Recent advances in the development of genome editing technologies based on programmable nucleases have substantially improved our ability to make precise changes in the genomes of eukaryotic cells. Genome editing is already broadening our ability to elucidate the contribution of genetics to disease by facilitating the creation of more accurate cellular and animal models of pathological processes. A particularly tantalizing application of programmable nucleases is the potential to directly correct genetic mutations in affected tissues and cells to treat diseases that are refractory to traditional therapies. Here we discuss current progress toward developing programmable nuclease–based therapies as well as future prospects and challenges.

Therapeutic genome editing: prospects and challenges

A device and method for ablating tissue is disclosed comprising the steps of acquiring an anatomical image of a patient, correlating the image to the patient, guiding an ablating member within the patient while tracking the position of the ablating member in the patient, positioning the ablating member in a desired position to ablate tissue, emitting ablating energy from the ablating member to form an ablated tissue area and removing the ablating member from the patient.

Methods of using high intensity focused ultrasound to form an ablated tissue area containing a plurality of lesions

A catheter and catheter system can use energy tailored for remodeling and/or removal of target material along a body lumen, often of atherosclerotic material of a blood vessel of a patient. An elongate flexible catheter body with a radially expandable structure may have a plurality of electrodes or other electrosurgical energy delivery surfaces to radially engage atherosclerotic material when the structure expands. An atherosclerotic material detector system may measure and/or characterize the atherosclerotic material and its location, optionally using impedance monitoring.

Tuned rf energy and electrical tissue characterization for selective treatment of target tissues

This work introduces a method of continuous particle separation through standing surface acoustic wave (SSAW)-induced acoustophoresis in a microfluidic channel. Using this SSAW-based method, particles in a continous laminar flow can be separated based on their volume, density and compressibility. In this work, a mixture of particles of equal density but dissimilar volumes was injected into a microchannel through two side inlets, sandwiching a deonized water sheath flow injected through a central inlet. A one-dimensional SSAW generated by two parallel interdigital transducers (IDTs) was established across the channel, with the channel spanning a single SSAW pressure node located at the channel center. Application of the SSAW induced larger axial acoustic forces on the particles of larger volume, repositioning them closer to the wave pressure node at the center of the channel. Thus particles were laterally moved to different regions of the channel cross-section based on particle volume. The particle separation method presented here is simple and versatile, capable of separating virtually all kinds of particles (regardless of charge/polarization or optical properties) with high separation efficiency and low power consumption.

Continuous particle separation in a microfluidic channel via standing surface acoustic waves (SSAW).

A catheter and catheter system for eccentric remodeling and/or removal of atherosclerotic material of a blood vessel of a patient include an elongate flexible catheter body with a radially expandable structure. A plurality of electrodes or other electrosurgical energy delivery surfaces can radially engage atherosclerotic material when the structure expands. An atherosclerotic material detector near the distal end of the catheter body may measure circumferential atherosclerotic material distribution, and a power source selectively energizes the electrodes to eccentrically remodel the measured atherosclerotic material.

Selectable Eccentric Remodeling and/or Ablation of Atherosclerotic Material

Sepsis is a lethal disease caused by a systemic microbial infection that spreads via the bloodstream to overwhelm the body's defenses. Current therapeutic approaches are often suboptimal, in part, because they do not fully eliminate the pathogen, and hence the source of deadly toxins. Here we describe an extracorporeal blood cleansing device to selectively remove pathogens from contaminated blood and thereby enhance the patient's response to antibiotic therapy. Immunomagnetic microbeads were modified to create magnetic opsonins that were used to cleanse flowing human whole blood of Candida albicans fungi, a leading cause of sepsis-related deaths. The micromagnetic–microfluidic blood cleansing device generates magnetic field gradients across vertically stacked channels to enable continuous and high throughput separation of fungi from flowing whole blood. A multiplexed version of the device containing four parallel channels achieved over 80% clearance of fungi from contaminated blood at a flow rate of 20 mL/h in a single pass, a rate 1000 times faster than a previously described prototype micromagnetic–microfluidic cell separation system. These results provide the first proof-of-principle that a multiplexed micromagnetic–microfluidic separation system can be used to cleanse pathogens from flowing human blood at a rate and separation efficiency that is relevant for clinical applications.

Micromagnetic–microfluidic blood cleansing device

A real time three dimensional ultrasound imaging probe apparatus is configured to be placed inside a body. The apparatus comprises an elongated body having proximal and distal ends with an ultrasonic transducer phased array connected to and positioned on the distal end of the elongated body. The ultrasonic transducer phased array is positioned to emit and receive ultrasonic energy for volumetric forward scanning from the distal end of the elongated body. The ultrasonic transducer phased array includes a plurality of sites occupied by ultrasonic transducer elements. At least one ultrasonic transducer element is absent from at least one of the sites, thereby defining an interstitial site. A tool is positioned at the interstitial site. In particular, the tool can be a fiber optic lead, a suction tool, a guide wire, an electrophysiological electrode, or an ablation electrode. Related systems are also discussed.

Imaging probes and catheters for volumetric intraluminal ultrasound imaging and related systems

http://transducers.bme.duke.edu/pubs/ui_1998_1-16.pdf

Progress in Two-Dimensional Arrays for Real-Time Volumetric Imaging

Inner ear drug delivery via a reciprocating perfusion system in the guinea pig

A variable, closed-loop apparatus for regulating a microfluidic flow that employs a low-power deflection assembly, which is surface-mounted over a flexible membrane overlying a chamber integrated into a microfabricated platform. A flexible membrane, moveable between two positions, sealingly overlies the chamber. One of the positions of the membrane restricts the flow through the chamber to a greater degree than the other position. A deflection assembly disposed on the substrate over the membrane unidirectionally deflects the membrane, thereby regulating the flow through the chamber.

Jason O. Fiering

Papers

Micromagnetic–microfluidic blood cleansing device

Imaging probes and catheters for volumetric intraluminal ultrasound imaging and related systems

Progress in Two-Dimensional Arrays for Real-Time Volumetric Imaging

Inner ear drug delivery via a reciprocating perfusion system in the guinea pig

Electromagnetically-actuated microfluidic flow regulators and related applications