Cell Deformation by Single-beam Acoustic Trapping: A Promising Tool for Measurements of Cell Mechanics

We demonstrate a noncontact single-beam acoustic trapping method for the quantification of the mechanical properties of a single suspended cell with label-free. Experimentally results show that the single-beam acoustic trapping force results in morphological deformation of a trapped cell. While a cancer cell was trapped in an acoustic beam focus, the morphological changes of the immobilized cell were monitored using bright-field imaging. The cell deformability was then compared with that of a trapped polystyrene microbead as a function of the applied acoustic pressure for a better understanding of the relationship between the pressure and degree of cell deformation. Cell deformation was found to become more pronounced as higher pressure levels were applied. Furthermore, to determine if this acoustic trapping method can be exploited in quantifying the cell mechanics in a suspension and in a non-contact manner, the deformability levels of breast cancer cells with different degrees of invasiveness due to acoustic trapping were compared. It was found that highly-invasive breast cancer cells exhibited greater deformability than weakly-invasive breast cancer cells. These results clearly demonstrate that the single-beam acoustic trapping technique is a promising tool for non-contact quantitative assessments of the mechanical properties of single cells in suspensions with label-free.1

Non-contact acoustic radiation force impulse microscopy via photoacoustic detection for probing breast cancer cell mechanics

We demonstrate a novel non-contact method: acoustic radiation force impulse microscopy via photoacoustic detection (PA-ARFI), capable of probing cell mechanics. A 30 MHz lithium niobate ultrasound transducer is utilized for both detection of phatoacoustic signals and generation of acoustic radiation force. To track cell membrane displacements by acoustic radiation force, functionalized single-walled carbon nanotubes are attached to cell membrane. Using the developed microscopy evaluated with agar phantoms, the mechanics of highly- and weakly-metastatic breast cancer cells are quantified. These results clearly show that the PA-ARFI microscopy may serve as a novel tool to probe mechanics of single breast cancer cells. © 2014 Optical Society of America.1

5-FU-hydrogel inhibits colorectal peritoneal carcinomatosis and tumor growth in mice

<p>Abstract</p> <p>Background</p> <p>Colorectal peritoneal carcinomatosis (CRPC) is a common form of systemic metastasis of intra-abdominal cancers. Intraperitoneal chemotherapy is a preferable option for colorectal cancer. Here we reported that a new system, 5-FU-loaded hydrogel system, can improve the therapeutic effects of intraperitoneal chemotherapy.</p> <p>Methods</p> <p>A biodegradable PEG-PCL-PEG (PECE) triblock copolymer was successfully synthesized. The biodegradable and temperature sensitive hydrogel was developed to load 5-FU. Methylene blue-loaded hydrogel were also developed for visible observation of the drug release. The effects and toxicity of the 5-FU-hydrogel system were evaluated in a murine CRPC model.</p> <p>Results</p> <p>The hydrogel system is an injectable flowing solution at ambient temperature and forms a non-flowing gel depot at physiological temperature. 5-FU-hydrogel was subsequently injected into abdominal cavity in mice with CT26 cancer cells peritoneal dissemination. The results showed that the hydrogel delivery system prolonged the release of methylene blue; the 5-FU-hydrogel significantly inhibited the peritoneal dissemination and growth of CT26 cells. Furthermore, intraperitoneal administration of the 5-FU-hydrogel was well tolerated and showed less hematologic toxicity.</p> <p>Conclusions</p> <p>Our data indicate that the 5-FU-hydrogel system can be considered as a new strategy for peritoneal carcinomatosis, and the hydrogel may provide a potential delivery system to load different chemotherapeutic drugs for peritoneal carcinomatosis of cancers.</p

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The measurement of cell mechanics is crucial for a better understanding of cellular responses during the progression of certain diseases and for the identification of the cell's nature. Many techniques using optical tweezers, atomic force microscopy, and micro-pipettes have been developed to probe and manipulate cells in the spatial domain. In particular, we recently proposed a two-dimensional acoustic trapping method as an alternative technique for small particle manipulation. Although the proposed method may have advantages over optical tweezers, its applications to cellular mechanics have not yet been vigorously investigated. This study represents an initial attempt to use acoustic tweezers as a tool in the field of cellular mechanics in which cancer cell membrane deformability is studied. A press-focused 193-MHz single-element lithium niobate (LiNbO3) transducer was designed and fabricated to trap a 5-μm polystyrene microbead near the ultrasound beam focus. The microbeads were coated with fibronectin, and trapped before being attached to the surface of a human breast cancer cell (MCF-7). The cell membrane was then stretched by remotely pulling a cell-attached microbead with the acoustic trap. The maximum cell membrane stretched lengths were measured to be 0.15, 0.54, and 1.41 μm at input voltages to the transducer of 6.3, 9.5, and 12.6 Vpp, respectively. The stretched length was found to increase nonlinearly as a function of the voltage input. No significant cytotoxicity was observed to result from the bead or the trapping force on the cell during or after the deformation procedure. Hence, the results convincingly demonstrated the possible application of the acoustic trapping technique as a tool for cell manipulation.Department of Electrical Engineerin

Non-contact multi-particle annular patterning and manipulation with ultrasound microbeam

Multiparticle-trapping offers diverse opportunities and applications in biotechnology. It can be applied to creating various functional materials or organizing reactive particles. In this paper, we demonstrate that it is possible to trap and manipulate multi-particles in an annular pattern with a 24 MHz focused ring-type single element ultrasound transducer. Acoustic ring trap can be useful in undertaking biotropism studies due to an equal-distance condition from the center. Also, this ring trap could serve as a force shield to protect analysis area from other cells. The experimental results showed the capability of the proposed method as a multi-cell manipulator in formatting specific patterns of small cells like sperms

A simple method for evaluating the trapping performance of acoustic tweezers

The purpose of this paper is to present a rapid and simple method to evaluate the trapping performance of high frequency focused ultrasonic transducers for acoustic tweezer applications. The method takes into consideration the friction between the particle to be trapped and the surface that it resides on. As a result it should be more reliable and accurate than the methods proposed previously. The trapping force produced by a 70-MHz press-focused transducer was measured to evaluate the performance of this approach. This method demonstrates its potential in optimizing the excitation conditions for acoustic tweezer applications and the design of acoustic tweezers

Magnetically Actuated Forward-Looking Interventional Ultrasound Imaging: Feasibility Studies

Objective: Interventional ultrasound imaging is a prerequisite for guiding implants and treatment within the hearts and blood vessels. Due to limitations on the catheter&apos;s diameter, interventional ultrasonic transducers have side-looking structures although forward-looking imaging may provide more intuitive and real time guidance in treating diseased sites ahead of catheters. To address the issue, a magnetically actuated forward-looking interventional ultrasound imaging device is implemented for the first time. Methods: A forward-looking catheter containing a 1 mm ring type focused 35 MHz ultrasound transducer and a micro magnet, was fabricated. For imaging, the transducer was placed at the center of four electromagnetic coils positioned on four sides of a squared acrylic housing. By modifying the magnetic field, the catheter tip could be remotely translated for sector scanning. Results: The scanning angle could reach up to 3° in 1 Hz with 15 mT, while wider angles of 5° could be achieved with a higher magnetic field of 25 mT for ex-vivo imaging. The position of the transducer could be detected by monitoring the motion with a CCD camera, mimicking clinical X-ray imaging. In the wire target and tissue mimicking phantom studies, the measured hole size, spatial resolution and distance between wires by the proposed system were comparable with the values from a linear scanner. Multi-frame real time data acquisition was demonstrated via ex-vivo imaging on a pig&apos;s coronary artery. Conclusion/Significance: The feasibility of magnetically actuated forward-looking interventional ultrasound imaging was demonstrated. The remote-controlled scanning method may allow to simplify the structures of forward-looking interventional ultrasound imaging catheters.1

Ultrahigh frequency ultrasound microbeam for biomedical applications

Several 200-MHz lithium niobate (LN) single crystal single-element press-focused ultrasonic transducers were developed for biomedical applications. Micro-particle trapping experiments were carried out to demonstrate that the acoustic device can manipulate a single microbead as small as 5 µm within the range of hundreds of micrometers in distilled water. As the result suggests that the 200-MHz microbeam device is capable of manipulating particles two-dimensionally at the cellular level, the device was used for studying red blood cell (RBC) mechanical deformation. It was found that by attaching the trapped microbead to a RBC, the RBC could be stretched by moving the trapped microbead. This preliminary result demonstrates the acoustic microbeam may be promising tool for studying the RBC membrane elastic properties