Patent Application
20130199298
The present disclosure relates generally to ultrasonic systems and more particularly to ultrasonic processing of fluid samples.
Devices utilizing ultrasonic waves for processing fluid samples are used in many applications such as mixing of solvent compounds, heating, cooling, and shearing DNA. In many operational settings, the application of the acoustic energy to the fluid samples may result in a loss in the sample fluid volume, due to droplet ejection or ultrasonic nebulization (or “atomization”) of the fluid, thereby resulting in a degradation of processed sample. Thus, there is a need for improved systems and related methods directed towards ultrasonic processing of fluid samples.
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 ultrasonic processing of fluid samples and related technologies. 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.
Typically the transducer assembly 106 includes a piezoelectric plate (e.g., Lead zirconate titanate (PZT)) sandwiched between metal electrodes so that ultrasonic BLU waves 110 are generated by the application of an electrical signal to the piezoelectric plate. The sample vessel 102 (or chamber) in which the fluid sample 104 is placed is typically an industry standard tube or micro-well plate. The sample vessel 102 is typically located at a predefined location relative to the transducer assembly 106. The coupling medium 108, which may be any acoustically transmitting medium such as water or a gel or a phase-changing material that changes from liquid to solid, fills the space between the transducer assembly 106 and the sample vessel 102 to effectively couple the ultrasonic waves 110 to the sample vessel 102. A suitable acoustic wave-directing device such as a Fresnel lens or a spherical lens is typically fabricated on the transducer plate of the transducer assembly 106 to concentrate the ultrasonic waves 112 in the sample vessel 102. It is also possible to combine the transducer and wave directing element in a single unit by suitably patterning the electrodes of the transducer. See, for example, U.S. Pat. No. 6,682,214, and U.S. Pat. No. 7,521,023, each of which is incorporated herein by reference in its entirety.
Under typical ultrasonic processing conditions, the ultrasonic waves 112 sent to the sample vessel 102 may result in unwanted generation of drops due to acoustic radiation pressure or ultrasonic nebulization. As the ejected droplets or the “atomized” fluid particles are expelled from the fluid sample 104, they may stick to the sidewall(s) or the cap of the sample vessel 102, resulting in a net loss of the amount of fluid in the bottom of the sample vessel 102. If the fluid loss becomes excessive, the processing of the sample 104 by the ultrasonic waves 112 may lose its accuracy or the process may stop completely. Worse yet, if the fluid in the sample vessel 102 were completely depleted, the acoustic waves would be reflected from the bottom of the sample vessel 102 and this reflection may cause the sample vessel bottom to degrade or perhaps melt. In addition, those drops or fluid particles captured on the side walls or the cap of the sample vessel 102 would not have sufficient ultrasonic processing, since they are not acoustically coupled to the fluid at the bottom of the vessel 102. Therefore, it is beneficial to perform the sample processing such that there will not be an excessive fluid loss at the bottom of the sample vessel 102.
One method used in the current state-of-the-art to reduce excessive fluid loss is to stop the ultrasonic processing periodically, remove the sample vessel 102 from the processing instrument and centrifuge the sample vessel 102 in a suitable centrifuging device to re-collect the fluid material stuck on the sidewall(s) or the cap of the sample vessel 102 back to the bottom of the sample vessel 102. However, such a process may be cumbersome for the user, it may be more costly because of the need for a centrifuging instrument and it may slow down the overall processing time significantly.
As discussed below, certain embodiments relate to an ultrasonic apparatus and method with an in-situ centrifuge, incorporating design features to provide the alignment of the sample vessel 102 (or chamber) and transducer assembly 106 with the precision needed for high-quality ultrasonic sample processing.
Four sample chambers 206 are connected to the centrifuge assembly 202 at pivots 208. In a non-rotating configuration, each sample chamber 206 can be positioned above a corresponding transducer assembly 210 for ultrasonic processing (e.g., as in
When the sample chambers 206 are engaged with from the coupling medium, ultrasonic processing can be carried out (e.g., as in
When the sample chambers 206 are disengaged from the coupling medium, the rotation component of the rotation and lift assembly 204 enables the rotation of the as shown in
This process can be repeated in sequence, for example, by alternating between the ultrasonic-processing configuration, where the centrifuge assembly 202 is lowered and the sample chambers 206 are aligned with the transducer assemblies 216, and the rotating configuration, where the centrifuge assembly 202 is raised and then rotated. The processing may be alternated until the fluid samples in the sample chambers 206 are fully processed. For example, the ultrasonic processing time may range from a few seconds to several tens of minutes. The rotation time may have a similar range.
Ideally for the system 200 including the horizontal centrifuge assembly 202, the centrifuge-assembly axis and the lift-assembly axis are precisely aligned with a vertical (e.g., gravitational) direction and the horizontal centrifuge assembly 202 lies in the plane perpendicular to the vertical direction. Depending on the requirements of the operational setting, these directions may be substantially aligned or substantially perpendicular with respect to some error tolerance. For example, in a high-accuracy setting the tolerance may be on the order of a micro-radian as an angular tolerance or a micron as a length tolerance although in some cases the tolerance may be much less restrictive (e.g., a few millimeters or a few degrees).
Typically the rotation rate of the centrifuge assembly 202 in the rotating configuration is 100-1,000 RPM (revolutions per minute). In order for the sample chambers 206 to rotate to a horizontal position (e.g., for the central axis of a cylindrical chamber), the centrifugal force must dominate the prevailing gravitational force. In this context the relevant mass value can be scaled out to make a comparison between centrifugal (or centripetal) acceleration and gravitational acceleration (e.g., g=9.8 m/s2). In general, the acceleration due to the centrifugal force can be expressed as rω2, where r is the radius measured outwardly from the centrifuge-assembly axis (e.g., in meters) and ω is the angular velocity about the centrifuge-assembly axis (e.g., in radians/sec). For example, in the system 200 with r=15 cm and ω=200 RPM, the ratio of the resulting centrifugal acceleration to gravitational acceleration is on the order of 103.
In addition to the horizontal centrifuge assembly 202 of
The system 300 includes four symmetrically placed sample chambers 306 that are rigidly connected to the centrifuge assembly 302. At least one sample chamber 306 can be positioned relative to a transducer assembly 308 to enable ultrasonic processing, where a coupling medium (not shown) provides acoustic coupling between the transducer assembly 308 and the aligned sample chamber 306. This design can provide similar centrifugation as compared with the system 200 of
With reference to the embodiments described above, the electrical signals applied to the motor can be chosen to provide the spinning of the sample chambers at a high velocity, typically from hundreds to several thousands of revolutions per minute, to produce a high centrifugal force on the fluid in the sample chamber. The centrifugal force pushes any fluid collected on the sidewall(s) and the cap of the sample chamber to move towards the bottom of the sample chamber and recombine with the bulk of the sample fluid at the bottom. When the spinning process is deemed sufficient to collect all of the fluid in the bottom of the sample chamber, the motor is stopped. However, for the ultrasonic sample processing to proceed in a controlled fashion, it is critical to position the sample chamber relative to the transducer precisely after spinning. Therefore, these systems may include a mechanism to stop the rotation of the sample chamber at a precise location. Using a servo and feedback mechanism, such as a motor with an encoder, the position of the sample chamber can be recorded with reference to the transducer. After the spinning is completed, the servo mechanism can then get the sample vessel back in the original position (e.g., at the desired height above a corresponding transducer assembly 210 as in
After the spin cycle (e.g., rotation) is completed, the ultrasonic process can be re-started by the application of electric signals into the ultrasonic transducer. Thus, the process of alternating between the ultrasonic processing and spinning cycles is continued until it is deemed that the desired level of ultrasonic processing is reached. In the process of alternating ultrasonic processing and spinning described in the preceding paragraphs, the duration of the each cycle of ultrasonic processing is chosen such that, based on the previous knowledge of sample fluid loss as a function of ultrasonic processing time, the level of processing time is always less than the maximum level of sample loss the process can tolerate, to guarantee continuous, controlled operation of the ultrasonic sample process.
A fourth operation 908 includes a repeated sequence of sub-operations 910, 912, 914. A first sub-operation 910 includes positioning the first sample on top of the transducer assembly and providing ultrasonic coupling between the transducer and sample vessel. A second sub-operation 912 includes starting the ultrasonic sample process (with periodic sample interrogation) for time T2. A third sub-operation 914 includes removing the ultrasonic coupling and spinning the sample vessel with a predetermined acceleration, velocity and deceleration for time T3. The fourth operation 908 can be repeated N times and then rerun for the remaining samples.
A fifth operation 916 includes running the centrifuge for time T1 for a final spin down of the samples. A sixth operation 918 includes unloading the samples from the instrument. (It should be noted that words such as first and second are used here and elsewhere for labeling purposes only and are not intended to denote any specific spatial or temporal ordering. Furthermore, the labeling of a first element does not imply the presence of a second element.)
A second operation 1004 includes, after rotating the centrifuge assembly 202 about the centrifuge-assembly axis, adjusting a position of the centrifuge assembly 202 to effect an acoustic coupling between the one or more sample containers 206 and a transducer assembly 210 configured to direct ultrasonic energy towards the one or more sample containers. For example, the acoustic coupling may be effected through a coupling medium (e.g., liquid or gel) that acoustically couples the transducer assembly 210 and the one or more sample containers 206. A third operation 1006 includes, after adjusting the position of the centrifuge assembly 202 to effect the acoustic coupling between the one or more sample containers 206 and the transducer assembly 210, using the transducer assembly 210 to direct ultrasonic energy towards the one or more sample containers 206.
This sequence of operations may be continued (e.g., as in
As discussed above with reference to
The example computer system 1200 includes a processor 1202 (e.g., a central processing unit (CPU), a graphics processing unit (GPU) or both), a main memory 1204, and a static memory 1206, which communicate with each other via a bus 1208. The computer system 1200 may further include a video display unit 1210 (e.g., a liquid crystal display (LCD) or a cathode ray tube (CRT)). The computer system 1200 also includes an alphanumeric input device 1212 (e.g., a keyboard), a user interface (UI) cursor control device 1214 (e.g., a mouse), a disk drive unit 1216, a signal generation device 1218 (e.g., a speaker), and a network interface device 1220.
In some contexts, a computer-readable medium may be described as a machine-readable medium. The disk drive unit 1216 includes a machine-readable medium 1222 on which is stored one or more sets of data structures and instructions 1224 (e.g., software) embodying or utilizing any one or more of the methodologies or functions described herein. The instructions 1224 may also reside, completely or at least partially, within the static memory 1206, within the main memory 1204, or within the processor 1202 during execution thereof by the computer system 1200, with the static memory 1206, the main memory 1204, and the processor 1202 also constituting machine-readable media.
While the machine-readable medium 1222 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 1224. 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 1224 may further be transmitted or received over a communications network 1226 using a transmission medium. The instructions 1224 may be transmitted using the network interface device 1220 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 U.S. Provisional Application No. 61/594,917, filed Feb. 3, 2012, which is incorporated herein by reference in its entirety.
| Number | Date | Country | |
|---|---|---|---|
| 61594917 | Feb 2012 | US |
