The present disclosure relates to systems and methods for using rotating sample processing devices to, e.g., amplify genetic materials, etc.
Many different chemical, biochemical, and other reactions are sensitive to temperature variations. Examples of thermal processes in the area of genetic amplification include, but are not limited to, Polymerase Chain Reaction (PCR), Sanger sequencing, etc. One approach to reducing the time and cost of thermally processing multiple samples is to use a device including multiple chambers in which different portions of one sample or different samples can be processed simultaneously. Examples of some reactions that may require accurate chamber-to-chamber temperature control, comparable temperature transition rates, and/or rapid transitions between temperatures include, e.g., the manipulation of nucleic acid samples to assist in the deciphering of the genetic code. Nucleic acid manipulation techniques include amplification methods such as polymerase chain reaction (PCR); target polynucleotide amplification methods such as self-sustained sequence replication (3SR) and strand-displacement amplification (SDA); methods based on amplification of a signal attached to the target polynucleotide, such as “branched chain” DNA amplification; methods based on amplification of probe DNA, such as ligase chain reaction (LCR) and QB replicase amplification (QBR); transcription-based methods, such as ligation activated transcription (LAT) and nucleic acid sequence-based amplification (NASBA); and various other amplification methods, such as repair chain reaction (RCR) and cycling probe reaction (CPR). Other examples of nucleic acid manipulation techniques include, e.g., Sanger sequencing, ligand-binding assays, etc.
Some systems used to process rotating sample processing devices are described in U.S. Pat. No. 6,889,468 titled MODULAR SYSTEMS AND METHODS FOR USING SAMPLE PROCESSING DEVICES and U.S. Pat. No. 6,734,401 titled ENHANCED SAMPLE PROCESSING DEVICES SYSTEMS AND METHODS (Bedingham et al.).
Some embodiments of the present disclosure provide a system for processing sample processing devices. The system can include a base plate operatively coupled to a drive system, wherein the drive system rotates the base plate about a rotation axis, and wherein the rotation axis defines a z-axis. The system can further include a thermal structure operatively coupled to the base plate, wherein the thermal structure comprises a transfer surface exposed proximate a first surface of the base plate. The system can further include at least one first magnetic element operatively coupled to the base plate, and a sample processing device comprising at least one thermal process chamber. The system can further include an annular cover adapted to face the transfer surface. The annular cover can include a center, an inner edge, and an outer edge. The sample processing device can be adapted to be positioned between the base plate and the annular cover. The inner edge of the annular cover can be configured to be positioned inwardly of the at least one thermal process chamber, relative to the center of the annular cover, for example, when the sample processing device is positioned adjacent the annular cover. The system can further include at least one second magnetic element operatively coupled to the annular cover. The at least one second magnetic element can be configured to attract the at least one first magnetic element to force the annular cover in a first direction along the z-axis, such that at least a portion of the sample processing device is urged into contact with the transfer surface of the base plate.
Some embodiments of the present disclosure provide a system for processing sample processing devices. The system can include a base plate operatively coupled to a drive system, wherein the drive system rotates the base plate about a rotation axis, and wherein the rotation axis defines a z-axis. The system can further include a thermal structure operatively coupled to the base plate, wherein the thermal structure comprises a transfer surface exposed proximate a first surface of the base plate. The system can further include a first annulus of magnetic elements operatively coupled to the base plate, and a sample processing device comprising at least one thermal process chamber. The system can further include an annular cover adapted to face the transfer surface. The annular cover can include an inner edge and an outer edge. The inner edge can be positioned inwardly of the at least one thermal process chamber, and the sample processing device can be adapted to be positioned between the base plate and the annular cover. The system can further include a second annulus of magnetic elements operatively coupled to the annular cover. The second annulus of magnetic elements can be configured to attract the first annulus of magnetic elements to force the annular cover in a first direction along the z-axis, such that at least a portion of the sample processing device is urged into contact with the transfer surface of the base plate.
Some embodiments of the present disclosure provide a method for processing sample processing devices. The method can include providing a base plate operatively coupled to a drive system, and providing a thermal structure operatively coupled to the base plate. The thermal structure can include a transfer surface exposed proximate a first surface of the base plate. The method can further include providing a sample processing device comprising at least one thermal process chamber, and providing an annular cover facing the transfer surface. The annular cover can include an inner edge and an outer edge. The method can further include providing at least one first magnetic element operatively coupled to the base plate and at least one second magnetic element operatively coupled to the annular cover. The method can further include positioning the sample processing device between the base plate and the annular cover, such that the inner edge of the annular cover is positioned inwardly of the at least one thermal process chamber, and such that the at least one first magnetic element attracts the at least one second magnetic element to force the annular cover in a first direction along the z-axis, such that at least a portion of the sample processing device is urged into contact with the transfer surface of the base plate. The method can further include rotating the base plate about a rotation axis, wherein the rotation axis defines a z-axis.
Other features and aspects of the present disclosure will become apparent by consideration of the detailed description and accompanying drawings.
Before any embodiments of the present disclosure are explained in detail, it is to be understood that the invention is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the following drawings. The invention is capable of other embodiments and of being practiced or of being carried out in various ways. Also, it is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. The use of “including,” “comprising,” or “having” and variations thereof herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items. Unless specified or limited otherwise, the terms “mounted,” and “coupled” and variations thereof are used broadly and encompass both direct and indirect mountings and couplings. Further, “coupled” is not restricted to physical or mechanical couplings. It is to be understood that other embodiments may be utilized, and structural or logical changes may be made without departing from the scope of the present disclosure. Furthermore, terms such as “front,” “rear,” “top,” “bottom,” and the like are only used to describe elements as they relate to one another, but are in no way meant to recite specific orientations of the apparatus, to indicate or imply necessary or required orientations of the apparatus, or to specify how the invention described herein will be used, mounted, displayed, or positioned in use.
The present disclosure generally relates to annular compression systems and methods for sample processing devices. Such annular compression systems can include an open area (e.g., an open central area), such that the annular compression system can perform and/or facilitate the desired thermal control and rotation functions for the sample processing device, while allowing access to at least a portion of the sample processing device. For example, some existing systems cover a top surface of a sample processing device in order to hold the sample processing device onto a rotating base plate and/or to thermally control and isolate portions of the sample processing device (e.g., from one another and/or ambience). The annular compression systems and methods of the present disclosure, however, provide the desired positioning and holding functions as well as the desired thermal control functions, while also allowing a portion of the sample processing device to be exposed to other devices or systems for which it may be desirable to have direct access to the sample processing device. For example, in some embodiments, sample delivery (e.g., manual or automatic pipetting) can be accomplished after the sample processing device has already been positioned between an annular cover and a base plate. By way of further example, in some embodiments, a portion of the sample processing device can be optically accessible (e.g., to electromagnetic radiation), for example, which can enable more efficient laser addressing of the sample processing device, or which can be used for optical interrogation (e.g., absorption, reflectance, fluorescence, etc.). Such laser addressing can be used, for example, for fluid (e.g., microfluidic) manipulation of a sample in the sample processing device.
Furthermore, in some embodiments, the annular compression systems and methods of the present disclosure can enable unique temperature control of various portions of the sample processing device. For example, fluid (e.g., air) can be moved over an exposed surface of the sample processing device in areas that are desired to be rapidly cooled, while the areas that are desired to be heated or maintained at a desired temperature can be covered and isolated from other portions of the sample processing device and/or from ambience.
In addition, in some embodiments, annular compression systems and methods of the present disclosure can allow a portion of the sample processing device to be exposed to interact with other (e.g., external or internal) devices or equipment, such as robotic workstations, pipettes, interrogation instruments, and the like, or combinations thereof. Similarly, the annular compression systems and methods of the present disclosure can protect desired portions of the sample processing device from contact.
As a result, “accessing” at least a portion of a sample processing device can refer to a variety of processing steps and can include, but is not limited to, physically or mechanically accessing the sample processing device (e.g., delivering or retrieving a sample via direct or indirect contact, moving or manipulating a sample in the sample processing device via direct or indirect contact, etc.); optically accessing the sample processing device (e.g., laser addressing); thermally accessing the sample processing device (e.g., selectively heating or cooling an exposed portion of the sample processing device); and the like; and combinations thereof.
The present disclosure provides methods and systems for sample processing devices that can be used in methods that involve thermal processing, e.g., sensitive chemical processes such as polymerase chain reaction (PCR) amplification, transcription-mediated amplification (TMA), nucleic acid sequence-based amplification (NASBA), ligase chain reaction (LCR), self-sustaining sequence replication, enzyme kinetic studies, homogeneous ligand binding assays, and more complex biochemical or other processes that require precise thermal control and/or rapid thermal variations. The sample processing systems are capable of providing simultaneous rotation of the sample processing device in addition to effecting control over the temperature of sample materials in process chambers on the devices.
Some examples of suitable sample processing devices that may be used in connection with the methods and systems of the present disclosure may be described in, e.g., commonly-assigned U.S. Patent Publication No. 2007/0010007 titled SAMPLE PROCESSING DEVICE COMPRESSION SYSTEMS AND METHODS (Aysta et al.); U.S. Patent Publication No. 2007/0009391 titled COMPLIANT MICROFLUIDIC SAMPLE PROCESSING DISKS (Bedingham et al.); U.S. Patent Publication No. 2008/0050276 titled MODULAR SAMPLE PROCESSING APPARATUS KITS AND MODULES (Bedingham et al.); U.S. Pat. No. 6,734,401 titled ENHANCED SAMPLE PROCESSING DEVICES SYSTEMS AND METHODS (Bedingham et al.) and U.S. Pat. No. 7,026,168 titled SAMPLE PROCESSING DEVICES (Bedingham et al.). Other useable device constructions may be found in, e.g., U.S. Pat. No. 7,435,933 (Bedingham et al.) titled ENHANCED SAMPLE PROCESSING DEVICES, SYSTEMS AND METHODS; U.S. Provisional Patent Application Ser. No. 60/237,151 filed on Oct. 2, 2000 and entitled SAMPLE PROCESSING DEVICES, SYSTEMS AND METHODS (Bedingham et al.); and U.S. Pat. No. 6,814,935 titled SAMPLE PROCESSING DEVICES AND CARRIERS (Harms et al.). Other potential device constructions may be found in, e.g., U.S. Pat. No. 6,627,159 titled CENTRIFUGAL FILLING OF SAMPLE PROCESSING DEVICES (Bedingham et al.); PCT Patent Publication No. WO 2008/134470 titled METHODS FOR NUCLEIC ACID AMPLIFICATION (Parthasarathy et al.); and U.S. Patent Publication No. 2008/0152546 titled ENHANCED SAMPLE PROCESSING DEVICES, SYSTEMS AND METHODS (Bedingham et al.).
Some embodiments of the sample processing systems of the present disclosure can include base plates attached to a drive system in a manner that provides for rotation of the base plate about an axis of rotation. When a sample processing device is secured to the base plate, the sample processing device can be rotated with the base plate. The base plate can include at least one thermal structure that can be used to heat portions of the sample processing device and may include a variety of other components as well, e.g., temperature sensors, resistance heaters, thermoelectric modules, light sources, light detectors, transmitters, receivers, etc.
Other elements and features of systems and methods for processing sample processing devices can be found in patent application Ser. No. ______ (Attorney Docket No. 65917US002), filed on even date herewith, which is incorporated herein by reference in its entirety.
One illustrative sample processing system 100 is shown in
Also depicted in
As shown in
As a result, by way of example only, the sample processing device 150 illustrated in
In some embodiments, as shown in
As shown in
As used herein, the term “annular” or derivations thereof can refer to a structure having an outer edge and an inner edge, such that the inner edge defines an opening. For example, an annular cover can have a circular or round shape (e.g., a circular ring) or any other suitable shape, including, but not limited to, triangular, rectangular, square, trapezoidal, polygonal, etc., or combinations thereof. Furthermore, an “annulus” of the present invention need not necessarily be symmetrical, but rather can be an asymmetrical or irregular shape; however, certain advantages may be possible with symmetrical and/or circular shapes.
The compressive forces developed between the base plate 110 and the cover 160 may be accomplished using a variety of different structures or combination of structures. One exemplary compression structure depicted in the embodiment of
As used herein, a “magnetic element” is a structure or article that exhibits or is influenced by magnetic fields. In some embodiments, the magnetic fields can be of sufficient strength to develop the desired compressive force that results in thermal coupling between a sample processing device 150 and the thermal structure 130 of the base plate 110 as discussed herein. The magnetic elements can include magnetic materials, i.e., materials that either exhibit a permanent magnetic field, materials that are capable of exhibiting a temporary magnetic field, and/or materials that are influenced by permanent or temporary magnetic fields.
Some examples of potentially suitable magnetic materials include, e.g., magnetic ferrite or “ferrite” which is a substance including mixed oxides of iron and one or more other metals, e.g., nanocrystalline cobalt ferrite. However, other ferrite materials may be used. Other magnetic materials which may be used in the system 100 may include, but are not limited to, ceramic and flexible magnetic materials made from strontium ferrous oxide which may be combined with a polymeric substance (such as, e.g., plastic, rubber, etc.); NdFeB (this magnetic material may also include Dysprosium); neodymium boride; SmCo (samarium cobalt); and combinations of aluminum, nickel, cobalt, copper, iron, titanium, etc.; as well as other materials. Magnetic materials may also include, for example, stainless steel, paramagnetic materials, or other magnetizable materials that may be rendered sufficiently magnetic by subjecting the magnetizable material to a sufficient electric and/or magnetic field.
In some embodiments, the magnetic elements 170 and/or the magnetic elements 172 can include strongly ferromagnetic material to reduce magnetization loss with time, such that the magnetic elements 170 and 172 can be coupled with a reliable magnetic force, without substantial loss of that force over time.
Furthermore, in some embodiments, the magnetic elements of the present disclosure may include electromagnets, in which the magnetic fields can be switched on and off between a first magnetic state and a second non-magnetic state to activate magnetic fields in various areas of the system 100 in desired configurations when desired.
In some embodiments, the magnetic elements 170 and 172 can be discrete articles operatively coupled to the cover 160 and the base plate 110, as depicted in the embodiment of
As shown in
The inner edge 163 can be positioned a first distance d1 (e.g., a first radial distance or “first radius”) from the center 161 of the annular cover 160. In such embodiments, if the annular cover 160 has a substantially circular ring shape, the opening 166 can have a diameter equal to twice the first distance d1. In addition, the outer edge 165 can be positioned a second distance d2 (e.g., a second radial distance or “second radius”) from the center 161 of the annular cover 160. In some embodiments, the first distance d1 can be at least about 50% of the second distance. In some embodiments, at least about 60%, and in some embodiments, at least about 70%. In addition, in some embodiments, the first distance d1 can be no greater than about 95% of the second distance, in some embodiments, no greater than about 85%, and in some embodiments, no greater than about 80%. In some embodiments, the first distance d1 can be about 75% of the second distance d2.
Furthermore, in some embodiments, the outer edge 165 can be positioned a distance d2 (e.g., a radial distance) from the center 161, which can define a first area, and in some embodiments, the area of the opening 166 can be at least about 30% of the first area, in some embodiments, at least about 40%, and in some embodiments, at least about 50%. In some embodiments, the opening 166 can be no greater than about 95% of the first area, in some embodiments, no greater than about 75%, and in some embodiments, no greater than about 60%. In some embodiments, the opening 166 can be about 53% of the first area.
In addition, the annular cover 160 can include an inner wall 162 (e.g., an “inner circumferential wall” or “inner radial wall”; which can function as an inner compression ring, in some embodiments, as described below) and an outer wall 164 (e.g., an “outer circumferential wall” or “outer radial wall”; which can function as an outer compression ring, in some embodiments, as described below). In some embodiments, inner and outer walls 162 and 164 can include or define the inner and outer edges 163 and 165, respectively, such that the inner wall 162 can be positioned inwardly (e.g., radially inwardly) of the thermal process chambers 152, and the outer wall 164 can be positioned outwardly (e.g., radially outwardly) of the thermal process chambers 152. As further shown in
As shown in
In some embodiments, at least a portion of the cover 160, such as one or more of the inner wall 162, the outer wall 164, and the upper wall 167, can be optically clear. As used herein, the phrase “optically clear” can refer to an object that is transparent to electromagnetic radiation ranging from the infrared to the ultraviolet spectrum (e.g., from about 10 nm to about 10 μm (10,000 nm)); however, in some embodiments, the phrase “optically clear” can refer to an object that is transparent to electromagnetic radiation in the visible spectrum (e.g., about 400 nm to about 700 nm). In some embodiments, the phrase “optically clear” can refer to an object with a transmittance of at least about 80% within the wavelength ranges above.
Such configurations of the annular cover 160 can function to effectively or substantially isolate the thermal process chambers 152 of the sample processing device 150 when the cover 160 is coupled to or positioned adjacent the sample processing device 150. For example, the cover 160 can physically, optically, and/or thermally isolate a portion of the sample processing device 150, such as a portion comprising the thermal process chambers 152. In some embodiments, as shown in
In addition, in some embodiments, the ability of the annular cover 160 to cover and effectively thermally isolate the thermal process chambers 152 from ambience and/or from other portions of the system 100 can be important, because otherwise, as the base plate 110 and the sample processing device 150 are rotated about the rotation axis 111, air can be caused to move quickly past the thermal process chambers 152, which, for example, can undesirably cool the thermal process chambers 152 when it is desired for the chambers 152 to be heated. Thus, in some embodiments, depending on the configuration of the sample processing device 150, one or more of the inner wall 162, the upper wall 167 and the outer wall 164 can be important for thermal isolation.
As shown in
In some embodiments, the outer wall 155 of the sample processing device 150 and the one or more input wells 154 formed in the body 153 of the sample processing device 150 can effectively define a recess (e.g., an annular recess) 156 in the sample processing device 150 (e.g., in a top surface of the sample processing device 150) in which at least a portion of the annular cover 160 can be positioned. For example, as shown in
In some embodiments, as shown in
As a result, in some embodiments, the magnetic elements 170 can be restricted to an area of the cover 160 where the magnetic elements 170 are positioned outwardly (e.g., radially outwardly) of the input wells 154 (or other protrusions, chambers, recesses, or formations in the body 153) and inwardly (e.g., radially inwardly) of the thermal process chambers 152. In such configurations, the magnetic elements 170 can be said to be configured to maximize the open area of the sample processing device 150 that is available for access by other devices or for other functions. In addition, in such embodiments, the magnetic elements 170 can be positioned so as not to interrupt or disturb the processing of a sample positioned in the thermal process chambers 152.
In some embodiments, as shown in
In addition, the arrangement of the magnetic elements 170 in the cover 160 and the corresponding arrangement of the magnetic elements 172 in the base plate 110 can provide additional positioning assistance for the cover 160 with respect to one or both of the sample processing device 150 and the base plate 110. For example, in some embodiments, the magnetic elements 170 and 172 can each include sections of alternating polarity and/or a specific configuration or arrangement of magnetic elements, such that the magnetic elements 170 of the cover 160 and the magnetic elements 172 of the base plate 110 can be “keyed” with respect to each other to allow the cover 160 to reliably be positioned in a desired orientation (e.g., angular position relative to the rotation axis 111) with respect to at least one of the sample processing device 150 and the base plate 110.
In some embodiments, as described below and illustrated in
In some embodiments, compliance of sample processing devices of the present disclosure may be enhanced if the devices include annular processing rings that are formed as composite structures including cores and covers attached thereto using pressure sensitive adhesives. The sample processing device 150 shown in
The body 153 and the different covers 182 and 186 used to seal any fluid structures (such as the thermal process chambers 152) in the sample processing device 150 may be manufactured of any suitable material or materials. Examples of suitable materials may include, e.g., polymeric materials (e.g., polypropylene, polyester, polycarbonate, polyethylene, etc.), metals (e.g., metal foils), etc. The covers can, but not necessarily, be provided in generally flat sheet-like pieces of, e.g., metal foil, polymeric material, multi-layer composite, etc. In some embodiments, the materials selected for the body 153 and the cover(s) 182 and/or 186 can exhibit good water barrier properties.
In some embodiments, at least one of the covers 182 and 186 can be constructed of a material or materials that substantially transmit electromagnetic energy of selected wavelengths. For example, in some embodiments, one or both of the covers 182 and 186 can be optically clear. By way of further example, in some embodiments, one or both of the covers 182 and 186 can be constructed of a material that allows for visual or machine monitoring of fluorescence or color changes within the thermal process chambers 152.
In some embodiments, at least one of the covers 182 and 186 can include a metallic layer, e.g., a metallic foil. If provided as a metallic foil, the cover 182 or 186 can include a passivation layer on the surface that faces the interior of the fluid structures to prevent contact between the sample materials and the metal. Such a passivation layer may also function as a bonding structure where it can be used in, e.g., hot melt bonding of polymers. As an alternative to a separate passivation layer, any adhesive layer used to attach the cover to the body 153 may also serve as a passivation layer to prevent contact between the sample materials and any metals in the cover.
In some embodiments, one cover 182 or 186 can be manufactured of a polymeric film (e.g., polypropylene) while the other cover 186 or 182 on the opposite side of the device 150 can include a metallic layer (e.g., a metallic foil layer of aluminum, etc.). For example, in such an embodiment, the cover 182 can transmit electromagnetic radiation of selected wavelengths, e.g., the visible spectrum, the ultraviolet spectrum, etc. into and/or out of the process chambers (e.g., thermal process chambers 152) while the metallic layer of cover 186 can facilitate thermal energy transfer into and/or out of the process chambers using thermal structures/surfaces as described herein.
The covers 182 and 186 can be coupled to the body 153 by any suitable technique or techniques, e.g., melt bonding, adhesives, combinations of melt bonding and adhesives, etc. If melt bonded, the cover and the surface to which it is attached can include, e.g., polypropylene or some other melt bondable material, to facilitate melt bonding. In some embodiments, the covers 182 and 186 can be coupled using pressure sensitive adhesive. The pressure sensitive adhesive may be provided in the form of a layer of pressure sensitive adhesive that, in some embodiments, can be provided as a continuous, unbroken layer between the cover and the opposing surface of the body 153. Examples of some potentially suitable attachment techniques, adhesives, etc. may be described in, e.g., U.S. Pat. No. 6,734,401 titled ENHANCED SAMPLE PROCESSING DEVICES SYSTEMS AND METHODS (Bedingham et al.) and U.S. Pat. No. 7,026,168 titled SAMPLE PROCESSING DEVICES (Bedingham et al.).
Pressure sensitive adhesives can exhibit viscoelastic properties that in some embodiments can allow for some movement of one or more of the covers 182 and/or 186 relative to the underlying body 153 to which the covers 182 and/or 186 are attached. The movement may be the result of deformation of the annular processing ring to, e.g., conform to a shaped transfer surface, such as those described in greater detail below. The relative movement may also be the result of different thermal expansion rates between the covers 182, 186 and the body 153. Regardless of the cause of the relative movement between covers and bodies in the sample processing devices of the present disclosure, in some embodiments, the viscoelastic properties of the pressure sensitive adhesive can allow the process chambers (e.g., the thermal process chambers 152) and other fluid features of the fluid structures to retain their fluidic integrity (i.e., they do not leak) in spite of the deformation.
Sample processing devices that include annular processing rings formed as composite structures using covers attached to bodies with viscoelastic pressure sensitive adhesives may, as described herein, exhibit compliance in response to forces applied to conform the annular processing rings to shaped transfer surfaces. Compliance of annular processing rings in sample processing devices used in connection with the present disclosure may alternatively be provided by, e.g., locating the process chambers in an (e.g., circular) array within the annular processing ring in which a majority of the area is occupied by voids in the body 153. For example, as shown in
In some embodiments, the inner compression ring (e.g., the inner wall 162 of the cover 160) can contact the sample processing device 150 along the inner edge 187 of the annular processing ring or between the inner edge 187 and the innermost portion of the thermal process chambers 152. Furthermore, in some embodiments, the outer compression ring (e.g., the outer wall 164 of the cover 160) can contact the sample processing device 150 along the outer edge 185 of the annular processing ring or between the outer edge 185 and the outermost portion of the thermal process chambers 152.
Compliance of the annular processing rings in sample processing devices used in connection with the present disclosure can be provided with a combination of an annular processing ring formed as a composite structure using viscoelastic pressure sensitive adhesive and voids located within the annular processing ring. Such a combination may provide more compliance than either approach taken alone.
In the embodiment illustrated in
The annular cover 160 is shown in
As mentioned above, in some embodiments, the cover 160 and/or the base plate 110 can include one or more magnetic elements 170 and 172 in the form of electromagnets that can be activated as needed, for example, to provide the compressive force in place of passive magnetic elements. In such an embodiment, electric power can be provided to the electromagnets during rotation of the sample processing device 150.
Although not explicitly depicted in
Alternatively or in addition, exposing the thermal structure 130 on the bottom surface 114 of the base plate 110 may provide an advantage when the thermal structure 130 is to be heated by electromagnetic energy emitted by a source directing electromagnetic energy onto the bottom surface 114 of the base plate 110.
By way of example only, the system 100 includes an electromagnetic energy source 190 positioned to deliver thermal energy to the thermal structure 130, with the electromagnetic energy emitted by the source 190 directed onto the bottom surface 114 of the base plate 110 and the portion of the thermal structure 130 exposed on the bottom surface 114 of the base plate 110. Examples of some suitable electromagnetic energy sources may include, but are not limited to, lasers, broadband electromagnetic energy sources (e.g., white light), etc.
While the system 100 is illustrated as including the electromagnetic energy source 190, in some embodiments, the temperature of the thermal structure 130 can be controlled by any suitable energy source that can deliver thermal energy to the thermal structure 130. Examples of potentially suitable energy sources for use in connection with the present disclosure other than electromagnetic energy sources may include, e.g., Peltier elements, electrical resistance heaters, etc.
As used in connection with the present disclosure, the term “electromagnetic energy” (and variations thereof) means electromagnetic energy (regardless of the wavelength/frequency) capable of being delivered from a source to a desired location or material in the absence of physical contact. Nonlimiting examples of electromagnetic energy can include, but are not limited to, laser energy, radio-frequency (RF), microwave radiation, light energy (including the ultraviolet through infrared spectrum), etc. In some embodiments, electromagnetic energy can be limited to energy falling within the spectrum of ultraviolet to infrared radiation (including the visible spectrum).
Where the thermal structure 130 is to be heated by a remote energy source, i.e., an energy source that does not deliver thermal energy to the thermal structure 130 by direct contact, the thermal structure 130 can be constructed to absorb electromagnetic energy and convert the absorbed electromagnetic energy into thermal energy. As a result, the materials used in the thermal structure 130 can possess sufficient thermal conductivity and absorb electromagnetic energy generated by the electromagnetic source 190 at sufficient rates. In addition, it may also be desirable that the material or materials used for the thermal structures 130 have sufficient heat capacity to provide a heat capacitance effect. Examples of some suitable materials include, but are not limited to: aluminum, copper, gold, etc. If the thermal structure 130 is constructed of materials that do not, themselves, absorb electromagnetic energy at a sufficient rate, in some embodiments, the thermal structure 130 can include a material that improves energy absorption. For example, the thermal structure 130 can be coated with an electromagnetic energy absorptive material such as carbon black, polypyrrole, inks, etc.
In addition to selection of suitable materials for the thermal structure 130, it may also be possible to include grooves or other surface structure facing the electromagnetic energy source 190 to increase the amount of surface area exposed to the electromagnetic energy emitted by the source 190. Increasing the surface area of the thermal structure 130 exposed to the electromagnetic energy from source 190 may enhance the rate at which energy is absorbed by the thermal structure 130. The increased surface area used in the thermal structure(s) 130 may also increase the efficiency of electromagnetic energy absorption.
In some embodiments, the thermal structure 130 can be relatively thermally isolated from the remainder of the base plate 110 such that only limited amounts (if any) of the thermal energy in the thermal structure 130 is transferred to the remainder of the base plate 110. That thermal isolation may be achieved, for example, by manufacturing the support structure of the base plate 110 of materials that absorb only limited amounts of thermal energy, e.g. polymers, etc. Some suitable materials for the support structure of base plate 110 include, e.g., glass-filled plastics (e.g., polyetheresterketone), silicones, ceramics, etc.
Although the base plate 110 includes a thermal structure 130 in the form of a substantially continuous circular ring, the thermal structures 130 can alternatively be provided as a series of discontinuous thermal elements, e.g., circles, squares, located beneath the thermal process chambers 152 on the sample processing device 150. One potential advantage, however, of a continuous (e.g., continuous ring) thermal structure 130 is that the temperature of the thermal structure 130 may equilibrate during heating. If a group of thermal process chambers 152 in a sample processing device 150 are arranged such that they are in direct contact with the transfer surface 132 of the thermal structure 130, there is a potential to improve chamber-to-chamber temperature uniformity for all thermal process chambers 152 located above the continuous thermal structure 130.
Although the depicted base plate 110 includes only one thermal structure 130, it will be understood that the base plate can include any number of thermal structures 130 that are necessary to transfer thermal energy to or from the selected thermal process chambers 152 in a sample processing device 150 located thereon. Further, in some embodiments, where more than one thermal structure 130 is provided, the different thermal structures 130 can be independent of each other such that no significant amount of thermal energy is transferred between the different independent thermal structures 130. One example of an alternative in which independent thermal structures 130 are provided may be in the form of concentric annular rings.
Other features of the system 100 of
The system 200 includes a base plate 210 that rotates about an axis of rotation 211. The base plate 210 can also be attached to a drive system (not shown) in a manner similar to that described above with respect to the system 100, or any suitable alternative arrangement.
As shown in
As further shown in
By way of further example, the sample processing device 250 can include various features and elements, such as those described in PCT Patent Publication No. WO 2008/134470 titled METHODS FOR NUCLEIC ACID AMPLIFICATION (Parthasarathy et al.) and U.S. Patent Publication No. 2008/0152546 titled ENHANCED SAMPLE PROCESSING DEVICES, SYSTEMS AND METHODS (Bedingham et al.).
Similar to the system 100 described above, the annular cover 260 and the base plate 210 can compress a sample processing device 250 located therebetween, for example, to enhance thermal coupling between the thermal structure 230 on the base plate 210 and the sample processing device 250, in addition to holding and/or maintaining the sample processing device 250 on the base plate 210 for rotation about the rotation axis 211. As a result, the rotation axis 211 can define a z-axis of the system 200.
Furthermore, by way of example only and similar to the system 100, the system 200 is depicted in
As shown in
Similar to the system 100, the inner edge 263 can be positioned a first distance d1′ (e.g., a first radial distance or “first radius”) from the center 261 of the annular cover 260, and the outer edge 265 can be positioned a second distance d2′ (e.g., a second radial distance or “second radius”) from the center 261 of the annular cover 260. The first distance d1′ and the second distance d2′ (and the areas associated with these distances) can have similar relationships as those described above with respect to the system 100.
Similar to the annular cover 160, the annular cover 260 can include an inner wall 262 (e.g., an “inner circumferential wall” or “inner radial wall”; which can function as an inner compression ring, in some embodiments, as described below). As shown, the inner wall 262 can include or define the inner edge 263, and the inner wall 262 can be positioned inwardly (e.g., radially inwardly) of the thermal process chambers 252.
As further shown in
However, unlike the annular cover 160, the annular cover 260 does not include an outer wall and, as a result, does not provide an outer compression ring to the system 200. Rather, in the system 200, an outer compression ring can be provided by the sample processing device 250.
As shown in
In addition, as shown in
Furthermore, by way of example only, as shown in
As shown in
In some embodiments, the sample processing device 250 can include a recess (e.g., an annular recess) 256 formed in the body 253 (e.g., in a top surface of the sample processing device 250) that is dimensioned to receive at least a portion of the annular cover 260. For example, as shown in
In addition, as shown in
In some embodiments, the annulus or portion of the cover 260 that includes the magnetic elements 270 can include an inner edge (e.g., an inner radial edge) 273 and an outer edge (e.g., an outer radial edge) 275. As shown in
Furthermore, in some embodiments, the annulus of magnetic elements 270 can be positioned outwardly (e.g., radially outwardly) of the one or more input wells 254, or a portion of the sample processing device 250 (or a portion of the body 253) that includes the input wells 254. In addition, in some embodiments, the input wells 254 (or the portion of the sample processing device 250 that includes or defines the input wells 254) and/or the recess 256 can provide reliable positioning of the cover 260 with respect to the sample processing device 250.
As a result, in some embodiments, the magnetic elements 270 can be restricted to an area of the cover 260 where the magnetic elements 270 are positioned outwardly (e.g., radially outwardly) of the input wells 254 (or other protrusions, chambers, recesses, or formations in the body 253) and inwardly (e.g., radially inwardly) of the thermal process chambers 252. In such configurations, the magnetic elements 270 can be said to be configured to maximize the open area of the sample processing device 250 that is available for access by other devices or for other functions. In addition, in such embodiments, the magnetic elements 270 are not positioned to interrupt or disturb the processing of a sample positioned in the thermal process chambers 252. Furthermore, similar to the system 100, the magnetic elements 270 and 272 can be “keyed” with respect to each other to positioned the cover 260 relative to at least one of the sample processing device 250 and the base plate 210 in a desired orientation.
Similar to the covers 182 and 186 described above with respect to
The system 300 includes a cover 360, a sample processing device 350, and a base plate 310. The system 300 is substantially the same as the system 200 of
In the embodiment illustrated in
As shown in
Similar to the covers 182 and 186 described above with respect to
Returning to the system 100 described above,
As depicted in
As discussed herein, one optional feature of systems of the present disclosure is the floating or suspended attachment of the thermal structure 130 such that the thermal structure 130 and the cover 160 are resiliently biased towards each other. For example, in some embodiments, the thermal structure 130 can be coupled to the base plate 110 by one or more resilient members, with the one or more resilient members providing a biasing force opposing the force applied by the compression structure (e.g., one or more of the magnetic elements 170 and 172). In some embodiments, the thermal structure 130 can be capable of movement relative to the main body 116 of the base plate 110 in response to compressive forces between the base plate 110 and the cover 160. For example, movement of the thermal structure 130 can be limited to a z-axis direction that can be aligned with (e.g., parallel to) the axis of rotation 111 (e.g., along the first direction D1).
Resilient coupling of the thermal structure 130 can be advantageous by providing improved compliance with the surface of the sample processing device 150. The floating attachment of the thermal structure 130 can help to compensate for, e.g., surfaces that are not flat, variations in thickness, etc. Resilient coupling of the thermal structure 130 may also improve uniformity in the compressive forces developed between the cover 160 and the thermal structure 130 when a sample processing device 150 is compressed between the two components.
Many different mechanisms can be used to resiliently couple the thermal structure 130. One exemplary mechanism is depicted in
The forces generated by the flat spring 140 can be adjusted by changing the length of the cuts 145 at least partially defining the spring arms 144, changing the radial width of the spring arms 144, changing the thickness of the spring arms 144 (e.g., in the z-axis direction), selection of materials for the spring 140, etc., or combinations thereof.
In some embodiments, the force urging the base plate 110 and cover 160 towards each other can result in physical contact between the main body 116 of the base plate 110 and the cover 160 within the boundary (e.g., circle) defined by the inner edge of the transfer surface 132 of the thermal structure 130. In other words, the magnetic attraction force in the embodiment shown in
To achieve the result described in the preceding paragraph, in some embodiments, the clamping force can be generated between the cover 160 and the main body 116 of the base plate 110 be greater than the biasing force operating to force the transfer surface 132 of the thermal structure 130 towards the cover 160. As a result, the cover 160 can be drawn into contact with the main body 116, and the resilient member (e.g., the flat spring 40) can control the forces applied to the sample processing device 150 between the cover 160 and the transfer surface 132.
In some embodiments, as shown, an insulating element 138 (see also
Although a flat spring 140 is one example of a resilient member that can be used to resiliently couple the thermal structure 130, many other resilient members could be used in place of or in addition to the depicted flat spring 140. Examples of some other potentially suitable resilient members may include, e.g., leaf springs, elastomeric elements, pneumatic structures (e.g., pistons, bladders, etc.), etc., or combinations thereof.
Although the flat spring 140 and the main body 116 of the base plate 110 are depicted as separate components, alternatives may be possible in which the functions of the main body 116 and the spring 140 are accomplished in a single, unitary component.
As shown in
In the embodiment shown in
In the depicted embodiment, the plane 501 extends through the outer edge 533 of the shaped transfer surface 532. Unlike the transfer surface 432 of
As discussed herein, the shaped transfer surface 532 can include a raised portion between the inner edge 531 and the outer edge 533. The height (h) of the raised portion is depicted in
Although the shaped transfer surfaces 432 and 532 depicted in
Unlike the transfer surfaces of
The amount by which the transfer surfaces 432, 532 deviate from a planar surface may be exaggerated in
Returning to
In embodiments in which the sample processing device 450 includes process chambers (see, e.g., thermal process chambers 152 on sample processing device 150 in
To further promote deformation of the sample processing device 450 to conform to the shape of the transfer surface 432, in some embodiments, the cover 460 can include compression rings 462 and 464 in the cover 460, such that the rings 462 and 464 contact the sample processing device 450—essentially spanning the portion of the sample processing device 450 facing the transfer surface 432. In some embodiments, substantially all compression force transfer between the cover 460 and the thermal structure 430 can occur through the inner and outer compression rings 462 and 464 of the cover 460.
To potentially further enhance conformance of the sample processing device 450 to the transfer surface 432, in some embodiments, the inner and outer compression rings 462 and 464 can include an edge treatment 469 such that minor variations in dimensions of the different components (cover, sample processing device, thermal structure, etc.) can be at least partially compensated for by the edge treatments 469. One example of suitable edge treatments may be a rounded structure that promotes point contact between the sample processing device 450 and the compression rings 462 and 464. Other potential examples of potentially suitable edge treatments may include, e.g., a resilient gasket 469a depicted in
In another variation, it should be understood that although the depicted systems include resilient members coupling the thermal structures to the base plates, an alternative arrangement could be used in which the inner and outer compression rings 462 and 464 are resiliently coupled to the cover 460 by one or more resilient members. Resiliently mounting the compression rings 462 and 464 on the cover 460 may also serve to provide some compensation in the system 400 for, e.g., surfaces that are not flat, variations in thickness, etc. Resilient coupling of the compression rings 462 and/or 464 may also improve uniformity in the compressive forces developed between the cover 460 and the thermal structure 430 when a sample processing device 450 is compressed between the two components.
As discussed herein, in some embodiments, the portion of the sample processing device 450 in contact with the transfer surface 432 (or other shaped transfer surfaces) can exhibit some compliance that, under compression, enables the sample processing device 450 to conform to the shape of the transfer surface 432. That compliance may be limited to the portions of the sample processing device located in contact with the transfer surface 432. Some potentially suitable sample processing devices that may include a compliant portion adapted to conform to a shaped thermal transfer surface are described in, e.g., U.S. Patent Publication No. 2007/0009391 titled COMPLIANT MICROFLUIDIC SAMPLE PROCESSING DISKS (Bedingham et al.) and U.S. Patent Publication No. 2008/0050276 titled MODULAR SAMPLE PROCESSING APPARATUS KITS AND MODULES (Bedingham et al.).
One embodiment of the present disclosure includes a system for processing sample processing devices, the system comprising: a base plate operatively coupled to a drive system, wherein the drive system rotates the base plate about a rotation axis, and wherein the rotation axis defines a z-axis; a thermal structure operatively coupled to the base plate, wherein the thermal structure comprises a transfer surface exposed proximate a first surface of the base plate; at least one first magnetic element operatively coupled to the base plate; a sample processing device comprising at least one thermal process chamber; an annular cover adapted to face the transfer surface, the annular cover having a center, an inner edge, and an outer edge, the sample processing device adapted to be positioned between the base plate and the annular cover, the inner edge of the annular cover configured to be positioned inwardly of the at least one thermal process chamber, relative to the center of the annular cover, when the sample processing device is positioned adjacent the annular cover; and at least one second magnetic element operatively coupled to the annular cover, the at least one second magnetic element configured to attract the at least one first magnetic element to force the annular cover in a first direction along the z-axis, such that at least a portion of the sample processing device is urged into contact with the transfer surface of the base plate.
Another embodiment of the present disclosure includes a system for processing sample processing devices, the system comprising: a base plate operatively coupled to a drive system, wherein the drive system rotates the base plate about a rotation axis, and wherein the rotation axis defines a z-axis; a thermal structure operatively coupled to the base plate, wherein the thermal structure comprises a transfer surface exposed proximate a first surface of the base plate; a first annulus of magnetic elements operatively coupled to the base plate; a sample processing device comprising at least one thermal process chamber; an annular cover adapted to face the transfer surface, the annular cover having an inner edge and an outer edge, the inner edge being positioned inwardly of the at least one thermal process chamber, the sample processing device adapted to be positioned between the base plate and the annular cover; and a second annulus of magnetic elements operatively coupled to the annular cover, the second annulus of magnetic elements configured to attract the first annulus of magnetic elements to force the annular cover in a first direction along the z-axis, such that at least a portion of the sample processing device is urged into contact with the transfer surface of the base plate.
Another embodiment of the present disclosure includes a method for processing sample processing devices, the method comprising: providing a base plate operatively coupled to a drive system; providing a thermal structure operatively coupled to the base plate, wherein the thermal structure comprises a transfer surface exposed proximate a first surface of the base plate; providing a sample processing device comprising at least one thermal process chamber; providing an annular cover facing the transfer surface, the annular cover having an inner edge and an outer edge; providing at least one first magnetic element operatively coupled to the base plate and at least one second magnetic element operatively coupled to the annular cover; positioning the sample processing device between the base plate and the annular cover, such that the inner edge of the annular cover is positioned inwardly of the at least one thermal process chamber, and such that the at least one first magnetic element attracts the at least one second magnetic element to force the annular cover in a first direction along the z-axis, such that at least a portion of the sample processing device is urged into contact with the transfer surface of the base plate; and rotating the base plate about a rotation axis, wherein the rotation axis defines a z-axis.
In any of the embodiments above, the sample processing device can further comprise at least one non-thermal process chamber positioned inwardly of the inner edge of the annular cover when the sample processing device is positioned adjacent the annular cover.
In any of the embodiments above, the inner edge of the annular cover can include an inner radial edge, and the inner radial edge can be positioned radially inwardly of the at least one thermal process chamber.
In any of the embodiments above, the outer edge of the annular cover can include an outer radial edge.
In any of the embodiments above, the at least a portion of the sample processing device can include the at least one thermal process chamber.
In any of the embodiments above, the sample processing device can include a recess, and the annular cover can include a portion dimensioned to be received in the recess of the sample processing device.
In any of the embodiments above, the at least one thermal process chamber can be arranged in an annulus about the rotation axis.
In any of the embodiments above, the at least one thermal process chamber can be arranged within an annular processing ring, and the at least a portion of the sample processing device can include the annular processing ring.
In any of the embodiments above, the outer edge of the annular cover can be positioned inwardly of the at least one thermal process chamber.
In any of the embodiments above, the outer edge of the annular cover can be positioned outwardly of the at least one thermal process chamber.
In any of the embodiments above, the annular cover can include a wall adapted to be positioned over the at least one thermal process chamber. In some embodiments, the wall can be optically clear.
In any of the embodiments above, at least a portion of the annular cover can be optically clear.
In any of the embodiments above, at least one of the annular cover and the sample processing device can include an outer wall that is positioned outwardly of the at least one thermal process chamber to thermally isolate the at least one thermal process chamber.
In any of the embodiments above, the inner edge can be an inner radial edge positioned a first radial distance from a center of the annular cover, and the outer edge can be an outer radial edge positioned a second radial distance from the center of the annular cover.
In any of the embodiments above, the first radial distance can be at least about 50% of the second radial distance.
In any of the embodiments above, the annular cover can include an opening positioned to provide access to the sample processing device.
In any of the embodiments above, the outer edge of the annular cover can be positioned a first radius from a center of the annular cover, and the first radius can define a first area. In such embodiments, the area of the opening can be at least 30% of the first area.
In any of the embodiments above, the sample processing device can include at least one input well adapted to be in fluid communication with at least one of the at least one thermal process chamber, and the at least one input well can be further positioned between a center of the sample processing device and at least one of the at least one thermal process chamber.
In any of the embodiments above, the annular cover can be adapted to allow access to at least one of the at least one input well when the sample processing device is positioned adjacent the annular cover.
In any of the embodiments above, the annular cover can include an opening positioned to provide access to at least one of the at least one input well when the sample processing device is positioned adjacent the annular cover.
In any of the embodiments above, the annular cover can include a portion that covers at least one of the at least one thermal process chamber when the sample processing device is positioned adjacent the annular cover.
In any of the embodiments above, the annular cover can be integrally formed with the sample processing device.
In any of the embodiments above, at least one of the at least one first magnetic element and the at least one second magnetic element can include a ferromagnetic material.
In any of the embodiments above, the at least one second magnetic element can include an inner edge and an outer edge, and both the inner edge and the outer edge can be positioned inwardly of the at least one thermal process chamber.
In any of the embodiments above, the annular cover can include an inner wall comprising the at least one second magnetic element and an outer wall positioned outwardly of the at least one thermal process chamber when the sample processing device is positioned adjacent the annular cover.
In any of the embodiments above, the at least one first magnetic element and the at least one second magnetic element can be keyed with respect to each other, such that the annular cover and the base plate can be adapted to be positioned in a prescribed orientation with respect to each other.
In any of the embodiments above, at least one of the at least one first magnetic element and the at least one second magnetic element can be in the form of an annulus, positioned about the rotation axis.
In any of the embodiments above, at least one of the at least one first magnetic element and the at least one second magnetic element can include a substantially uniform distribution of magnetic force about the annulus.
In any of the embodiments above, the at least one second magnetic element can be arranged in the form of an annulus about the rotation axis, and the annulus can include an outer edge. In such embodiments, the outer edge of the annular cover can be positioned adjacent the outer edge of the annulus.
In any of the embodiments above, the at least one second magnetic element can be arranged in the form of an annulus about the rotation axis, the annulus can include an outer edge, and the outer edge can be positioned inwardly of the at least one thermal process chamber, for example, when the sample processing device is positioned adjacent the annular cover.
In any of the embodiments above, the second annulus of magnetic elements can include an inner edge and an outer edge, and both the inner edge and the outer edge can be positioned inwardly of the at least one thermal process chamber.
In any of the embodiments above, the annular cover can include an inner wall comprising the second annulus of magnetic elements and an outer wall positioned outwardly of the at least one thermal process chamber when the sample processing device is positioned adjacent the annular cover.
In any of the embodiments above, the first annulus of magnetic elements and the second annulus of magnetic elements can be keyed with respect to each other, such that the annular cover and the base plate are adapted to be positioned in a prescribed orientation.
In any of the embodiments above, at least one of the first annulus of magnetic elements and the second annulus of magnetic elements can include a substantially uniform distribution of magnetic force about the annulus.
In any of the embodiments above, the second annulus of magnetic elements can include an outer edge, and the outer edge of the annular cover can be positioned adjacent the outer edge of the second annulus of magnetic elements.
In any of the embodiments above, the second annulus of magnetic elements can include an outer edge, and the outer edge can be positioned inwardly of the at least one thermal process chamber when the sample processing device is positioned adjacent the annular cover.
In any of the embodiments above, the inner edge of the annular cover can define an opening, and any of the method embodiments above can further include accessing at least a portion of the sample processing device via the opening in the annular cover, wherein accessing can include at least one of physically accessing, optically accessing, and thermally accessing at least a portion of the sample processing device.
While various embodiments of the present disclosure are shown in the accompanying drawings by way of example only, it should be understood that a variety of combinations of the embodiments described and illustrated herein can be employed without departing from the scope of the present disclosure. For example, some embodiments of the system of the present disclosure can include a base plate from one embodiment, a sample processing device from another embodiment, and a cover from another embodiment.
In addition, the embodiments described above and illustrated in the figures are presented by way of example only and are not intended as a limitation upon the concepts and principles of the present disclosure. As such, it will be appreciated by one having ordinary skill in the art that various changes in the elements and their configuration and arrangement are possible without departing from the spirit and scope of the present disclosure.
All references and publications cited herein are expressly incorporated herein by reference in their entirety into this disclosure.
Various features and aspects of the present disclosure are set forth in the following claims.