WOBURN, MA, United States
WOBURN, MA, United States

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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.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 223.20K | Year: 2016

Summary Sequencing of human DNA has become relatively inexpensive in recent years The DNA sequence the order in which the chemical constituents of the DNA are attached to one another in the DNA molecule holds important information about susceptibility to disease as well as possible usefulness of various therapies for diseases Also modifications to DNA such as methylation where a chemical group is added to the DNA impact health because they can suppress or promote the way genes are used to create proteins For sequencing an entire genome of an individual or understanding the methylation of the sequence a significant amount of DNA that is chemically intact is required A good way to get this DNA is by extracting it from the white blood cells of whole blood But whole blood is difficult to collect and store for later analysis Other fluids such as saliva or cheek cells obtained using a swab have variable amounts of DNA that also might be broken For several years blood spots have been dried on filter paper This allows storage of the DNA until it needs to be used But the application of blood to spots can be variable especially if people do it on their own at home And the extraction of DNA using current methods is not that efficient so that getting enough DNA for analysis is a problem This project aims to create a system for easy collection and storage of blood with high yields of good quality DNA We will do this in two steps First blood will be collected into a special device designed for easy application of the blood and which can dry the blood rapidly in a closed container The container can be handled immediately and shipped even before drying is complete In the second step the part of the device containing the dry blood will be subject to focused ultrasound This has been proven to extract larger quantities of DNA from devices such as blood spot paper than the usual chemical methods employed by doctors and researchers This system thus improves three steps in the blood analysis process Blood collection is made easier by providing a small surface on which the blood is placed drying is made easier because the user does not need to worry about how long to dry or maintaining the drying container in an upright orientation or a special environment shipping and storage is made easier because the samples can be shipped immediately or stored indefinitely in the same container and extraction of the DNA is made more efficient using ultrasound Additionally ultrasound has been proven to break the DNA up into the desired lengths that sequencing machines work with best This project will develop new blood collection drying and DNA extraction systems appropriate for sequencing applications An easy to use collection and drying consumable will have improved ease of use than existing methods such as saliva swabs and dried blood spots and the use of focused ultrasound for extraction will provide greater DNA yields than these methods A validation of a manufacturable consumable coupled with a commercial focused ultrasonicator will be performed by comparing DNA yields from fresh whole blood and dried extracted blood using patient samples


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 1.23M | Year: 2016

Summary Many samples taken from individuals and animals are stored by treating them with a chemical formalin and then encasing them in paraffin or wax these are called formalin fixed paraffin encased FFPE samples Usually this storage is very good for preserving them for observation under microscopes but it presents some problems in terms of analysis of their DNA Genetic analyses are important because many of these preserved samples are biopsies of cancer tissue and cancers are diseases brought on by changes in the DNA By understanding the genetic content of these samples we can look for specific DNA sequences that can be used to diagnose cancer We can also use the information in these samples to determine what therapies might work best and to measure how well the therapies applied are working There are some instruments and kits of reagents available for getting at the DNA in FFPE samples but they are usually complicated Often they use dangerous chemicals They are inconsistent in the quality of DNA extracted which can sometimes end up broken into small pieces or bound with proteins that make them unusable for genetic analysis techniques like sequencing where the order of the different components of DNA are read out Often they just extract too little of the DNA And they require significant hands on time Adaptive Focused Acoustics AFA is an ultrasonic technology that focuses sound energy onto small volumes It is used for many processes like breaking up tissue samples to extract proteins and DNA and grinding solids into uniformly sized particles Recently AFA was applied to FFPE samples in a process performed manually The process removes the paraffin and breaks the tissue down to extract the DNA It provides times as much DNA as other methods and that DNA is of higher quality This project will develop a system that uses AFA for FFPE samples with a special instrument and a special plastic cartridge Air pressure on the instrument will move the liquids in the cartridge and AFA will remove the wax extract the DNA and mix the liquids and reagents in the cartridge The DNA that AFA removes from samples will also be purified by binding to little magnetic beads which are held in place by magnets on the machine This makes the extracted DNA ready for use in other applications like DNA sequencing This instrument and cartridge will provide a reliable reproducible and labor saving way to use FFPE samples that are very valuable and sometimes irreplaceable and that can be used for research or by doctors in diagnosing and treating patients We will do this by breaking down the whole process into small pieces and developing those individually The pieces are the extraction of DNA using AFA chemical treatment to remove proteins and to break any chemical bonds between the DNA and itself or remaining protein contamination and purifying the DNA The performance of each step will be compared to the manual method The ways we will measure the performance include determining just how much DNA there is by adding a fluorescent dye and measuring the fluorescence measuring the length of the DNA molecules which tells us if they are too broken up to be used for other applications measuring the contamination by residual protein by seeing how much UV light is absorbed by the DNA solutions and finally by using a DNA amplification method called quantitative PCR that only works well if the DNA is intact and not bound to other contaminants in the sample We will also sequence a few samples that have been processed by the prototype When all of the pieces have been developed individually they will be put together For the project the cartridge to do this work will be made using a computerized milling or cutting machine that can make high quality models of structures with features of size less than that of the diameter of a human hair When the cartridge is made into a product it will be made from molded plastic The instrument will be run by a computer and modified from an existing Covaris AFA instrument If this project is successful the next phase will be to solve manufacturing problems including storing reagents on the cartridge and scaling the cartridge up to many samples Extracting nucleic acids from formalin fixed paraffin embedded tissues is vital to cancer research but it is usually labor intensive and suffers from low yield and poor quality We will develop a robust standardized system to extract and purify nucleic acids from these tissues A cartridge based microfluidic system will implement high frequency ultrasonic technology Adaptive Focused Acoustics which has already been proven to provide high quantity and quality extractions when used in manual protocols


Patent
Covaris, Inc. | Date: 2015-10-13

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


Patent
Covaris, Inc. | Date: 2015-08-04

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.


The present disclosure relates to a composition that includes an apolipoprotein and a lipid bilayer, and methods and systems for preparing the composition. The apolipoprotein may be incorporated within at least a portion of the lipid bilayer. The lipid bilayer may form a liposome or other suitable carrier for transporting the apolipoprotein. The apolipoprotein incorporated lipid bilayer may provide a suitable delivery vehicle for the apolipoprotein to the body. Compositions of the present disclosure may be formed by exposing a mixture of an apolipoprotein and a lipid formulation to focused acoustic energy which, in some embodiments, may result in a liposome that at least partially encapsulates the apolipoprotein. In some embodiments, apolipoprotein A-V may be incorporated within a liposome, where the apolipoprotein A-V is suitably bioactive, or therapeutic, when delivered to cells and/or into the body of a patient.


Patent
Covaris, Inc. | Date: 2015-09-16

This invention relates to systems and methods for applying acoustic energy to a sample. According to one aspect of the invention, a system comprises a housing, a chamber for receiving the sample, an acoustic energy source for providing a focused acoustic field to the sample according to a treatment protocol, a processor for determining the treatment protocol, a sensor for detecting information about the sample, and a user interface for communicating with a user.


Patent
Covaris, Inc. | Date: 2015-12-16

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.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 222.48K | Year: 2016

DESCRIPTION provided by applicant Analysis of single cells or cells that are not present in large numbers in the body is important to understanding basic biology and diseases A specific example is cancer in which changes in DNA in a single cell can lead to that cell reproducing rapidly Similarly studying the proteins that make up these cells can tell us how the changes in DNA result in changes in cells The structure can gives us specific targets for therapies such as chemicals that interfere with the binding of different proteins to one another To measure the contents of single cells they must be isolated broken open lysed to release their contents and measured When samples are moved from tube to tube small amounts of liquid are lost and cells can stick to the surfaces of the vessels Also the volumes used are larger than that of a cell so once the cell is lysed its contents get diluted Combining isolation lysis and detectin without liquid transfers results better sensitivity We would like to create a cell lysis method tat can be used with small samples Adaptive Focused Acoustics AFA focuses ultrasound into a small volume It works well with for the analysis of proteins and DNA in larger volumes But closed systems of tubing flowing the sample from step to step in its analysis are not usually used We will use AFA with such a closed system to prevent sample loss and dilution We will examine use different frequencies of ultrasound which can focus the sound to a small volume as well as cause more fluctuations in the pressure to break the cells the part of the system put into the AFA will include andquot cell trapsandquot made by creating plugs inside tubing That way the AFA can be applied as the cells sit on the trap The traps will also be used as andquot microreactorsandquot For understanding proteins these contain enzymes that break down proteins into components The mechanism that lyses cells with ultrasound is called andquot cavitationandquot Little bubbles of form in response to the pressure pulses caused by the ultrasound they oscillate and collapse causing turbulent motion Part of the project will look at ways to make cavitation happen much more frequently One way is to modify the inside of the tubes capillaries that are used by making them rough or adding particles to them The presence of these structures gives bubbles a surface to form on Another method is to make small chambers which have one wall that has structure To do this we will drill small holes with a laser into materials and seal them into chambers We will measure whether more cavitation happens with these devices using either high speed microscopy to see the bubbles or an ultrasound sensor which can andquot hearandquot the sound of bubbles collapsing Finally we will measure the efficiency of the devices we make by measuring the proteins and DNA released by different numbers of cells starting from large numbers of tens of thousands and moving to cell PUBLIC HEALTH RELEVANCE Single and limited cell analyses often suffer from cell loss analyte loss non specific binding and sample dilution when performed using liquid transfers between standard consumables We propose to integrate acoustic lysis into a closed system preparative workflow appropriate for low and high throughput applications with special emphasis on LC MS analysis in this project A variety of focused acoustic systems operating at different frequencies and surface modifications to induce cavitation critical to efficient cell lysis will be examined with the optimal choices integrated into a prototype instrument interfaceable to conventional low volume fluid tubing


Patent
Covaris, Inc. | Date: 2015-06-11

Method and apparatus for processing paraffin embedded samples, e.g., to disassociate paraffin from tissue components and/or other biomolecules from the paraffin. The sample may be exposed to focused acoustic energy while held in a vessel containing a non-solvent, aqueous solution. Disassociated paraffin may be emulsified into the liquid or otherwise separated from the sample.

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