Beating Signals Research Articles

Dual-comb source with a reconfigurable repetition frequency difference using intracavity Brillouin lasers

A Brillouin-assisted 80-GHz-spaced dual-comb source with a reconfigurable repetition frequency difference ranging from 48 MHz to 1.486 GHz is demonstrated. Two pairs of dual-pump seeds with an interval offset produce the corresponding dual Brillouin lasers in two fiber loops, and then the Brillouin lasers give rise to dual combs via the cavity-enhanced cascaded four-wave mixing effect. The repetition frequency difference is determined by the interval offset of the dual-pump seeds, which is induced by the Brillouin frequency shift difference between different fibers in a frequency shifter. Each comb provides 22 lasing lines, and the central 10 lines in a 20-dB power deviation feature high optical signal-to-noise ratios exceeding 50 dB. The linewidths of the dual-comb beating signals are less than 300 Hz, and the absolute linewidths of the comb lines are around 1.5 kHz. The dual-comb source enables substantial repetition frequency differences from 48 MHz to 1.486 GHz by changing the pluggable fibers in the frequency shifter.

An intelligent biosensing platform using phase space reconstruction‐assisted convolutional neural network for drug‐induced cardiotoxicity assessment

AbstractDrug‐induced cardiotoxicity often leads to patient deaths and drug recalls. Interdigitated electrode (IDE)‐based cellular impedance detection instrument has been integrated with intelligent algorithms to screen cardiotoxicity based on cardiomyocytes. These intelligent biosensing systems generally employ traditional machine learning methods to assess drug‐induced cardiotoxicity by analyzing cardiomyocytes mechanical beating signals. However, modern deep learning methods with robustness and flexibility have not been integrated in IDE‐based platform to screen cardiotoxicity. Here, for the first time, we implemented deep convolutional neural network (CNN) to analyze cardiomyocytes mechanical beating signals for cardiotoxicity assessment. This method can eliminate the feature engineering procedures, such as manual design and extraction of signal features required by traditional machine learning methods. To facilitate two‐dimensional (2‐D) CNN analysis, we utilized phase space reconstruction to convert one‐dimensional beating signals into 2‐D image representations as well as take into account nonlinear dynamic information. The phase space reconstruction‐assisted convolutional neural network (PSRCNN) is capable of accurately categorizing drug‐induced cardiotoxicities and predicting cardiotoxicity levels. It obtains accuracies ranging from 0.82 to 0.99 when recognizing the cardiotoxicity of newly developed drugs, which are represented by drugs that are not used during model training. Furthermore, we explore in depth to compare the performance of CNN with other traditional machine learning methods. The PSRCNN method can achieve higher accuracies when compared to other methods. The PSRCNN‐based biosensing platform is highly potential in improving the efficiency and accuracy of high‐throughput screening of newly developed drugs for cardiotoxicity during drug discovery.

Two-Dimensional Deep Learning Frameworks for Drug-Induced Cardiotoxicity Detection.

The identification of drug-induced cardiotoxicity remains a pressing challenge with far-reaching clinical and economic ramifications, often leading to patient harm and resource-intensive drug recalls. Current methodologies, including in vivo and in vitro models, have severe limitations in accurate identification of cardiotoxic substances. Pioneering a paradigm shift from these conventional techniques, our study presents two deep learning-based frameworks, STFT-CNN and SST-CNN, to assess cardiotoxicity with markedly improved accuracy and reliability. Leveraging the power of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) as a more human-relevant cell model, we record mechanical beating signals through impedance measurements. These temporal signals were converted into enriched two-dimensional representations through advanced transformation techniques, specifically short-time Fourier transform (STFT) and synchro-squeezing transform (SST). These transformed data are fed into the proposed frameworks for comprehensive analysis, including drug type classification, concentration classification, cardiotoxicity classification, and new drug identification. Compared to traditional models like recurrent neural network (RNN) and 1-dimensional convolutional neural network (1D-CNN), SST-CNN delivered an impressive test accuracy of 98.55% in drug type classification and 99% in distinguishing cardiotoxic and noncardiotoxic drugs. Its feasibility is further highlighted with a stellar 98.5% average accuracy for classification of various concentrations, and the superiority of our proposed frameworks underscores their promise in revolutionizing drug safety assessments. With a potential for scalability, they represent a major leap in drug safety assessments, offering a pathway to more robust, efficient, and human-relevant cardiotoxicity evaluations.

Relative phase locking of a terahertz laser system configured with a frequency comb and a single-mode laser

Stable operation is one of the most important requirements for a laser source for high-precision applications. Many efforts have been made to improve the stability of lasers by employing various techniques, e.g., electrical and/or optical injection and phase locking. However, these techniques normally involve complex experimental facilities. Therefore, an easy implementation of the stability evaluation of a laser is still challenging, especially for lasers emitting in the terahertz (THz) frequency range because the broadband photodetectors and mature locking techniques are limited. In this work, we propose a simple method, i.e., relative phase locking, to quickly evaluate the stability of THz lasers without a need of a THz local oscillator. The THz laser system consists of a THz quantum cascade laser (QCL) frequency comb and a single-mode QCL. Using the single-mode laser as a fast detector, heterodyne signals resulting from the beating between the single-mode laser and the comb laser are obtained. One of the heterodyne beating signals is selected and sent to a phase-locked loop (PLL) for implementing the relative phase locking. Two kinds of locks are performed by feeding the output error signal of the PLL, either to the comb laser or to the single-mode laser. By analyzing the current change and the corresponding frequency change of the PLL-controlled QCL in each phase-locking condition, we, in principle, are able to experimentally compare the stability of the emission frequency of the single-mode QCL (fs) and the carrier envelope offset frequency (fCEO) of the QCL comb. The experimental results reveal that the QCL comb with the repetition frequency injection locked demonstrates much higher stability than the single-mode laser. The work provides a simple heterodyne scheme for understanding the stability of THz lasers, which paves the way for the further locking of the lasers and their high-precision applications in the THz frequency range.

Rotational Doppler shift tripling via third-harmonic generation of spatially structured light in a quasi-periodically poled crystal

The rotational Doppler effect—the angular version of the Doppler effect—shows a frequency shift phenomenon happening when light passes through a rotating object and its angular momentum is changed. The rotational Doppler effect has been widely studied with various light waves based on different angular momentum transform mechanisms and successfully utilized to detect the rotation of objects. However, these studies are mostly limited to linear optics. As the rotational Doppler effect is closely related to the frequency degree of freedom and frequency conversion always happens in nonlinear optics, it is of great significance to explore the rotational Doppler effect in nonlinear optics. Although nonlinear rotational Doppler phenomena have been observed in second-harmonic generation with circularly polarized Gaussian fundamental light and a rotating nonlinear crystal, there is still the open challenge of how to realize Doppler frequency shift conversion (similar to conventional nonlinear frequency conversion), such as doubling or tripling. Here we report the experiment observation of rotational Doppler shift conversion in nonlinear optics. We demonstrate the tripling of a rotational Doppler frequency shift in third-harmonic generation of a spatially structured fundamental wave. Frequency shifts can be extracted from the intensity beating signals with the interference of two components of vector fields with opposite topological charges and the measured modulation frequency of the beating signal for the generated third harmonic. Our results will excite more research on nonlinear optics with spatially structured light, and our method may create opportunities for precision measurement of frequency shifts.

Universal and Sensitive Drug Assessment Biosensing Platform Using Optimal Mechanical Beating Detection of Single Cardiomyocyte.

The preclinical assessment of efficacy and safety is essential for cardiovascular drug development in order to guarantee effective prevention and treatment of cardiovascular disease and avoid human health endangerment and a huge waste of resources. Rhythmic mechanical beating as one of the crucial cardiomyocyte properties has been exploited to establish a drug assessment biosensing platform. However, the conventional label-free biosensing platforms are difficult to perform high-throughput and high-resolution mechanical beating detection for a single cardiomyocyte, while label-based strategies are limited by pharmacologically adverse effects and phototoxicity. Herein, we propose a biosensing platform involving the multichannel electrode array device and the universal mechanical beating detection system. The platform can determine the optimal characteristic working frequency of different devices and dynamically interrogate the viability of multisite single cardiomyocytes to establish the optimized cell-based model for sensitive drug assessment. The subtle changes of mechanical beating signals induced by cardiovascular drugs can be detected by the platform, thereby demonstrating its high performance in pharmacological assessment. The universal and sensitive drug assessment biosensing platform is believed to be widely applied in cardiology investigating and preclinical drug screening.

Beating signals in CdSe quantum dots measured by low-temperature 2D spectroscopy.

Advances in ultrafast spectroscopy can provide access to dynamics involving nontrivial quantum correlations and their evolutions. In coherent 2D spectroscopy, the oscillatory time dependence of a signal is a signature of such quantum dynamics. Here, we study such beating signals in electronic coherent 2D spectroscopy of CdSe quantum dots (CdSe QDs) at 77K. The beating signals are analyzed in terms of their positive and negative Fourier components. We conclude that the beatings originate from coherent LO-phonons of CdSe QDs. No evidence for the QD size dependence of the LO-phonon frequency was identified.

Multi-labeled neural network model for automatically processing cardiomyocyte mechanical beating signals in drug assessment

High-throughput cardiotoxicity assessment is important for large-scale preclinical screening in novel drug development. To improve the efficiency of drug development and avoid drug-induced cardiotoxicity, there is a huge demand to explore the automatic and intelligent drug assessment platforms for preclinical cardiotoxicity investigations. In this work, we proposed an automatic and intelligent strategy that combined automatic feature extraction and multi-labeled neural network (MLNN) to process cardiomyocytes mechanical beating signals detected by an interdigital electrode biosensor for the assessment of drug-induced cardiotoxicity. Taking advantages of artificial neural network, our work not only classified different drugs inducing different cardiotoxicities but also predicted drug concentrations representing severity of cardiotoxicity. This has not been achieved by conventional strategies like principal component analysis and visualized heatmap. MLNN analysis showed high accuracy (up to 96%) and large AUC (more than 98%) for classification of different drug-induced cardiotoxicities. There was a high correlation (over 0.90) between concentrations reported by MLNN and experimentally treated concentrations of various drugs, demonstrating great capacity of our intelligent strategy to predict the severity of drug-induced cardiotoxicity. This new intelligent bio-signal processing algorithm is a promising method for identification and classification of drug-induced cardiotoxicity in cardiological and pharmaceutical applications.

Envelope Extraction for Vibration Locating in Coherent Φ-OTDR.

In a coherent phase-sensitive optical time-domain reflectometry (Φ-OTDR) sensing system, a frequency shift of hundreds of MHz generated by the pulse modulation of an acoustic optic modulator results in a high central frequency of a beating signal spectrum. In order to reduce the high-performance hardware requirement of signal acquisition, the coherent Φ-OTDR based on envelope extraction is proposed in this paper. Firstly, a theoretical model of a quasi-sinusoidal amplitude-modulated signal is built for the beating signal between local oscillator light and Rayleigh backward scattering light. An envelope detector is then utilized to realize the envelope extraction of beating signals with advantages of a simple structure and quick response. The extracted envelope can be directly used for vibration locating without the conventional orthogonal demodulation. Experiment results present that the sampling rate can be reduced to 10 MHz under the spatial resolution of 10 m and the sensing distance of 31 km. This scheme proves that envelope extraction is a reliable technical route for vibration locating, which can effectively reduce the sampling rate and simplify the data demodulation.

Increasing noise immunity of the receiving device at reception of digital signal due to use of additional channel with phase converter

The rapid development of digital information transmission systems using radio signals has led to the need to improve receiving systems. This article considers the possibility of using an improved theory of narrow-band noise to increase the sensitivity of the receiving device when receiving digital signals. It is generally admitted that the task of detection is to make a decision about the presence or absence of a useful signal against the background of interference and noise, which is fundamentally impossible to get rid of. The narrow-band random process structurally is close to the amplitude-modulated oscillation with suppressed carrier and represents a beating signal of two sidebands. It follows from the theory of vibration beats that the phase of the high-frequency component changes by π when the signal envelope passes through 0. Consequently, phase jumps are explained by the fact that narrow-band noises are beating signals of two sidebands. It has been shown that by using the structural differences in the mixture of useful signal and noise and simply narrow-band noise, it is possible to significantly increase the reliability of receiving a digital signal in the field of small signal-to-noise ratios. The article describes in details the mathematical models of the receiving device with an additional receiving channel that uses the phase features of the useful signal and noise mixture and simply narrow-band noise for signal detection. A diagram of a receiving device with an additional channel for the implementation of the receiver on laboratory equipment is given in order to obtain real experimental data. In addition, comparative detection characteristics are presented for a classic single-channel receiver and a receiver with an additional receive channel.

Wideband Doppler frequency shift measurement and direction discrimination based on optical single sideband modulation with a fixed low-frequency reference signal

A wideband Doppler frequency shift (DFS) measurement and direction discrimination method based on optical single sideband (OSSB) modulation with a fixed low-frequency reference signal is proposed and experimentally demonstrated. In the proposed approach, the transmitted signal and the fixed low-frequency reference signal are applied to the lower and upper Mach–Zehnder modulators (MZMs) of a dual-drive dual-parallel MZM (DD-DPMZM) respectively, for realizing OSSB modulation independently. The echo signal is applied to a conventional MZM for optical double sideband (ODSB) modulation. A low-speed photodetector (PD) is used to implement optical-to-electrical conversion and generate three low-frequency beating signals. Both the value and direction of the DFS can be simply obtained by analyzing the frequencies of the three low-frequency beating signals. The proposed scheme has a simple structure, a wideband operating frequency range, and a low requirement of the receiving circuit. Experiments demonstrate that wideband DFS measurement and direction discrimination within 5∼18 GHz with a measurement error of less than ±0.06 Hz are achieved by using a 20 MHz reference signal.

Hybrid Integrated Cardiomyocyte Biosensors for Bitter Detection and Cardiotoxicity Assessment.

Among basic taste sensations, bitter taste is vital to the survival of mammals due to its indispensable role in toxin prediction or identification, so the identification of bitter compounds is of great value in the pharmaceutical and food industry. Recently, bitter taste receptor (T2Rs)-based biosensors have been developed for specific bitter detection. However, the taste biosensors based on taste cells/tissues suffer from simple function, low sensitivity, low content, and limited parameters. Here, to establish a high-content, highly sensitive, and multifunctional taste biosensor, we developed a multifunctional hybrid integrated cardiomyocyte biosensor (HICB) for bitter detection. Due to the expression of bitter taste receptors in cardiomyocytes, the HICB can recognize the specific bitter agonists by synchronously recording the extracellular field potential (EFP) and mechanical beating (MB) signals from the cultured cardiomyocytes in vitro. Multiple feature parameters were defined and extracted from the electromechanical signals of cardiomyocytes to analyze the specific responses to four typical bitter compounds. The radar map, heat map, and principal component analysis (PCA) were used to visualize and classify the specific responses. Moreover, bitter-induced cardiotoxicity also was chronically evaluated, and these bitter compounds presented an inhibition effect on the electrophysiological and contractile activities of cardiomyocytes. This high-content HICB offers an alternative platform for both bitter detection and cardiotoxicity assessment, showing promising applications in the fields of taste detection and toxicity screening.

Cardiomyocyte electrical-mechanical synchronized model for high-content, dose-quantitative and time-dependent drug assessment

Cardiovascular diseases have emerged as a significant threat to human health. However, drug development is a time-consuming and costly process, and few drugs pass the preclinical assessment of safety and efficacy. The existing patch-clamp, Ca2+ imaging, and microelectrode array technologies in cardiomyocyte models for drug preclinical screening have suffered from issues of low throughput, limited long-term assessment, or inability to synchronously and correlatively analyze electrical and mechanical signals. Here, we develop a high-content, dose-quantitative and time-dependent drug assessment platform based on an electrical-mechanical synchronized (EMS) biosensing system. This microfabricated EMS can record both firing potential (FP) and mechanical beating (MB) signals from cardiomyocytes and extract a variety of characteristic parameters from these two signals (FP–MB) for further analysis. This system was applied to test typical ion channel drugs (lidocaine and isradipine), and the dynamic responses of cardiomyocytes to the tested drugs were recorded and analyzed. The high-throughput characteristics of the system can facilitate simultaneous experiments on a large number of samples. Furthermore, a database of various cardiac drugs can be established by heat map analysis for rapid and effective screening of drugs. The EMS biosensing system is highly promising as a powerful tool for the preclinical development of new medicines.

Recognition of high-specificity hERG K+ channel inhibitor-induced arrhythmia in cardiomyocytes by automated template matching

Cardiovascular disease (CVD) is the number one cause of death in humans. Arrhythmia induced by gene mutations, heart disease, or hERG K+ channel inhibitors is a serious CVD that can lead to sudden death or heart failure. Conventional cardiomyocyte-based biosensors can record extracellular potentials and mechanical beating signals. However, parameter extraction and examination by the naked eye are the traditional methods for analyzing arrhythmic beats, and it is difficult to achieve automated and efficient arrhythmic recognition with these methods. In this work, we developed a unique automated template matching (ATM) cardiomyocyte beating model to achieve arrhythmic recognition at the single beat level with an interdigitated electrode impedance detection system. The ATM model was established based on a rhythmic template with a data length that was dynamically adjusted to match the data length of the target beat by spline interpolation. The performance of the ATM model under long-term astemizole, droperidol, and sertindole treatment at different doses was determined. The results indicated that the ATM model based on a random rhythmic template of a signal segment obtained after astemizole treatment presented a higher recognition accuracy (100% for astemizole treatment and 99.14% for droperidol and sertindole treatment) than the ATM model based on arrhythmic multitemplates. We believe this highly specific ATM method based on a cardiomyocyte beating model has the potential to be used for arrhythmia screening in the fields of cardiology and pharmacology.

Polarization Manipulated Fourier Domain Mode-Locked Optoelectronic Oscillator

We report a polarization manipulated Fourier domain mode-locked optoelectronic oscillator (FDML-OEO) using a polarization modulator (PolM). Frequency and bandwidth doubling linearly chirped microwave waveforms (LCMWs) are generated from a PolM-based FDML-OEO. The multiplying operation is capable of increasing the frequency and bandwidth of LCMWs, which doubles the time-bandwidth product of the LCMWs and makes it possible to increase the center frequency of the LCMWs beyond the bandwidth of the optical modulator. Moreover, by simply adding the other laser diode, it is also possible to generate a dual-chirp LCMW. The polarization manipulated of two optical signals avoids the undesired beating signals from optical carriers. Thus, an electrical bandpass filter which is essential in previous work is no longer required. To the best of our knowledge, this is the first time that polarization manipulation is used in FDML-OEO, which can further satisfy the demands of modern radars in terms of improved range-Doppler resolution, higher carrier frequency, and larger bandwidth.

Theoretical Study on the Effect of Environment on Excitation Energy Transfer in Photosynthetic Light-Harvesting Systems.

In recent years, two-dimensional (2D) electronic spectroscopy experiments prove that the excitation energy transfer (EET) in photosynthetic light-harvesting systems presents long-lived electronic quantum beating signals. After being discovered in the light-harvesting system, the quantum coherence effect has aroused widespread discussion. To illustrate the EET process in the Fenna-Matthews-Olson (FMO) and phycocyanin 645 (PC645) complex, the local protein environment is often thought to be the same; however, this is ambivalent to the practical structural analysis of the light-harvesting complex. By adopting the dissipaton equation of motion theory, we present the effect of a heterogeneous protein environment on the energy transfer process with accurate numerical results. We demonstrate that the energy transfer process relies on the local heterogeneous environment for the FMO complex. A similar good agreement is found for the PC645 complex. Furthermore, we discuss the optimal value of different chromophores in the excitation energy transfer process by controlling the environmental characteristics.

Remote detection of a rotator based on rotational Doppler effect

Based on the rotational Doppler effect arising from optical orbital angular momentum , we proposed the detection system of a rotator over a distance, by probing the object with a Laguerre–Gauss beam and a Kepler telescope. The angular velocities in tens of meters detection distances can be detected by analyzing the returned beating signals. Different probe beams with various topological charges from l = ± 25 to l = ± 45 are employed. The biggest measurement error is 1.15 Hz. This scheme proves the feasibility of a practical sensor to detect a rotator remotely.

Dynamic manipulation of probe pulse and coherent generation of beating signals based on tunneling-induced inference in triangular quantum dot molecules**Project supported by the National Natural Science Foundation of China (Grant Nos. 11704151 and 11247201), the Twelfth Five-Year Program for Science and Technology of Education Department of Jilin Province, China (Grant No. 20150215), and the Innovation and Entrepreneurship Program of Liaoning

We investigate the dynamic propagation of a probe field via the tunneling-induced interference effect in a triple model of quantum dot molecules. By theoretical analysis and numerical simulation, we find that the number of transparency window relate to the energy splitting and the group velocity of probe field can be effectively controlled by the tunneling coupling intensity. In addition, in the process of light storage and retrieval, when the excited states have no energy splitting in the storage stage but opposite values of the energy splitting in the retrieval stage, the beating signals can be generated.

DNA scaffold supports long-lived vibronic coherence in an indodicarbocyanine (Cy5) dimer.

Vibronic coupling between pigment molecules is believed to prolong coherences in photosynthetic pigment–protein complexes. Reproducing long-lived coherences using vibronically coupled chromophores in synthetic DNA constructs presents a biomimetic route to efficient artificial light harvesting. Here, we present two-dimensional (2D) electronic spectra of one monomeric Cy5 construct and two dimeric Cy5 constructs (0 bp and 1 bp between dyes) on a DNA scaffold and perform beating frequency analysis to interpret observed coherences. Power spectra of quantum beating signals of the dimers reveal high frequency oscillations that correspond to coherences between vibronic exciton states. Beating frequency maps confirm that these oscillations, 1270 cm−1 and 1545 cm−1 for the 0-bp dimer and 1100 cm−1 for the 1-bp dimer, are coherences between vibronic exciton states and that these coherences persist for ∼300 fs. Our observations are well described by a vibronic exciton model, which predicts the excitonic coupling strength in the dimers and the resulting molecular exciton states. The energy spacing between those states closely corresponds to the observed beat frequencies. MD simulations indicate that the dyes in our constructs lie largely internal to the DNA base stacking region, similar to the native design of biological light harvesting complexes. Observed coherences persist on the timescale of photosynthetic energy transfer yielding further parallels to observed biological coherences, establishing DNA as an attractive scaffold for synthetic light harvesting applications.

Detection of angular acceleration based on optical rotational Doppler effect.

The angular acceleration of a spinning object can be estimated by probing the object with Laguerre-Gauss (LG) beams and analyzing the rotational Doppler frequency shift of returned signals. The frequency shift is time dependent because of the change of the rotational angular velocity over time. The detection system is built to collect the beating signals of LG beams back-scattered from a non-uniform spinning body. Then a time-frequency analysis method is proposed to study the evolution of the angular velocity in time. The experimental results of different angular accelerations of the rotator are consistent with expectations. The measurement errors of different probe beams with various topological charges from l = ± 10 to l = ± 100 are also investigated.