The present disclosure relates generally to ultrasonic devices and more particularly to ultrasonic devices for processing genetic material.
Genomic research, including the study of nucleic acids such as DNA (Deoxyribonucleic acid) and RNA (Ribonucleic acid), has become increasingly important for life sciences, since it is well established that the complete information for the development and functioning of a living organism is encoded in its DNA. Therefore, there is a growing demand for reading the genomic sequence (e.g., DNA sequence) of humans and other organisms.
In order to perform sequencing operations accurately, conventional analysis tools (e.g., sequence readers) typically require that the initially long chains of nucleic acid be reduced to smaller chains. For example, the initial genomic sample may include chains with ten thousand or more base pairs or even billions of base pairs, and the operational setting for the sequence reader may require that the average length for the base-pair chains is less than five thousand (e.g., 300, 400, 600, 800, or 1,500 base pairs). Conventional approaches to fragmenting (or shearing) long chains, including enzymatic digestion, nebulization, hydroshear, and sonication, may also impose additional restrictions and disadvantages, including sample size requirements, sample loss, potential contamination, operational cost, and limited control. Thus, there is a need for improved systems and related methods for fragmenting genetic samples that include chains of nucleic acid.
Some embodiments are illustrated by way of example and not limitation in the figures of the accompanying drawings.
Example methods and systems are directed to controlled fragmentation of genetic samples that include chains of nucleic acid. The disclosed examples merely typify possible variations. Unless explicitly stated otherwise, components and functions are optional and may be combined or subdivided, and operations may vary in sequence or be combined or subdivided. In the following description, for purposes of explanation, numerous specific details are set forth to provide a thorough understanding of example embodiments. It will be evident to one skilled in the art, however, that the present subject matter may be practiced without these specific details.
The sample container 110 contains a genetic sample 112 that includes chains of nucleic acid. For example, the genetic sample may include DNA, RNA, or lysed cells (e.g., cells that have been broken down by viral, enzymatic, or osmotic mechanisms or related mechanisms). Sidewalls 114 are disposed relative to the substrate material 104 to enclose a coupling medium 116 (e.g., a fluid such as water) that provides acoustic coupling between the substrate material 104 and the sample container 110. Additional details for the transducer system 100 may include a mechanical support (e.g., a support arm) that maintains the position of the sample container 110 relative to the transducer 102. Depending on the operational setting, an electrically insulating layer may be added to separate the top electrode 106 from the coupling medium 116.
In
Typically the RF source 109 in
For example,
Additional embodiments relate to alternative FASA configurations. For example FASA transducers of a suitable angle can with a small gap (e.g., a few microns to a few millimeters) between them to form a composite transducer.
Additional embodiments relate to alternative FASA configurations. For example, a combination of FASA transducers, each with a suitable angle and a relatively small gap between them (e.g., a few microns to a few millimeters), can form a composite transducer that produces a higher level of mechanical energy to speed up the shearing process, while still resulting in a fair amount of lateral acoustic field in the coupling medium.
Similarly as in
By using a composite type of transducer such as the composite FASA transducer 400 in
In particular, when the other parameters are set, the total processing time and the voltage amplitude are easily controllable and reproducible in a variety of operational settings.
With reference to the system 100 of
Additional embodiments also relate to alternative FASA configurations that replace the annularly shaped electrode segments (e.g., as in
In some operational settings, it may be desirable to process multiple genetic samples simultaneously.
A computer system may be used to access a database that characterizes relationships between the parameters of the tone-burst signal as well as other configurations parameters that characterize the system including the position of the sample container 110 relative to the transducer 102 in
With reference to the transducer system 100 of
The example computer system 1400 includes a processor 1402 (e.g., a central processing unit (CPU), a graphics processing unit (GPU) or both), a main memory 1404, and a static memory 1406, which communicate with each other via a bus 1408. The computer system 1400 may further include a video display unit 1410 (e.g., a liquid crystal display (LCD) or a cathode ray tube (CRT)). The computer system 1400 also includes an alphanumeric input device 1412 (e.g., a keyboard), a user interface (UI) cursor control device 1414 (e.g., a mouse), a disk drive unit 1416, a signal generation device 1418 (e.g., a speaker), and a network interface device 1420.
In some contexts, a computer-readable medium may be described as a machine-readable medium. The disk drive unit 1416 includes a machine-readable medium 1422 on which is stored one or more sets of data structures and instructions 1424 (e.g., software) embodying or utilizing any one or more of the methodologies or functions described herein. The instructions 1424 may also reside, completely or at least partially, within the static memory 1406, within the main memory 1404, or within the processor 1402 during execution thereof by the computer system 1400, with the static memory 1406, the main memory 1404, and the processor 1402 also constituting machine-readable media.
While the machine-readable medium 1422 is shown in an example embodiment to be a single medium, the terms “machine-readable medium” and “computer-readable medium” may each refer to a single medium or multiple media (e.g., a centralized or distributed database, and/or associated caches and servers) that store the one or more sets of data structures and instructions 1424. These terms shall also be taken to include any tangible or non-transitory medium that is capable of storing, encoding or carrying instructions for execution by the machine and that cause the machine to perform any one or more of the methodologies disclosed herein, or that is capable of storing, encoding or carrying data structures utilized by or associated with such instructions. These terms shall accordingly be taken to include, but not be limited to, solid-state memories, optical media, and magnetic media. Specific examples of machine-readable or computer-readable media include non-volatile memory, including by way of example semiconductor memory devices, e.g., erasable programmable read-only memory (EPROM), electrically erasable programmable read-only memory (EEPROM), and flash memory devices; magnetic disks such as internal hard disks and removable disks; magneto-optical disks; compact disc read-only memory (CD-ROM) and digital versatile disc read-only memory (DVD-ROM).
The instructions 1424 may further be transmitted or received over a communications network 1426 using a transmission medium. The instructions 1424 may be transmitted using the network interface device 1420 and any one of a number of well-known transfer protocols (e.g., hypertext transfer protocol (HTTP)). Examples of communication networks include a local area network (LAN), a wide area network (WAN), the Internet, mobile telephone networks, plain old telephone (POTS) networks, and wireless data networks (e.g., WiFi and WiMax networks). The term “transmission medium” shall be taken to include any intangible medium that is capable of storing, encoding or carrying instructions for execution by the machine, and includes digital or analog communications signals or other intangible media to facilitate communication of such software.
Certain embodiments are described herein as including logic or a number of components, modules, or mechanisms. Modules may constitute either software modules or hardware-implemented modules. A hardware-implemented module is a tangible unit capable of performing certain operations and may be configured or arranged in a certain manner In example embodiments, one or more computer systems (e.g., a standalone, client or server computer system) or one or more processors may be configured by software (e.g., an application or application portion) as a hardware-implemented module that operates to perform certain operations as described herein.
In various embodiments, a hardware-implemented module (e.g., a computer-implemented module) may be implemented mechanically or electronically. For example, a hardware-implemented module may comprise dedicated circuitry or logic that is permanently configured (e.g., as a special-purpose processor, such as a field programmable gate array (FPGA) or an application-specific integrated circuit (ASIC)) to perform certain operations. A hardware-implemented module may also comprise programmable logic or circuitry (e.g., as encompassed within a general-purpose processor or other programmable processor) that is temporarily configured by software to perform certain operations. It will be appreciated that the decision to implement a hardware-implemented module mechanically, in dedicated and permanently configured circuitry, or in temporarily configured circuitry (e.g., configured by software) may be driven by cost and time considerations.
Accordingly, the term “hardware-implemented module” (e.g., a “computer-implemented module”) should be understood to encompass a tangible entity, be that an entity that is physically constructed, permanently configured (e.g., hardwired), or temporarily or transitorily configured (e.g., programmed) to operate in a certain manner and/or to perform certain operations described herein. Considering embodiments in which hardware-implemented modules are temporarily configured (e.g., programmed), each of the hardware-implemented modules need not be configured or instantiated at any one instance in time. For example, where the hardware-implemented modules comprise a general-purpose processor configured using software, the general-purpose processor may be configured as respective different hardware-implemented modules at different times. Software may accordingly configure a processor, for example, to constitute a particular hardware-implemented module at one instance of time and to constitute a different hardware-implemented module at a different instance of time.
Hardware-implemented modules can provide information to, and receive information from, other hardware-implemented modules. Accordingly, the described hardware-implemented modules may be regarded as being communicatively coupled. Where multiple of such hardware-implemented modules exist contemporaneously, communications may be achieved through signal transmission (e.g., over appropriate circuits and buses) that connect the hardware-implemented modules. In embodiments in which multiple hardware-implemented modules are configured or instantiated at different times, communications between such hardware-implemented modules may be achieved, for example, through the storage and retrieval of information in memory structures to which the multiple hardware-implemented modules have access. For example, one hardware-implemented module may perform an operation and store the output of that operation in a memory device to which it is communicatively coupled. A further hardware-implemented module may then, at a later time, access the memory device to retrieve and process the stored output. Hardware-implemented modules may also initiate communications with input or output devices and may operate on a resource (e.g., a collection of information).
The various operations of example methods described herein may be performed, at least partially, by one or more processors that are temporarily configured (e.g., by software) or permanently configured to perform the relevant operations. Whether temporarily or permanently configured, such processors may constitute processor-implemented modules that operate to perform one or more operations or functions. The modules referred to herein may, in some example embodiments, comprise processor-implemented modules.
Similarly, the methods described herein may be at least partially processor-implemented. For example, at least some of the operations of a method may be performed by one or more processors or processor-implemented modules. The performance of certain of the operations may be distributed among the one or more processors, not only residing within a single machine, but deployed across a number of machines. In some example embodiments, the processor or processors may be located in a single location (e.g., within a home environment, an office environment or as a server farm), while in other embodiments the processors may be distributed across a number of locations.
The one or more processors may also operate to support performance of the relevant operations in a “cloud computing” environment or as a “software as a service” (SaaS). For example, at least some of the operations may be performed by a group of computers (as examples of machines including processors), these operations being accessible via a network (e.g., the Internet) and via one or more appropriate interfaces (e.g., application program interfaces (APIs)).
Although only certain embodiments have been described in detail above, those skilled in the art will readily appreciate that many modifications are possible without materially departing from the novel teachings of this disclosure. For example, aspects of embodiments disclosed above can be combined in other combinations to form additional embodiments. Accordingly, all such modifications are intended to be included within the scope of this disclosure.
This application claims the benefit of priority under 35 U.S.C. 119(e) to U.S. Provisional Application No. Ser. 61/546,757, filed Oct. 13, 2011, which is incorporated herein by reference in its entirety.
Number | Date | Country | |
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61546757 | Oct 2011 | US |