Multilayer processing devices and methods

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MULTILAYER PROCESSING DEVICES AND
METHODS

BACKGROUND

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A variety of devices have been designed for the simultaneous processing of chemical, biochemical, and other reactions. The devices typically include a number of wells or process chambers in which the processing is performed. Detection of various analytes or process products may be 10 performed by detecting signal light emitted from the process chambers. The signal light may be caused by, e.g., reactions within the process chambers. In other instances, the signal light may be in response to excitation by interrogating light directed into the process chamber from an external source 15 (e.g., a laser, etc.), where the signal light results from, e.g., chemiluminescence, etc.

Regardless of the mechanism or technique used to cause the emission of signal light from the process chambers, its detection and correlation to specific process chambers may be 20 required. If, for example, the signal light emitted from one process chamber is attributed to a different process chamber, erroneous test results may result. The phenomenon of signal light emitted from a first process chamber and transmitted to a second process chamber is commonly referred to as "cross- 25 talk." Cross-talk can lead to erroneous results when, for example, the second process chamber would not emit any signal light alone, but the signal light transmitted to the second process chamber from the first process chamber is detected and recorded as a false positive result. 30

Attempts to avoid cross-talk may include increasing the distance between the process chambers such that any signal light reaching the second process chamber is too weak to register as a positive result with a detector. Other approaches include masking or shrouding the process chambers using an 35 external device located over the process chambers such as is described in International Publication No. WO 02/01180 A2 (Bedingham et al.). One problem with these approaches is that process chamber density on a device may be limited, resulting in a less than desired number of tests being per- 40 formed on a given sample processing device. Another potential problem with these approaches is that they require the use of articles or materials (e.g., masks, shrouds, etc.) in addition to the sample processing devices, thus increasing the cost and complexity of using the sample processing devices. 45

Another situation in which the issue of isolation between process chambers from cross-talk may arise in the delivery of interrogating light to the process chambers. For example, it may be desired that not all of the process chambers be interrogated at the same time. In other words, the process cham- 50 bers may be interrogated serially (i.e., one at a time) or only selected groups of process chambers may be interrogated at the same time. In such a situation, it may be preferred that none or limited amounts of the interrogating light be transmitted to the process chambers that are not the subject of 55 interrogation. With known processing devices, the control over interrogating light may require the use of masks or shrouds, thus raising the same problems of limited process chamber density, as well as the cost and complexity added by the additional articles/process steps. 60

Otherproblems associated with processing devices include control over the feature size, shape, and location. For example, it may be desired that variations in process chamber sizes, shapes, locations, etc., as well as the size, shape and location of other features in the devices (e.g., delivery con- 65 duits, loading chambers, etc.) be limited. Variations in feature size may detrimentally affect test accuracy by, e.g., changing

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the volume of analyte in the different process chambers. Further, variations in feature size may require additional sample volume to, e.g., ensure filling of all process chambers, etc. Variations in feature shape may, e.g., affect the signal light density emitted from a process chamber. Variations in feature location may, e.g., reduce test accuracy if process chamber location is not repeatable between different processing devices.

SUMMARY

The present invention provides sample processing devices that include transmissive layers and control layers to reduce or eliminate cross-talk between process chambers in the processing device. The transmissive layers preferably transmit significant portions of signal light and/or interrogation light while the control layers block significant portions of signal light and/or interrogation light.

The present invention also provides methods of manufacturing processing devices that include transmissive layers and control layers. The methods may, in some embodiments, involve continuous forming processes including co-extrusion of materials to form the transmissive layer and control layer in a processing device, followed by formation of the process chambers in the control layer. In other embodiments, the methods may involve extrusion of materials for the control layer, followed by formation of process chambers in the control layer.

The control layers used in processing devices and methods of the present invention are provided to block the transmission of selected light where the "selected light" may be light of one or more particular wavelengths, one or more ranges of wavelengths, one or more polarization states, or combinations thereof. As used in connection with the present invention, "blocking" of light involves one or more of absorption, reflection, refraction, or diffusion of the selected light. In the case of signal light, transmission of the signal light through the control layer is preferably prevented or reduced to levels that will not result in false positive readings from process chambers. In the case of interrogation light, transmission of the interrogation light through the control layer is preferably prevented or reduced to levels that will not result in unwanted interrogation of process chambers. The control layers may block light of selected wavelengths or ranges of wavelengths. The control layers may also block light of one or more selected polarization states (e.g., s polarization, p polarization, circular polarization, etc).

As used in connection with the present invention, the term "light" will be used to refer to electromagnetic energy, whether visible to the human eye or not. It may be preferred that the light fall within a range of ultraviolet to infrared electromagnetic energy, and, in some instances, it may be preferred that light include electromagnetic energy in the spectrum visible to the human eye.

The processing devices of the present invention may provide a number of potential advantages. For example, by blocking the transmission of signal light, cross-talk during emission of signal light can be reduced or eliminated. With respect to the delivery of interrogation light, blocking the transmission of interrogation light to selected process chambers can reduce or eliminate unwanted interrogation of the selected process chambers.

Furthermore, the methods of the present invention may provide for fast and economical manufacturing of processing devices including both transmissive layers and control layers. Further, the methods may provide processing devices includ3

ing features (e.g., process chambers, distribution conduits, etc.) that are accurately sized shaped and located.

In one aspect, the present invention provides a sample processing device including a body with a transmissive layer that transmits selected light and a control layer that blocks the 5 selected light, wherein the control layer is attached to the transmissive layer with a first major surface of the control layer facing the transmissive layer and a secondmajor surface facing away from the transmissive layer; a plurality of process chamber structures formed in the control layer, wherein each 10 oftheprocess chamber structures includes an interior window surface and an interior side surface formed by the control layer; a cover sheet attached to the second maj or surface of the control layer, wherein the cover sheet and the plurality of process chamber structures define a plurality of process 15 chambers in the sample processing device, wherein the selected light can be transmitted into or out of each process chamber through the interior window surface; and a conduit in the sample processing device, wherein each process chamber of the plurality of process chambers is in fluid communi- 20 cation with the conduit.

In another aspect, the present invention provides a sample processing device including a body with a transmissive layer that transmits selected light and a control layer that blocks the selected light, wherein a first major surface of the control 25 layer faces and is melt-bonded to the transmissive layer, and wherein a second major surface of the control layer faces away from the transmissive layer; a plurality of process chamber structures formed in the body, wherein each of the process chamber structures includes a void formed through the first 30 major surface and the second major surface of the control layer, wherein the void exposes an interior window surface formed by the transmissive layer within each process chamber structure; a cover sheet attached to the second major surface of the control layer, wherein the cover sheet and the 35 plurality of process chamber structures define a plurality of process chambers in the sample processing device, and wherein the cover sheet blocks the selected light; and a conduit formed between the cover sheet and the control layer in the sample processing device, wherein each process chamber 40 of the plurality of process chambers is in fluid communication with the conduit.

In another aspect, the present invention provides a method of manufacturing a sample processing device, the method including providing a body that includes a transmissive layer 45 that transmits selected light; a control layer that blocks the selected light, wherein the control layer is attached to the transmissive layer with a first major surface of the control layer facing the transmissive layer and a secondmajor surface facing away from the transmissive layer; a plurality of process 50 chamber structures formed in the control layer, wherein each oftheprocess chamber structures includes an interior window surface and an interior side surface formed by the control layer; and attaching a cover sheet to the second major surface of the control layer, wherein the cover sheet and the plurality 55 of process chamber structures define a plurality of process chambers in the sample processing device, and wherein attaching the cover sheet forms a conduit in the sample processing device, wherein each process chamber of the plurality of process chambers is in fluid communication with the con- 60 duit.

In another aspect, the present invention provides a sample processing device including a body with a first major surface and a second maj or surface, wherein the second maj or surface is flat, and wherein the body blocks selected light; a plurality 65 of process chamber structures formed in the body, wherein the process chamber structures are formed into the first major

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surface of the body; a cover sheet attached to the first major surface of the body, wherein the cover sheet and the plurality of process chamber structures define a plurality of process chambers in the sample processing device, and wherein the cover sheet transmits the selected light; and a conduit located between the body and the cover sheet, wherein each process chamber of the plurality of process chambers is in fluid communication with the conduit.

In another aspect, the present invention provides a method of manufacturing a sample processing device, the method including providing a body that includes a first major surface and a second maj or surface, wherein the second major surface is flat, and wherein the body blocks selected light, wherein the body further includes a plurality of process chamber structures formed in the first major surface of the body; and attaching a cover sheet to the first major surface of the body, wherein the cover sheet and the plurality of process chamber structures define a plurality of process chambers in the sample processing device; and wherein attaching the cover sheet forms a conduit in the sample processing device, wherein each process chamber of the plurality of process chambers is in fluid communication with the conduit.

These and other features and advantages may be described below in connection with various illustrative embodiments of the invention.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 is a perspective view of one illustrative processing device according to the present invention with the cover removed to expose the structures formed therein.

FIG. 2 is an enlarged view of a portion of the processing device of FIG. 1.

FIG. 3 is a cross-sectional view of FIG. 2 taken along line 3-3 in FIG. 2, with the cover located thereon.

FIG. 4 is a cross-sectional view of an alternative processing device according to the present invention.

FIG. 5 is a schematic diagram of a portion of one manufacturing process according to the present invention.

FIG. 6 is a schematic diagram of a system for manufacturing processing devices according to the present invention.

FIG. 7 is a schematic diagram of a portion of another manufacturing process according to the present invention.

FIG. 8 is a schematic diagram of a system for manufacturing processing devices according to the present invention.

DETAILED DESCRIPTION OF ILLUSTRATIVE
EMBODIMENTS OF THE INVENTION

In the following detailed description of illustrative embodiments, 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 present invention provides a sample processing device that can be used in the processing of liquid sample materials (or sample materials entrained in a liquid) in multiple process chambers to obtain desired reactions, e.g., PCR amplification, ligase chain reaction (LCR), self-sustaining sequence replication, enzyme kinetic studies, homogeneous ligand binding assays, and other chemical, biochemical, or other reactions that may, e.g., require precise and/or rapid thermal variations. More particularly, the present invention provides sample processing devices that include one or more process 5

arrays, each of which include a loading chamber, a plurality of process chambers and a main conduit placing the process chambers in fluid communication with the loading chamber.

Although various constructions of illustrative embodiments are described below, sample processing devices of the 5 present invention may be similar to those described in, e.g., International Publication Nos. WO 02/01180 and WO 02/00347 (both to Bedingham et al.). The documents identified above all disclose a variety of different features that could be incorporated into sample processing devices of the present 10 invention.

One illustrative sample processing device manufactured according to the principles of the present invention is illustrated in FIGS. 1 & 2, where FIG. 1 is a perspective view of one sample processing device 10 and FIG. 2 is an enlarged 15 plan view of a portion of the sample processing device 10. In both views, a cover (described below in connection with FIG. 3) has been removed to expose structures formed in the body 60 of the device 10.

The sample processing device 10 includes at least one, and 20 preferably a plurality of process arrays 20. Each of the depicted process arrays 20 preferably extends from proximate a first end 12 towards the second end 14 of the sample processing device 10. The process arrays 20 are depicted as being substantially parallel in their arrangement on the 25 sample processing device 10. Although this arrangement may be preferred, it will be understood that any arrangement of process arrays 20 may alternatively be preferred.

Alignment of the process arrays 20 as depicted may be useful if the main conduits 40 of the process arrays are to be 30 closed simultaneously as discussed in, e.g., International Publication No. WO 02/01180. Alignment of the process arrays 20 may also be useful if sample materials are to be distributed throughout the sample processing device by rotation about an axis of rotation proximate the first end 12 of the 35 device 10 as discussed in, e.g., International Publication No. WO 02/01180.

Each of the process arrays 20 in the depicted embodiment includes at least one main conduit 40, and a plurality of process chambers 50 located along each main conduit 40. The 40 process arrays 20 may also preferably include a loading structure in fluid communication with a main conduit 40 to facilitate delivery of sample material to the process chambers 50 through the main conduit 40. It may be preferred that, as depicted in FIG. 1, each of the process arrays include only one 45 loading structure 30 and only one main conduit 40.

The loading structure 30 may be designed to mate with an external apparatus (e.g., a pipette, hollow syringe, or other fluid delivery apparatus) to receive the sample material. The loading structure 30 itself may define a volume or it may 50 define no specific volume, but, instead, be a location at which sample material is to be introduced. For example, the loading structure may be provided in the form of a port through which a pipette or needle is to be inserted. In one embodiment, the loading structure may be, e.g., a designated location along the 55 main conduit that is adapted to receive a pipette, syringe needle, etc. The loading may be performed manually or by an automated system (e.g., robotic, etc.). Further, the processing device 10 may be loaded directly from another device (using an automated system or manually). 60

The loading chamber depicted in FIG. 1 is only one embodiment of a loading structure 30 in fluid communication with the main conduit 40. It may be preferred that the loading chamber volume, i.e., the volume defined by the loading chamber (if so provided), be equal to or greater than the 65 combined volume of the main conduit 40, process chambers 50, and feeder conduits 42 (if any).

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The process chambers 50 are in fluid communication with the main conduit 40 through feeder conduits 42. As a result, the loading structure 30 in each of the process arrays 20 is in fluid communication with each of the process chambers 50 located along the main conduit 40 leading to the loading structure 30. If desired, each of the process arrays 20 may also include an optional drain chamber (not shown) located at the end of the main conduit 40 opposite the loading structure 30.

FIG. 3 is a cross-sectional view of the portion of the processing device 10 depicted in FIG. 2 taken along line 3-3 in FIG. 2. The processing device 10 includes a body 60 that includes a transmissive layer 62 and control layer 64. It may be preferred that the transmissive layer 62 and control layer 64 be attached by a melt bond. As used herein, a "melt bond" is a bond formed by the melting and/or mixing of materials such as that occurring during, e.g., heat sealing, thermal welding, ultrasonic welding, chemical welding, solvent bonding, coextrusion, extrusion casting, etc. In such a bond, the materials facing each other in transmissive layer 62 and control layer 64 must be compatible with melt bonding so that an attachment of sufficient integrity can be formed to withstand the forces experienced during processing of sample materials in the process chambers.

Alternatively, the transmissive layer 62 and control layer 64 may be attached to each other using, e.g., adhesives, combinations of melt bonding and adhesives, etc. Examples of some attachment techniques may be described in, e.g., International Publication No. WO 02/01180.

The transmissive layer 62 is preferably constructed of one or more materials such that the transmissive layer 62 transmits significant portions of selected light. For the purposes of the present invention, significant portions may be, e.g., 50% or more of normal incident selected light, more preferably 75% or more of normal incident selected light. As discussed above, the selected light may be light of one or more particular wavelengths, one or more ranges of wavelengths, one or more polarization states, or combinations thereof. Examples of some suitable materials for the transmissive layer 62 include, but are not limited to, e.g., polypropylenes, polyesters, polycarbonates, polyethylenes, polypropylene-polyethylene copolymers, cyclo-olefin polymers (e.g., polydicyclopentadiene), etc.

The control layer 64 is preferably constructed of one or more materials such that the control layer 64 blocks significant portions of selected light. For the purposes of the present invention, significant portions of blocked light may be, e.g., 50% or more of normal incident selected light, more preferably 75% or more of normal incident selected light, and even more preferably 90% or more of normal incident selected light. As discussed above, the selected light may be one or more particular wavelengths, one or more ranges of wavelengths, one or more polarization states, or combinations thereof. Examples of some suitable materials for the control layer 64 include, but are not limited to, e.g., polypropylenes, polyesters, polycarbonates, polyethylenes, polypropylenepolyethylene copolymers, cyclo-olefin polymers (e.g., polydicyclopentadiene), etc., that have been modified to provide the desired light blocking function. For example, the material used for the control layer 64 may include a light blocking filler (e.g., colorants, carbon black, metallic particles, etc.) to prevent or reduce transmission of selected light through the control layer 64. In other instances, the control layer 64 may include a coating or other treatment that provides the desired light blocking function.

Where a melt bond between transmissive layer 62 and control layer 64 is to be formed, it may be preferred that the transmissive layer 62 and the control layer 64 be formed of