Sensitive Optical Detection Research Articles

Improving the Signal-to-Background Ratio during Catalytic Hairpin Assembly through Both-End-Blocked DNAzyme.

Catalyzed hairpin assembly (CHA) is an important DNA engineering tool for a variety of applications such as DNA nanotechnology and biosensing. Here we report a hairpin-type of both-end-blocked DNAzyme to improve the signal-to-background ratio during the CHA process. In the design, the DNAzyme activity can be blocked efficiently via locking both ends of the G-rich DNAzyme sequence in the loop and stem (blocking efficiency = 96%) and can be easily recovered during the CHA process (activation efficiency = 94%). The both-end-blocked DNAzyme is by far the most sensitive optical detection mode for monitoring the CHA process that can be used for determination of 0.05 fmol miRNA-21. The fabricated CHA-DNAzyme sensing system was also able to discriminate miRNA-21 from single-/three-base mismatch miRNA-21. The feasibility of real application was also tested via detection of miRNA-21 levels in tumor cell samples. Therefore, the sensing system with the advantages of convenience, high sensitivity, and selectivity is an appealing strategy for miRNA detection.

Sensitive singular-phase optical detection without phase measurements with Tamm plasmons

Spectrally-tailored interactions of light with material interfaces offer many exciting applications in sensing, photo-detection, and optical energy conversion. In particular, complete suppression of light reflectance at select frequencies accompanied by sharp phase variations in the reflected signal forms the basis for the development of ultra-sensitive singular-phase optical detection schemes such as Brewster and surface plasmon interferometry. However, both the Brewster effect and surface-plasmon-mediated absorption on planar interfaces are limited to one polarization of the incident light and oblique excitation angles, and may have limited bandwidth dictated by the material dielectric index and plasma frequency. To alleviate these limitations, we design narrow-band super-absorbers composed of plasmonic materials embedded into dielectric photonic nanostructures with topologically-protected interfacial Tamm plasmon states. These structures have planar geometry and do not require nanopatterning to achieve perfect absorption of both polarizations of the incident light in a wide range of incident angles, including the normal incidence. Their absorption lines are tunable across a very broad spectral range via engineering of the photon bandstructure of the dielectric photonic nanostructures to achieve reversal of the geometrical phase across the interface with the plasmonic absorber. We outline the design strategy to achieve perfect absorptance in Tamm structures with dissipative losses via conjugate impedance matching. We further demonstrate via modeling how these structures can be engineered to support sharp asymmetric amplitude resonances, which can be used to improve the sensitivity of optical sensors in the amplitude-only detection scheme that does not require use of bulky and expensive ellipsometry equipment.

ICP etched position sensitive silicon sensors on silicon and SOI substrates

Position sensitive optical detectors have many applications in measurement technology. In this paper we investigate the influence of a trench in the vicinity of the p-n junction of the silicon detector. The trenches were fabricated by deep reactive ion etching (DRIE) using an inductive coupled plasma (ICP). Both, the detectors with and without trenches were processed at the same wafer for comparable results. Furthermore, we discuss the influence of the trench in view of electrical parameters and cross-talk behaviour in a 4-quadrants silicon photodiode. For the silicon four-quadrant photodiode with passivated trench sidewalls a minimum distance of 4.8 μm is determined. For high temperature applications a position sensitive line array based on SOI (silicon on insulator) material was fabricated. The experimental determined cutoff frequency equals 160 MHz.

Sulfide Species Optical Monitoring by a Miniaturized Silicon Photomultiplier.

The monitoring of water-soluble pollutants is receiving a growing interest from the scientific community. In this context, sulfide anion species S2− and HS− are particularly relevant since they can cause acute and chronic toxicity including neurological effects and at high concentrations, even death. In this study, a new strategy for fast and sensitive optical detection of sulfide species in water samples is described. The method uses an integrated silicon photomultiplier (SiPM) device coupled with the appropriate analytical strategy applied in a plastic microchip with dried reagents on board. More specifically, all sulfide species (H2S, HS− and S2−) in water samples are detected by the fluorescence signal emitted upon the reaction with N,N-dimethyl-phenylenediamine sulfate in the presence of Fe3+, leading to the formation of the fluorescent methylene blue (MB) species. It has been proven that the system herein proposed is able to measure sulfide concentration in a linear range from 0–10 mg L−1 with a sensitivity value of about 6.7 µA mg−1 L and a detection limit of 0.5 mg L−1. A comparison with conventional UV-Vis detection method has been also carried out. Data show a very good linear correlation (R2 = 0.98093), proving the effectiveness of the method. Results pave the way toward the development of portable and low-cost device systems for water-soluble sulfide pollutants.

A compact and low-cost laser induced fluorescence detector with silicon based photodetector assembly for capillary flow systems

A compact and low-cost laser induced fluorescence (LIF) detector based on confocal structure for capillary flow systems was developed and applied for analysis of Her2 protein on single Hela cells. A low-power and low-cost 450 nm laser diode (LD) instead of a high quality laser was used as excitation light source. A compact optical design together with shortened optical path length improved the optical efficiency and detection sensitivity. A superior silicon based photodetector assembly was used for fluorescence detection instead of a photomultiplier (PMT). The limit of detection (LOD) for fluorescein sodium was 3 × 10–12 M or 165 fluorescein molecules in detection volume measured on a homemade capillary electroosmotic driven (EOD)-LIF system, which was similar to commercial LIFs. Compared to commercial LIFs, the whole volume of our LIF was reduced to 1/2–1/3, and the cost was less than 1/3 of them.

Highly Sensitive Optical Detector for Precision Measurement of Coulomb Coupling Strength Based on a Double-Oscillator Optomechanical System

An optomechanical system combining a Coulomb interaction degree of freedom provides a unique platform for precision measurement of electrical charges via the optomechanically induced transparency. A new property of a second-order sideband in a double-oscillator optomechanical system is investigated beyond the conventional linearized description of optomechanical interaction. The results show that the single-second-order sideband will split into the double-second-order sideband under a weak driving field, and the separation of the split second-order sideband shows a strong dependence on the Coulomb coupling strength. Based on the current experimental conditions, such a Coulomb-interaction-induced split of the second-order sideband may enable an all-optical sensor for precision measurement of the Coulomb coupling strength with lower power.

Room-Temperature-Phosphorescence-Based Dissolved Oxygen Detection by Core-Shell Polymer Nanoparticles Containing Metal-Free Organic Phosphors.

The highly sensitive optical detection of oxygen including dissolved oxygen (DO) is of great interest in various applications. We devised a novel room-temperature-phosphorescence (RTP)-based oxygen detection platform by constructing core-shell nanoparticles with water-soluble polymethyloxazoline shells and oxygen-permeable polystyrene cores crosslinked with metal-free purely organic phosphors. The resulting nanoparticles show a very high sensitivity for DO with a limit of detection (LOD) of 60 nm and can be readily used for oxygen quantification in aqueous environments as well as the gaseous phase.

Room‐Temperature‐Phosphorescence‐Based Dissolved Oxygen Detection by Core‐Shell Polymer Nanoparticles Containing Metal‐Free Organic Phosphors

AbstractThe highly sensitive optical detection of oxygen including dissolved oxygen (DO) is of great interest in various applications. We devised a novel room‐temperature‐phosphorescence (RTP)‐based oxygen detection platform by constructing core–shell nanoparticles with water‐soluble polymethyloxazoline shells and oxygen‐permeable polystyrene cores crosslinked with metal‐free purely organic phosphors. The resulting nanoparticles show a very high sensitivity for DO with a limit of detection (LOD) of 60 nm and can be readily used for oxygen quantification in aqueous environments as well as the gaseous phase.

Sensitive optical detection of clinically relevant biomarkers in affordable microfluidic devices: Overcoming substrate diffusion limitations

Abstract One of the biggest challenges in miniaturization of optical immunoassays is the short light path distance of microchannels/microcapillaries. Protein biomarkers are often presented in circulating blood in the picomolar-femtomolar range, requiring exceptional levels of sensitivity that cannot be met with traditional chromogenic substrates and without sophisticated, bulky detection systems. This study discloses an effective strategy for increasing the sensitivity and shorten the total test time for sandwich ELISAs in microfluidic devices optically interrogated, based on enhancing enzymatic amplification. We found that activity of Horseradish Peroxidase (HRP) in mesofluidic systems is highly limited by diffusion, therefore increasing the concentration of enzymatic substrate in these systems does not translate into an enhancement in enzymatic conversation. The opposite happens in microfluidic systems due to short diffusion distances, however increased concentration of the second enzymatic substrate, hydrogen peroxide (H2O2), leads to enzyme inhibition as herein reported. Consequently, we found that the molar ratio of o-phenylenediamine (OPD) to hydrogen peroxide from commercially substrate formulations is not suitable for miniaturized systems. Sandwich ELISA quantitation of a cancer biomarker PSA and human cytokine IL-1β in fluoropolymer microfluidic strips revealed over one order of magnitude increase in sensitivity and 10-fold decrease in incubation time by simply changing the molar ratio of OPD:H2O2 from 1:3 to 1:1 and increasing OPD concentration from 1 to 4 mg/ml. This enhancement in enzymatic amplification offers finally the sensitivity required for optical interrogation of novel portable and affordable microfluidic devices with inexpensive and ubiquitous smartphones and flatbed scanners.

Graphene-Insulator-Semiconductor Junction for Hybrid Photodetection Modalities

A sensitive optical detector is presented based on a deeply depleted graphene-insulator-semiconducting (D2GIS) junction, which offers the possibility of simultaneously leveraging the advantages of both charge integration and localized amplification. Direct read-out and built-in amplification are accomplished via photogating of a graphene field-effect transistor (GFET) by carriers generated within a deeply depleted low-doped silicon substrate. Analogous to a depleted metal-oxide-semiconducting junction, photo-generated charge collects in the potential well that forms at the semiconductor/insulator interface and induces charges of opposite polarity within the graphene film modifying its conductivity. This device enables simultaneous photo-induced charge integration with continuous “on detector” readout through use of graphene. The resulting devices exhibit responsivities as high as 2,500 A/W (25,000 S/W) for visible wavelengths and a dynamic range of 30 dB. As both the graphene and device principles are transferrable to arbitrary semiconductor absorbers, D2GIS devices offer a high-performance paradigm for imaging across the electromagnetic spectrum.

Optical Power Monitoring with Ultrahigh Sensitivity in Silicon Waveguides and Ring Resonators

We demonstrate optical power monitoring using a silicon resistor enabled by the surface and defect states-induced photoconductance effect. Ultrahigh optical power detection sensitivity of −40 dBm under a low AC drive voltage of 5 mV is obtained with the facilitation of a lock-in amplifier circuitry. The detection scheme is applied to monitor the resonances in single and coupled-ring resonators. Intracavity resonance spectrum is successfully measured at both the static and the thermal tuning conditions. The demonstration opens a compelling new way for nonintrusive on-chip optical power detection by exploiting doped silicon resistor-based thermooptic heaters.

A Single-Ion Reservoir as a High-Sensitive Sensor of Electric Signals

A single-ion reservoir has been tested, and characterized in order to be used as a highly sensitive optical detector of electric signals arriving at the trapping electrodes. Our system consists of a single laser-cooled 40Ca+ ion stored in a Paul trap with rotational symmetry. The performance is observed through the axial motion of the ion, which is equivalent to an underdamped and forced oscillator. Thus, the results can be projected also to Penning traps. We have found that, for an ion oscillator temperature Taxial ≲ 10 mK in the forced-frequency range ωz = 2π × (80,200 kHz), the reservoir is sensitive to a time-varying electric field equivalent to an electric force of 5.3(2) neV/μm, for a measured quality factor Q = 3875(45), and a decay time constant γz = 88(2) s−1. This method can be applied to measure optically the strength of an oscillating field or induced (driven) charge in this frequency range within times of tens of milliseconds. Furthermore the ion reservoir has been proven to be sensitive to electrostatic forces by measuring the ion displacement. Since the heating rate is below 0.3 μeV/s, this reservoir might be used as optical detector for any ion or bunch of charged particles stored in an adjacent trap.

Towards highly selective detection using metal nanoparticles: A case of silver triangular nanoplates and chlorine

The article describes a novel approach towards improving selectivity of volatile compounds detection using metal nanoparticles. It is based on combination of sensitive optical detection using convenient nanoparticle-modified paper test strips and dynamic gas extraction improving selectivity to volatile compounds. A simple and inexpensive setup allowing for realization of this combination is described. Analytical prospects of the approach are shown by the example of chlorine determination in highly salted aqueous solutions using silver triangular nanoplates and digital colorimetry. The limit of detection is equal to 0.03mgL−1 and the determination range is 0.1–2mgL−1. This determination can be successfully carried out in solutions containing at least 2·105 greater molar amounts of Na+, K+, Zn2+, Cl–, SO42–, and H2PO4– with no sample pretreatment. The approach seems to be compatible with different types of nanoparticles with respect to detection of various analytes, thus having good opportunities for further development.

Near-infrared persistent luminescence phosphors ZnGa2O4:Cr3 + as an accurately tracker to photothermal therapy in vivo for visual treatment

The photothermal therapy agents induced by 808 nm near infrared light laser have good potential for photothermal therapy (PTT) in vivo, with the advantages of harmless treatment, minimally invasion, high efficiency and deep tissue penetration. For the traditional photothermal therapy agents, however, it was impossible to track them in vivo because of the low signal-to-noise ratio, so we cannot conduct the extra near infrared light laser to radiate tumors sites accurately. Herein, we introduce a new complex: indocyanine green (ICG), near-infrared persistent luminescence (PL) phosphors ZnGa2O4:Cr3+ (ZGC) and mesoporous silica nanoparticles (MSNs) (ICG@mZGC nanoparticles) were assembled for long-lasting optical imaging to guide PTT. The results revealed that the novel nanoparticle, ICG@mZGC, could lower signal-to-noise ratio, enable highly sensitive optical detection during optical imaging-guided PTT and perform a good effect of photothermal therapy in vivo, and thus providing possibilities for mZGC to improve the localization precision of tumor sites in photothermal therapy in the body.

Immunodetection of salivary biomarkers by an optical microfluidic biosensor with polyethylenimine-modified polythiophene-C70 organic photodetectors

This work reports a novel optical microfluidic biosensor with highly sensitive organic photodetectors (OPDs) for absorbance-based detection of salivary protein biomarkers at the point of care. The compact and miniaturized biosensor has comprised OPDs made of polythiophene-C70 bulk heterojunction for the photoactive layer; whilst a calcium-free cathode interfacial layer, made of linear polyethylenimine, was incorporated to the photodetectors to enhance the low cost. The OPDs realized onto a glass chip were aligned to antibody-functionalized chambers of a poly(methyl methacrylate) microfluidic chip, in where immunogold-silver assays were conducted. The biosensor has detected IL-8, IL-1β and MMP-8 protein in spiked saliva with high detection specificity and short analysis time exhibiting detection limits between 80pgmL−1 and 120pgmL−1. The result for IL-8 was below the clinical established cut-off of 600pgmL−1, which revealed the potential of the biosensor to early detection of oral cancer. The detection limit was also comparable to other previously reported immunosensors performed with bulky instrumentation or using inorganic photodetectors. The optical detection sensitivity of the polythiophene-C70 OPD was enhanced by optimizing the thickness of the photoactive layer and anode interfacial layer prior to the saliva immunoassays. Further, the biosensor was tested with unspiked human saliva samples, and the results of measuring IL-8 and IL-1β were in statistical agreement with those provided by two commercial assays of ELISA. The optical microfluidic biosensor reported hereby offers an attractive and cost-effective tool to diagnostics or screening purposes at the point of care.

Zn2+‐Ion Sensing by Fluorescent Schiff Base Calix[4]arene Macrocycles

A macrocyclic ligand (H2 L) containing two o,o'-bis(iminomethyl)phenol and two calix[4]arene head units has been synthesized and its coordination chemistry towards divalent Ni and Zn investigated. The new macrocycle forms complexes of composition [ML] (M=Zn, M=Ni) and [ZnL(py)2 ], which were characterized by elemental analysis; IR, UV/Vis, and NMR spectroscopy; electrospray ionization mass spectrometry (ESI-MS); and X-ray crystallography (for [ZnL(py)2 ] and [NiL]). H2 L allows the sensitive optical detection of Zn2+ among a series of biologically relevant metal ions by a dual fluorescence enhancement/quenching effect in solution. The fluorescence intensity of the macrocycle increases by a factor of ten in the presence of Zn2+ with a detection limit in the lower nanomolar region.

All-Electrical Graphene DNA Sensor Array.

Electrical sensing of biomolecules has been an important pursuit due to the label-free operation and chip-scale construct such sensing modality can enable. In particular, electrical biomolecular sensors based on nanomaterials such as semiconductor nanowires, carbon nanotubes, and graphene have demonstrated high sensitivity, which in the case of nanowires and carbon nanotubes can surpass typical optical detection sensitivity. Among these nanomaterials, graphene is well suited for a practical candidate for implementing a large-scale array of biomolecular sensors, as its two-dimensional morphology is readily compatible with industry standard top-down fabrication techniques. In our recent work published in 2014 Nature Communications, we demonstrated these benefits by creating DNA sensor arrays from chemical vapor deposition (CVD) graphene. The present chapter, which is a review of this recent work, outlines procedures demonstrating the use of individual graphene sites of the array in dual roles--electrophoretic electrodes for site specific probe DNA immobilization and field effect transistor (FET) sensors for detection of target DNA hybridization. The 100fM detection sensitivity achieved in 7 out of 8 graphene FET sensors in the array combined with the alternative use of the graphene channels as electrophoretic electrodes for probe deposition represent steps toward creating an all-electrical multiplexed DNA array.

Paper matrix based array for rapid and sensitive optical detection of mercury ions using silver enhancement

The authors describe a nitrocellulose membrane based paper matrix array for detection of mercury(II) with high throughput and repeatability. A thymine-rich signal reporting ssDNA probe labeled with gold nanoparticles (AuNPs) was designed, and detection is based on the strong T-Hg-T interaction which leads to a significant color change. In addition, catalytic signal amplification is accomplished by silver staining in order to enhance coloration. The method has a detection limit as low 0.5 ppt. This is at least 500-fold better than that of existing methods. By using an array, multiple sets of duplicate detections can be carried out simultaneously and in parallel. This improves the efficiency and accuracy of the assay. The method shows remarkable specificity since the signal of other competing metal ions is negligible compared to that of mercury(II) even at 100-fold higher concentration. The protocol was successfully applied to the determination of Hg(II) in spiked tap water and lake water samples. In our perception, this assay is a most promising tool for optical determination f ultra-low levels of Hg(II).

A novel lab-on-chip platform with integrated solid phase PCR and Supercritical Angle Fluorescence (SAF) microlens array for highly sensitive and multiplexed pathogen detection

Solid-phase PCR (SP-PCR) has become increasingly popular for molecular diagnosis and there have been a few attempts to incorporate SP-PCR into lab-on-a-chip (LOC) devices. However, their applicability for on-line diagnosis is hindered by the lack of sensitive and portable on-chip optical detection technology. In this paper, we addressed this challenge by combining the SP-PCR with super critical angle fluorescence (SAF) microlens array embedded in a microchip. We fabricated miniaturized SAF microlens array as part of a microfluidic chamber in thermoplastic material and performed multiplexed SP-PCR directly on top of the SAF microlens array. Attribute to the high fluorescence collection efficiency of the SAF microlens array, the SP-PCR assay on the LOC platform demonstrated a high sensitivity of 1.6 copies/µL, comparable to off-chip detection using conventional laser scanner. The combination of SP-PCR and SAF microlens array allows for on-chip highly sensitive and multiplexed pathogen detection with low-cost and compact optical components. The LOC platform would be widely used as a high-throughput biosensor to analyze food, clinical and environmental samples.

Development of quantum-dot-encapsulated liposome-based optical nanobiosensor for detection of telomerase activity without target amplification.

Reactivation of telomerase, which is observed in more than 85% of all known human tumours, is considered a promising tumour marker for cancer diagnosis. With respect to the biomedical importance of telomerase, we have developed a simple strategy based on liposomal fluorescent signal amplification for highly sensitive optical detection of telomerase activity using liposome-encapsulated cadmium telluride quantum dots. In this strategy, telomerase extracted from A549 cells elongated the biotinylated telomerase substrate primer, which was then immobilized on streptavidine-coated microplate wells. After the hybridization of the telomerase-elongated product with biotinylated capture probe, streptavidin was added to the assembly. In the next step, biotinylated liposome was conjugated with capture probe through streptavidin. Finally, QD-encapsulated liposomes were disrupted by Triton X-100, and the fluorescence intensity of the released QDs was measured to detect telomerase activity. The results showed that the proposed nanobiosensor was able to detect telomerase activity from as few as 10 A549 cells without the enzymatic amplification of telomerase extension products. In short, this method is not only convenient and sensitive, but also has a simple operating protocol and a wide detection range (10-5000 cells). A linear range was observed between 50 and 800 cells with a correlation coefficient of 0.982 and regression equation of y = 0.0444 x + 17.137. The proposed method is economical, more user-friendly, without error-prone PCR, with a wide detection range and simple operating protocol without the requirement for sophisticated equipment. Graphical Abstract Schematic representation of the QD-encapsulated liposome-based strategy to amplify fluorescence signal for optical detection of telomerase activity.