New immunodiagnostic methods for human tegumentary leishmaniasis in the last 10 years: Technological prospecting.

Leishmaniasis is a neglected disease and more than 1 billion people live in endemic areas with the risk of infection worldwide. Although it is an important epidemiological issue, the gold standard method of diagnosis requires invasive sample collection and is accompanied by a high level of sensitivity variation in results. The present study aims to conduct a patent prospection of immunodiagnostic methods for human tegumentary leishmaniasis in the last 10 years, focused on those with high sensitivity and specificity, and simple usability. We searched seven patent databases: The LENS, WIPO, EPO, USPTO, Patent Inspiration, Google patents, and INPI. Eleven patents were found that satisfy our search criteria, with six of them being registered in 2017. Most patents were registered in Brazil. The information obtained here covers the main characteristics of the immunodiagnostic methods evaluated. Moreover, our prospective study reveals the latest biotechnological advancements achieved in the immunodiagnosis of tegumentary leishmaniasis, especially in Brazil, which holds the majority of patents in this subject. However, no patent for immunodiagnostic methods was found in the last three years, which raises concerns about the present and future trends of leishmaniasis diagnosis.

Acoustic levitation of axisymmetric Mie objects above a transducer array by engineering the acoustic radiation force and torque.

Transducer arrays are a versatile tool for the contactless manipulation of spherical Rayleigh objects. Here we propose an analytical model for stable levitation of axisymmetric Mie objects through directly engineering the desired radiation force and torque. Acoustic contributions from multiple transducers are superimposed through the translation addition theorem, and the nonspherical objects are mapped into a sphere using the conformal transformation technique so that the scattered field can be asymptotically obtained. Then we give the acoustic radiation force and torque applied to a rigid nonspherical Mie object, which can be reconstructed as a series of quasiexplicit functions of the transducer (amplitude and phase) parameters. Through specifying the desired radiation force and torque exerted on the objects, a system of nonlinear equations is produced, which could be iteratively solved to retrieve appropriate transducer parameters that stabilize the object in an equilibrium position. Practically, we demonstrate several examples of stable levitation of a sphere, a spheroid, and a disk with an averaged radius of a=7mm (size parameter of ka≈5.18) above a transducer array. The absolute acoustic pressure field surrounding the objects simulated by the finite-element method is illustrated to verify the trapping results. The developed analytical model provides an alternative approach to retrieve the transducer parameters for levitating macroscopic nonspherical rigid objects, which may help design the systematic dynamical manipulation of Mie particles.

Development and Characterization of a Superresolution Ultrasonic Transducer.

Highly sensitive ultrasound probes are needed to expand the capabilities of biomedical ultrasound and industrial nondestructive testing (NDT). Pursuing better imaging quality, while keeping fabrication costs low, is an important trend in the current development of ultrasound imaging systems. In this article, we report the development and characterization of an ultrasonic transducer that (super)focuses ultrasonic waves beyond the so-called diffraction limit, that is, the beamwaist is roughly narrower than one wavelength. The transducer comprises an additive manufactured case with a circular flat piezoelectric actuator fixed at the bottom and a core-shell lens (with a stainless steel core and a polymer shell) placed at the probe's conical tip. The core-shell lens is responsible to superfocusing effect of ultrasonic waves. Operating at approximately 3 MHz, the transverse and axial resolution for C- and B-scan images are, respectively, 0.65λ and 3λ/2 , with the wavelength being [Formula: see text]. The system depth-of-field is 6.3λ . To demonstrate the transducer capability to resolve subwavelength structures, we successfully obtain images of a copper wire forming a Y-intersection, whose branches a diameter similar to human hair ( [Formula: see text]). Our results represent a solid step toward the development of ultrasonic superresolution transducer applied for biomedical imaging and shallow NDT of materials.

Mean acoustic fields exerted on a subwavelength axisymmetric particle.

The acoustic radiation force produced by ultrasonic waves is the "workhorse" of particle manipulation in acoustofluidics. Nonspherical particles are also subjected to a mean torque known as the acoustic radiation torque. Together they constitute the mean acoustic fields exerted on the particle. Analytical methods alone cannot calculate these fields on arbitrarily shaped particles in actual fluids and are no longer fit for purpose. Here, a semi-analytical approach is introduced for handling subwavelength axisymmetric particles immersed in an isotropic Newtonian fluid. The obtained mean acoustic fields depend on the scattering coefficients that reflect the monopole and dipole modes. These coefficients are determined by numerically solving the scattering problem. Our method is benchmarked by comparison with the exact result for a subwavelength rigid sphere in water. Besides, a more realistic case of a red blood cell immersed in blood plasma under a standing ultrasonic wave is investigated with our methodology.

Acoustic radiation force and torque on spheroidal particles in an ideal cylindrical chamber.

In this article, the acoustic radiation force and torque exerted on a small spheroidal particle immersed in a nonviscous fluid inside an ideal cylindrical chamber is theoretically investigated. The ideal chamber comprises a hard top and bottom (rigid boundary condition) and a soft or hard lateral wall. By assuming that the particle is much smaller than the acoustic wavelength, analytical expressions of the radiation force and torque caused by an acoustic wave of arbitrary shape are presented. Unlike previous results, these expressions are given relative to a fixed laboratory frame. The model is showcased for analyzing the behavior of an elongated metallic microspheroid (with a 10:1 aspect ratio) in a half-wavelength acoustofluidic chamber with a diameter of a few millimeters. The results show that the radiation torque aligns the microspheroid along the nodal plane, and the radiation force causes a translational motion with a speed of up to one body length per second. Finally, the implications of this study on propelled nanorods by ultrasound are discussed.

Acoustic radiation force due to incident plane-progressive waves on coated spheres.

The acoustic radiation force exerted by a traveling plane wave on a coated sphere was theoretically investigated. After carefully re-calculating the scattering coefficients of a model presented by Mitri [Eur. Phys. J. B 43, 379-386 (2005)], a missing term is found that is related to absorption in the particle shell. By amending the theory, it is shown that nonphysical consequences predicted earlier disappear. The homogeneous sphere results in the long-wavelength limit are also correctly recovered.

Acoustic radiation torque exerted on a subwavelength spheroidal particle by a traveling and standing plane wave.

The nonlinear interaction of ultrasonic waves with a nonspherical particle may give rise to the acoustic radiation torque on the particle. This phenomenon is investigated here considering a rigid prolate spheroidal particle of subwavelength dimensions that is much smaller than the wavelength. Using the partial wave expansion in spheroidal coordinates, the radiation torque of a traveling and standing plane wave with arbitrary orientation is exactly derived in the dipole approximation. In this paper, asymptotic expressions of the torque as the particle geometry approaches a sphere and a straight line are obtained. As the particle is trapped in a pressure node of a standing plane wave, its radiation torque equals that of a traveling plane wave. This paper also finds how the torque changes with the particle aspect ratio. The findings in this paper are in excellent agreement with previous numerical computations. Also, by analyzing the torque potential energy, the stable and unstable spatial configurations available for the particle are determined.

Acoustic spin transfer to a subwavelength spheroidal particle.

We demonstrate that the acoustic spin of a first-order Bessel beam can be transferred to a subwavelength (prolate) spheroidal particle at the beam axis in a viscous fluid. The induced radiation torque is proportional to the acoustic spin, which scales with the beam energy density. The analysis of the particle rotational dynamics in a Stokes flow regime reveals that its angular velocity varies linearly with the acoustic spin. Asymptotic expressions of the radiation torque and angular velocity are obtained for a quasispherical and infinitely thin particle. Excellent agreement is found between the theoretical results of radiation torque and finite-element simulations. The induced particle spin is predicted and analyzed using the typical parameter values of the acoustical vortex tweezer and levitation devices. We discuss how the beam energy density and fluid viscosity can be assessed by measuring the induced spin of the particle.

Acoustic deformation for the extraction of mechanical properties of lipid vesicle populations.

We use an ultrasonic standing wave to simultaneously trap and deform thousands of soft lipid vesicles immersed in a liquid solution. In our device, acoustic radiation stresses comparable in magnitude to those generated in optical stretching devices are achieved over a spatial extent of more than ten acoustic wavelengths. We solve the acoustic scattering problem in the long-wavelength limit to obtain the radiation stress. The result is then combined with thin-shell elasticity theory to form expressions that relate the deformed geometry to the applied acoustic field intensity. Using observation of the deformed geometry and this model, we rapidly extract mechanical properties, such as the membrane Young's modulus, from populations of lipid vesicles.

Acoustic radiation force exerted on a small spheroidal rigid particle by a beam of arbitrary wavefront: Examples of traveling and standing plane waves.

The analytical solution of the acoustic radiation force exerted by a beam of arbitrary shape on a small spheroidal rigid particle suspended in an ideal fluid is presented. The particle is assumed to be much smaller than the wavelength, i.e., the so-called long-wavelength approximation. Based on this theoretical development, closed-form expressions for the radiation force of a traveling and standing plane wave exerted on a prolate spheroidal particle are derived in the dipole approximation. As validation, the previous analytical result considering a standing wave interacting with a spheroid in axisymmetric configuration is recovered, as well as numerical results obtained with the boundary-element method.

Acoustic Interaction Forces and Torques Acting on Suspended Spheres in an Ideal Fluid.

In this paper, the acoustic interaction forces and torques exerted by an arbitrary time-harmonic wave on a set of N objects suspended in an inviscid fluid are theoretically analyzed. We utilize the partial-wave expansion method with translational addition theorem and re-expansion of multipole series to solve the related multiple scattering problem. We show that the acoustic interaction force and torque can be obtained using the farfield radiation force and torque formulas. To exemplify the method, we calculate the interaction forces exerted by an external traveling and standing plane wave on an arrangement of two and three olive-oil droplets in water. The droplets' radii are comparable to the wavelength (i.e., Mie scattering regime). The results show that the acoustic interaction forces present an oscillatory spatial distribution which follows the pattern formed by interference between the external and rescattered waves. In addition, acoustic interaction torques arise on the absorbing droplets whenever a nonsymmetric wavefront is formed by the external and rescattered waves' interference.

Computing the acoustic radiation force exerted on a sphere using the translational addition theorem.

In this paper, the translational addition theorem for spherical functions is employed to calculate the acoustic radiation force produced by an arbitrary shaped beam on a sphere arbitrarily suspended in an inviscid fluid. The procedure is also based on the partial-wave expansion method, which depends on the beam-shape and scattering coefficients. Given a set of beam-shape coefficients (BSCs) for an acoustic beam relative to a reference frame, the translational addition theorem can be used to obtain the BSCs relative to the sphere positioned anywhere in the medium. The scattering coefficients are obtained from the acoustic boundary conditions across the sphere's surface. The method based on the addition theorem is particularly useful to avoid quadrature schemes to obtain the BSCs. We use it to compute the acoustic radiation force exerted by a spherically focused beam (in the paraxial approximation) on a silicone-oil droplet (compressible fluid sphere). The analysis is carried out in the Rayleigh (i.e., the particle diameter is much smaller than the wavelength) and Mie (i.e., the particle diameter is of the order of the wavelength or larger) scattering regimes. The obtained results show that the paraxial focused beam can only trap particles in the Rayleigh scattering regime.

Designing single-beam multitrapping acoustical tweezers.

The concept of a single-beam acoustical tweezer device which can simultaneously trap microparticles at different points is proposed and demonstrated through computational simulations. The device employs an ultrasound beam produced by a circular focused transducer operating at 1 MHz in water medium. The ultrasound beam exerts a radiation force that may tweeze suspended microparticles in the medium. Simulations show that the acoustical tweezer can simultaneously trap microparticles in the pre-focal zone along the beam axis, i.e. between the transducer surface and its geometric focus. As acoustical tweezers are fast becoming a key instrument in microparticle handling, the development of acoustic multitrapping concept may turn into a useful tool in engineering these devices.

Acoustic radiation force and torque on an absorbing compressible particle in an inviscid fluid.

Exact formulas of the acoustic radiation force and torque exerted by an arbitrary time-harmonic wave on an absorbing compressible particle that is suspended in an inviscid fluid are presented. It is considered that the particle diameter is much smaller than the incident wavelength, i.e., the so-called Rayleigh scattering limit. Moreover, the particle absorption assumed here is due to the attenuation of compressional waves only. Shear waves inside and outside the particle are neglected, since the inner and outer viscous boundary layer of the particle are supposed to be much smaller than the particle radius. The obtained radiation force formulas are used to establish the trapping conditions of a particle by a single-beam acoustical tweezer based on a spherically focused ultrasound transducer. In this case, it is shown that the particle absorption has a pivotal role in single-beam trapping at the transducer focal region. Furthermore, it is found that only the first-order Bessel vortex beam can generate the radiation torque on a small particle. In addition, numerical evaluation of the radiation force and torque exerted on a benzene and an olive oil droplet suspended in water are presented and discussed.

Acoustic interaction forces between small particles in an ideal fluid.

We present a theoretical expression for the acoustic interaction force between small spherical particles suspended in an ideal fluid exposed to an external acoustic wave. The acoustic interaction force is the part of the acoustic radiation force on one given particle involving the scattered waves from the other particles. The particles, either compressible liquid droplets or elastic microspheres, are considered to be much smaller than the acoustic wavelength. In this so-called Rayleigh limit, the acoustic interaction forces between the particles are well approximated by gradients of pair-interaction potentials with no restriction on the interparticle distance. The theory is applied to studies of the acoustic interaction force on a particle suspension in either standing or traveling plane waves. The results show aggregation regions along the wave propagation direction, while particles may attract or repel each other in the transverse direction. In addition, a mean-field approximation is developed to describe the acoustic interaction force in an emulsion of oil droplets in water.

Deconvolution of vibroacoustic images using a simulation model based on a three dimensional point spread function.

Vibro-acoustography (VA) is a medical imaging method based on the difference-frequency generation produced by the mixture of two focused ultrasound beams. VA has been applied to different problems in medical imaging such as imaging bones, microcalcifications in the breast, mass lesions, and calcified arteries. The obtained images may have a resolution of 0.7-0.8mm. Current VA systems based on confocal or linear array transducers generate C-scan images at the beam focal plane. Images on the axial plane are also possible, however the system resolution along depth worsens when compared to the lateral one. Typical axial resolution is about 1.0cm. Furthermore, the elevation resolution of linear array systems is larger than that in lateral direction. This asymmetry degrades C-scan images obtained using linear arrays. The purpose of this article is to study VA image restoration based on a 3D point spread function (PSF) using classical deconvolution algorithms: Wiener, constrained least-squares (CLSs), and geometric mean filters. To assess the filters' performance on the restored images, we use an image quality index that accounts for correlation loss, luminance and contrast distortion. Results for simulated VA images show that the quality index achieved with the Wiener filter is 0.9 (when the index is 1.0 this indicates perfect restoration). This filter yielded the best result in comparison with the other ones. Moreover, the deconvolution algorithms were applied to an experimental VA image of a phantom composed of three stretched 0.5mm wires. Experiments were performed using transducer driven at two frequencies, 3075kHz and 3125kHz, which resulted in the difference-frequency of 50kHz. Restorations with the theoretical line spread function (LSF) did not recover sufficient information to identify the wires in the images. However, using an estimated LSF the obtained results displayed enough information to spot the wires in the images. It is demonstrated that the phase of the theoretical and the experimental PSFs are dissimilar. This fact prevents VA image restoration with the current theoretical PSF. This study is a preliminary step towards understanding the restoration of VA images through the application of deconvolution filters.

Difference-frequency generation in nonlinear scattering of acoustic waves by a rigid sphere.

In this paper, the partial-wave expansion method is applied to describe the difference-frequency pressure generated in a nonlinear scattering of two acoustic waves with an arbitrary wavefront by means of a rigid sphere. Particularly, the difference-frequency generation is analyzed in the nonlinear scattering with a spherical scatterer involving two intersecting plane waves in the following configurations: collinear, crossing at right angles, and counter-propagating. For the sake of simplicity, the plane waves are assumed to be spatially located in a spherical region which diameter is smaller than the difference-frequency wavelength. Such arrangements can be experimentally accomplished in vibro-acoustography and nonlinear acoustic tomography techniques. It turns out to be that when the sphere radius is of the order of the primary wavelengths, and the downshift ratio (i.e. the ratio between the fundamental frequency and the difference-frequency) is larger than five, difference-frequency generation is mostly due to a nonlinear interaction between the primary scattered waves. The exception to this is the collinear scattering for which the nonlinear interaction of the primary incident waves is also relevant. In addition, the difference-frequency scattered pressure in all scattering configurations decays as r(-1)lnr and 1/r, where r is the radial distance from the scatterer to the observation point.

Off-axial acoustic radiation force of repulsor and tractor bessel beams on a sphere.

Acoustic Bessel beams are known to produce an axial radiation force on a sphere centered on the beam axis (on-axial configuration) that exhibits both repulsor and tractor behaviors. The repulsor and the tractor forces are oriented along the beam's direction of propagation and opposite to it, respectively. The behavior of the acoustic radiation force generated by Bessel beams when the sphere lies outside the beam's axis (off-axial configuration) is unknown. Using the 3-D radiation force formulas given in terms of the partial wave expansion coefficients for the incident and scattered waves, both axial and transverse components of the force exerted on a silicone- oil sphere are obtained for a zero- and a first-order Bessel vortex beam. As the sphere departs from the beam's axis, the tractor force becomes weaker. Moreover, the behavior of the transverse radiation force field may vary with the sphere's size factor ka (where k is the wavenumber and a is the sphere radius). Both stable and unstable equilibrium regions around the beam's axis are found, depending on ka values. These results are particularly important for the design of acoustical tractor beam devices operating with Bessel beams.

Difference-frequency generation in vibro-acoustography.

Vibro-acoustography (VA) is a medical imaging method based on the nonlinear interaction of two or more distinct ultrasound beams whose frequencies differ by several kHz. In turn, the interacting waves produce a difference-frequency signal which carries the information of the imaged tissue region. Two mechanisms are responsible for the difference-frequency generation (DFG) in VA, namely the dynamic (oscillatory) radiation force and the scattering of sound-by-sound. The role and importance of each phenomenon in VA is assessed here. A theoretical model based on Westervelt's equation for the DFG in the nonlinear scattering of two incident ultrasound waves by a small rigid sphere (compared to the incident wavelengths) is presented. Furthermore, a scattering experiment using VA is devised and the data show very good agreement with the proposed theory. The results reveal that the effect of scattering of sound-by-sound is the dominant component in the DFG in VA rather than the dynamic radiation force.

Off-axis scattering of an ultrasound bessel beam by a sphere.

In this paper, the scattering of an ultrasound zero-order Bessel beam by a rigid sphere in the off-axis configuration is studied. The beam is described through the partial wave expansion. The beam-shape coefficients which represent the amplitude of each multipole mode of the partial wave expansion are computed by numerical quadrature. Calculations are presented for both near- and far-field off-axis scattering. The far-field scattering is examined in both Rayleigh and geometrical acoustic limits. Results demonstrate that the scattered pressure in the off-axis case may significantly deviate from that in the on-axis configuration. In addition, the directive pattern of the scattered pressure is highly dependent on the relative position of the beam to the sphere.