The ability to control the position of micron-size particles with high precision using tools such as optical tweezers has led to major advances in fields such as biology, physics and material science. In this paper, we present a novel optical strategy to confine particles in solution with high spatial control using feedback-controlled thermoviscous flows. We show that this technique allows micron-size particles to be positioned and confined with subdiffraction precision (24 nm), effectively suppressing their diffusion. Due to its physical characteristics, our approach might be particular attractive where laser exposure is of concern or materials are inherently incompatible with optical tweezing since it does not rely on contrast in the refractive index.

The use of optical tweezers to measure forces acting upon microscopic particles has revolutionised fields from material science to cell biology. However, despite optical control capabilities, this technology is highly constrained by the material properties of the probe, and its use may be limited due to concerns about the effect on biological processes. Here we present a novel, optically controlled trapping method based on light-induced hydrodynamic flows. Specifically, we leverage optical control capabilities to convert a translationally invariant topological defect of a flow field into an attractor for colloids in an effectively one-dimensional harmonic, yet freely rotatable system. Circumventing the need to stabilise particle dynamics along an unstable axis, this novel trap closely resembles the isotropic dynamics of optical tweezers. Using magnetic beads, we explicitly show the existence of a linear force-extension relationship that can be used to detect femtoNewton-range forces with sensitivity close to the thermal limit. Our force measurements remove the need for laser-particle contact, while also lifting material constraints, which renders them a particularly interesting tool for the life sciences and engineering.

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The nucleus is highly organized to facilitate coordinated gene transcription. Measuring the rheological properties of the nucleus and its sub-compartments will be crucial to understand the principles underlying nuclear organization. Here, we show that strongly localized temperature gradients (approaching 1°C /μm) can lead to substantial intra-nuclear chromatin displacements (>1 μm), while nuclear area and lamina shape remain unaffected. Using particle image velocimetry (PIV), intra-nuclear displacement fields can be calculated and converted into spatio-temporally resolved maps of various strain components. Using this approach, we show that chromatin displacements are highly reversible, indicating that elastic contributions are dominant in maintaining nuclear organization on the time scale of seconds. In genetically inverted nuclei, centrally compacted heterochromatin displays high resistance to deformation, giving a rigid, solid-like appearance. Correlating spatially resolved strain maps with fluorescent reporters in conventional interphase nuclei reveals that various nuclear compartments possess distinct mechanical identities. Surprisingly, both densely and loosely packed chromatin showed high resistance to deformation, compared to medium dense chromatin. Equally, nucleoli display particularly high rigidity and strong local anchoring to heterochromatin. Our results establish how localized temperature gradients can be used to drive nuclear compartments out of mechanical equilibrium to obtain spatial maps of their material responses.Main FindingsNovel non-invasive active micro-rheology method to probe spatial intranuclear material responses, unhindered by the nuclear lamina, using strongly localized temperature gradientsChromatin shows both elastic and viscous properties at the mesoscale with a retardation time of τ ∼ 1sCompacted heterochromatin in a model of nuclear inversion shows high resistance to deformation, suggesting dominantly solid-like behaviorThe nucleus displays spatially distinct material properties for different compartmentsThe nucleolus shows high resistance to deformation on the time scale of secondsImmobile nucleoli appear solidly anchored to and retain the deformation of surrounding chromatin

Recently, it has been demonstrated that thermoviscous flows can be used for a range of fine micromanipulations, such as moving the cytoplasm of cells and developing embryos, intracellular rheology, and femtonewton-range force measurements. These flows, also known as focused-light-induced cytoplasmic streaming (FLUCS), are induced by mid-infrared laser scanning of a temperature spot through the sample. However, localized laser scanning can inflict temperature perturbations of several Kelvins on the sample, potentially eliciting unspecific biological responses. In this study, we demonstrate how exploiting symmetry relations during laser scanning effectively disentangles laser heating and flow induction. We introduce flow-neutral scan sequences that use dynamic photothermal stimuli and spatiotemporal symmetry relations of scanning bridging up to three distinct time scales. We leverage further insights from a recently published analytical model of flow fields to present quasi-homogenous temperature distributions that leave flow lines and their local and directed character largely invariant. We present practical, intuitive solutions through predesigned sets of scan lines with near isothermal distributions and demonstrate that they are sufficient to generate and control flows in Caenorhabditis elegans embryos on a magnitude well in excess of endogenous flow velocities. Our results enable the separation of two previously tightly linked classes of physical stimuli, introduce a new, even less invasive standard for performing FLUCS perturbations, and pave the way for new unexplored avenues in the fields of soft matter and biomedicine. Graphical Abstract

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Recent experiments in cell biology have probed the impact of artificially-induced intracellular flows in the spatiotemporal organisation of cells and organisms. In these experiments, mild dynamical heating (a few kelvins) via focused infrared light from a laser leads to long-range, thermoviscous flows of the cytoplasm inside a cell. To extend future use of this method in cell biology, popularised as focused-light-induced cytoplasmic streaming (FLUCS), new quantitative models are needed to link the external light forcing to the produced flows and transport. Here, we present a fully analytical, theoretical model describing the fluid flow induced by the dynamical laser stimulus at all length scales (both near the scan path of the laser beam and in the far field) in two-dimensional confinement. We model the effect of the focused light as a small, local temperature change in the fluid, which causes a small change in both the density and the viscosity of the fluid locally. In turn, this results in a locally compressible fluid flow. We analytically solve for the instantaneous flow field induced by the translation of a heat spot of arbitrary time-dependent amplitude along a scan path of arbitrary length. We show that the leading-order instantaneous flow field results from the thermal expansion of the fluid and is independent of the thermal viscosity coefficient. This leadingorder velocity field is proportional to the thermal expansion coefficient and the magnitude of the temperature perturbation, with far-field behaviour typically dominated by a source or sink flow and proportional to the rate of change of the heat-spot amplitude. In contrast, and in agreement with experimental measurements, the net displacement of a material point due to a full scan of the heat spot is quadratic in the heat-spot amplitude, as it results from the interplay of thermal expansion and thermal viscosity changes. The corresponding average velocity of material points over a scan is a hydrodynamic source dipole in the far field, with direction dependent on the relative importance of thermal expansion and thermal viscosity changes. Our quantitative findings show excellent agreement with recent experimental results and will enable the design of new controlled experiments to establish the physiological role of physical transport processes inside cells.

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