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Wednesday, October 7, 2020

Quantifying Fibrinogen-Dependent Aggregation of Red Blood Cells in Type 2 Diabetes Mellitus

Yixiang Deng, Dimitrios P. Papageorgiou, Xuejin Li, Nikolaos Perakakis, Christos S. Mantzoros, Ming Dao, George Em Karniadakis

Fibrinogen is regarded as the main glycoprotein in the aggregation of red blood cells (RBCs), a normally occurring phenomenon that has a major impact on blood rheology and hemodynamics, especially under pathological conditions, including type 2 diabetes mellitus (T2DM). In this study, we investigate the fibrinogen-dependent aggregation dynamics of T2DM RBCs through patient-specific predictive computational simulations that invoke key parameters derived from microfluidic experiments. We first calibrate our model parameters at the doublet (a rouleau consisting of two aggregated RBCs) level for healthy blood samples by matching the detaching force required to fully separate RBC doublets with measurements using atomic force microscopy and optical tweezers. Using results from companion microfluidic experiments that also provide in vitro quantitative information on cell-cell adhesive dynamics, we then quantify the rouleau dissociation dynamics at the doublet and multiplet (a rouleau consisting of three or more aggregated RBCs) levels for obese patients with or without T2DM. Specifically, we examine the rouleau breakup rate when it passes through microgates at doublet level and investigate the effect of rouleau alignment in altering its breakup pattern at multiplet level. This study seamlessly integrates in vitro experiments and simulations and consequently enhances our understanding of the complex cell-cell interaction, highlighting the importance of the aggregation and disaggregation dynamics of RBCs in patients at increased risk of microvascular complications.

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Displacement Detection Decoupling in Counter-Propagating Dual-Beams Optical Tweezers with Large-Sized Particle

Xunmin Zhu, Nan Li, Jianyu Yang, Xingfan Chen and Huizhu Hu

As a kind of ultra-sensitive acceleration sensing platform, optical tweezers show a minimum measurable value inversely proportional to the square of the diameter of the levitated spherical particle. However, with increasing diameter, the coupling of the displacement measurement between the axes becomes noticeable. This paper analyzes the source of coupling in a forward-scattering far-field detection regime and proposes a novel method of suppression. We theoretically and experimentally demonstrated that when three variable irises are added into the detection optics without changing other parts of optical structures, the decoupling of triaxial displacement signals mixed with each other show significant improvement. A coupling detection ratio reduction of 49.1 dB and 22.9 dB was realized in radial and axial directions, respectively, which is principally in accord with the simulations. This low-cost and robust approach makes it possible to accurately measure three-dimensional mechanical quantities simultaneously and may be helpful to actively cool the particle motion in optical tweezers even to the quantum ground state in the future.

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Experimental Realization of Diffusion with Stochastic Resetting

Ofir Tal-Friedman, Arnab Pal, Amandeep Sekhon, Shlomi Reuveni, and Yael Roichman

Stochastic resetting is prevalent in natural and man-made systems, giving rise to a long series of nonequilibrium phenomena. Diffusion with stochastic resetting serves as a paradigmatic model to study these phenomena, but the lack of a well-controlled platform by which this process can be studied experimentally has been a major impediment to research in the field. Here, we report the experimental realization of colloidal particle diffusion and resetting via holographic optical tweezers. We provide the first experimental corroboration of central theoretical results and go on to measure the energetic cost of resetting in steady-state and first-passage scenarios. In both cases, we show that this cost cannot be made arbitrarily small because of fundamental constraints on realistic resetting protocols. The methods developed herein open the door to future experimental study of resetting phenomena beyond diffusion.

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Plasmonic tweezers for optical manipulation and biomedical applications

Hongtao Tan, Huiqian Hu, Lin Huang and Kun Qian

Plasmonic tweezers are an emerging research topic because of their breakthrough in the conventional diffraction limit and precise manipulation at the nanoscale. Notably, their compatibility with analytical techniques (e.g. fluorescence, surface-enhanced Raman scattering (SERS), and laser desorption/ionization mass spectrometry (LDI MS)) opens up opportunities in optical manipulation and biomedical applications. Herein, we first introduce the structures and trapping forces, followed by a summary of the properties of plasmonic tweezers. The optical trapping of biosamples by plasmonic tweezers are then reviewed, including microorganisms and biomolecules. Finally, we highlight the integration of plasmonic tweezers with analytical techniques towards bioanalytical applications. We conclude with perspectives on the future directions for this topic. We foresee the upcoming era of biological detection by plasmonic tweezing in both academy and industry, which calls for the interest and efforts of scientists from diverse fields.

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Angular Trapping of Spherical Janus Particles

Xiaoqing Gao Yali Wang Xuehao He Mengjun Xu Jintao Zhu Xiaodong Hu Xiaotang Hu Hongbin Li Chunguang Hu

Developing angular trapping methods, which enable optical tweezers to rotate a micronsized bead, is of great importance for studies of biomacromolecules in a wide range of torque‐generation processes. Here a novel controlled angular trapping method based on model composite Janus particles is reported, which consist of two hemispheres made of polystyrene and poly(methyl methacrylate). Through computational and experimental studies, the feasibility to control the rotation of a Janus particle in a linearly polarized laser trap is demonstrated. The results show that the Janus particle aligned its two hemispheres interface parallel to the laser propagation direction and polarization direction. The rotational state of the particle can be directly visualized by using a camera. The rotation of the Janus particle in the laser trap can be fully controlled in real time by controlling the laser polarization direction. The newly developed angular trapping technique has the great advantage of easy implementation and real‐time controllability. Considering the easy chemical preparation of Janus particles and implementation of the angular trapping, this novel method has the potential of becoming a general angular trapping method. It is anticipated that this new method will significantly broaden the availability of angular trapping in the biophysics community.

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Tuesday, October 6, 2020

Paraxial and tightly focused behaviour of the double ring perfect optical vortex

Carolina Rickenstorff, Luz del Carmen Gómez-Pavón, Citlalli Teresa Sosa-Sánchez, and Gilberto Silva-Ortigoza

In this paper we compare the intensity distributions in the paraxial and tightly focused regimes corresponding to a double ring perfect optical vortex (DR-POV). Using the scalar diffraction theory and the Richards-Wolf formalism, the fields in the back focal plane of a low and high (tight focusing) NA lens are calculated. In the paraxial case we experimentally observed a DR-POV whose rings enclose a dark zone thanks to the destructive interference introduced by a π phase shift. In the tightly focused regime, however, the numerical simulations showed that the intensity near the focus is influenced by the input field polarization and it is not intuitive. In both cases we found that the dark region subtended between the rings has a minimal width that is inversely proportional to the pupil radius of the system, reaching 0.42λ for the radially polarized DR-POV. For the tightly focused case, we calculated the optical forces in the transversal and longitudinal coordinates exerted on a metallic particle. As a result, it is theoretically demonstrated that the circularly polarized DR-POV can trap Au metallic particles in 3D using a light wavelength close to its resonance.

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Surface plasmon resonance effect on laser trapping and swarming of gold nanoparticles at an interface

Chih-Hao Huang, Tetsuhiro Kudo, Roger Bresolí-Obach, Johan Hofkens, Teruki Sugiyama, and Hiroshi Masuhara

Laser trapping at an interface is a unique platform for aligning and assembling nanomaterials outside the focal spot. In our previous studies, Au nanoparticles form a dynamically evolved assembly outside the focus, leading to the formation of an antenna-like structure with their fluctuating swarms. Herein, we unravel the role of surface plasmon resonance on the swarming phenomena by tuning the trapping laser wavelength concerning the dipole mode for Au nanoparticles of different sizes. We clearly show that the swarm is formed when the laser wavelength is near to the resonance peak of the dipole mode together with an increase in the swarming area. The interpretation is well supported by the scattering spectra and the spatial light scattering profiles from single nanoparticle simulations. These findings indicate that whether the first trapped particle is resonant with trapping laser or not essentially determines the evolution of the swarming.

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Particle size measurement using a fibre-trap-based interference approach

Zhihai Liu, Lu Wang, Yu Zhang, Yaxun Zhang, Xiaoyun Tang, Chunyu Sha, Jianzhong Zhang, Jun Yang, Libo Yuan

We propose and demonstrate the measurement of the particle size using an all-fibre interference approach via a single fibre tweezer with a coaxial core fibre. The coaxial core fibre has an external annular core and a centre core. The external annular core is used to trap the microparticle and the centre core sends and receives interference signals for size measurement. The reflected lights from the fibre end face and the trapped particle surface will cause interference and the particle size is obtained from the FSR of the interference spectrum. Using this interference approach, we conduct a label-free, non-contact, and real-time particle size measurement. The proposed measurement approach can be further applied in biology, medical science, and lab-on-fibre technology research.

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Optically trapped particle dynamic responses under varying frequency sinusoidal stimulus

Tan Xu, Qingchuan Zhang, Shangquan Wu, Zhaoxiang Jiang, Xiaoping Wu

Optical tweezers have become indispensable and powerful micro-manipulation tools and acute force probes in biomedical fields. Therefore, calibrating the optical trap is essential for precise force measurements in biomolecular interactions. Currently, however, mainstream calibration methods mainly focus on analyzing nanometer level Brownian motions of trapped particles. There is thus an urgent need to investigate trapped particle dynamic processes in slightly large range to address practical situations for the biological application of optical tweezers. This paper proposes a varying frequency sinusoidal excitation method to probe trapped particle responses and develops a mathematical model to extract trap stiffness. Experimental results revealed that the proposed method achieved significantly lower relative error ( < 5%) even when particle size or laser power varied, and that the excitation frequency didn’t have much impact on trap stiffness. Thanks to its simplicity, effectiveness and robustness, our method provides an ideal candidate for further picoNewton force measurement studies for dynamic interactions in biomedical applications.

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Axial displacement calibration and tracking of optically trapped beads

Guoteng Ma, Chunguang Hu, Shuai Li, Xiaoqin Gao, Hongbin Li, Xiaotang Hu

High-precision axial displacement tracking of trapped beads is an indispensable feature of optical tweezers in advanced single-molecule studies. Here, we demonstrate an alternative method that enables axial calibration and tracking to be carried out on the same sample to avoid unnecessary errors. This method works by applying a dynamic force balance on a bead trapped between a piezoelectrically driven glass slide and an optical trap; in this configuration, the bead can be stopped precisely in different positions and imaged by a camera. A simple gradient algorithm is used to process the images into calibration data. After optimization of the calibration method and samples, our method exhibited better than 5 nm experimental axial resolution, with a measurement range of +/-500 nm around the objective focus at video speed. Moreover, for the first time, the deviation of the focusing plane in dual-trap optical tweezers was measured. We confirmed the axial deviation between two optical traps in our setup to be ~10 nm, corresponding to a force spectroscopy gage error of ~1 pN. This approach offers a favorable solution for in-use setup updating, as it can be seamlessly integrated into any optical tweezers system without requiring new hardware updates.

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Monday, October 5, 2020

Real-time measurement of three-dimensional morphology of blood cells in batches by non-orthogonal phase imaging

Hao Han, Yuanyuan Xu, Jingrong Liao, Shuangshuang Xue, Yawei Wang

In order to overcome the shortcoming of traditional tomography requires the vast amount of data and the limitation of intersection angle between two beams existed in a microscope objective to realize the real-time detection of three-dimensional (3D) morphological distribution of blood cells in batches, a method of reconstructing cell substructure with only two non-orthogonal phases is proposed in this paper. In this work, an optimized maximum entropy tomography (MET) algorithm is used for rapid 3D reconstruction which requires less phase information from non-orthogonal directions. Moreover, two phase images can be obtained simultaneously by the phase imaging system combined with flow cytometry and optical tweezers (OT). We perform simulations of two types of cell models and experiments of red blood cell (RBC), thrombocyte and lymphocyte. Results demonstrate this method is of great significance for 3D morphological analysis of blood cells in the field of clinical diagnosis or even life sciences.

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A concise review of microfluidic particle manipulation methods

Shuaizhong Zhang, Ye Wang, Patrick Onck & Jaap den Toonder

Particle manipulation is often required in many applications such as bioanalysis, disease diagnostics, drug delivery and self-cleaning surfaces. The fast progress in micro- and nano-engineering has contributed to the rapid development of a variety of technologies to manipulate particles including more established methods based on microfluidics, as well as recently proposed innovative methods that still are in the initial phases of development, based on self-driven microbots and artificial cilia. Here, we review these techniques with respect to their operation principles and main applications. We summarize the shortcomings and give perspectives on the future development of particle manipulation techniques. Rather than offering an in-depth, detailed, and complete account of all the methods, this review aims to provide a broad but concise overview that helps to understand the overall progress and current status of the diverse particle manipulation methods. The two novel developments, self-driven microbots and artificial cilia-based manipulation, are highlighted in more detail.

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Strong optical force of a molecule enabled by the plasmonic nanogap hot spot in a tip-enhanced Raman spectroscopy system

Li Long, Jianfeng Chen, Huakang Yu, and Zhi-Yuan Li

Tip-enhanced Raman spectroscopy (TERS) offers a powerful means to enhance the Raman scattering signal of a molecule as the localized surface plasmonic resonance will induce a significant local electric field enhancement in the nanoscale hot spot located within the nanogap of the TERS system. In this work, we theoretically show that this nanoscale hot spot can also serve as powerful optical tweezers to tightly trap a molecule. We calculate and analyze the local electric field and field gradient distribution of this nanogap plasmon hot spot. Due to the highly localized electric field, a three-dimensional optical trap can form at the hot spot. Moreover, the optical energy density and optical force acting on a molecule can be greatly enhanced to a level far exceeding the conventional single laser beam optical tweezers. Calculations show that for a single H2TBPP organic molecule, which is modeled as a spherical molecule with a radius of 𝑟𝑚=1  nm, a dielectric coefficient 𝜀=3, and a polarizability 𝛼=4.5×10−38  C·m2/V, the stiffness of the hot-spot trap can reach a high value of about 2  pN/[(W/cm2)·m] and 40  pN/[(W/cm2)·m] in the direction perpendicular and parallel to the TERS tip axis, which is far larger than the stiffness of single-beam tweezers, ∼0.4  pN/[(W/cm2)·m]. This hard-stiffness will enable the molecules to be stably captured in the plasmon hot spot. Our results indicate that TERS can become a promising tool of optical tweezers for trapping a microscopic object like molecules while implementing Raman spectroscopic imaging and analysis at the same time.

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Stand-off trapping and manipulation of sub-10 nm objects and biomolecules using opto-thermo-electrohydrodynamic tweezers

Chuchuan Hong, Sen Yang & Justus C. Ndukaife

Optical tweezers have emerged as a powerful tool for the non-invasive trapping and manipulation of colloidal particles and biological cells1,2. However, the diffraction limit precludes the low-power trapping of nanometre-scale objects. Substantially increasing the laser power can provide enough trapping potential depth to trap nanoscale objects. Unfortunately, the substantial optical intensity required causes photo-toxicity and thermal stress in the trapped biological specimens3. Low-power near-field nano-optical tweezers comprising plasmonic nanoantennas and photonic crystal cavities have been explored for stable nanoscale object trapping4,5,6,7,8,9,10,11,12,13. However, the demonstrated approaches still require that the object is trapped at the high-light-intensity region. We report a new kind of optically controlled nanotweezers, called opto-thermo-electrohydrodynamic tweezers, that enable the trapping and dynamic manipulation of nanometre-scale objects at locations that are several micrometres away from the high-intensity laser focus. At the trapping locations, the nanoscale objects experience both negligible photothermal heating and light intensity. Opto-thermo-electrohydrodynamic tweezers employ a finite array of plasmonic nanoholes illuminated with light and an applied a.c. electric field to create the spatially varying electrohydrodynamic potential that can rapidly trap sub-10 nm biomolecules at femtomolar concentrations on demand. This non-invasive optical nanotweezing approach is expected to open new opportunities in nanoscience and life science by offering an unprecedented level of control of nano-sized objects, including photo-sensitive biological molecules.

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RNA Nanoparticles as Rubber for Compelling Vessel Extravasation to Enhance Tumor Targeting and for Fast Renal Excretion to Reduce Toxicity

Chiran Ghimire, Hongzhi Wang, Hui Li, Mario Vieweger, Congcong Xu, and Peixuan Guo

Rubber is a fascinating material in both industry and daily life. The development of elastomeric material in nanotechnology is imperative due to its economic and technological potential. By virtue of their distinctive physicochemical properties, nucleic acids have been extensively explored in material science. The Phi29 DNA packaging motor contains a 3WJ with three angles of 97°, 125°, and 138°. Here, the rubber-like property of RNA architectures was investigated using optical tweezers and in vivo imaging technologies. The 3WJ 97° interior angle was contracted or stretched to 60°, 90°, and 108° at will to build elegant RNA triangles, squares, pentagons, cubes, tetrahedrons, dendrimers, and prisms. RNA nanoarchitecture was stretchable and shrinkable by optical tweezer with multiple extension and relaxation repeats like a rubber. Comparing to gold and iron nanoparticles with the same size, RNA nanoparticles display stronger cancer-targeting outcomes, while less accumulation in healthy organs. Generally, the upper limit of renal excretion is 5.5 nm; however, the 5, 10, and 20 nm RNA nanoparticles passed the renal filtration and resumed their original structure identified in urine. These findings solve two previous mysteries: (1) Why RNA nanoparticles have an unusually high tumor targeting efficiency since their rubber or amoeba-like deformation property enables them to squeeze out of the leaky vasculature to improve the EPR effect; and (2) why RNA nanoparticles remain non-toxic since they can be rapidly cleared from the body via renal excretion into urine with little accumulation in the body. Considering its controllable shape and size plus its rubber-like property, RNA holds great promises for industrial and biomedical applications especially in cancer therapeutics delivery.

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Saturday, October 3, 2020

Statistics of work performed by optical tweezers with general time-variation of their stiffness

Petr Chvosta, Dominik Lips, Viktor Holubec, Artem Ryabov and Philipp Maass

We derive an exact expression for the probability density of work done on a particle that diffuses in a parabolic potential with a stiffness varying by an arbitrary piecewise constant protocol. Based on this result, the work distribution for time-continuous protocols of the stiffness can be determined up to any degree of accuracy. This is achieved by replacing the continuous driving by a piecewise constant one with a number n of positive or negative steps of increasing or decreasing stiffness. With increasing n, the work distributions for the piecewise protocols approach that for the continuous protocol. The moment generating function of the work is given by the inverse square root of a polynomial of degree n, whose coefficients are efficiently calculated from a recurrence relation. The roots of the polynomials are real and positive (negative) steps of the protocol are associated with negative (positive) roots. Using these properties the inverse Laplace transform of the moment generating function is carried out explicitly. Fluctuation theorems are used to derive further properties of the polynomials and their roots.

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Enantioselective manipulation of single chiral nanoparticles using optical tweezers

Rfaqat Ali, Felipe A. Pinheiro, Rafael S. Dutra, Felipe S. S. Rosa and Paulo A. Maia Neto

We put forward an enantioselective method for chiral nanoparticles using optical tweezers. We demonstrate that the optical trapping force in a typical, realistic optical tweezing setup with circularly-polarized trapping beams is sensitive to the chirality of core–shell nanoparticles, allowing for efficient enantioselection. It turns out that the handedness of the trapped particles can be selected by choosing the appropriate circular polarization of the trapping beam. The chirality of each individual trapped nanoparticle can be characterized by measuring the rotation of the equilibrium position under the effect of a transverse Stokes drag force. We show that the chirality of the shell gives rise to an additional twist, leading to a strong enhancement of the optical torque driving the rotation. Both methods are shown to be robust against variations of size and material parameters, demonstrating that they are particularly useful in (but not restricted to) several situations of practical interest in chiral plasmonics, where enantioselection and characterization of single chiral nanoparticles, each and every one with its unique handedness and optical properties, are in order. In particular, our method could be employed to unveil the chiral response arising from disorder in individual plasmonic raspberries, synthesized by close-packing a large number of metallic nanospheres around a dielectric core.

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Laser-triggered dynamical plasmonic optical trapping targets advanced Raman detection sensitivity

Yan Kang, Feng Yang, Ting Wu, Siqian Lu, Yiping Du and Haifeng Yang

A novel method of laser-triggered Ag nanoparticles-based plasmonic optical trapping targets is developed. Such dynamically optimized Raman enhanced protocol exhibits superior detection sensitivity for Serratia marcescens and tetrabromobisphenol A with the LODs of 5×105 CFU mL-1 and 6×10-7 M, respectively.

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