Abstract: cfDNA reference material, for example, 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, for example, 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: A sample holder for holding a liquid sample for laboratory processing, such as PCR thermal cycling. The sample holder includes at least one vessel having a bottom and sidewall defining an interior volume and a rim defining an opening to the interior volume. The vessel has a first portion that defines at least a part of the bottom and sidewall of the vessel and is made of a first material, and a second portion that defines the rim of the vessel and is made of a second material different from the first material.

Abstract: Methods and systems for acoustically treating material using an acoustic energy system having a movable outer surface that contacts a sample holder. The outer surface may be cylindrical and rotate about a central axis, e.g., so that a sample holder may be driven to move by the outer surface. Acoustic energy may be emitted from within the outer surface to a treatment area outside of, and near, the outer surface. Thus, a sample holder in contact with the outer surface may have a sample exposed to acoustic energy while rotation of the outer surface may move the sample holder relative to treatment area. One or more additional rollers or other components may bias the sample holder into contact with the outer surface, e.g., so the sample holder is squeezed between the outer surface and a roller or other biasing component.

Abstract: Focused acoustic treatment of samples may be used to differentially shear different fragment lengths of DNA or other nucleic acid portions of a sample. Relatively larger fragment lengths may be sheared while smaller fragment lengths are unaffected by the focused acoustic based shearing.

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: 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: A method for lysing cells and shearing genomic DNA to reduce viscosity of the cell lysate. Cells may be lysed to release cell lysate, and the cell lysate may be treated with focused acoustic energy to shear genomic DNA so that the genomic DNA is sheared to DNA fragments having a fragment size no larger than 50% of the starting base pair size of the genomic DNA. Lysing and DNA shearing may be done by acoustic energy and in a single vessel, allowing for automated handling of cell lysate.

Abstract: Apparatus and method for lysing and recovering released material, such as proteins or other biomolecules. Sample material including cells may be at least partially frozen, thawed, cells lysed and biomolecules recovered in a single conduit, e.g., as the sample flows through the conduit. The conduit may include different zones for sample treatment, including a freezing zone, thawing zone, lysing/disassociation zone, etc., and protein or other recovered material may be delivered directly from the conduit to analysis equipment, such as a mass spectrometer. This allows a flow-through type processing of cells that avoids handling and transfer of sample material between different sample holders.

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: Apparatus and method for separating whole cells from a mixture, e.g., including liquid, other cell types, nucleic acid material, or other components. Focused acoustic energy may be used to move whole cells in a chamber so that the cells exit the chamber via a first outlet rather than a second outlet. A filter may, or need not, be used to assist in separation.

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: 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: The present disclosure relates to a vessel configured to apply pressure greater than ambient pressure and/or provide a reduced headspace to a sample, while subject to focused acoustic treatment. Such treatment may generally result in enhanced effects of sterilization and/or other processing than if the sample is otherwise treated under ambient conditions. The sample may be a medicament that is sterilized under pressure using focused acoustic energy, where the sterilized sample is subsequently delivered to a patient. A fluid delivery cartridge may include a vessel having a transfer end opposite a plunger end. The transfer end may include a sealed cover. A plunger may be movably disposed in the vessel to accommodate entry of a liquid via piercing of the sealed cover. Upon processing (e.g., sterilizing) of the sample with focused acoustic energy, the sample may be appropriately dispensed through the pierced sealed cover.

Abstract: Apparatus and method for removing liquid from exterior surfaces of sample wells in a well plate. Wells that have water or other liquid on an exterior surface, e.g., after acoustic energy treatment in a water bath, may have the liquid removed by contacting the exterior surfaces of the sample wells with an absorbent material. A pad made of absorbent material may have a plurality of openings arranged to receive an array of sample wells inserted into the openings so that liquid can be removed from each of the sample wells.

Abstract: System and method for enhancing ligation of nucleic acid portions using focused acoustic energy.

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

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: Focused acoustic treatment of samples may be used to differentially shear different fragment lengths of DNA or other nucleic acid portions of a sample. Relatively larger fragment lengths may be sheared while smaller fragment lengths are unaffected by the focused acoustic based shearing.

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