular depolarization ratios of ice particles were generally higher than linear depolarization and depended mostly on the particle orientation as well as their sizes. The fraction of non-detectable ice crystals (δ<0.05) was smaller considering a circular polarized light source, reaching 4.5%. However, water droplets also depolarized light circularly for scattering angles smaller than 179° and size parameters smaller than 6 at side- and backscattering regions. Differentiation between ice crystals and water droplets might be difficult for experiments performed at backscattering angles which deviate from 180° unlike LIDAR applications. Instruments exploiting the difference in the P44/P11 ratio at a scattering angle around 115° are significantly constrained in distinguishing between water and ice because small droplets with size parameters between 5 and 10 do cause very high circular depolarizations at this angle. If the absence of the liquid phase is confirmed, the use of circular depolarization in single particle detection is more sensitive and less affected by particle orientation.

Electrical detection of single pollen allergen particles using electrode-embedded microchannels

We report on the development of a microfluidic system for the electrical detection of single pollen allergen particles. Our device consists of 500 nm electrode gaps fabricated in an 800 nm wide fluidic channel. We flowed pollen allergen particles of average size 330 nm along the channel via fluid pumping and simultaneously monitored temporal change in dc current flowing through the sensing electrodes. Current spikes were detected, which can be attributed to a capacitance discharging upon trapping/detrapping of single allergens in the electrode gap. This sensing mechanism may open new avenues for a highly sensitive pollen allergen sensor.

Surface-Enhanced Raman Scattering Detection of DNAs Derived from Virus Genomes Using Au-Coated Paramagnetic Nanoparticles

A magnetic capture-based, surface-enhanced Raman scattering (SERS) assay for DNA detection has been developed which utilizes Au-coated paramagnetic nanoparticles (Au@PMPs) as both a SERS substrate and effective bioseparation reagent for the selective removal of target DNAs from solution. Hybridization reactions contained two target DNAs, sequence complementary reporter probes conjugated with spectrally distinct Raman dyes distinct for each target, and Au@PMPs conjugated with sequence complementary capture probes. In this case, target DNAs were derived from the RNA genomes of the Rift Valley Fever virus (RVFV) or West Nile virus (WNV). The hybridization reactions were incubated for a short period and then concentrated within the focus beam of an interrogating laser by magnetic pull-down. The attendant SERS response of each individually captured DNA provided a limit of detection sensitivity in the range 20-100 nM. X-ray diffraction and UV-vis analysis validated both the desired surface plasmon resonance properties and bimetallic composition of synthesized Au@PMPs, and UV-vis spectroscopy confirmed conjugation of the Raman dye compounds malachite green (MG) and erythrosin B (EB) with the RVFV and WNV reporter probes, respectively. Finally, hybridization reactions assembled for multiplexed detection of both targets yielded mixed MG/EB spectra and clearly differentiated peaks which facilitate the quantitative detection of each DNA target. On the basis of the simple design of a single-particle DNA detection assay, the opportunity is provided to develop magnetic capture-based SERS assays that are easily assembled and adapted for high-level multiplex detection using low-cost Raman instrumentation.

Sensitivity of a superconducting nanowire detector for single ions at low energy

We report on the characterization of a superconducting nanowire detector for ions at low kinetic energies. We measure the absolute single-particle detection efficiency η and trace its increase with energy up to η = 100%. We discuss the influence of noble gas adsorbates on the cryogenic surface and analyze their relevance for the detection of slow massive particles. We apply a recent model for the hot-spot formation to the incidence of atomic ions at energies between 0.2 and 1 keV. We suggest how the differences observed for photons and atoms or molecules can be related to the surface condition of the detector and we propose that the restoration of proper surface conditions may open a new avenue for SSPD-based optical spectroscopy on molecules and nanoparticles.