Dynamic monitoring of hemostatic equilibrium is indispensable for clinical safety in high-risk scenarios, while current clinical methods are limited by sample volume, detection speed, and physiological relevance. These shortcomings underscore the demand for novel sensing platforms. Optical biosensors, leveraging label-free detection, rapid response, and multi-level characterization, could serve as a transformative solution for decentralized and point-of-care monitoring. This review systematically summarizes advances in optical coagulation testing, encompassing light transmission aggregometry, laser speckle rheology, optical coherence tomography/elastography, optic–acoustic coupled methods, and fluorescence biosensing. These technologies complementarily capture structural and mechanical and some molecular and cellular dynamics of coagulation, bridging gaps in traditional assays. Despite promising preclinical and clinical correlations, translation barriers persist in lack of standardization of metrics, interference mitigation, and multi-center validation in diverse patient cohorts. Future development of optical biosensing platforms for coagulation testing should focus on modular integration, AI-aided interference correction, and microfluidic miniaturization to realize actionable, real-time coagulation assessment. Optical biosensors hold unparalleled potential to transform hemostatic monitoring from static endpoint testing to dynamic, interpretable evaluation, guiding personalized clinical decisions.
Plasma shielding is a critical limiting factor in enhancing the quality and efficiency of femtosecond laser processing. This study investigates the temporal evolution of femtosecond-laser-induced plasma in water, unveiling a transient recovery window occurring between plasma recombination completion and shockwave generation. During this window, the plasma density returns to baseline levels and exerts a negligible influence on probe light transmission. Furthermore, the plasma recombination time exhibits a strong dependence on the pump pulse energy. The pump pulse energy densities of 2.15, 2.77, and 3.72 J/cm2 correspond to plasma recombination time of 231.0, 125.4, and 112.2 ps, respectively. This advancement could potentially offer a valuable reference for optimizing pulse sequences in high-repetition-rate processing.
We present a single-shot laser speckle optical micro-rheology technique that measures tissue viscoelasticity from a single elongated speckle image, avoiding the need for high-speed cameras used in traditional optical micro-rheology. By calculating the intensity autocorrelation between rows of a rolling shutter speckle image with different inter-row delays, we can extract the decorrelation time of dynamic speckles, which directly related to the viscoelastic modulus of multiple scattering samples. Our method extends the range of measured viscoelastic modulus in optical micro-rheology by capturing speckle images with equivalent frame rates over 100,000 frame per second. This enables precise viscoelasticity assessments of diverse biological tissues and tissue phantoms.
Anomalous diffusion of different particlelike entities, the deviation from typical Brownian motion, is ubiquitous in complex physical and biological systems. While optical vortices move randomly in evolving speckle fields, optical vortices have only been observed to exhibit pure Brownian motion in random speckle fields. Here we present direct experimental evidence of the anomalous diffusion of optical vortices in temporally varying speckle patterns from multiple-scattering viscoelastic media. Moreover, we observe two characteristic features, i.e., the self-similarity and the antipersistent correlation of the optical vortex motion, indicating that the mechanism of the observed subdiffusion of optical vortices can only be attributed to fractional Brownian motion (FBM). We further demonstrate that the vortex displacements exhibit a non-Gaussian heavy-tailed distribution. Additionally, we modulate the extent of subdiffusion, such as diffusive scaling exponents, and the non-Gaussianity of optical vortices by altering the viscoelasticity of samples. The discovery of the complex FBM but non-Gaussian subdiffusion of optical vortices may not only offer insight into certain fundamental physics, including the anomalous diffusion of vortices in fluids and the decoupling between Brownianity and Gaussianity, but also suggest a strong potential for utilizing optical vortices as tracers in microrheology instead of the introduced exogenous probe particles in particle tracking microrheology.
We propose a novel optical microrheology technique that assesses tissue viscoelasticity by tracking the stochastic motion of optical vortices in speckles from turbid tissues. We validate the optical vortex tracking microrheology by illustrating the universal inverse relation between vortex displacements and the viscoelastic modulus. Moreover, we notice the phase angle of the viscoelastic sample is directly related to the vortices subdiffusion exponent. We also observe that the subdiffusion of optical vortices exhibits diverse characteristics for homogeneous and inhomogeneous samples. We believe the optical vortex tracking microrheology may find wide applications in different clinical scenarios like localizing tumors and fabricating biomaterials.
We investigate the dynamic behavior of optical vortices, or phase singularities, in random wavefields and demonstrate the direct experimental observation of the anomalous diffusion of optical vortices. The observed subdiffusion of optical vortices show excellent agreement with the fractional Brownian motion, a Gaussian process. Paradoxically, the vortex displacements are observed exhibiting a non-Gaussian heavy-tailed distribution. We also tune the extent of subdiffusion and non-Gaussianity of optical vortex by varying the viscoelasticity of light scattering media. This complex motion of optical vortices is reminiscent of particles in viscoelastic environments suggesting a vortex tracking based microrheology approach. The fractional Brownian yet non-Gaussian subdiffusion of optical vortices may not only offer insights into the dynamics of phase singularities, but also contribute to the understanding certain general physics, including vortex diffusion in fluids and the decoupling between Brownian and Gaussian.
Background Developing biocompatible nerve conduits that accelerate peripheral nerve regeneration, lengthening and functional recovery remains a challenge. The combined application of nerve microtissues and platelet-rich plasma (PRP) provides abundant Schwann cells (SCs) and various natural growth factors and can compensate for the deficiency of SCs in the nerve bridge, as well as the limitations of applying a single type of growth factor. Multimodal ultrasound evaluation can provide additional information on the stiffness and microvascular flow perfusion of the tissue. This study was designed to investigate the effectiveness of a novel tissue-engineered nerve graft composed of an autogenous vein, nerve microtissues and PRP in reconstructing a 12-mm tibial nerve defect and to explore the value of multimodal ultrasound techniques in evaluating the prognosis of nerve repair. Methods In vitro, nerve microtissue activity was first investigated, and the effects on SC proliferation, migration, factor secretion, and axonal regeneration of dorsal root ganglia (DRG) were evaluated by coculture with nerve microtissues and PRP. In vivo, seventy-five rabbits were equally and randomly divided into Hollow, PRP, Micro-T (Microtissues), Micro-T + PRP and Autograft groups. By analysing the neurological function, electrophysiological recovery, and the comparative results of multimodal ultrasound and histological evaluation, we investigated the effect of these new nerve grafts in repairing tibial nerve defects. Results Our results showed that the combined application of nerve microtissues and PRP could significantly promote the proliferation, secretion and migration of SCs and the regeneration of axons in the early stage. The Micro-T + PRP group and Autograft groups exhibited the best nerve repair 12 weeks postoperatively. In addition, the changes in target tissue stiffness and microvascular perfusion on multimodal ultrasound (shear wave elastography; contrast-enhanced ultrasonography; Angio PlaneWave UltrasenSitive, AngioPLUS) were significantly correlated with the histological results, such as collagen area percentage and VEGF expression, respectively. Conclusion Our novel tissue-engineered nerve graft shows excellent efficacy in repairing 12-mm defects of the tibial nerve in rabbits. Moreover, multimodal ultrasound may provide a clinical reference for prognosis by quantitatively evaluating the stiffness and microvescular flow of nerve grafts and targeted muscles.
Blood coagulation is a complicated dynamic process that maintains the blood's fluid state and prevents uncontrollable bleeding. The real-time monitoring of coagulation dynamics is critical for blood transfusion guidance, emergency management of trauma-induced coagulopathy, perioperative bleeding, and targeted hemostatic therapy. Here, we utilize optical vortex dynamics to detect the blood coagulation dynamic process in a rapid and non-contact manner. To characterize the temporal changes in viscoelastic properties of blood during coagulation, we track the stochastic motion of optical vortices in the time-varying speckles reflected from 100 blood samples with varied coagulation profiles. The mean square displacement (MSD) of the vortices increases nonlinearly with time lag during blood coagulation reminiscent of the particles in viscoelastic fluids. The MSD curves with coagulation time are similar to the tracings of thromboelastography (TEG) during the blood coagulation. The retrieved coagulation parameters, such as reaction time and activated clotting time measured using the optical vortex method, exhibit a close correlation to those parameters acquired from TEG. These results demonstrate the feasibility of the optical vortex method for monitoring blood coagulation at the point of care. Our method is also applicable to measuring the viscoelasticity of complex fluids and turbid soft matters.
We proposed a new approach to evaluate tissue rheological properties by assessing the stochastic motion of optical vortices in the pseudo-phase representation of laser speckles. By studying the vortex MSD and VAF, we observed the anomalous diffusion of optical vortices and evaluated the viscoelastic modulus of different gel phantoms and tissue samples with diverse mechanical and optical properties. We established the direct relationship which connects the microscopic motion of the optical vortices to the macroscopic viscoelastic response of the multiple scattering viscoelastic media. We can imagine amounts of biomedical applications including blood coagulability monitoring, atherosclerotic plaque characterization, and tumor localization.
The whole dynamic process of blood coagulation can be characterized by tracking the MSD of optical vortices with our previous coagulation measurement system. To develop a portable prototype of the coagulation detection system, we use an embedded system for whole blood laser speckle image acquisition, and apply deep learning methods for the temporal and spatial interpolation of the acquired images and the fast localization of optical vortex. The prototype implementation with a compact optical design and experimental validation provide a feasible idea and method for the miniaturization of blood coagulation devices.
We investigated a new optical approach for the detection of the coagulation dynamic process by means of the information on the optical vortex. In our study, laser speckle was captured using a high-speed CMOS camera, and the statistical information of the optical vortex characterized the change in coagulation properties with time. Similar to the scattering particles, the motion of the optical vortex is restricted during coagulation, as a result, the whole process of coagulation can be detected by calculating the mean square displacement(MSD) of the optical vortex. The results demonstrate a close correlation between coagulation parameters measured using the optical vortex method and thrombelastography(TEG), creating a powerful opportunity for self-testing and real-time detection of coagulation.
We report an imaging approach applying the atomic force acoustic microscopy (AFAM), which has unique potential for nondestructive imaging of cell internal structures. To obtain high spatial resolution images, we optimized the significant imaging parameters, including scanning speeds, feedback configurations and acoustic frequencies of an AFAM system, to increase the amplitude of the acoustic signal and to stabilize the morphological signals. We also combined the acoustic amplitude and phase signals, and generated pseudo-color figures for better illustration of subcellular features such as pseudopodia, membranes and nucleus-like. The subcellular structural image atlas can describe nanoscale details of multiple samples and provide clearer images of the subcellular features compared to other conventional techniques. This study builds a strong basis of transmission AFAM for cell imaging, which can help researchers to clarify the cell structures in diverse biological fields and push the understanding of biology evolution to a new stage.
Exosomes, a class of small extracellular vesicles, play important roles in various physiological and pathological processes by serving as vehicles for transferring and delivering membrane and cytosolic molecules between cells. Since exosomes widely exist in various body fluids and carry molecular information on their originating cells, they are being regarded as potential noninvasive biomarkers. Nevertheless, the development of convenient and quantitative exosome analysis methods is still technically challenging. Here, we present a low-cost assay for direct capture and rapid detection of exosomes based on a copper-mediated signal amplification strategy. The assay involves three steps. First, bulk nanovesicles are magnetically captured by cholesterol-modified magnetic beads (MB) via hydrophobic interaction between cholesterol moieties and lipid membranes. Second, bead-binding nanovesicles of exosomes with a specific membrane protein are anchored with aptamer-modified copper oxide nanoparticles (CuO NPs) to form sandwich complexes (MB-exosome-CuO NP). Third, the resultant sandwich complexes are dissolved by acidolysis to turn CuO NP into copper(II) ions (Cu2+), which can be reduced to fluorescent copper nanoparticles (CuNPs) by sodium ascorbate in the presence of poly(thymine). The fluorescence emission of CuNPs increases with the increase of Cu2+ concentration, which is directly proportional to the concentration of exosomes. Our method allows quantitative analysis of exosomes in the range of 7.5 × 104 to 1.5 × 107 particles/μL with a detection of limit of 4.8 × 104 particles/μL in biological sample. The total working time is about 2 h. The assay has the potential to be a simple and cost-effective method for routine exosome analysis in biological samples.
Order processing system is the beginning and core part of distribution center operations, and efficient order processing operations can not only improve customer satisfaction but also reduce costs. Therefore, the trade-off analysis between order processing difficulty and quick response time, improving the handling capacity and efficiency while reducing order processing costs are regarded as two big challenges for e-commercial enterprise. Based on queuing model as well as some data collected from Jingdong, a Chinese E-commerce giant, this paper constructed a 3D simulation model by using Flexsim, aiming at solving the bottleneck of the whole system of E-commerce order processing. According to the simulation, the author gives two order processing optimization solution, service stations optimization and queuing optimization to solve the two challenges.
A number of disease conditions including coronary atherosclerosis, peripheral artery disease and gastro-intestinal malignancies are associated with alterations in tissue mechanical properties. Laser speckle rheology (LSR) has been demonstrated to provide important information on tissue mechanical properties by analyzing the time scale of temporal speckle intensity fluctuations, which serves as an index of tissue viscoelasticity. In order to measure the mechanical properties of luminal organs in vivo, LSR must be conducted via a miniature endoscope or catheter. Here we demonstrate the capability of an omni-directional LSR catheter to quantify tissue mechanical properties over the entire luminal circumference without the need for rotational motion. Retracting the catheter using a motor-drive assembly enables the reconstruction of cylindrical maps of tissue mechanical properties. The performance of the LSR catheter is tested using a luminal phantom with mechanical moduli that vary in both circumferential and longitudinal directions. 2D cylindrical maps of phantom viscoelastic properties are reconstructed over four quadrants of the coronary circumference simultaneously during catheter pullback. The reconstructed cylindrical maps of the decorrelation time constants easily distinguish the different gel components of the phantom with different viscoelastic moduli. The average values of decorrelation times calculated for each gel component of the phantom show a strong correspondence with the viscoelastic moduli measured via standard mechanical rheometry. These results highlight the capability for cylindrical mapping of tissue viscoelastic properties using LSR in luminal organs using a miniature catheter, thus opening the opportunity for improved diagnosis of several disease conditions.
Acute myocardial infarction is frequently caused by the rupture of coronary plaques with severely compromised viscoelastic properties. We have developed a new optical technology termed intravascular laser speckle imaging (ILSI) that evaluates plaque viscoelastic properties, by measuring the time scale (time constant, τ) of temporally evolving laser speckle fluctuations. To enable coronary evaluation in vivo, an optical ILSI catheter has been developed that accomplishes omni-directional illumination and viewing of the entire coronary circumference without the need for mechanical rotation. Here, we describe the capability of ILSI for evaluating human coronary atherosclerosis in cadaveric hearts. ILSI was conducted in conjunction with optical coherence tomography (OCT) imaging in five human cadaveric hearts. The left coronary artery (LCA), left anterior descending (LAD), left circumflex artery (LCx), and right coronary artery (RCA) segments were resected and secured on custom-developed coronary holders to enable accurate co-registration between ILSI, OCT, and histopathology. Speckle time constants, τ, calculated from each ILSI section were compared with lipid and collagen content measured from quantitative Histopathological analysis of the corresponding Oil Red O and Picrosirius Red stained sections. Because the presence of low viscosity lipid elicits rapid speckle fluctuations, we observed an inverse correlation between τ measured by ILSI and lipid content (R= -0.64, p< 0.05). In contrast, the higher viscoelastic modulus of fibrous regions resulted in a positive correlation between τ and collagen content (R= 0.54, p< 0.05). These results demonstrate the feasibility of conducting ILSI evaluation of arterial mechanical properties using a miniaturized omni-directional catheter.
A analytical hedging rule based on a double triggering mechanism was proposed .The new rule was composed of three sub‐rules and considered the relationship between potential water shortage and water availability .First ,the sub‐hedging rule was invoked based on the relationship between ini‐tial storage and rule curves .When to start hedging was then decided by the current water availability in each sub rule .The proposed rule was analytically derived and the parameters on hedging were opti‐mized by serial master‐slaver swarms shuffling evolution algorithm based on particle swarm optimiza‐tion .The Xujiahe reservoir was employed as a case study to verify the efficiency of the proposed rule . The operation results show that the proposed rule is more effective and reasonable to handle water supply operation problems ,compared with the standard operation policy and conventional hedging rules .