SAMPLE PROCESSING DEVICE WITH OPTICAL ELEMENTS

Sample processing devices including process chambers in which various chemical or biological processes are performed play an increasing role in scientific and diagnostic investigations. The process chambers provided in such devices are preferably small in volume to reduce the amount of sample material required to perform the processes.

One persistent issue associated with sample processing devices including process chambers is in the transfer of fluids between different features in the devices. Conventional approaches to separate and transfer fluidic contents of process chambers have often required human intervention (e.g., manual pipetting) and/or robotic manipulation. Such transfer processes suffer from a number of disadvantages including, but not limited to, the potential for errors, complexity and associated high costs, etc.

SUMMARY

The present invention provides sample processing devices including two chambers, a valve located within the conduit for at least substantially blocking fluid communication between the two chambers, and an optical element to deliver energy to the valve for opening a normally closed valve to provide fluid communication between the two chambers or closing a normally open valve to isolate the first chamber from fluid communication with the second chamber.

The valve may be opened or closed during processing (e.g., while the sample processing device is being rotated) without physical contact, e.g., with a laser or other source of electromagnetic energy. As a result, the valve may be actuated (i.e., opened or closed) without piercing the outermost layers of the sample processing device, thus limiting the possibility of leakage of the sample material from the sample processing device.

In one aspect, the present invention provides a processing device including a first chamber located within a body; a second chamber located within the body; a normally closed valve located within the body between the first chamber and the second chamber, wherein the valve isolates the first chamber from fluid communication with the second chamber when the valve is in its normally closed configuration; and an

optical element attached to the body, wherein the optical element includes an inlet, an outlet, and a reflective surface located along an optical path defined within the optical element, and wherein the optical element is arranged such that electromagnetic energy entering the inlet travels along the optical path where it is reflected towards the outlet, and wherein the electromagnetic energy exiting the outlet is incident on the valve such that the electromagnetic energy can open the normally closed valve.

In another aspect, the present invention may provide a processing device that includes a first chamber located within a body; a second chamber located within the body; a normally open valve located within the body between the first chamber and the second chamber, wherein the valve comprises an opening through which the first chamber is in fluid communication with the second chamber when the valve is in its normally open configuration; and an optical element attached to the body, wherein the optical element includes an inlet, an outlet, and a reflective surface located along an optical path defined within the optical element, and wherein the optical element is arranged such that electromagnetic energy entering the inlet travels along the optical path where it is reflected towards the outlet, and wherein the electromagnetic energy exiting the outlet is incident on the valve such that the electromagnetic energy can close the normally open valve.

In various embodiments, the processing devices described above may include one or more of the following features: a conduit may extend between the first chamber and the second chamber, wherein the valve is located within the conduit; the valve may include shape memory material; the optical element may include two or more separate reflective surfaces such that the electromagnetic energy is reflected at least twice along the optical path within the optical element; the optical element may include a focusing feature; the reflective surface may define a refractive index differential sufficient to reflect electromagnetic energy following the optical path due to total internal reflection; the optical element may transmit a first bandwidth of electromagnetic energy and block a second bandwidth of electromagnetic energy; the body may block transmission of the first bandwidth of electromagnetic energy; the first chamber, the second chamber and the valve may define a process array, and the device may include two or more process arrays, each of the process arrays including a first chamber, a second chamber and a valve located between the first chamber and the second chamber; the two or more process arrays (if provided) may be arranged radially with respect to a center of the

body such that the second chambers of the process arrays are located further from the center of the body than the first chambers; etc.

In another aspect, the present invention may provide a method of operating a valve in a processing device, wherein the method includes providing a processing device that includes a first chamber located within a body; a second chamber located within the body; a normally closed valve located within the body between the first chamber and the second chamber, wherein the valve isolates the first chamber from fluid communication with the second chamber when the valve is in its normally closed configuration; and an optical element attached to the body, wherein the optical element includes an inlet, an outlet, and a reflective surface located along an optical path defined within the optical element. The method may further include providing a first material in the first chamber; rotating the processing device about an axis of rotation; and opening the valve from the normally closed configuration by directing electromagnetic energy at the inlet of the optical element, wherein at least a portion of the electromagnetic energy enters the inlet of the optical element and travels along the optical path through the optical element to the outlet, where at least a portion of the electromagnetic energy traveling through the optical element exits the optical element through the outlet and is incident on the valve to open the valve to an open configuration in which the valve permits fluid communication between the first chamber and the second chamber.

In another aspect, the present invention provides a method of operating a valve in a processing device, the method including providing a processing device that includes a first chamber located within a body; a second chamber located within the body; a normally open valve located within the body between the first chamber and the second chamber, wherein the valve includes an opening through which the first chamber is in fluid communication with the second chamber when the valve is in its normally open configuration; and an optical element attached to the body, wherein the optical element includes an inlet, an outlet, and a reflective surface located along an optical path defined within the optical element; providing a first material in the first chamber; rotating the processing device about an axis of rotation; and closing the valve from the normally open configuration by directing electromagnetic energy at the inlet of the optical element, wherein at least a portion of the electromagnetic energy enters the inlet of the optical element and travels along the optical path through the optical

element to the outlet, where at least a portion of the electromagnetic energy traveling through the optical element exits the optical element through the outlet and is incident on the valve to close the valve to a closed configuration in which the valve isolates the first chamber from fluid communication with the second chamber. The methods may also include one or more of the following: the electromagnetic energy may be directed at the optical element while rotating the processing device; the second chamber may be located farther from the axis of rotation than the first chamber; the optical element may focus at least a portion of the electromagnetic energy on the valve; opening a normally closed valve may include forming an opening in a valve body; closing a normally open valve may include expanding a valve body; the valve may include shape memory material; the reflective surface may reflect the electromagnetic energy traveling along the optical path by total internal reflection; etc.

In another aspect, the present invention may provide actuation of valves on a microfluidic disk using integrated optical elements, such as prisms and/or lenses. The micro fluidic disk may contain a series of chambers and channels for processing of biological samples. Samples can be retained in a channel or chamber by a removable blockage, or valve, that is actuated by an energy source (e.g., a light source). The valves may include an absorbing material that upon illumination, melts the blockage, and opens a fluidic pathway. The method of actuation may be performed remotely by activating an energy source (e.g., a light source), whose emission is coupled to the valve by at least one integrated optical element.

The above summary of the present invention is not intended to describe each disclosed embodiment or every implementation of the present invention. The Figures and the detailed description which follow more particularly exemplify illustrative embodiments.

BRIEF DESCRIPTIONS OF THE FIGURES OF THE DRAWING FIG. 1 is a plan view of one exemplary sample processing device according to the present invention.

FIG. 2 is an enlarged cross-sectional view of a portion of the sample processing device of FIG. 1, taken along line 2-2' in FIG. 1.

FIG. 3 is an enlarged cross-sectional view of a portion of the sample processing device of FIG. 1, taken along line 3-3' in FIG. 1.

FIG. 4 is an enlarged cross-sectional view of a portion of an alternative embodiment of the sample processing device of FIG. 1, taken along line 3-3' in FIG. 1. FIG. 5 is an enlarged cross-sectional view of a portion of yet another alternative embodiment of the sample processing device of FIG. 1, taken along line 3-3' in FIG. 1.

FIG. 6 is an enlarged cross-sectional view of a portion of yet another alternative embodiment of the sample processing device of FIG. 1, taken along line 3-3' in FIG. 1.

FIG. 7 is a schematic diagram of one sample processing system according to the present invention.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

In the following detailed description of illustrative embodiments of the invention, reference is made to the accompanying figures of the drawing which form a part hereof, and in which are shown, by way of illustration, specific embodiments in which the invention may be practiced. It is to be understood that other embodiments may be utilized and structural changes may be made without departing from the scope of the present invention.

The words "preferred" and "preferably" refer to embodiments of the invention that may afford certain benefits, under certain circumstances. However, other embodiments may also be preferred, under the same or other circumstances. Furthermore, the recitation of one or more preferred embodiments does not imply that other embodiments are not useful, and is not intended to exclude other embodiments from the scope of the invention. As used herein, "a," "an," "the," "at least one," and "one or more" are used interchangeably. The term "and/or" (if used) means one or all of the identified elements/features or a combination of any two or more of the identified elements/features.

The term "and/or" means one or all of the listed elements/features or a combination of any two or more of the listed elements/features.

The present invention provides a sample processing device that can be used in the processing of fluid sample materials (or sample materials entrained in a fluid) in multiple process chambers to obtain desired reactions, e.g., polymerase chain reaction

(PCR), ligase chain reaction (LCR), self-sustaining sequence replication, enzyme kinetic studies, homogeneous ligand binding assays, and other chemical, biochemical, and/or other reactions that may, e.g., require precise and/or rapid thermal variations.

Examples of some such processes involve chemical reactions on samples, e.g., nucleic acid amplification. For example, samples may be mixed with a polynucleotide, a polymerase (such as Taq polymerase), nucleoside triphosphates, a first primer hybridizable with the sample polynucleotide, and a second primer hybridizable with a sequence complementary to the polynucleotide. Some or all of the required reagents may be present in the device as manufactured, they may be loaded into the chambers after manufacture of the device, they may be loaded in the chambers just before introduction of the sample, or they may be mixed with sample before loading into the chambers.

Although polynucleotide amplification by PCR is described in the most detail herein, the devices and methods of using them may be used for a variety of other polynucleotide amplification reactions and ligand-binding assays. The additional reactions may be thermally cycled between alternating upper and lower temperatures, such as PCR, or they may be carried out at a single temperature, e.g., nucleic acid sequence-based amplification (NASBA). The reactions can use a variety of amplification reagents and enzymes, including DNA ligase, T7 RNA polymerase and/or reverse transcriptase, etc. Polynucleotide amplification reactions that may be performed using the devices and/or methods of the invention include, but are not limited to a) target polynucleotide amplification methods such as self-sustained sequence replication (3SR) and strand-displacement amplification (SDA); b) methods based on amplification of a signal attached to the target polynucleotide, such as "branched chain" DNA amplification; c) methods based on amplification of probe

DNA, such as ligase chain reaction and QB replicase amplification (QBR); d) transcription-based methods, such as ligation activated transcription (LAT) and nucleic acid sequence-based amplification (NASBA); and e) various other amplification methods, such as repair chain reaction (RCR) and cycling probe reaction (CPR). In addition to genetic amplification methods, other chemical or biochemical reaction applications may also be performed using the devices and/or methods of the invention. For example, temperature controlled lysis of cells may or may not be practiced in connection with the amplification processes discussed above.

Furthermore, the devices and methods may be used to control and interrogate chemical reactions. By rapidly transitioning between desired temperatures, unwanted side reactions that occur at intermediate temperatures can be reduced or eliminated, potentially increasing measurement accuracy and improving product purity. Other applications other than those discussed herein may also benefit from the devices, methods, and systems of the present invention.

Although various constructions of illustrative embodiments are described below, sample processing devices of the present invention may be similar to those described in, e.g., U.S. Patent Application Publication Nos. 2004/0179974 Al (Bedingham et al), 2005/0130177 (Bedingham et al), and 2007/0009391 Al; as well as U.S. Patent Nos. 6,627,159 Bl (Bedingham et al.), 6,720,187 B2 (Bedingham et al.), 6,814,935 (Bedingham et al.), 6,734,401 B2 (Bedingham et al.), 6,987,253 B2 (Bedingham et al.), 7,026,168 (Bedingham et al.), 7,164,107 B2 (Bedingham et al.), and 7,192,560 (Parthasarathy et al.) and 7,322,254 (Bedingham et al.). The documents identified above disclose a variety of different constructions of sample processing devices that could be used to manufacture sample processing devices according to the principles of the present invention.

Although relative positional terms such as "upper" and "lower" may be used herein, it should be understood that those terms are used in their relative sense only. For example, when used in connection with the devices of the present invention,

"upper" and "lower" are used to signify opposing sides of the devices. In actual use, elements described as "upper" and "lower" may be found in any orientation or location and should not be considered as limiting the methods, systems, and devices to any particular orientation or location. For example, the upper surface of the device may actually be located below the lower surface of the device in use (although it would still be found on the opposite side of the device from the lower surface).

One illustrative sample processing device manufactured according to the principles of the present invention is illustrated in FIGS. 1-3, where FIG. 1 is a top plan view of one sample processing device 10, FIG. 2 is an enlarged cross-sectional view of a portion of the sample processing device 10 (taken along line 2-2' in FIG. 1), and FIG.

3 is an enlarged cross-sectional view of a portion of the sample processing device 10 (taken along line 3-3' in FIG. 1). The sample processing device 10 may preferably be

in the shape of a circular disk as illustrated in FIG. 1, although any other shape that can be rotated could be used in place of a circular disk.

The circular disk-shaped sample processing device 10 has a thickness between opposing major surfaces that is substantially less than the dimensions across the major surfaces 16 and 18 of the device 10.

The sample processing device 10 may include a substrate 14 that may be manufactured of any suitable material or combination of materials. Examples of some suitable materials for substrate 14 include, but are not limited to, polymeric material, glass, silicon, quartz, ceramics, etc. For the portions of the substrate 14 that may be in contact with the sample materials, it may be preferred that the material or materials used for those portions be non-reactive with the sample materials. Examples of some suitable polymeric materials that could be used for the substrate in many different bioanalytical applications may include, but are not limited to, polycarbonate, polypropylene (e.g., isotactic polypropylene), polyethylene, polyester, etc. Although the substrate 14 is depicted as a single, homogeneous construction, it will be understood that the substrate 14 could be formed of one or more layers. If the substrate is formed of layers, the layers may be attached to each other by any suitable technique or combination of techniques. Suitable attachment techniques preferably have sufficient integrity such that the attachment can withstand the forces experienced during processing of sample materials in the process chambers. Examples of some of the suitable attachment techniques may include, e.g., adhesive attachment (using pressure sensitive adhesives, curable adhesives, hot melt adhesives, etc.), heat sealing, thermal welding, ultrasonic welding, chemical welding, solvent bonding, coextrusion, extrusion casting, etc. and combinations thereof. Furthermore, the techniques used to attach the different layers may be the same or different.

The sample processing device 10 includes at least one group of interconnected chambers and other features that will be referred to herein as a process array 20, which may be formed within the substrate 14. Although FIG. 1 shows that the sample processing device 10 includes four process arrays 20, the exact number of process arrays provided in connection with a sample processing device manufactured according to the present invention may be greater than or less than four. Each of the depicted process arrays 20 may extend from a center 12 of the sample processing device 10 towards the periphery of the sample processing device 10. The process arrays 20 are

depicted as being substantially aligned radially with respect to the center 12 of the sample processing device 10. However, any arrangement of process arrays 20 may alternatively be used.

It should be understood that a number of the features associated with one or more of the process arrays 20 may be included. For example, one or more valves, loading chambers, processing chambers, mixing chambers, conduits, etc. may be included in each process array.

Each of the process arrays 20 (in the depicted embodiment) includes a first chamber 22, a second chamber 24, a conduit 26, a valve 28, and an optical element 30. The first chamber 22 and the second chamber 24 may be formed within the substrate

14. FIG. 2 depicts a cross-section that includes a portion of the first chamber 22 and a portion of the second chamber 24. As shown, the chambers 22, 24 in the FIGS. 1-3 are contained within the substrate 14. However, in other embodiments, the chambers 22, 24 may include one or more openings through the upper surface 16 or lower surface 18 of the substrate 14 (e.g., for loading).

The chambers 22, 24 of device 10 in FIG. 1 are in the form of circular chambers, although the chambers in devices of the present invention may be provided in the form of capillaries, passageways, channels, grooves, or any other suitably defined volume. The conduit 26 extending between the first chamber 22 and the second chamber

24 may preferably be used to place the first chamber 22 in fluid communication with the second chamber 24 by opening the valve 28. The conduit 26 may be formed by a variety of techniques (e.g., a microreplication, etc.). Examples of suitable microreplication techniques include micromilling, injection molding, vacuum molding, laser ablation, photolithography, thermo forming, embossing, etc.

The conduit 26 may have a circular cross-section, or any other suitable cross- sectional shape (e.g., a rectangle). The conduit 26 may have a cross-sectional area of about 0.1 millimeters squared to about 2 millimeters squared. The length of the conduit, i.e., the distance between the first chamber 22 and the second chamber 24 following the path of the conduit 26, may be about 0.2 millimeters to about 100 millimeters. The path of the conduit 26 may be straight (as depicted), but need not necessarily be straight.

The conduit 26 may be located substantially equally between the upper surface 16 and lower surface 18 of the substrate 14, or may be located closer to either surface 16, 18 of the substrate 14. Generally, the conduit 26 may extend substantially radially from the center 12 of the device 10. However, the conduit 26 may extend in any selected direction.

At least in one alternative embodiment (not shown), the sample processing device may not include a conduit, and instead, the first chamber and the second chamber would be directly adjacent one another and would share a wall. The shared wall may contain a void that may be blocked by a valve, e.g., a valve 28, as to isolate the two chambers from fluid communication with each other.

The valve 28 may be located within the conduit 26 to isolate the first chamber 22 from fluid communication with the second chamber 24. In FIGS. 1 & 2, the valve 28 is located approximately halfway between the first chamber 22 and the second chamber 24. The valve 28 may, however, be located anywhere along the conduit 26 between the first chamber 22 and second chamber 24. The valve 28 may be located between the upper surface 16 and the lower surface 18 of the substrate 14 so that the valve 28 may be shielded from any electromagnetic radiation incident on the upper surface 16 or the lower surface 18 of the substrate 14. The valve 28 may be larger that the conduit 26 as to fit within the conduit 26 to provide a fluid-tight seal. Although not shown, the valve 28 may also be substantially larger than the conduit 26, wherein exterior edges of the valve 28 may fit within a groove, or other void, within the interior walls of the conduit 26.

The valve 28 may have a circular cross-section, or any other suitable cross- sectional shape (e.g., a rectangle) so as to fill the cross-section of the conduit 26. The valve 28 may have a cross-sectional area of about 0.5 millimeters squared to about 5 millimeters squared. The valve 28 may be about 0.05 millimeters to about 0.5 millimeters thick, i.e., the distance from the side of the valve facing the first chamber 22 to the side of the valve facing the second chamber 24.

Although it may be preferred that valve 28 prevent fluid communication between the first chamber 22 and the second chamber 24, a valve 28 may not completely block fluid communication between the first chamber 22 and the second chamber 24. For example, the valve 28 may only partially seal the conduit 26 as to allow a limited amount of fluid communication between the chambers 22, 24. It may,

however, be preferred that the valve 28 isolates the first chamber 22 from the second chamber 24, i.e., the valve 28 prevents fluid movement between the first chamber 22 and the second chamber 24.

The valve 28 may be provided in many forms, e.g., a thermal plug (e.g., waxes, polymers etc.), shape-memory materials, expandable materials (e.g., foams, etc.), or other structures/materials that can substantially block fluid communication through the conduit 26 and can be opened and/or closed by the application of electromagnetic energy in the absence of direct physical contact. Upon the application of electromagnetic energy to the valve 28, the valve 28 may provide an opening through which fluid can pass between the first chamber 22 and the second chamber 24. In the alternative, upon the application of electromagnetic energy to the valve 28, the valve 28 may close preventing fluid communication between the first chamber 22 and the second chamber 24.

As used in connection with the present invention, 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. Non-limiting examples of electromagnetic energy include laser energy, radio-frequency (RF), microwave radiation, light energy (including the ultraviolet through infrared spectrum), etc. It may be preferred that electromagnetic energy is limited to energy falling within the spectrum of ultraviolet to infrared radiation (including the visible spectrum).

The valve 28 may be formed of material such that the valve 28 only opens or closes in response to the application of selected electromagnetic energy at a specific amplitude, wavelength, polarization, etc. The selected electromagnetic energy may be provided by any suitable technique/apparatus, e.g., lasers, lamps, radio frequency (RF) emitters, etc.

The valve 28 may be opened and closed in many different ways, e.g., the valve 28 (or portions thereof) may be ablated, melted, deformed, shrunk, expanded, dissolved, phase changed (e.g., from a solid to a gas), etc. and combinations of two or more of these options. It may be preferred that the valve 28 include energy absorbent materials capable of absorbing electromagnetic energy to convert the electromagnetic energy into thermal energy.

In addition to opening and/or closing the valve 28, it may be desirable to close conduit 26 after, e.g., the second chamber 24 is loaded with sample material. Closing the conduit 26 may be accomplished mechanically, e.g., by simply crushing the conduit 26. Alternatively, sufficient isolation may be achieved by continuously rotating the device 10 during processing, such that the sample materials are retained in the desired chambers by centrifugal forces.

The valve, as described herein, may be shielded from electromagnetic radiation as to, e.g., remain closed until it is desired to be opened, or remain open until it is desired to be closed. An optical element may be provided to direct electromagnetic energy to the valve to facilitate opening and/or closing the valve.

The valve 28 may be actuated (i.e., opened or closed) by electromagnetic energy delivered to the valve 28 through the optical element 30. The optical element 30 may include an inlet 34 and an outlet 36. In the embodiment depicted in FIG. 3, the inlet 34 of the optical element 30 is flush with the upper surface 16 of the substrate 14. In other embodiments, at least a portion of the optical element 30 may extend above or sit below the upper surface 16 (or lower surface 18) of the substrate 14. The optical element 30 as depicted in FIG. 3 is located immediately adjacent the valve 28. In other embodiments the outlet 36 may be located a distance away from the valve 28, as long as electromagnetic energy exiting the outlet 36 may still be incident on the valve 28. The optical element 30 may form a fluid-tight fit with the substrate 14 and the valve 28 so that the sample material may not leak from and/or around the optical element 30.

The optical element 30 may be of any size and/or shape, e.g., in the depiction in FIG. 3, the optical element 30 has a triangular prismatic shape. Further, the optical element 30 may be larger or smaller than the valve 28. The optical element 30 may be formed of any suitable material. Examples of some potentially suitable materials for the optical element 30 include, but are not limited to, e.g., an optical grade polymer, a glass, quartz, fused silica, gel, etc. Further, the interior of the optical element 30 or at least a portion of the interior of the optical element 30 may be open space, i.e., the optical element 30 may be hollow. The optical element 30 may be configured to transmit only a particular bandwidth of electromagnetic energy and/or may block another particular bandwidth of electromagnetic energy. The bandwidth of the electromagnetic energy that is blocked may be reflected, refracted, absorbed, dispersed, etc. For example, the optical element

30 may transmit electromagnetic energy that has a wavelength of about 750 nanometers (nm) to about 10,000 nm. Further, for example, the optical element 30 may block electromagnetic energy that has a wavelength of about 200 nm to about 700 nm. Further, the optical element 30 may be configured to be polarization sensitive. For example, the optical element 30 may selectively transit only light with s, p, or circular polarization.

The optical element 30 defines an optical path. The optical path within the optical element 30 may start at the inlet 34 and end at the outlet 36. The inlet 34 may be designed to receive electromagnetic energy while the outlet 36 may be designed to transmit electromagnetic energy out of the optical element 30.

FIG. 3 depicts an enlarged cross-sectional view of a portion of the sample processing device of FIG. 1, taken along line 3-3' in FIG. 1. In FIG. 3, the optical element 30 is designed to substantially change the direction of the electromagnetic energy approximately 90 degrees, although optical elements may be provided to change the direction of the electromagnetic energy by any selected amount.

The electromagnetic energy 32 is depicted following the optical path of the optical element 30. Line 4-4' is substantially perpendicular to the plane of the upper surface 16 of the substrate 14. The electromagnetic energy 32 enters the inlet 34 substantially perpendicular to the plane of the upper surface 16 of the substrate 14 along line 4-4'. While the electromagnetic energy 32 is passing through the optical element 30, the electromagnetic energy 32 may be reflected from surface 35 and/or refracted within the optical element 30 such that the electromagnetic energy 32 travels substantially parallel to the plane of the upper surface 16 of the substrate 14 along line 5-5' as it exits the optical element through outlet surface 36. As shown, angle α (alpha) is approximately 90 degrees. After the electromagnetic energy 32 exits the outlet 36 of the optical element 30, the electromagnetic energy 32 may be incident on the valve 28. The optical element 30 may be configured so that angle α (alpha) may be any selected angle, with the range of angles being determined by the refractive index of the optical material according to Snell's Law. In some cases, the reflecting side 35 of the optical element 30 may include reflective material, such as, e.g., silver, gold, aluminum, etc. The inlet 34 may also include an anti-reflective coating to enhance transmission of electromagnetic energy into the optical element 30.

The optical element 30 may include and/or define refracting, reflecting, focusing, and/or collimating structures. For example, the optical element 30 may include prisms, mirrors, fiber optics, light pipes, concave lenses, convex lenses, biconvex lenses, meniscus lenses, polarizing filters, Fresnel lenses, bandpass filters, parabolic mirrors, microreplicated reflecting films, ball lenses, etc.

It may be preferred that the focusing features be provided at, e.g., the outlet 36 or other location such that the electromagnetic energy passing through the optical element 30 can be focused on a valve when it exits the optical element 30. The addition of a focusing feature in the optical element 30 can be advantageous in that it can allow for the use of non- focused electromagnetic energy (e.g., a fixed laser emitting a collimated beam of energy) as delivered to the optical element 30. Elimination of the need to focus the energy before the electromagnetic energy is delivered to the optical element 30 provides flexibility in placement of the optical elements 30 relative to the source used to provide the electromagnetic energy. Further, the energy density of the non- focused electromagnetic energy can also be reduced if that energy is focused by the optical element 30.

Each of the embodiments depicted in FIGS. 4-7 show different variations of the optical element and/or its configuration within a sample processing device according to the present invention. More specifically, FIGS. 4-7 depict enlarged cross-sectional views of a portion of each alternative exemplary sample processing device. Further, the enlarged cross-sectional views are taken along what would be line 3-3' in FIG. 1 if the device depicted in FIG. 1 contained such alternative embodiments of optical elements and/or their configuration.

In FIG. 4, a portion of the optical element 130 extends above the upper surface 116 of the substrate 114 and the optical element 130 is designed to change the direction of the electromagnetic energy by approximately 180 degrees. The electromagnetic energy 132 is depicted following the optical path of the optical element 130. The electromagnetic energy 132 enters the inlet 134 substantially parallel to the plane of the upper surface 116 of the substrate 114 along line 6-6'. While the electromagnetic energy 132 passes through the optical element 130, the electromagnetic energy 132 may be reflected from the first reflective surface 138, further reflected from the second reflective surface 140, and/or refracted within the optical element 130 such that the electromagnetic energy 132 travels substantially parallel to the plane of the upper

surface 116 of the substrate 114 along line 8-8' upon exiting the optical element 130. Further, while the electromagnetic energy 132 is within the optical element 130, the direction of the electromagnetic energy 132 may be changed more than once, e.g., once from substantially parallel to the plane of the upper surface 116 (line 6-6') to substantially perpendicular to the plane of the upper surface 116 (line 7-7') and once from substantially perpendicular to the plane of the upper surface 116 (line 7-7') to substantially parallel to the plane of the upper surface 116 (line 8-8').

As depicted, both angle γ (gamma) and angle β (beta) may be approximately 90 degrees. After the electromagnetic energy 132 exits the outlet 136 of the optical element 130, the electromagnetic energy 132 may be incident on the valve 128. The ranges of angle β (beta) and angle γ (gamma) are determined according to Snell's law based on the refractive indices of the materials being used.

The optical element 130 may be formed of the same material disclosed with reference to optical element 30 of FIG. 3. Further, the interior of the optical element 130 or at least a portion of the interior of the optical element 130 may be open space

(i.e., hollow).

In FIGS. 3-4, the optical elements 30, 130 are depicted as being flush against the valves 28, 128. However, in other embodiments (e.g., the embodiment depicted in FIG. 5), a void may exist between the outlet of the optical element and the valve. In FIG. 5, the optical element 230 extends above the upper surface 216 of the substrate

214. The electromagnetic energy 232 is depicted following the optical path of the optical element 230. The electromagnetic energy 232 enters the inlet 234 at a substantially 45 degree angle to the plane of the upper surface 216 of the substrate 214 along line 9-9'. While the electromagnetic energy 232 is passes through the optical element 230, the electromagnetic energy 232 is reflected from surfaces 238, 240 and/or refracted such that the electromagnetic energy 232 travels substantially parallel to the plane of the upper surface 216 of the substrate 214 along line 11-11' upon exiting the optical element 230. Further, while the electromagnetic energy 232 is within the optical element 230, the direction of the electromagnetic energy 232 may be changed more than once, e.g., once from a substantially 45 degree angle to the plane of the upper surface 216 (line 9-9') to substantially perpendicular to the plane of the upper surface 216 (line 10-10') and once from substantially perpendicular to the plane of the upper surface 216 (line 10-10') to substantially parallel to the plane of the upper surface

216 (line 11-11'). As shown, angle ζ (zeta) is approximately 135 degrees and angle ε (epsilon) is approximately 90 degrees. After the electromagnetic energy 232 exits the outlet 236 of the optical element 230, the electromagnetic energy 232 travels through the void 242 before striking the valve 228. The ranges of angle ζ (zeta) and angle ε (epsilon) are determined according to Snell's law based on the refractive indices of the materials being used.

The void 242 may be open space within the substrate 214. When the valve 228 is actuated by electromagnetic energy and is opened, the void 242 may be in fluid communication with the conduit. Consequently, sample material that may be moving through the conduit may enter the void 242. However, the optical element 230 may have a fluid-tight fit with the substrate 214 so that the sample material may not leak from the void 242.

In FIG 6, the optical element assembly 330 may include an optical window 338 and a reflective member 340. The electromagnetic energy 332 is depicted following the optical path of the optical element assembly 330. The electromagnetic energy 332 enters the inlet 334 through the optical window 338 substantially perpendicular to the plane of the upper surface 316 of the substrate 314 along line 12-12'. After the electromagnetic energy 332 enters the optical element assembly 330, the electromagnetic energy 332 may be incident on the reflective member 340 to substantially change the direction of the electromagnetic energy 332 such that it is substantially parallel to the plane of the upper surface 316 of the substrate 314 along line 13-13'. As shown, angle η (eta) may be approximately 90 degrees. The optical element assembly 330 may be configured so that angle η (eta) may be about 60 degrees to about 120 degrees. The interior 344 of the optical element assembly 330 may be open space within the substrate 314. In the alternative, the interior 344 of the optical element assembly 330 may be formed of a substance that is transmissive to electromagnetic energy.

FIG. 7 is a schematic diagram of one sample processing system according to the present invention. The sample processing system 400 shows a sample processing device 402 as described herein mounted on a rotatable spindle 404. The rotatable spindle 404 and the sample processing device 400 may spin counterclockwise as indicated by the arrow 450 around axis 452 and/or may spin clockwise around axis 452. The rotatable spindle 404 may be rotated by, e.g., an electric motor.

The system 400 further includes an electromagnetic energy source 406. The electromagnetic energy source 406 may be detached from the sample processing device 402, i.e., it is not located on the device 402 itself. Examples of some potentially suitable electromagnetic energy sources may include, but are not limited to, lasers, broadband electromagnetic energy sources (e.g., white light), etc. The electromagnetic energy source 406 may be operated to emit electromagnetic energy continuously or intermittently based on a variety of factors, e.g., the desired temperature, the desired rate of temperature change, whether the optical properties of the optical elements, etc. Generally, the electromagnetic energy source 406 may be fixed and the electromagnetic energy 408 emitted from the electromagnetic energy source 406 may be incident on the circular path defined by optical elements 430 of the sample processing device 402 while rotating. As such, the inlet of each optical element 430 only receives electromagnetic energy for the time period that the electromagnetic energy is incident on the inlet, which depending on the speed of the rotation, may be a short time period. The electromagnetic energy source 406 may be mounted anywhere as long as the electromagnetic energy 408 that it emits is incident on the optical elements 430 along a path that allows a sufficient amount of the electromagnetic energy to enter the optical elements 430.

The system 400 may also include various other components such as a detection system provided to detect the results of processing of the sample materials in the chambers. For example, the detection system and method may involve active interrogation of the chambers to detect fluorescent reaction products in the chambers as the sample processing device rotates. The detection may be qualitative or quantitative. Other detection systems may be provided to monitor, e.g., the temperatures or other properties of the materials in the chambers.

Moving sample material through sample processing devices may be facilitated by alternately accelerating and decelerating the device during rotation, essentially burping the sample materials through the conduits and chambers. The rotating may be performed using at least two acceleration/deceleration cycles, i.e., an initial acceleration, followed by deceleration, second round of acceleration, and second round of deceleration. It may further be helpful if the acceleration and/or deceleration are rapid. The rotation may also preferably only be in one direction, i.e., it may not be necessary to reverse the direction of rotation during the loading process. Such a

loading process allows sample materials to displace the air in those portions of the process arrays that are located farther from the center of rotation of the device.

The actual acceleration and deceleration rates may vary based on a variety of factors such as temperature, size of the device, distance of the sample material from the axis of rotation, materials used to manufacture the devices, properties of the sample materials (e.g., viscosity), etc. One example of a useful acceleration/deceleration process may include an initial acceleration to about 5000 revolutions per minute (rpm), followed by deceleration to about 1000 rpm over a period of about 1 second, with oscillations in rotational speed of the device between 1000 rpm and 5000 rpm at 1 second intervals until the sample materials have traveled the desired distance.

All references and publications cited herein are expressly incorporated herein by reference in their entirety into this disclosure. Illustrative embodiments of this invention are discussed and reference has been made to possible variations within the scope of this invention. These and other variations and modifications in the invention will be apparent to those skilled in the art without departing from the scope of the invention, and it should be understood that this invention is not limited to the illustrative embodiments set forth herein. Accordingly, the invention is to be limited only by the claims provided below and equivalents thereof.