Single cell analysis has received increasing attention recently in both academia and clinics, and there is an urgent need for effective upstream cell sample preparation. Two extremely challenging tasks in cell sample preparation-high-efficiency cell enrichment and precise single cell capture-have now entered into an era full of exciting technological advances, which are mostly enabled by microfluidics. In this review, we summarize the category of technologies that provide new solutions and creative insights into the two tasks of cell manipulation, with a focus on the latest development in the recent five years by highlighting the representative works. By doing so, we aim both to outline the framework and to showcase example applications of each task. In most cases for cell enrichment, we take circulating tumor cells (CTCs) as the target cells because of their research and clinical importance in cancer. For single cell capture, we review related technologies for many kinds of target cells because the technologies are supposed to be more universal to all cells rather than CTCs. Most of the mentioned technologies can be used for both cell enrichment and precise single cell capture. Each technology has its own advantages and specific challenges, which provide opportunities for researchers in their own area. Overall, these technologies have shown great promise and now evolve into real clinical applications.

/pdf/microfluidics-cell-sample-preparation-for-analysis-advances-1etjhnsd1f.pdf

Microfluidics cell sample preparation for analysis: Advances in efficient cell enrichment and precise single cell capture.

Acoustic backscattering and radiation force on a rigid elliptical cylinder in plane progressive waves.

Non-contact precise manipulation of single microparticles, cells, and organisms has attracted considerable interest in biophysics and biomedical engineering. Similar to optical tweezers, acoustic tweezers have been proposed to be capable of manipulating microparticles and even cells. Although there have been concerted efforts to develop tools for non-contact manipulation, no alternative to complex, unifunctional tweezer has yet been found. Here we report a simple, low-cost, multifunctional single beam acoustic tweezer (SBAT) that is capable of manipulating an individual micrometer scale non-spherical cell at Rayleigh regime and even a single millimeter scale organism at Mie regime, and imaging tissue as well. We experimentally demonstrate that the SBAT with an ultralow f-number (f# = focal length/aperture size) could manipulate an individual red blood cell and a single 1.6 mm-diameter fertilized Zebrafish egg, respectively. Besides, in vitro rat aorta images were collected successfully at dynamic foci in which the lumen and the outer surface of the aorta could be clearly seen. With the ultralow f-number, the SBAT offers the combination of large acoustic radiation force and narrow beam width, leading to strong trapping and high-resolution imaging capabilities. These attributes enable the feasibility of using a single acoustic device to perform non-invasive multi-functions simultaneously for biomedical and biophysical applications.

/pdf/multifunctional-single-beam-acoustic-tweezer-for-non-248f8yz38e.pdf

Multifunctional single beam acoustic tweezer for non-invasive cell/organism manipulation and tissue imaging

Precise cell positioning is indispensable in the fields of biophysics and cellular biology. Acoustic microbeam produced by a highly focused ultrasound transducer has recently been investigated for a particle or cell manipulation. By virtue of the relatively good piezoelectric property, Sc doped AlN film was introduced for a highly focused ultrasound transducer application. Using a sputtering approach, a self-focused AlScN film based device has been designed, fabricated, and characterized at a frequency of ∼230 MHz. It had a narrow lateral beam width (∼8.2 μm). The AlScN ultrasound transducer was not only shown to be capable of remote controlling a single 10 μm polystyrene microsphere in distilled water, but also demonstrated to possess the capability to manipulate without contact individual 10 μm epidermoid carcinoma cell in two dimensions within a range of hundreds of micrometers in phosphate buffered saline. Most importantly, the cell manipulation was realized in continuous mode and no switch-on and -of...

Self-Focused AlScN Film Ultrasound Transducer for Individual Cell Manipulation.

Recently, acoustic levitation for non-contact micro-particle manipulation has been attracting great interest in physical, biological, and medical applications. Among the state-of-the-art manipulation technologies, single beam acoustic tweezing exhibits advantages of providing stronger trapping force and deeper penetration depth in tissues, inducing less tissue damage, and a simple configuration involving only one device. However, particle trapping by the single beam acoustic tweezer could only be operated on a smooth two-dimensional substrate, which limits the potential for real applications. Here, we report an initial attempt to acoustically levitate an individual micro-particle stably in water and manipulate the levitated micro-particle arbitrarily two-dimensionally by simply employing a 60-MHz focused ring ultrasonic transducer. The proposed working mechanism agrees well with the phenomenon. This approach could not only acoustically levitate and manipulate a micro-particle on a culture dish and on a mylar film, but could also work properly in levitating and manipulating a micro-particle placed inside the polyimide tube. This simple and low-cost approach is extremely useful for effective non-contact micro-particle manipulation without having critical concerns on the substrate properties.

Acoustic levitation and manipulation by a high-frequency focused ring ultrasonic transducer

https://research-information.bris.ac.uk/ws/files/68467947/PaperV3.pdf

Acoustic radiation force on a rigid cylinder in a focused Gaussian beam

Acoustic manipulation of porous spherical shells, widely used as drug delivery carriers and magnetic resonance imaging contrast agents, is investigated analytically. The technique used for this purpose is based on the application of high-order Bessel beams as a single-beam acoustic manipulation device, by which particles lying on the axis of the beam can be pulled toward the beam source. The exerted acoustic radiation force is calculated using the standard partial-wave series method, and the wave propagation within the porous media is modeled using Biot's theory of poro-elasticity. Numerical simulations are performed for porous aluminum and silica shells of different thickness and porosity. Results indicate that manipulation of low-porosity shells is possible using Bessel beams with large conical angles, over a number of broadband frequency ranges, whereas manipulation of highly porous shells can occur over both narrowband and broadband frequency domains.

/pdf/application-of-acoustic-bessel-beams-for-handling-of-hollow-5czm5yuvq2.pdf

Mohammad Azarpeyvand

Papers

Acoustic radiation force on a rigid cylinder in a focused Gaussian beam

Application of acoustic bessel beams for handling of hollow porous spheres.

Corrigendum to “Acoustic radiation force on a rigid cylinder in a focused Gaussian beam” [J. Sound Vib. 332 (2013) 2338–2349]