Background-free Signal Research Articles

Enhanced chiral sensing by optical whispering gallery mode microresonator.

Chiral sensing is essential in biochemistry, biomedicine, and food industries. Traditional chiral sensing mainly focuses on enhancing the chiral near fields, where the quality factor of the resonator has largely been ignored. Here, we propose a whispering gallery mode (WGM) optical microresonator to enhance the chiral signal by exploiting its high quality factor. The enhancement factor in the WGM resonator is linearly dependent on the quality factor of the microresonator and exponentially increases with the decreasing thickness of the chiral analyte. Based on this, we achieve a chiral enhancement factor of more than two orders of magnitude, which features a background-free chiroptical signal. Our results open a route to attain highly sensitive chiral sensing based on the WGM optical resonator, which promotes the realization of chiral applications in integrated optics.

Access to the Antenna System of Photosystem I via Single-Molecule Excitation-Emission Spectroscopy.

In the development of single-molecule spectroscopy, the simultaneous detection of the excitation and emission spectra has been limited. The fluorescence excitation spectrum based on background-free signals is compatible with the fluorescence-emission-based detection of single molecules and can provide insight into the variations in the input energy of the different terminal emitters. Here, we implement single-molecule excitation-emission spectroscopy (SMEES) for photosystem I (PSI) via a cryogenic optical microscope. To this end, we extended our line-focus-based excitation-spectral microscope system to the cryogenic temperature-compatible version. PSI is one of the two photosystems embedded in the thylakoid membrane in oxygen-free photosynthetic organisms. PSI plays an essential role in electron transfer in the photosynthesis reaction. PSIs of many organisms contain a few red-shifted chlorophylls (Chls) with much lower excitation energies than ordinary antenna Chls. The fluorescence emission spectrum originates primarily from the red-shifted Chls, whereas the excitation spectrum is sensitive to the antenna Chls that are upstream of red-shifted Chls. Using SMEES, we obtained the inclining two-dimensional excitation-emission matrix (2D-EEM) of PSI particles isolated from a cyanobacterium, Thermosynechococcus vestitus (equivalent to elongatus), at about 80 K. Interestingly, by decomposing the inclining 2D-EEMs within time course observation, we found prominent variations in the excitation spectra of the red-shifted Chl pools with different emission wavelengths, strongly indicating the variable excitation energy transfer (EET) pathway from the antenna to the terminal emitting pools. SMEES helps us to directly gain information about the antenna system, which is fundamental to depicting the EET within pigment-protein complexes.

Photonic Generation of Background-Free Phase-Coded Pulses With Low Power Fluctuation Over the Multi-Octave Frequency Range

In this article, a photonic microwave signals generation scheme for background-free phase-coded (PC) radar pulse with multioctave tuning is experimentally demonstrated. Firstly, an optical frequency comb (OFC) demultiplexing technology based on optical injection locking (OIL) provides a power-equalized coherent optical local oscillator (LO) with ultra-broadband tuning capability. Then, a phase-modulated optical signal is produced based on the conversion intensity modulation to phase modulation. Finally, a background-free phase-coded signal can be obtained by beating the optical signal with LO at a balanced photodetector (BPD). The proposed scheme features a flat frequency response over an ultra-wideband frequency range without needing a broadband modulator and radio frequency (RF) synthesizer. A proof-of-concept experiment demonstrates that the power fluctuation of 0.5 Gbps background-free PC pulses is lower than 3.12 dB within 3∼24 GHz carrier frequency. Furthermore, the pulse compression performance and system stability are investigated, respectively.

ZGSO Spinel Nanoparticles with Dual Emission of NIR Persistent Luminescence for Anti-Counterfeiting Applications.

The property of persistent luminescence shows great potential for anti-counterfeiting technology and imaging by taking advantage of a background-free signal. Current anti-counterfeiting technologies face the challenge of low security and the inconvenience of being limited to visible light emission, as emitters in the NIR optical windows are required for such applications. Here, we report the preparation of a series of Zn1+xGa2-2xSnxO4 nanoparticles (ZGSO NPs) with persistent luminescence in the first and second near-infrared window to overcome these challenges. ZGSO NPs, doped with transition-metal (Cr3+ and/or Ni2+) and in some cases co-doped with rare-earth (Er3+) ions, were successfully prepared using an improved solid-state method with a subsequent milling process to reach sub-200 nm size particles. X-ray diffraction and absorption spectroscopy were used for the analysis of the structure and local crystal field around the dopant ions at different Sn4+/Ga3+ ratios. The size of the NPs was ~150 nm, measured by DLS. Doped ZGSO NPs exhibited intense photoluminescence in the range from red, NIR-I to NIR-II, and even NIR-III, under UV radiation, and showed persistent luminescence at 700 nm (NIR-I) and 1300 nm (NIR-II) after excitation removal. Hence, these NPs were evaluated for multi-level anti-counterfeiting technology.

Flexible and Zwitterionic Fluorinated Hydrogel Scaffold with High Fluorine Content for Noninvasive 19 F Magnetic Resonance Imaging under Ultrahigh Scanning Resolution.

The imaging of hydrogel scaffolds by 19 F magnetic resonance imaging (MRI) represents an attractive tool for straightforward and noninvasive monitoring of their morphology and in vivo fate. However, their further applications are significantly limited by a dilemma of insufficient signal resolution with low 19 F content, and/or hydrophobic aggregation of fluorine moieties-induced signal attenuation with high 19 F content. Herein, a novel label-free fluorinated hydrogel (PFCB) is fabricated with high fluorine content to realize noninvasive monitoring through 19 F MRI under ultrahigh scanning resolution (1 mm of scanning thickness). The integration of a zwitterionic unit into each fluorine moiety completely overcame the hydrophobic aggregation-induced signal attenuation, manifesting as high 19 F content and imaging performance. Importantly, 3D reconstruction of the PFCB hydrogel in vivo can be facilely and accurately performed with background free signals, providing detailed biological information of the implanted hydrogel. Additionally, PFCB hydrogel showed adjustable and high mechanical performance, and exhibited minimum foreign body reaction after implantation. As a proof of concept, PFCB hydrogel could be further applied as gel electrodes and wireless flexible sensors for healthcare monitoring. Overall, such label-free fluorinated PFCB hydrogel is an ideal flexible scaffold for eventual clinical applications integrating 19 F MRI-guided unequivocally 3D reconstruction and healthcare monitoring.

Isothermal Background-Free Nucleic Acid Quantification by a One-Pot Cas13a Assay Using Droplet Microfluidics.

High sensitivity and specificity nucleic acid detection has been achieved by the Cas13a collateral effect in combination with a separate recombinase polymerase amplification (RPA). However, these emerging methods cannot provide accurate quantification of nucleic acids because the two-step assay performance may be compromised if the RPA and Cas13a reactions are simply unified in a single step. In this work, we first addressed the challenges associated with enzymatic incompatibility and the macromolecular crowding effect in the one-pot assay development, making the consolidated RPA-Cas13a assay a facile and robust diagnostic tool. Next, we found that the one-pot reaction cannot precisely quantify the targets at low concentrations. Thus, by leveraging droplet microfluidics, we converted the one-pot assay to a digital quantification format, termed Microfluidics-Enabled Digital Isothermal Cas13a Assay (MEDICA). Due to the droplet compartmentation, MEDICA greatly accelerates the reaction and enables relative detection in 10 min and the end-point quantification in 25 min. Moreover, MEDICA facilitates the droplet binarization for counting because of background-free signals generated by trans-cleavage reporting of Cas13a. Our clinical validation highlights that CRISPR-based isothermal assays are promising for the next generation of nucleic acid quantification methods.

In-situ monitoring of nitrile-bearing pesticide residues by background-free surface-enhanced Raman spectroscopy

In-situ monitoring of pesticide residues during crop growth or/and in related products is of great significance in avoiding the abuse of pesticides but remains challenging thus far. In this report, we proposed a background-free surface-enhanced Raman spectroscopy (bf-SERS) platform to non-destructively track the nitrile-bearing pesticide residues in soybean leaves with high sensitivity and selectivity. The outstanding feature of the assay stems from the dramatic Raman enhancement effect of the 50 nm-sized gold nanoparticles (AuNPs) towards the pesticides and simultaneously the background-free Raman signal of the nitrile group in the so-called Raman-silent region (1800–2800 cm‒1). This bf-SERS assay was applied to evaluate the penetration effects of nitrile-bearing pesticides and monitor their residues in soybean leaves after rinsing with various solutions, providing a reliable tool for guiding the safe use of nitrile-bearing pesticides in agriculture.

Resonator-assisted single-molecule quantum state detection

We propose a state-sensitive scheme to optically detect a single molecule without a closed transition, through strong coupling to a high-Q whispering-gallery mode high-Q resonator. A background-free signal can be obtained by detecting a molecule-induced transparency in a photon bus waveguide that is critically coupled to the resonator, with a suppressed depumping rate to other molecular states by the cooperativity parameter $C$. We numerically calculate the dynamics of the molecule-resonator coupled system using Lindblad master equations, and develop analytical solutions through the evolution of quasi-steady states in the weak-driving regime. Using Rb$_2$ triplet ground state molecules as an example, we show that high fidelity state readout can be achieved using realistic resonator parameters. We further discuss the case of multiple molecules collectively coupled to a resonator, demonstrating near-unity detection fidelity and negligible population loss.

Synchronously Amplified Photoacoustic Image Recovery (SAPhIRe)

In molecular and cellular photoacoustic imaging with exogenous contrast agents, image contrast is plagued by background resulting from endogenous absorbers in tissue. By using optically modulatable nanoparticles, we develop ultra-sensitive photoacoustic imaging by rejecting endogenous background signals and drastically improving signal contrast through time-delayed pump-probe pulsed laser illumination. Gated by prior pump excitation, modulatable photoacoustic (mPA) signals are recovered from unmodulatable background through simple, real-time image processing to yield background-free photoacoustic signal recovery within tissue mimicking phantoms and from ex-vivo tissues. Inherently multimodal, the fluorescence and mPA sensitivity improvements demonstrate the promise of Synchronously Amplified Photoacoustic Image Recovery (SAPhIRe) for PA imaging in diagnosis and therapy.

First-Principles Simulations of X-ray Transient Absorption for Probing Attosecond Electron Dynamics.

X-ray transient absorption spectroscopy (XTAS) is a promising technique for measuring electron dynamics in molecules and solids with attosecond time resolutions. In XTAS, the elemental specificity and spatial locality of core-to-valence X-ray absorption is exploited to relate modulations in the time-resolved absorption spectra to local electron density variations around particular atoms. However, interpreting these absorption modulations and frequency shifts as a function of the time delay in terms of dynamics can be challenging. In this paper, we present a first-principles study of attosecond XTAS in a selection of simple molecules based on real-time time-dependent density functional theory (RT-TDDFT) with constrained DFT to emulate the state of the system following the interaction with a ultraviolet pump laser. In general, there is a decrease in the optical density and a blue shift in the frequency with increasing electron density around the absorbing atom. In carbon monoxide (CO), modulations in the O K-edge occur at the frequency of the valence electron dynamics, while for dioxygen (O2) they occur at twice the frequency, due to the indistinguishability of the oxygen atoms. In 4-aminophenol (H2NC6H4OH), likewise, there is a decrease in the optical density and a blue shift in the frequency for the oxygen and nitrogen K-edges with increasing charge density on the O and N, respectively. Similar effects are observed in the nitrogen K-edge for a long-range charge-transfer excitation in a benzene (C6H6)–tetracyanoethylene (C6N4; TCNE) dimer but with weaker modulations due to the delocalization of the charge across the entire TCNE molecule. Additionally, in all cases, there are pre-edge features corresponding to core transitions to depopulated orbitals. These potentially offer a background-free signal that only appears in pumped molecules.

Energy transfer within the hydrogen bonding network of water following resonant terahertz excitation.

Energy dissipation in water is very fast and more efficient than in many other liquids. This behavior is commonly attributed to the intermolecular interactions associated with hydrogen bonding. Here, we investigate the dynamic energy flow in the hydrogen bond network of liquid water by a pump-probe experiment. We resonantly excite intermolecular degrees of freedom with ultrashort single-cycle terahertz pulses and monitor its Raman response. By using ultrathin sample cell windows, a background-free bipolar signal whose tail relaxes monoexponentially is obtained. The relaxation is attributed to the molecular translational motions, using complementary experiments, force field, and ab initio molecular dynamics simulations. They reveal an initial coupling of the terahertz electric field to the molecular rotational degrees of freedom whose energy is rapidly transferred, within the excitation pulse duration, to the restricted translational motion of neighboring molecules. This rapid energy transfer may be rationalized by the strong anharmonicity of the intermolecular interactions.

A screening method based on 1D CSSF-TOCSY for the identification and quantification of 11 illegal adulterants in herbal medicines

In this work, an NMR analytical procedure based on highly chemical-shift-selective filtration (CSSF) with total correlation spectroscopy (TOCSY) was used for the rapid identification and quantification of trimethoprim, benproperine phosphate, diclofenac sodium, pentoxyverine citrate, diphenhydramine hydrochloride, sulfamethoxazole, dioxopromethazine hydrochloride, chlorphenamine maleate, prednisone acetate, theophylline, and diazepam in antitussive and antiasthmatic herbal medicinal products. This method is advantageous for content determination owing to its specific background-free signals for each chemical adulterant and easy-to-perform pretreatment operations. Satisfactory results in terms of limit of quantification (0.70–1.35 mg/g), precision (relative standard deviation, RSD%: 2.05–7.08), accuracy (bias%: 0.16–6.51), and recovery (85.4%–106.5%) were achieved. Among 28 batches of antitussive and antiasthmatic herbal medicinal products, 27 batches contained illegal adulterants, which differed in terms of the amount and type of compounds. The established method was employed for the qualitative screening and quantitative detection of illegal adulterants in herbal medicinal products because of its strong selectivity and fast analysis.

An efficient NIR-to-NIR signal-based LRET system for homogeneous competitive immunoassay

Upconversion nanoparticles (UCNPs) are promising materials for biological applications based on luminescence resonance energy transfer (LRET). In contrast to classical RET donors such as quantum dots, gold nanoparticles, UCNPs can emit near-infrared (NIR) upon the NIR irradiation, which provides enhanced signal-to-noise due to strong penetration and low autofluorescence in the NIR region known as the diagnostic window. Here we report the first efficient NIR-to-NIR signal-based LRET system for the detection of progesterone, chosen as a proof-of-concept target, via homogeneous competitive immunoassay. To enhance the efficiency of LRET, we constructed inert-core/active-shell/inert-ultrathin shell UCNPs (NaYF4@NaYF4:Yb,Tm@NaYF4) as an LRET donor and a compact progesterone/horseradish peroxidase/IRdyeQC-1 (P-HRP-dyes) complex as an LRET acceptor. The designed donor and acceptor showed significantly improved LRET efficiencies (95% and 85% for donor and acceptor, respectively) compared with conventional donor and acceptor (70% and 50%, respectively). Using the developed NIR-to-NIR LRET system, progesterone was successfully detected with a background-free signal and low limit of detection (1.36 pg/ml in ten-fold diluted human serum). We believe that the efficient NIR-to-NIR signal-based LRET system developed here has potential as a simple probe for homogeneous competitive immunoassay, with the ability to rapidly detect biomarkers.

Upconversion Luminescence Sandwich Assay For Detection of Influenza H7 Subtype.

With large anti-Stokes shifts and background-free signals, upconversion luminescent (UCL) screening assays have been a promising method to reduce the transmission of influenza epidemic, which can critically alleviate the disease burden and extra annual deaths. In this work, a luminescent resonance energy transfer sandwich assay is developed, which utilizes core-shell upconversion nanoparticles and gold nanoparticles as the donor and acceptor, respectively. The influenza H7 gene of H7N9 virus is used as the target for optimization of the assay. Importantly, the hybridization time of the assay is ≈40 min and the specificity test indicates the probes are specific toward the H7 target. The limit of detection of the system is ≈134 × 10-12 m (≈3.22 × 1010 molecules). Moreover, the assay is tested with the use of polymerase chain reaction validated samples from human isolates. The results are promising for implanting future on-site rapid influenza screening application.

Exploring the multiparameter nature of EUV-visible wave mixing at the FERMI FEL.

The rapid development of extreme ultraviolet (EUV) and x-ray ultrafast coherent light sources such as free electron lasers (FELs) has triggered the extension of wave-mixing techniques to short wavelengths. This class of experiments, based on the interaction of matter with multiple light pulses through the Nth order susceptibility, holds the promise of combining intrinsic ultrafast time resolution and background-free signal detection with nanometer spatial resolution and chemical specificity. A successful approach in this direction has been the combination of the unique characteristics of the seeded FEL FERMI with dedicated four-wave-mixing (FWM) setups, which leads to the demonstration of EUV-based transient grating (TG) spectroscopy. In this perspective paper, we discuss how the TG approach can be extended toward more general FWM spectroscopies by exploring the intrinsic multiparameter nature of nonlinear processes, which derives from the ability of controlling the properties of each field independently.

Two-photon absorption coefficient determination using the differential F-scan technique

In this paper we present a modification to the recently proposed transmission F-scan technique, the differential F-scan technique. In the differential F-scan technique, the programmed focal distance in the electronic-tunable lens is modulated, allowing the light detector in the setup to record a signal proportional to the derivative of the signal recorded with the F-scan. As with the differential Z-scan a background-free signal is obtained, but in this case the optical setup is simplified and the available laser power is twice that for the F-scan. We also present and validate a new fitting-procedure protocol that increases the accuracy of the technique. Finally, we show that fitting a signal from a differential F-scan or the derivate of the signal of a transmission F-scan is more accurate than simply fitting the signal from the F-scan directly. Results for two-photon absorption at 790 nm of CdS, ZnSe and CdSe are presented.

Photonic Generation of Ultra-Wideband Signal by Truncating a Continuous Wave into a Pulse

We propose and demonstrate a background-free millimeter-wave (MMW) ultra-wideband (UWB) signal generator using a dual-polarization dual-parallel Mach–Zehnder modulator. The MMW-UWB signal is generated by truncating a continuous-wave (CW) radio-frequency (RF) signal into an RF pulse. The upper dual-parallel Mach–Zehnder modulator (DPMZM1) is properly set to act as a phase modulator, while the lower DPMZM2 is well biased to generate a carrier-suppressed double-sideband (CS-DSB) modulated signal. By shifting the phase of the optical carrier through DPMZM1, a CW RF signal is truncated into a pulse one in a photodetector (PD). The baseband frequency components and local oscillator signal are well suppressed, since the optical power sent to the PD is constant. Moreover, there is no optical or electrical filters involved, which ensures a broad operation bandwidth and wide tunability. The proposed scheme is theoretically analyzed and experimentally verified. The generated background-free UWB signal at an RF carrier frequency of 26 GHz meets well the Federal Communications Commission spectral mask for outdoor UWB systems.

NMR Quantification of Carbohydrates in Complex Mixtures. A Challenge on Honey.

The knowledge of carbohydrate composition is greatly important to determine the properties of natural matrices such as foodstuff and food ingredients. However, because of the structural similarity and the multiple isomeric forms of carbohydrates in solution, their analysis is often a complex task. Here we propose an NMR analytical procedure based on highly selective chemical shift filters followed by TOCSY, which allows us to acquire specific background-free signals for each sugar. The method was tested on raw honey samples dissolved in water with no other pretreatment. In total, 22 sugars typically found in honey were quantified: 4 monosaccharides (glucose, fructose, mannose, rhamnose), 11 disaccharides (sucrose, trehalose, turanose, maltose, maltulose, palatinose, melibiose and melezitose, isomaltose, gentiobiose nigerose, and kojibiose), and 7 trisaccharides (raffinose, isomaltotriose, erlose, melezitose, maltotriose, panose, and 1-kestose). Satisfactory results in terms of limit of quantification (0.03-0.4 g/100g honey), precision (% RSD: 0.99-4.03), trueness (bias % 0.4-4.2), and recovery (97-104%) were obtained. An accurate control of the instrumental temperature and of the sample pH endows an optimal chemical shift reproducibility, making the procedure amenable to automation and suitable to routine analysis. While validated on honey, which is one of the most complex natural matrices in terms of saccharides composition, this innovative approach can be easily transferred to other natural matrices.

Photonic generation of background-free millimeter-wave ultra-wideband signals (Invited Paper)

We review the recent progress of photonic generation of millimeter wave (MMW)-ultra-wideband (UWB) signals. To fully satisfy the standard defined by the Federal Communications Commission (FCC), the baseband signal (background signal) and the residual local oscillator (LO) signal should be well controlled. We discuss several schemes in this work for generating background-free MMW-UWB signals that are fully compliant with the FCC requirement.

Noncollinear wave mixing of attosecond XUV and few-cycle optical laser pulses in gas-phase atoms: Toward multidimensional spectroscopy involving XUV excitations

A method to realize table-top attosecond spectroscopy is demonstrated in which a link is provided between background-free nonlinear signals and the time evolution of individual quantum pathways.