Abstract: A treatment vessel may allow a user, or automated system, to manipulate sample material within a treatment area during processing (e.g., focused acoustic treatment), as well as subject the sample material to a staged processing protocol. The vessel may include openings for receiving/discharging the sample material. Walls within the vessel may be movable between various positions, to permit or obstruct flow of sample material into or out from a treatment area. The wall(s) may push the sample material within the vessel, as well as adjust pressure levels within the treatment area. In some embodiments, an acoustic treatment system may include a flexible coupling medium that may be deformed toward the vessel upon an application of suitable pressure thereto. When the medium presses up against the vessel, defects (e.g., particles, bubbles, interfaces, etc.) that may otherwise be present along the acoustic wave path may be reduced.

Abstract: Methods and systems for preparing crystalline particle compositions using focused acoustic processing to control a number or count of crystalline particles generated. Peak incident power of focused acoustic energy used to cause primary nucleation kinetics of a solute may be adjusted to adjust the number or count of crystalline particles.

Abstract: cfDNA reference material, e.g., for use in verifying the accuracy and effectiveness of a diagnostic test, is generated from chromatin which may be sourced from whole cells. The chromatin may be treated with formaldehyde to form crosslinks between DNA and histones, e.g., while the chromatin is contained within nuclear and/or plasma membranes. The fixed chromatin may be sheared by acoustic energy, which may also be used to lyse cell membranes within which the fixed chromatin may be contained. The sheared chromatin may be treated with an enzyme, such as micrococcal nuclease, to digest chromatin in linker regions of the DNA between nucleosomes and generate nucleosome material for use as cfDNA reference material.

Abstract: Methods and systems for acoustically treating material using a continuous process in which material may be caused to flow in a continuous or intermittent fashion into/out of an acoustic treatment chamber where the material is exposed to focused acoustic energy. The methods and systems may be arranged to permit continuous processing for extended periods while an acoustic energy source operates at a relatively high power output. Treatment chambers may include features such as an acoustic window and/or a chamber wall which may comprise an acoustically reflective material or a gas/wall interface that serves to reflect acoustic energy to form one or more secondary focal zones. Treatment system configurations relating to arrangements of a treatment chamber relative to an acoustic source and coupling medium, material flow paths, and others are provided.

Abstract: Systems and methods for the high yield extraction and recovery of higher quality target molecule(s) (e.g., DNA, RNA, protein, lipids, metabolites) from blood spots. High quality DNA recovered from dried blood spots can be an input source for high throughput analytical methods, such as for polymerase chain reaction (e.g., qPCR) and/or next generation sequencing (NGS). In various embodiments, at least 20.0 nanograms of nucleic acid (e.g., DNA, RNA), or at least 8.0 milligrams of protein, may be extracted and recovered per an amount of dried blood corresponding to approximately 5 microliters of fresh blood. In some embodiments, a majority (e.g., greater than 50%, greater than 60%, up to 95-100%) of the nucleic acid that is extracted and recovered from the blood spot via focused acoustics may be of a quality suitable for amplification via PCR or NGS.

Abstract: A sample holder and method for separating components of a viscous sample, such as a sputum sample, in a vessel having a porous element. Liquid may be flowed through the vessel during acoustic energy treatment, which may disrupt the viscous sample. Smaller components of the sample may pass through the porous element with liquid introduced into the vessel. Larger components, such a microbes, may be captured by the porous element and may remain intact and viable for subsequent analysis. The porous element may be removable from the vessel to recover the microbes.

Abstract: Method and apparatus for controlling acoustic treatment of a sample including a liquid. A processing volume in which the sample is acoustically treated may be controlled, e.g., by positioning a suitable element so as to reduce and/or eliminate a headspace size at a sample/gas interface. An interaction between the acoustic energy and the sample may be controlled, e.g., by using a headspace control element positioned at least partially in the sample that helps to reduce splashing or other sample ejection that would otherwise occur.

Abstract: Methods and systems for acoustically treating material are described. Acoustic energy is emitted into a waveguide having a wall with a shape that tapers away from the acoustic source. The wall may have a substantially conical or parabolic shape. When emitted therein, the waveguide causes convergence of the acoustic energy so as to form an acoustic focal zone at a vessel. In some embodiments, a substantial portion of the acoustic focal zone is located outside of the internal volume defined by the waveguide.

Abstract: Focused acoustic treatment of samples including a target biomolecule, such as cfDNA, may aid in the recovery of the biomolecule from a sample. cfDNA in a sample, whether chemically stabilized or not, may be linked or otherwise bound to histones or other proteins, e.g., by hydrogen bonds of histones or chaperone proteins to DNA and/or covalent crosslinks of such proteins to the DNA. Focused acoustic energy may remove or disrupt such links, aiding in isolation of the cfDNA from the sample.

Abstract: Focused ultrasonic acoustic processing is used to prepare formulations particles ranging between approximately 10 nm and approximately 50 microns (e.g., between 1 micron and 20 microns), or between approximately 10 nm approximately 400 nm (e.g., between 10 nm and 100 nm). Formulations (e.g., nanoformulations) may include a suspension (e.g., nanosuspension), an emulsion (e.g., nanoemulsion) or another small particle system. Formulations may be used as delivery systems for therapeutic agents, e.g., a formulation may include a bioactive agent and a carrier compound such as a surfactant that encapsulates the bioactive agent.

Abstract: Methods and apparatus for transmitting acoustic energy to a liquid sample within a vessel are described. The acoustic energy may have a peak incident power to enhance cooling of the sample.

Abstract: Systems and methods for collecting blood and other liquid samples. A sample holder may include a cap and porous element arranged to receive a blood or other liquid sample. The porous element may be stored in a sealed container, e.g., immediately after blood sample collection, and the sample dried while sealed in the container.

Abstract: Systems and methods are described for transfer of tissue samples from a substrate to a vessel, for subsequent processing (e.g., focused acoustic treatment) within the vessel. A transfer apparatus, having a transfer end and a handle end, may be used to collect a sample material from the substrate. When the sample material is collected from the substrate, the transfer end may be placed within a vessel for treatment of the sample material while the transfer end is also located within the vessel. In some embodiments, the transfer end may be decoupled or otherwise separated from the handle end so that only the transfer end portion of the transfer apparatus is located within the vessel during treatment.

Abstract: Method and apparatus for controlling acoustic treatment of a sample including a liquid. A processing volume in which the sample is acoustically treated may be controlled, e.g., by using a bead positioned in the sample that helps to enhance the shearing effects of acoustic energy on genomic fragments.

Abstract: Method and apparatus for transmitting acoustic energy to a sample for treatment by employing a phase change couplant at least adjacent a sample vessel. The phase change couplant may be solid before and after treatment, but liquid during treatment to improve acoustic energy transmission charactersitics.

Abstract: A vessel holder assembly is provided. A vessel holder, for receiving one or more vessels, includes a first set of attachment features. A cap assembly, for covering the vessel(s) includes a second set of attachment features. Respective attachment features of the vessel holder and the cap assembly may be complementary, such that engagement between complementary attachment members results in an attachment between the cap assembly and the vessel holder. Such an attachment may be manually removable, or may be locked so as to require a tool, or other suitable method, for detaching the cap assembly from the vessel holder.

Abstract: Systems and methods for processing tissue samples using acoustic energy. The tissue sample may be collected and placed on a substrate (e.g., microscope slide), or other sample holder. A transfer substrate may be positioned on the other side of the sample opposite the substrate. A microscope incorporated with the acoustic treatment system may be used to view, identify and select a portion of the sample to be transferred from the initial substrate to the transfer substrate. The selected portion of the sample is exposed to focused acoustic energy while disposed between the two substrates. The focused acoustic energy has characteristics (e.g., high frequency, small focal zone) that may be effective to transfer the selected portion of the sample from the initial substrate to the transfer substrate. Such transfer may occur with little to no damage to the sample, for example, at low temperature isothermal conditions and/or little to no cavitation of or around the sample.

Abstract: Methods and systems for treating material with focused acoustic energy and/or ultraviolet radiation are described. Sample material may be provided to a single batch vessel or may flow in a continuous or intermittent fashion into/out of a processing chamber within which the material is exposed to focused acoustic energy and/or ultraviolet radiation. Exposure to focused acoustics in a flow through environment may enhance the effects of the radiation on the sample material. Further, in flow-through or single batch arrangements, sample material may be retained exterior to or within a processing chamber by one or more retaining members (e.g., filter, valve, etc.) until a characteristic of the sample material reaches one or more particular criteria (e.g., physical, chemical, biological). Once the criteria of the sample material is attained (e.g., via further treatment), the material is then permitted to flow past the retaining member(s) and through the inlet or outlet of the chamber.

Abstract: Method and apparatus for controlling acoustic treatment of a sample to mediate a tagmentation process used on double stranded DNA.

Abstract: Method and apparatus for holding and/or transferring a sample material into a second holder. The sample holder may comprise a shoulder arranged on the outer surface to engage a second holder and to position a top opening of the sample holder for communication with the second holder. A sample may be expelled from a sample holder using a piston that moves from a lower portion to an upper portion of the sample holder.