Patent Application
20130008806
The present invention relates to fluidic testing devices.
Biochip and sensor technologies have become increasingly popular to test samples for biological or other parameters, in the research environment, as well as in clinical diagnostics and home spaces. However, there remains a need to provide easily assembled customizable or need-specific configurations.
Embodiments of the present invention are directed to fluid testing devices and kits thereof, as well as one or more of detectors, analyzers and methods of generating, detecting and/or analyzing fluid test data, directly or indirectly.
Embodiments of the invention are directed to a multi-channel test block with selectable test bars to analyze air, water, or food to monitor for and/or detect environmental toxins or hazards.
Other embodiments are directed to a multi-channel test block with selectable test bars to analyze biosamples such as, but not limited to, blood, saliva, urine, hair or tissue for DNA matching and/or for medical analysis.
Some embodiments of the present invention are directed to fluidic testing devices comprising a test block holder and one or more testing blocks, each having a test surface. The test block holder engages a testing block to form one or more fluidic flow channels in fluid communication with the test surface of the testing block. The test block holder may engage multiple testing blocks to form one or more fluidic flow channels in fluid communication with the test surfaces of the testing blocks. In some embodiments, the fluidic flow channel is a microfluidic flow channel.
In particular embodiments, the fluidic testing device includes multiple testing blocks, and may include between one and one thousand testing blocks. The testing blocks may be slidably and releasably attached to the test block holder. One or more testing blocks may reside side by side in the test block holder, and/or they may reside one on top of another.
In some embodiments, a testing block defines an electrode set alone or in combination with the test block holder. The electrode set includes one or more working electrodes, a reference electrode and a counter electrode. Each electrode in the electrode set may be positioned one above another. A testing block may include an electrical insulator positioned between each of the electrodes. The electrical insulator may isolate each of the electrodes from the other electrodes. A testing block may include multiple electrode sets.
In other embodiments, the testing block defines a biochip.
The test block holder may include a groove, positioned between the test block holder and each of the testing blocks to define a fluidic flow channel. In one embodiment, the testing blocks are substantially rectangular, and the test block holder has correspondingly-shaped substantially rectangular channels. The channels are spaced apart and substantially coplanar, and each channel is configured to slidably receive one testing block. In other embodiments the testing blocks engage with the test block holder substantially orthogonal to the groove(s).
In some embodiments, the testing blocks include one or more grooves positioned between the test block holder and the testing blocks to define one or more fluidic flow channels. The groove or grooves are positioned in the testing blocks such that when the testing blocks are engaged with the test block holder, the groove or grooves align to form one or more fluidic flow channels.
In some embodiments, at least a portion of the test surface of a testing block comprises a predetermined material analyte for contacting a sample flowing through one or more channels. The predetermined material may include a bioactive material of one or more of the following: an antibody, an antigen, a nucleic acid, a peptide nucleic acid, a ligand, a receptor, avidin, biotin, Protein A, Protein G, Protein L, a substrate for an enzyme and any combination thereof. In some embodiments, a second portion of the test surface comprises a different predetermined material analyte for contacting a sample flowing through one or more channels.
Other embodiments are directed to a fluidic testing kit for providing different test alternatives. A fluidic testing kit includes a plurality of testing blocks configured to slidably engage a holder. Each testing block is configured to test for at least one predetermined parameter. Different testing blocks may be configured to test for different predetermined parameters. The testing blocks may be packed individually or in sets in a sterile package.
In one embodiment, the testing blocks are sensors comprising a set of electrodes. In other embodiments, the testing blocks are biochips with one or more bioactive materials. In some embodiments, the kit includes some testing blocks that are sensors, and some testing blocks that are biochips.
Yet other embodiments are directed to methods of monitoring fluid samples for detecting parameters. The methods include: (a) providing a fluidic testing device including a test block holder and at least one testing block having a test surface configured to contact a liquid sample, wherein the test block holder engages the at least one testing block to form a fluidic flow channel bordering the test surface; (b) flowing fluid samples through the fluidic flow channels; and (c) detecting whether a fluid sample tests positive for a selected analyte based on a response of at least one testing block in a respective fluidic flow channel In some embodiments, the fluid sample is a biological sample from a human or animal.
In one embodiment, the flowing step includes flowing at least one of the fluid samples by a plurality of different testing blocks to test for different parameters. In other embodiments, the flowing step includes serially flowing a respective fluid sample through a plurality of different fluidic flow channels in the fluidic testing device. In some embodiments the flowing step includes both flowing at least one of the fluid samples by a plurality of different testing blocks to test for different parameters and serially flowing a respective fluid sample through a plurality of different fluidic flow channels in the fluidic testing device.
Still other embodiments are directed to systems for testing fluid samples. The systems include a test block holder, multiple user-selectable testing blocks, and a portable reader. The testing blocks are slidably attachable to the test block holder by a user. The portable reader couples to the testing blocks and detects whether a fluid sample tests positive for a selected parameter based on an output or response of at least one of the plurality of testing blocks
In some embodiments, the testing blocks reside orthogonal to flow channels. In other embodiments, the testing blocks reside parallel to flow channels.
It is noted that features of embodiments of the invention as described herein may be methods, systems, computer programs, or a combination of the same, although not specifically stated as such. The above and other embodiments will be described further below.
Further features, advantages and details of the present invention will be appreciated by those of ordinary skill in the art from a reading of the figures and the detailed description of the embodiments that follows, such description being merely illustrative of the present invention.
It is noted that aspects of the invention described with respect to one embodiment, may be incorporated in a different embodiment although not specifically described relative thereto. That is, all embodiments and/or features of any embodiment can be combined in any way and/or combination. Further, any feature or sub-feature claimed with respect to one claim may be included in another future claim without reservation and such shall be deemed supported in the claims as filed. Thus, for example, any feature claimed with respect to a method claim can be alternatively claimed as part of a device, system, circuit, computer readable program code or workstation. Applicant reserves the right to change any originally filed claim or file any new claim accordingly, including the right to be able to amend any originally filed claim to depend from and/or incorporate any feature of any other claim although not originally claimed in that manner. These and other objects and/or aspects of the present invention are explained in detail in the specification set forth below.
The present invention is now described more fully hereinafter with reference to the accompanying drawings, in which embodiments of the invention are shown. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather these embodiments are provided so that this disclosure will be thorough and complete and will fully convey the scope of the invention to those skilled in the art.
Like numbers refer to like elements throughout. In the figures, the thickness of certain lines, layers, components, elements or features may be exaggerated for clarity. Where used, broken lines illustrate optional features or operations unless specified otherwise.
The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the singular forms “a,” “an” and “the” are intended to include plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises” or “comprising,” when used in this specification, specify the presence of stated features, integers, steps, operations, elements components and/or groups or combinations thereof, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components and/or groups or combinations thereof
As used herein, the term “and/or” includes any and all possible combinations or one or more of the associated listed items, as well as the lack of combinations when interpreted in the alternative (“or”).
Also as used herein, phrases such as “between X and Y” and “between about X and Y” should be interpreted to include X and Y. Furthermore, phrases such as “between about X and Y” can mean “between about X and about Y.” Also, phrases such as “from about X to Y” can mean “from about X to about Y.”
Further, the term “about” as used herein when referring to a measurable value such as an amount or numerical value describing any sample, flow rate, composition or agent of this invention, as well as any dose, time, temperature, and the like, is meant to encompass variations of ±20% or lower, such as, for example, ±10%, ±5%, ±1%, ±0.5%, or even ±0.1% of the specified amount.
Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the specification and claims and should not be interpreted in an idealized or overly formal sense unless expressly so defined herein. Well-known functions or constructions may not be described in detail for brevity and/or clarity.
It will be understood that when an element is referred to as being “on,” “attached” to, “connected” to, “coupled” with, “contacting,” etc., another element, it can be directly on, attached to, connected to, coupled with and/or contacting the other element or intervening elements can also be present. In contrast, when an element is referred to as being, for example, “directly on,” “directly attached” to, “directly connected” to, “directly coupled” with or “directly contacting” another element, there are no intervening elements present. It will also be appreciated by those of skill in the art that references to a structure or feature that is disposed “adjacent” another feature can include portions that overlap or underlie the adjacent feature.
Spatially relative terms, such as “under,” “below,” “lower,” “over,” “upper” and the like, may be used herein for ease of description to describe an element's or feature's relationship to another element(s) or feature(s) as illustrated in the figures. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if the device in the figures is inverted, elements described as “under” or “beneath” other elements or features would then be oriented “over” the other elements or features. Thus the exemplary term “under” can encompass both an orientation of over and under. The device may otherwise be oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly. Similarly, the terms “upwardly,” “downwardly,” “vertical,” “horizontal” and the like are used herein for the purpose of explanation only, unless specifically indicated otherwise.
It will be understood that, although the terms first, second, etc., may be used herein to describe various elements, components, regions, layers and/or sections, these elements, components, regions, layers and/or sections should not be limited by these terms. Rather, these terms are only used to distinguish one element, component, region, layer and/or section, from another element, component, region, layer and/or section. Thus, a first element, component, region, layer or section discussed herein could be termed a second element, component, region, layer or section without departing from the teachings of the present invention. The sequence of operations (or steps) is not limited to the order presented in the claims or figures unless specifically indicated otherwise.
The term “testing block” refers to a bar, stick or other shaped member, typically an elongate member configured to test for one or more defined or predeteimined parameters. A respective testing block may have one or more test surfaces for performing analysis of a test sample, and a testing block may be coated with a testing material on one or more surfaces. A testing block may be configured to engage with a test block holder either before or after interacting with a test sample. In various embodiments, a testing block is configured to use in a lab, a doctor's office, a hospital, a veterinary office, in a home, office, school or in field work. A testing block may be configured for prompt onsite testing, analysis, and also typically can provide visual test results.
The term “sensor” refers to a device having one or more test surfaces or electrodes that can include analytical sites arranged on and/or in one or more substrates that permit one or more analyses to be performed on one or more fluid samples (e.g., microsamples) at the same time and/or at different times, typically, but not limited to, via flowable throughput through fluidic channels in a test device. The fluid test sample can be in or comprise substantially gas or liquid. The test sample may include solid or particulate matter in the fluid. The flowable throughput may, in some embodiments, be high throughput conditions at a rapid flow rate(s). Flow speed can range from about 1 ml per minute for a simple flow-through assay (e.g., a sample passes through a respective fluid channel relatively slowly and no incubation is needed) to about 10 ml per minute (or more) for some tests or assays. The term “3D” or “three-dimensional” sensor or sensor array refers to a sensor with a stacked (one over another) electrode arrangement. The term “sensor array” means that the device has more than one sensor, typically arranged in a repeating or partially repeating pattern or layout on one or more layers or surfaces. The term “4D” or “four-dimensional” sensor or sensor array refers to a sensor device that includes multiple sensors in a respective fluid channel that can carry out multiple tests per sample and/or analyze multiple samples, serially and/or in parallel. The multi-dimensional sensor arrays contemplated by embodiments of the present invention can be configured to concurrently accept and test multiple different samples and perform multiple different analyses on those samples and/or serially test a single sample or a plurality of samples.
A “fluidic flow channel” refers to a continuous or uninterrupted fluid pathway or channel typically extending through a fluidic testing device, and typically with an opening at either an outside edge, an end or top or bottom of the fluidic testing device (i.e., an inlet and an outlet) to allow the passage of fluid therethrough, from a sample entry location to a sample discharge location. The device can be configured to re-circulate or flow the fluid sample through one or more channels over time, such as by using different fluid delivery systems, including, for example, pumps, vacuums or capillaries. A “microfluidic” flow channel is a miniaturized fluidic flow channel that accommodates a small fluid volume, typically between microliters and nanoliters of fluid. The microfluidic flow channel typically can hold or accommodate microscale amounts, e.g., microliters or less, such as, for example, 100 microliters or less, including nanoliters of fluid, which can be in the form of a gas or liquid as noted above. In some particular embodiments, each channel can, for example, hold from a sub-microliter volume (e.g., about 0.1 μl) to about a 100 μl volume. In some embodiments, for example, a channel can hold between about a 1 μl volume to about a 10 μl volume. For example, if one channel holds about 2 μl of liquid, a fluidic testing device with 20 channels can process about 40 μl of sample. The testing device can be configured so that all flow channels are the same size or so that some flow channels are larger and can accommodate larger volumes than other flow channels.
The fluidic testing devices of the present invention can be configured into any suitable geometric shape. In some embodiments, the fluidic testing devices are configured as multi-layer boxes. The term “box” is not limited to a “box” shape, but is used broadly to refer to a box-like shape, such as a substantially rectangular shape or cube shape. However, the fluidic testing devices may have any desired geometric shape, and are not required to have a straight edge.
The term “bioactive” includes the term “bioreactive” and means an agent or material or composition that alone or when combined with another agent and exposed to a test sample will undergo a chemical or biological reaction and/or be altered in appearance or in another optically or electronically readable or detectable manner when a target analyte, e.g., constituent, antigen, antibody, bacterium, virus, ligand, protein contaminant, toxin, radioactive material and/or other material is present in the test sample. See, e.g., U.S. Pat. No. 6,294,107, the contents of which are hereby incorporated by reference as if recited in full herein.
Embodiments of the invention are directed to onsite assembly and office diagnostics. For example, embodiments of the present invention may be used to test biological samples such as blood, saliva, urine or other bodily fluids. Other biological samples include for example skin samples, hair, or inhaled/exhaled breath. Some embodiments of the invention may be also suitable for home, lab or field testing of water systems, terrestrial or extraterritorial environments or fluids. For example, embodiments of the present invention may be used to monitor commodities or environments that may be subject to a security and/or health risk, e.g., air sampling, sampling of water systems including water treatment systems, home or restaurant drinking water and sampling of components or environments in food industries such as food production systems or even at home or restaurants and the like.
In some embodiments, the test blocks and test device can be ordered online via a worldwide computer network, such as the Internet. A person can simply order the particular blocks (from a predefined list of different testing choices) desired to carry out the desired test or monitoring, e.g., a test set directed to monitoring a home environment for environmental hazards (e.g., air hazards or water hazards including radioactive and other toxins or hazards). The test blocks can be easily assembled to the test block and operated onsite. The test blocks may be configured to allow a non-sophisticated or trained user to analyze the results (e.g., a visual color or an indication of positive or negative results). It is also envisioned, that non-clinical (medical) personnel can do self-tests for strep or other diseases and the like, at a discounted price relative to medical testing services. Of course, medical personnel may also use the test blocks for office or laboratory medical and environmental testing.
Turning now to the figures,
The material 18 may reside on or over substantially all or all of the test surfaces 14 or the material 18 may be applied selectively to portions of one or more of the test surfaces 14. The same material may be applied to the entire test surface 14 or combinations of different materials may be applied to different locations on a respective primary testing block surface 14 in any combination. The material may be integrated with or applied to opposing primary surfaces (not shown). Each testing block 12 may have the same or different material or materials.
As shown in
In some embodiments, the test block holder 50 is configured to snugly receive one or more of the testing blocks 12. In one example, the test block holder 50 may include grooves 60 that define insertion slots 60s for receiving one or more testing blocks 12. The testing blocks 12 may be inserted (
In another embodiment, as shown in
While the cross-sectional area of the channels 72 in
Furthermore, while according to the illustrative embodiments of
According to one embodiment, the testing blocks 12 are biochips. Each testing block 12 may define a multiple panel biochip configured to test for multiple parameters. Additionally, a fluid testing device with multiple testing blocks 12 engaged to a test block holder 50 may define a multiple panel biochip configured to test for multiple parameters. The term “biochip” refers to a device having one or more analytical sites arranged on and/or in one or more substrates that permits one or more analyses to be performed on one or more fluid samples (e.g., microsamples) at the same time and/or at different times, typically via flowable throughput through fluidic channels in the device. The fluid test sample can be in substantially gas or liquid form, but is typically liquid. The test sample may include solid or particulate matter in the fluid. The flowable throughput may, in some embodiments, be high throughput conditions at a rapid flow rate(s). Flow speed ranges from about 1 μl per minute for a simple flow through assay (e.g., sample passes through the channel slowly and no incubation is needed) to about 10 ml per minute (or more) for some assays. The biochip is typically configured to concurrently accept and test multiple different samples and perform one or multiple different analyses on those samples.
According to another embodiment, the testing blocks 12 include electrode sets.
According to one feature, the working electrode 80 may include a material 18. When there are several working electrodes 80, each one may include the same material, each one may include a different material, or each one may include a different concentration or formulation of the same material for sensitivity or specificity of concentration or the like. Hence, a testing block 12 can carry out a number of different tests e.g., tests n=1, to n, where “n” is any number between 1 and 500,000, typically, less than 100,000, in some embodiments between about two and about 3000, and in some embodiments between about 1 and about 1000.
In particular embodiments, the working electrode 80 has a thickness that is between about 0.05 mm to about 12 mm. The counter electrode 88 may comprise inert materials, such as noble metals or graphic carbon to avoid dissolution. Commonly used reference electrodes 84 include silver/silver-chloride electrodes, calomel electrodes, and hydrogen electrodes. The surface of a working electrode 80 is typically where the biochemical reactions take place. Besides behaving as an electrode for electroanalysis, the capture biomolecules, such as proteins, antibodies, antigens, or DNA probes, may be coated or otherwise disposed on the surface of the working electrode 80. The surface chemical properties of a working electrode 80 may vary depending on applications. For coating proteins on a working electrode 80, for example, the surface may be plated with a thin layer of gold.
The insulators 82, 86 both electrically insulate and provide a fluid seal between the adjacent layers, at least upon assembly. That is, the entire stacked configuration can be compressed together and the insulators 82, 86 define the fluid seal. Alternately, the fluid seal can exist upon assembly of the adjacent layers, such as by size and configuration or attachment means, including adhesive, brazing, welding and the like. Examples of suitable insulator materials include, for example, silicone rubber and certain thermo elastomers such as, for example, Versaflex®, and can, in some embodiments, have thicknesses ranging from between about 0.05 mm to about 10.0 mm Different insulator materials can be used for different layers (or even partial layers).
Note that the term “insulator” refers to a material that can provide electrical insulation between one or more adjacent components, e.g., between a counter and reference electrode and/or between a reference and working electrode. The insulator may also be able to provide fluid isolation between stacked layers. In other embodiments, two or more insulator layers may be used: at least one for electrical isolation and at least another one for fluid sealant. The fluid sealant material can cooperate with adjacent layers to define a substantially fluid-tight seal. The fluid sealant may be a thin gasket layer of any suitable material, such as, for example, a polymer, rubber, and/or metal. In some embodiments, the fluid sealant can be integrated into the electrical insulator and/or laminated and/or otherwise attached thereto. Where gaskets are used, the gasket may have a thickness that is substantially the same or more or less than an adjacent electrode layer, and is typically thinner than at least the working electrode layer. In some embodiments, the gasket can be formed of an elastically compressible material. In some embodiments, the fluid sealant can comprise a gasket of thermoplastic elastomers (including but not limited to Viton®, Buna-N, EPDM, and Versaflex® materials) and/or silicone rubbers.
The testing block 12′ may be used in conjunction with multiple other similarly sized and shaped testing blocks 12′ or with multiple differently sized and/or shaped testing blocks 12′.
The testing block 12″ may be used in conjunction with multiple other similarly sized and shaped testing blocks.
While the fluidic testing device shown in
Each channel 220, 220′, 220″, and 220″′ resides in an X-Y location of the fluidic testing device and passes through a selected number of testing blocks 12. The testing blocks 12 may each be configured to test for a different predetermined element. Thus, in one example, if there are eight testing blocks 12, a sample passing through a fluid channel 220, 220′, 220″, 220″′ is tested for eight different elements. Furthermore, each testing block 12 may be configured to test for multiple different elements. In one example, a testing block 12 may be configured to test for a different element at each channel 220, 220′, 220″, 220″′. Each channel 220, 220′, 220″, and 220″′ may define a different sample flow channel, allowing for a relatively large number of test samples to pass through the fluidic testing device or for one sample to be tested in the different channels 220, 220′, 220″, 220″ over time. Thus, for example, if a fluidic testing device includes four rows, X=4, of twelve channels, Y=12, and if it has eight testing blocks 12 in each channel 220, 220′, 220″, 220″′, Z=8, then there are 384 tests (4×12×8) available in the fluidic testing device and up to 48 samples can be accommodated (one in each channel 220, 220′, 220″, 220″′).
The test block holder 50″″′ includes first 260, second 262, and third 264 segments. The first layer 251 of grooved testing blocks 12′ is positioned next to the first segment 260 of the test block holder 50″″′. The second layer 252 of grooved testing blocks 12″ is positioned between the first segment 260 and the second segment 262 of the test block holder 50 . The third layer 254 of grooved testing blocks 212′ is positioned between the second segment 262 and the third segment 264 of the test block holder 50.
The first segment 260 of the test block holder 50″″′ and the first layer 251 of grooved testing blocks 12′ cooperate to form a first set of fluid channels 270. The first segment 260 of the test block holder 50 and the second layer 252 of grooved testing blocks 12″ cooperate to form a second set of fluid channels 270′. The second segment 262 of the test block holder 50 and the second layer 252 of grooved testing blocks 12″ cooperate to form a third set of fluid channels 270″. The second segment 262 of the test block holder 50″″′ and the third layer 254 of grooved testing blocks 12″ cooperate to form a fourth set of fluid channels 270″′. The third segment 264 of the test block holder 50″″′ and the third layer 254 of grooved testing blocks 12″ cooperate to form a fifth set of fluid channels 270″″.
The fluidic sensor device of
According to some embodiments, the top sections 302a, 302b, and the bottom sections 302d, 302f, comprise a fluidics assembly, configured to cause the fluid sample(s) to flow through the fluidic testing device, which is positioned at the tapered section 302c. The fluidics assembly may sealably engage with a fluidic testing device and cause a fluid sample(s) to flow through the device as is well known to those of skill in the art. The fluidics assembly resides in fluid communication with one or more of the channels in the fluidic testing device. The fluidics assembly is discussed below with respect to
According to some embodiments, the top sections 332a, 332b comprise a fluidics assembly, configured to cause the fluid sample(s) to flow through a fluidic testing device positioned at or below the tapered section 332c.
Further embodiments of the present invention include a kit comprising various testing blocks configured to test for one or a variety of selected parameters. The testing blocks may be similarly sized, such that they may be used interchangeably in a fluidic testing device. The testing blocks may be packaged in a sterile package, where sterile is defined as meeting industry standards or guidelines for sterility for diagnostic testing.
The analyzer 600 includes a signal reader or detector 650 at a reading or detection station. The signal reader or detector 650 may include a CCD (charge coupled device) instrument 652 and optic circuits such as filters and lenses that optically communicate with the test surface of a testing block 12, 12′, 12″ of a fluidic testing device 662. Other signal readers or detectors may be used, such as, but not limited, to optic image recognition systems, intensity, luminescence, radioactivity, magnetism, mass, fluorescence, or color detectors and the like (or combinations of different types of signal detectors and readers). The system 600 can include a fluidic testing device waste disposal 670 that collects used testing blocks 12, 12′, 12″ so that a user can avoid contact therewith. A fluidic testing device holder 674 may obtain and present the fluidic testing device to the reader/detector 650. The signal reader 650 may include an analyzer that analyzes the signal of the different test sites or the analyzer may be remote. The analyzer may include a programmatic library of signals (not shown) that correlate detected signals to a positive or negative condition for each test. The fluidic testing device 662 and/or testing blocks 12, 12′, 12″ and reader 650 may cooperate to electronically correlate a sample and a test to the location of the particular test site on the testing block 12, 12′, 12″ and the test type based on the material and/or sample.
The signal reader 650 may selectively engage all or select ones of the analytical sites of a testing block 12, 12′, 12″ of the fluidic testing device 662 and detect and/or obtain a signal from the analytical site. The signal reader 650 may be in communication with a control circuit 680 configured to direct automated operation of the analyzer 600 to serially obtain one testing block 12, 12′, 12″ and present the obtained testing block to the signal reader 650 and analyze the obtained signal. In embodiments in which one or more than one testing block 12, 12′, 12″ of the fluidic testing device 610 comprises predetermined optically and/or electronically readable indicia as described herein, the control circuit 680 of the analyzer 600 may include a controller that is configured to direct the signal reader 650 to obtain a signal from the region(s) of the testing block 12, 12′, 12″ comprising such indicia.
The testing blocks 12, 12′, 12″ may be releasably attached in the test block holder of the fluidic testing device 662 so that one or more testing blocks 12, 12′, 12″ may be removed from the fluidic testing device 662 separately, sequentially, or in any order or combination.
One exemplary detector 760 is an electrochemical detector 770. The electrochemical detector 770 reads electrochemical signals generated by the testing block sensors in the fluidic testing block 750. The sensors convert chemical signals to electrical signals and those signals are relayed or transmitted to external electrical contacts using an interface 772 with an array of conductors. The electrochemical detector 770 may include de-multiplexers, amplifiers and A/D converters, filters and the like, as is known to those of skill in the art.
Another exemplary detector 760 is an optical detector 780 that comprises a light source, such as a laser 782, that can transmit a light into a sensor space to interrogate the sensors, and a light sensor 784 in communication with the fluidic testing device 750 and laser 782 to be able to receive transmitted light in response thereto. In this embodiment, the sensors of the fluidic testing device 750 are configured to optically change in opacity, color, intensity, transmissiveness, or the like, which can be optically detected. For example, sensors having fluorescent or chemiluminescent properties are examples of optical sensors. A sensing element or group of elements (e.g., working electrode) can be illuminated or excited and their light intensity can be converted to an electrical signal externally by using, for example, a PMT (photomultiplier tube). The detector 780 can include mirrors, lenses and other optical components suitable for optical detection as is known to those of skill in the art.
Non-limiting examples of a bioactive agent or material of this invention include an antibody, an antigen, a nucleic acid, a peptide nucleic acid, a ligand, a receptor, avidin, streptavidin, biotin, Protein A, Protein G, Protein L, a substrate for an enzyme, an anti-antibody, a toxin, a peptide, an oligonucleotide and any combination thereof
The bioactive agent or material may be attached directly to the testing block, (e.g., a surface of the testing block) and/or the bioactive agent or material may be attached indirectly (i.e., via a linker such as PEG (polyethylene glycol), EDC (N-3-Dimethylaminopropyl-N′-ethylcarbodiimide hydrochloride), glutaraldehyde, etc.). The bioactive agent may also be attached through a mediate layer of biotin, avidin, polylysine, BSA (bovine serum albumin), etc. as is known in the art. The bioactive agent or material of this invention may also be provided to an analytical site in a fluid solution, e.g., in order to detect a reaction at the analytical site.
In some embodiments, the bioactive material can be an antibody or antibody fragment and a signal is detected if an antigen/antibody complex is formed. In such embodiments, as an example, a first antibody or antibody fragment can be attached directly or indirectly to a surface of the fluidic testing device via any variety of attachment protocols standard in the art. Then a fluid test sample is passed through a microfluidic flow channel such that the sample contacts an analytical site that comprises the immobilized first antibody or antibody fragment. If there is an antigen in the test sample that is specific for the immobilized first antibody or antibody fragment, the antigen will be bound (i.e., “captured”) by the immobilized first antibody or antibody fragment, resulting in the formation of an antigen/antibody complex immobilized on the fluidic testing device. A fluid comprising a second antibody or antibody fragment that is detectably labeled is then passed through the microfluidic flow channel. The detectably labeled second antibody or antibody fragment is also specific for the antigen bound by the first immobilized antibody and will therefore bind to the captured antigen, thereby immobilizing the detectably labeled second antibody or antibody fragment at the analytical site. Upon subsequent analysis, the immobilized detectably labeled second antibody is detected at the analytical site according to the methods described herein and as are well known in the art for such detection. The result of the analytical testing is that the test sample comprises (e.g., is positive for) the target antigen.
In some embodiments, the bioactive material can be an antigen and a signal is detected if an antigen/antibody complex is formed. In such embodiments, as an example, an antigen (e.g., a peptide, polypeptide, amino acid sequence defining an epitope, etc.) is attached directly or indirectly to a surface of the fluidic testing device(s) via any variety of attachment protocols standard in the art. Then a fluid test sample is passed through a microfluidic flow channel such that the sample contacts an analytical site that comprises the immobilized antigen. If there is an antibody in the test sample that is specific for the immobilized antigen, the antibody in the sample will be bound (i.e., “captured”) by the immobilized antigen, resulting in formation of an antigen/antibody complex immobilized on the fluidic testing device. A fluid comprising a detectably labeled anti-antibody or antibody fragment specific for an antibody of the species from which the test sample was obtained is then passed through the microfluidic flow channel. The detectably labeled antibody or antibody fragment will bind the immobilized antibody captured by the antigen, thereby immobilizing the detectably labeled antibody or antibody fragment at the analytical site. Upon analysis, the immobilized detectably labeled antibody is detected at the analytical site according to the methods described herein and as are well known in the art for such detection. The result of the analytical testing is that the test sample comprises (e.g., is positive for) the target antibody.
In other embodiments, the bioactive material can be a nucleic acid or peptide nucleic acid and a signal is detected if a nucleic acid hybridization complex is formed. In such embodiments, as an example, a nucleic acid (e.g., an oligonucleotide) or peptide nucleic acid (PNA) is attached directly or indirectly to a surface of the sensor(s) via any variety of attachment protocols standard in the art. Then a fluid test sample is passed through a microfluidic flow channel such that the sample contacts an analytical site that comprises the immobilized nucleic acid or PNA. If there is a nucleic acid in the test sample that is complementary [either fully complementary or of sufficient partial complementarity to form a hybridization complex under the conditions of the assay (e.g., high stringency, medium stringency or low stringency as such terms are known in the art)], the nucleic acid in the sample will hybridize to (i.e., “be captured by”) the immobilized nucleic acid or PNA, resulting in formation of a hybridization complex immobilized on the fluidic testing device. Upon (subsequent) analysis, the immobilized hybridization complex is detected at the analytical site according to the methods described herein and as are well known in the art for such detection. The result of the analytical testing is that the test sample comprises (e.g., is positive for) the target nucleic acid. In some embodiments, the immobilized hybridization complex can be detected because the nucleic acid in the test sample has been modified to comprise a detectable signal (e.g., fluorescence, chemiluminescence, radioactivity, electrochemical detection, enzymatic detection, magnetic detection, mass spectroscopy etc.).
In one example, a pediatric or urgent care center may order single-use testing blocks 12, 12′, 12″ for use with an onsite test reader. The test block holder 50, 50′, 50″, 50″′, 50″″, 50″″′ may be reusable or single use disposable. A patient presents with a symptom, and the doctor selects a testing block 12, 12′, 12″ for diagnosing a condition (e.g., strep throat, bacterial infection, etc.). The doctor obtains a test sample from the patient and exposes the testing block(s) 12, 12′, 12″ to the test sample. The doctor uses the onsite test reader to analyze the testing block 12, 12′, 12″ and make a diagnosis.
In a similar example, a veterinary office may order single-use testing blocks 12, 12′, 12″ for use with an onsite test reader. When an animal presents with a symptom, the vet selects one or more testing blocks 12, 12′, 12″ for diagnosing the suspected condition. The vet obtains a test sample from the animal and exposes the testing block(s) 12, 12′, 12″ to the test sample. The vet exposes the testing block(s) 12, 12′, 12″ to the sample and uses the test reader to evaluate the results and make a diagnosis.
The examples set forth above describing various assays that can be carried out in the fluidic testing device of this invention are not intended to be limiting in any way. If a target analyte can be captured by a corresponding bioactive agent that can be attached to the sensor, and the analyte can be detected by one of the detection methods listed above or other methods, then the assay can be performed using the fluidic testing devices according to embodiments of this invention. The fluidic testing devices can be employed to carry out any type of direct immunoassay, indirect immunoassay, competitive binding assay, neutralization assay, diagnostic assay, and/or biochemical assay. For example, a prenatal and/or neonatal TORCH assay, antigens and/or antibodies specific to toxoplasmosis, rubella, cytomegalovirus and herpes simplex virus can be attached on the sensors for capturing both IgG and IgM antibodies and/or viral antigens corresponding to the pathogens in human serum. As another example, antibodies and/or antigens specific to human Hepatitis B and C can be attached for detecting antibodies specific to surface and core antigens of the virus and/or the antigens in human serum samples. Another example, a substrate is immobilized on the fluidic testing device and a fluid sample is passed over the immobilized substrate to detect an enzyme that specifically acts on the immobilized substrate. A product of such enzyme activity can be detected, resulting in the identification of a test sample positive for the target enzyme.
Non-limiting examples of pathogens, agents of interest and/or contaminants that can be detected, identified and/or quantitated according to methods and devices of embodiments of the inventions include a majority of pathogens causing infectious diseases in human and animal, food and air borne pathogens, and pathogens which can be used as bioterrorism agents. The fluidic testing devices can also be used to detect antibodies and proteins which can be used to diagnose a majority of infectious diseases and other diseases and conditions (e.g. thyroid function, pregnancy, cancers, cardiac disorders, autoimmune diseases, allergy, therapeutic drug monitoring, drug abuse tests, etc.). It would be well understood to one of ordinary skill in the art that the methods and fluidic testing devices according to embodiments of this invention can also be employed to detect, identify and/or quantitate specific nucleic acids in a sample (e.g., mutations such as insertions, deletions, substitutions, rearrangements, etc., as well as allelic variants (e.g., single nucleotide polymorphisms). Nucleic acid based assays of embodiments of this invention can also be employed as diagnostics (e.g., to detect nucleic acid of a pathogen in a sample). In some embodiments, mutations of cytochrome P450 genes and blood clotting factor genes can be detected and/or identified. The fluidic testing devices of embodiments of this invention can also be used to determine the level of a RNA transcript by hybridizing a labeled complex mixture of RNA samples onto surfaces coated with complementary strands of oligonucleotides or cDNAc. In other embodiments, the fluidic testing devices of the present invention may be used to complete a TORCH panel test, to detect mutations, or to complete veterinary panels.
The foregoing is illustrative of the present invention and is not to be construed as limiting thereof. Although a few exemplary embodiments of this invention have been described, those skilled in the art will readily appreciate that many modifications are possible in the exemplary embodiments without materially departing from the novel teachings and advantages of this invention. Accordingly, all such modifications are intended to be included within the scope of this invention as defined in the claims. The invention is defined by the following claims, with equivalents of the claims to be included therein.
This application claims the benefit of and priority to U.S. Provisional Application Ser. No. 61/447,287 filed Feb. 28, 2011, the contents of which are hereby incorporated by reference as if recited in full herein.
| Number | Date | Country | |
|---|---|---|---|
| 61447287 | Feb 2011 | US |
