Articles and methods for performing assays

Abstract

Instruments, their components, consumables therefor, and related methods are generally provided. Advantageously, some instruments described herein may be capable of and / or may be configured to perform assays at faster rates and / or require less input from an operator than assays performed by other methods. Some methods may include performing assays at such faster rates and / or involving such reduced input.

Description

[Technical field]

[0001] Related Applications This application claims priority under 35 U.S.C. §119(e) to U.S. Provisional Application No. 63 / 221,690, entitled "Articles and Methods for Performing Assays," filed July 14, 2021, which is incorporated by reference in its entirety for all purposes.

[0002] Technical Field Instruments and associated methods for performing the assays are generally described. [Background technology]

[0003] An assay generally requires the performance of several sequential steps, typically performed on a multi-well plate. Performing such steps on wells located on a multi-well plate can require a significant amount of effort and / or time. Much of the effort and / or time can require manual operator interaction, which can result in delays, operator-induced variability, and / or operator-induced failure.

[0004] One type of assay that may require a particularly large input of operator effort and / or time to perform on a multiwell plate is an ELISA assay. In such an assay, the operator must perform the following steps: (1) prepare the multiwell plate on which the assay is to be performed, which may involve coating it with a capture antibody, incubating the multiwell plate overnight, washing the multiwell plate, blocking the multiwell plate, and / or removing any excess liquid that has accumulated in one of the preceding steps; (2) react the samples and / or standards with the prepared multiwell plate, which may involve pipetting the samples and / or standards into the plate on the multiwell plate, incubating the multiwell plate, washing the multiwell plate, and / or removing any excess liquid that has accumulated in one of the preceding steps; (3) reacting additional reagents with the samples and / or standards to produce a detectable signal, which may include adding a detection antibody solution to the wells on the multiwell plate, incubating the multiwell plate, adding an enzyme linking solution to the wells on the multiwell plate, incubating the multiwell plate, washing the multiwell plate, adding a chromogenic substrate to each well on the multiwell plate, and / or adding a stop solution to each well on the multiwell plate, and / or (4) measuring a light signal from the multiwell plate.

[0005] Therefore, new instruments and methods for performing the assays are needed. Summary of the Invention

[0006] This disclosure generally describes articles and methods for performing assays. The subject matter described herein may in some cases involve interrelated products, alternative solutions to a particular problem, and / or multiple different uses of one or more systems and / or articles.

[0007] In some embodiments, an instrument for performing an assay is provided. The instrument for performing an assay includes a probe, a support structure positioned proximal to the probe, and a light detector configured to detect an optical signal. A reagent is immobilized on the probe. The probe is configured to be translated by the instrument between a plurality of locations where a plurality of fluids are located. The optical signal includes light emitted, transmitted, reflected, and / or scattered from a chemical species immobilized on the probe, light emitted, transmitted, reflected, and / or scattered from a chemical species generated from a chemical species immobilized on the probe, a lack of light due to absorption of light by a chemical species immobilized on the probe, and / or a lack of light due to absorption of light by a chemical species generated from a chemical species immobilized on the probe.

[0008] In some embodiments, an instrument for performing an assay includes a probe, a support structure positioned proximal to the probe, and a light detector configured to detect an optical signal. The probe is configured to transmit light. A reagent is immobilized on the probe. The probe is configured to be translated by the instrument between a plurality of locations where a plurality of fluids are located. The optical signal includes light emitted, polarized, and / or scattered from a species immobilized on the probe, light emitted, polarized, and / or scattered from a species generated from a species immobilized on the probe, a lack of light due to absorption of light by a species immobilized on the probe, and / or a lack of light due to absorption of light by a species generated from a species immobilized on the probe.

[0009] In some embodiments, an instrument for performing an assay includes a housing, an optical cable, and an optical detector configured to detect an optical signal. The housing includes a component configured to receive a probe. The housing includes a support structure positioned proximal to the component configured to receive the probe. The support structure is configured to receive one or more fluid containers. The instrument is configured to translate the probe between a plurality of locations proximal to a plurality of locations on the container. The optical cable transmits light to the optical detector. The optical signal includes light emitted, transmitted, reflected, and / or scattered from a chemical species immobilized on the probe, light emitted, transmitted, reflected, and / or scattered from a chemical species generated from a chemical species immobilized on the probe, a lack of light due to absorption of light by a chemical species immobilized on the probe, and / or a lack of light due to absorption of light by a chemical species generated from a chemical species immobilized on the probe.

[0010] In some embodiments, an instrument for performing an assay includes a housing, a probe, and a light detector configured to detect an optical signal. The housing includes a component configured to receive the probe. The probe is configured to transmit light. A reagent is immobilized on the probe. The housing includes a support structure positioned proximate to the component configured to receive the probe. The support structure is configured to receive one or more fluid containers. The instrument is configured to translate the probe between a plurality of locations proximate to a plurality of locations on the container. The optical signal includes light emitted, polarized, and / or scattered from a species immobilized on the probe, light emitted, polarized, and / or scattered from a species generated from a species immobilized on the probe, a lack of light due to absorption of light by a species immobilized on the probe, and / or a lack of light due to absorption of light by a species generated from a species immobilized on the probe.

[0011] In some embodiments, an instrument for performing an assay includes a probe, a support structure positioned proximal to the probe, and a light detector configured to detect an optical signal. A reagent is immobilized on the probe. The support structure is configured to be translated by the instrument such that a plurality of portions of the support structure are sequentially positioned proximal to the probe. The optical signal includes light emitted, transmitted, reflected, and / or scattered from a chemical species immobilized on the probe, light emitted, transmitted, reflected, and / or scattered from a chemical species generated from a chemical species immobilized on the probe, a lack of light due to absorption of light by a chemical species immobilized on the probe, and / or a lack of light due to absorption of light by a chemical species generated from a chemical species immobilized on the probe.

[0012] In some embodiments, an instrument for performing an assay includes a probe, a support structure positioned proximal to the probe, and a light detector configured to detect an optical signal. The probe is configured to transmit light. A reagent is immobilized on the probe. The support structure is configured to be translated by the instrument such that portions of the support structure are sequentially positioned proximal to the probe. The optical signal includes light emitted, polarized, and / or scattered from a species immobilized on the probe, light emitted, polarized, and / or scattered from a species generated from a species immobilized on the probe, a lack of light due to absorption of light by a species immobilized on the probe, and / or a lack of light due to absorption of light by a species generated from a species immobilized on the probe.

[0013] In some embodiments, an instrument for performing an assay includes a housing, a probe, and a photodetector configured to detect an optical signal. The housing includes a component configured to receive the probe. The housing includes a support structure positioned proximal to the component configured to receive the probe. The support structure is configured to receive one or more fluid containers. The support structure is configured to be translated by the instrument such that a plurality of locations on the container are sequentially positioned proximal to the probe when the probe is positioned on the component. The optical cable transmits light to the photodetector. The optical signal includes light emitted, transmitted, reflected, and / or scattered from the chemical species immobilized on the probe, light emitted, transmitted, reflected, and / or scattered from the chemical species generated from the chemical species immobilized on the probe, a lack of light due to absorption of light by the chemical species immobilized on the probe, and / or a lack of light due to absorption of light by the chemical species generated from the chemical species immobilized on the probe.

[0014] In some embodiments, an instrument for performing an assay includes a housing, a probe, and a light detector configured to detect an optical signal. A reagent is immobilized on the probe. The housing includes a component configured to receive the probe. The housing includes a support structure positioned proximal to the component configured to receive the probe. The support structure is configured to receive one or more fluid containers. The support structure is configured to be translated by the instrument such that a plurality of locations on the container are sequentially positioned proximal to the probe when the probe is positioned on the component. The optical signal includes light emitted, polarized, and / or scattered from a chemical species immobilized on the probe, light emitted, transmitted, reflected, and / or scattered from a chemical species generated from a chemical species immobilized on the probe, a lack of light due to absorption of light by a chemical species immobilized on the probe, and / or a lack of light due to absorption of light by a chemical species generated from a chemical species immobilized on the probe.

[0015] In some embodiments, a method of performing an assay is provided. The method includes sequentially contacting a probe with a plurality of fluids and detecting an optical signal. Reagents are immobilized on the probe. The optical signal includes light emitted, transmitted, reflected, and / or scattered from a species immobilized on the probe, light emitted, transmitted, reflected, and / or scattered from a species generated from a species immobilized on the probe, a lack of light due to absorption of light by a species immobilized on the probe, and / or a lack of light due to absorption of light by a species generated from a species immobilized on the probe.

[0016] In some embodiments, the method includes providing a probe, providing one or more fluid containers, and detecting an optical signal. A reagent is immobilized on the probe. Light is transmitted through one or more gaps on the probe. The optical signal includes light emitted, polarized, and / or scattered from a chemical species immobilized on the probe, light emitted, polarized, and / or scattered from a chemical species generated from a chemical species immobilized on the probe, a lack of light due to absorption of light by a chemical species immobilized on the probe, and / or a lack of light due to absorption of light by a chemical species generated from a chemical species immobilized on the probe.

[0017] Other advantages and novel features of the present invention will become apparent from the following detailed description of various non-limiting embodiments of the present invention when considered in conjunction with the accompanying figures. In cases where the present specification and a document incorporated by reference include conflicting and / or inconsistent disclosure, the present specification shall control. In cases where two or more documents incorporated by reference include conflicting and / or inconsistent disclosure with respect to each other, the document having the later effective date shall control. [Brief description of the drawings]

[0018] Non-limiting aspects of the present invention are described by way of example with reference to the accompanying figures, which are schematic and are not intended to be drawn to scale. In the figures, each identical or nearly identical component illustrated is typically represented by a single numeral. Where illustration is not necessary to enable a person skilled in the art to understand the invention, for purposes of clarity, not every component is labeled in every figure, and not every component of each aspect of the invention is shown.

[0019] [Figure 1A] 1 is a schematic illustration of an apparatus according to some embodiments. [Figure 1B] 1 is a schematic illustration of a support structure for supporting a multiwell plate according to some embodiments. [Diagram 2] 1 is a schematic illustration of a device including an optical cable according to some embodiments. [Diagram 3] 1 is a schematic illustration of a device including an optical cable according to some embodiments. [Figure 4] 1 is a schematic illustration of an apparatus including a light source according to some embodiments. [Diagram 5] 1 is a schematic illustration of an apparatus including a light source, a probe, and an optical cable according to some embodiments. [Figure 6] 1 is a schematic illustration of a device including a housing according to some embodiments. [Figure 7] 1 is a schematic illustration of a method. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0020] Instruments, their components, consumables therefor, and related methods are generally provided. Advantageously, some instruments described herein may be capable of and / or may be configured to perform assays at faster speeds, require less input from an operator, and / or use smaller sample volumes than assays performed by other methods. Some methods may include performing assays at such faster speeds, involving such reduced inputs, and / or using such smaller sample volumes.

[0021] Some of the instruments described herein may include a probe and / or may be configured to receive a probe. Advantageously, the probe may be capable of translating between multiple locations, e.g., locations where a fluid is located. The fluid may be a fluid suitable for performing an assay. Relatedly, in some embodiments, the probe may be used to perform an assay by sequentially contacting multiple fluids including a sample, one or more fluids including a reagent, and optionally one or more wash fluids. The probe may be able to contact these fluids in a manner that is relatively rapid (e.g., compared to methods of contacting fluids performed by an operator and / or compared to instruments having designs other than those described herein). For example, the fluids may first be located on a container(s) (e.g., a well on a multi-well plate) supported by a support structure, and the probe may be incubated with each such fluid in sequence. Sequentially incubating the probe in multiple environments may be relatively efficient, since it may allow for shortened incubation times and / or eliminate the need to perform manual wash steps.

[0022] In some embodiments, a probe suitable for use in the instruments described herein is functionalized. Functionalization may include immobilization of a reagent thereon, such as a reagent used in an assay. Advantageously, the use of a functionalized probe may eliminate the time and / or work associated with functionalizing a substrate on which an assay is to be performed prior to performing the assay. When used, such a functionalized probe may also be relatively easy to attach and / or detach from the instrument. This may allow for rapid and / or automated probe replacement, which may further facilitate efficient assay performance requiring reduced input from the operator.

[0023] Some of the instruments described herein are suitable for performing assays in which one or more reactions are mechanically stopped. Similarly, some of the methods described herein include performing assays in which one or more reactions are mechanically stopped. This can be achieved, for example, by removing probes on which reagents are immobilized from contact with fluids containing the reagents that are reacting with them. Mechanically stopping a reaction can advantageously eliminate the need for a stop reagent and / or a stop solution. Performing an assay without the use of a stop reagent and a stop solution (or with fewer stop reagents and stop solutions) can advantageously reduce the number of fluids and reagents required to perform an assay and / or allow for more precise control of when a reaction is stopped.

[0024] Some of the instruments described herein are capable of performing assays with improved reproducibility. Similarly, some of the methods described herein include performing assays with improved reproducibility. Improved reproducibility may result from increased automation and / or the presence of a reduced number of steps performed by an operator. Advantageously, improved reproducibility may reduce test-to-test variability and / or failures.

[0025] Some of the devices described herein can perform assays that include performing an agitation and / or mixing step. Similarly, some of the methods described herein include performing assays that include performing an agitation and / or mixing step. Such steps may include agitating and / or mixing a fluid with which the probe is in contact, will be in contact with, and / or has been in contact with the probe. In some embodiments, the agitation and / or mixing step includes using the probe to agitate the fluid with which it is in contact, thereby agitating and / or mixing the fluid. The agitation and mixing steps may be particularly well suited to increasing the rate at which chemical species in the fluid contact the chemical species immobilized on the probe and / or to homogenize the fluid with which the probe is in contact. Advantageously, such methods may thereby increase the rate of one or more reactions occurring during the performance of an assay.

[0026] In some embodiments, the instruments described herein are suitable for performing assays that result in optical signals, and / or the methods described herein include generating optical signals. In such embodiments, the instruments may be configured to detect optical signals, and / or the methods may include generating and / or detecting optical signals. The optical signals may indicate characteristics of the sample and / or the results of the assay. For example, in some embodiments, the optical signals include emitted, transmitted, reflected, scattered, polarized, and / or absorbed light, which indicates characteristics of the sample and / or the results of the assay. In some embodiments, the optical signals are generated by chemical species associated with the probe. As an example, the optical signals may include light emitted, transmitted, reflected, scattered, polarized, and / or absorbed by chemical species immobilized on the probe. As another example, the optical signals may include light emitted, transmitted, reflected, scattered, polarized, and / or absorbed by chemical species originating from chemical species immobilized on the probe. For example, a chemical species immobilized on a probe may react with a chemical species present in a fluid with which it is in contact to generate a chemical species that emits and / or absorbs light, and the optical signal may include light emitted, transmitted, reflected, scattered, polarized, and / or absorbed by the chemical species.

[0027] In some embodiments, the optical signal is detected and / or generated while the probe is in contact with a fluid (e.g., the fluid in which the species immobilized on the probe is initially present, the fluid in which the species generated from the species immobilized on the probe is generated, the fluid from which the optical signal originates, the fluid in which the probe is incubated). Some optical signals detected and / or generated while the probe is in contact with a fluid may be well suited for use in kinetic measurements (e.g., a series of measurements taken at two or more times during a reaction) and / or pulse measurements (e.g., flash luminescence and / or measurements performed during a flash reaction). In some embodiments, the optical signal is read at the time the probe is first contacted with the fluid.

[0028] The ability to detect optical signals originating from different locations (e.g., proximal to the probe, from a fluid in which the probe is co-incubated and / or co-incubated) may allow for the detection of optical signals originating in different ways. This may allow the instruments described herein to be suitable for performing a variety of assays. For example, as described above, the instruments may be suitable for detecting optical signals originating from the probe and / or from a fluid and / or chemical species therein. Desirably, this may allow for the detection of optical signals from assays in which a signal-generating species is immobilized on the probe (e.g., by reaction with a species initially immobilized on the probe and / or initially present in the sample) and / or from assays in which a signal-generating species is formed in a fluid with which the probe is in contact (e.g., the species may originate from a species immobilized on the probe). The latter scenario may be particularly useful for assays in which an enzyme is used that catalyzes a reaction that produces a species that produces an optical signal.

[0029] Some of the instruments described herein are suitable for performing assays involving binding reactions. Similarly, some of the methods described herein include performing assays involving binding reactions. Some such binding reactions may have very high sensitivity. This may advantageously allow the assay to be performed on samples having smaller volumes and / or containing analytes at relatively low concentrations. The sensitivity of the binding reaction may be enhanced by mixing and / or agitating the fluid in which the binding reaction is occurring (e.g., the fluid in contact with the probe). In some cases, the sensitivity of the binding reaction is enhanced by localization of the binding reaction to the probe, which may have a relatively small reaction surface.

[0030] In some embodiments, the devices described herein are suitable for performing multiplexed analyses. Similarly, some methods described herein include performing multiplexed analyses. Multiplexed analyses may take the form of performing two or more different assays on a single sample and / or detecting two or more different analytes present in a single sample. This may be facilitated by the use of different probes on which different reagents are immobilized. In some embodiments, the results of the assays and / or analyte detection may be quantitative. Multiplexed analyses may advantageously allow a relatively small volume of sample to be used to perform multiple assays and / or detect multiple chemical species.

[0031] In some embodiments, the system can perform an assay and / or the method includes performing an assay in which two or more different probes having the same surface chemistry (e.g., the same chemical species immobilized thereon) are contacted with a common sample. The assay can include performing the same step with both probes and / or detecting the same type of optical signal from both probes. Such an assay can advantageously include performing multiple replicates on a common sample with the different probes.

[0032] A review of the various components and their arrangement that may be included in the systems described herein is provided below. Further details on the preferred design of specific components are provided after this review. One example of an instrument is shown in FIG. 1A. The instrument 100 shown therein includes a probe 200, a support structure 300, and a photodetector 400.

[0033] As described elsewhere in this application, FIG. 1A and other figures of this application are not intended to be drawn to scale. Thus, an instrument may include a probe having a different shape than that of the probe shown in FIG. 1A, a support structure having a different shape than that of the support structure shown in FIG. 1A, and / or a photodetector having a different shape than that of the photodetector shown in FIG. 1A. In addition, an instrument may include a probe, a support structure, and a photodetector having a different size relative to one another than the relative sizes of the probe, support structure, and photodetector illustrated in FIG. 1A. It should also be understood that this application contemplates instruments and / or their components having shapes and / or relative sizes different from those illustrated in any of the figures of this application.

[0034] As shown in FIG. 1A, the support structure may be proximal to the probe. In some embodiments, the support structure is located below the probe. It is also possible that the device includes a support structure that is located proximal to the probe but not below the probe. For example, in some embodiments, the device includes a support structure that is located at the same height as the probe and / or above the probe. It is also possible that the device includes a support structure that is located next to the probe (e.g., at the same height as the probe, at a different height from the probe).

[0035] The support structure may be a structure that supports an article to be used during use of the device. For example, in some embodiments, the support structure supports one or more fluid containers used during an assay. Non-limiting examples of such containers include multi-well plates, microtiter plates, slides, droplet arrays, vials, microfluidic devices, microfluidic arrays, microarrays, and digital microfluidic chips. The support structure may support such articles in various ways. As one example, in some embodiments, the device includes a support structure that is positioned and / or configured to be positioned below one or more such articles. It is also possible for the support structure to support such articles by clamping them, partially or completely laterally surrounding them, and / or suspending them. FIG. 1B shows one non-limiting example of a support structure that supports a multi-well plate by being positioned below it. In FIG. 1B, the multi-well plate 390 is positioned on top of the support structure of the device shown in FIG. 1A. FIG. 1B also shows the device 100 including a probe 200, a support structure 300, and a photodetector 400.

[0036] As described in more detail below, in some embodiments, the device includes a probe configured to be translated by the device and / or a support structure configured to be translated by the device. In such embodiments, the positioning of the probe relative to the support structure can change over time. For example, the device can have a rest or storage state in which the probe and support structure are located at a pair of first locations, and an operating state in which the support structure and / or the probe are located at a location different from the rest or storage state. As another example, in some embodiments, the device can be configured to translate the support structure and / or the probe during use. In such embodiments, the support structure and / or the probe can be located at multiple locations and / or moved between locations.

[0037] As described above, it is also possible for an instrument to include both a static probe and a static support structure.

[0038] Also, as shown in Figures 1A and 1B, the instrument may include a photodetector, e.g., a photodetector configured to detect the light signal. The positioning of the photodetector may generally be selected as desired. In some embodiments, as in the embodiment shown in Figures 1A and 1B, the photodetector is located proximally relative to the support structure and / or probe (e.g., on the opposite side of the support structure from the probe, on the same side of the support structure as the probe). It is also possible for the photodetector to be located distally relative to the support structure and / or probe. In such embodiments, the photodetector may be optically coupled to the location where the light signal is generated. For example, in some embodiments, an optical cable may transmit light (e.g., light that is a light signal, light that indicates the absence of a light signal) from a location proximal to the location where the light signal is generated to the photodetector. Some instruments may include two or more photodetectors (e.g., one located proximally relative to the support structure, one located proximally relative to the probe, and two located proximally relative to two different probes).

[0039] Without wishing to be bound by any particular theory, it is believed that a photodetector located on the opposite side of the support structure from the probe and / or optically coupled to such a location may be particularly suitable for detecting optical signals including a lack of light (e.g., due to absorption, reflection, and / or scattering). Similarly, and without wishing to be bound by any particular theory, it is believed that a photodetector located on such a location may also be particularly suitable for detecting optical signals including transmitted light. As a third example, and without wishing to be bound by any particular theory, a photodetector located on the opposite side of the support structure from the probe, a photodetector located on the same side of the support structure as the probe, and / or optically coupled to either such location may be suitable for detecting optical signals including emitted light, reflected light, scattered light, and / or polarized light.

[0040] 2 and 3 show two examples of instruments including an optical cable configured to transmit light from a location proximal to where the light signal is generated to a photodetector. In FIG. 2, an optical cable 502 is configured to transmit light to the photodetector 402. Similarly, in FIG. 3, an optical cable 504 is configured to transmit light from the probe 204 to the photodetector 404. FIG. 2 further illustrates instrument 102 including an optical cable 502. Instrument 102 further includes probe 202, support structure 302, and photodetector 402. FIG. 3 further illustrates instrument 104 including an optical cable 504. Instrument 104 further includes probe 204, support structure 304, and photodetector 404.

[0041] An embodiment such as that shown in Figure 2 may be suitable for performing an assay in which a chemical species that generates an optical signal is present in a fluid that the probe may contact. In Figure 2, an optical cable transmits light from a location proximal to the support structure to a light detector. The support structure may serve as a support for a container of fluid in which the optical signal is generated. Additionally, in some such embodiments, the probe is not coupled to the detector by an optical cable.

[0042] Since the optical cable is configured to transmit light from the probe to the photodetector, an embodiment such as the one shown in FIG. 3 may be suitable for performing an assay in which a chemical species that generates an optical signal is immobilized on the probe. In some such embodiments, any fluid with which the probe is in contact is not coupled to the photodetector by an optical cable. It is also possible that neither the probe nor any fluid with which it is in contact is coupled to the photodetector by an optical cable. For example, an embodiment may include a photodetector positioned such that it can directly receive an optical signal from the probe and / or fluid, without the need for an optical cable positioned between them. It is also possible that the instrument includes additional optical elements that aid in the collection of light by the photodetector. By way of example, the instrument may include one or more lenses configured for this purpose.

[0043] Some instruments that include two or more photodetectors may include one optical cable configured to transmit light in a manner similar to that shown in Figure 2 and one optical cable configured to transmit light in a manner similar to that shown in Figure 3. It is also possible for an instrument to include a photodetector that is not in optical communication with an optical cable. By way of example, the photodetector may be positioned at a distance from and / or at an angle relative to the light source such that it can collect a light signal of sufficient strength for the assay without the aid of an optical cable.

[0044] In some embodiments, the instrument includes a light source. FIG. 4 shows a schematic illustration of one such embodiment. In FIG. 4, the instrument 106 includes a probe 206, a support structure 306, a light detector 406, and a light source 606. The light source can provide light to the instrument. In some embodiments, the light can be light used to form a light signal. For example, in embodiments where the light signal is fluorescent light, the light provided by the light source can be light that excites the emission of fluorescent light. As another example, in embodiments where the light signal is scattered (e.g., Raman scattered) light, the light can be light that generates the scattering (e.g., Raman scattering). As a third example, in embodiments where the light signal is transmitted light, the light can be light transmitted through one or more fluids present in the assay. As a fourth example, in embodiments where the light signal is reflected light, the light is light reflected by one or more fluids present in the assay. As a fifth example, in embodiments where the light signal is a lack of light due to absorption, the light can be light absorbed by a chemical species present in the assay. As a sixth example, in embodiments in which the light signal is polarized light, the light can be unpolarized light or light having a polarization that is affected by the chemical species present in the assay.

[0045] In some embodiments, the instrument includes a light source and an optical cable configured to transmit light from the light source to the probe. In such embodiments, the probe may illuminate one or more portions of the instrument and / or one or more fluids present in an assay being performed by the instrument. Figure 5 shows a schematic illustration of such an instrument. In Figure 5, the instrument 108 includes a probe 208, a support structure 308, a light detector 408, a light source 608, and an optical cable 708. The optical cable 708 in Figure 5 is configured to transmit light from the light source 608 to the probe 208.

[0046] It should be understood that some instruments may have a design that includes some of the features shown in two or more different figures shown in this application. For example, in some embodiments, the instrument includes an optical cable configured to transmit light to a photodetector (e.g., as shown in FIG. 2 and / or FIG. 3), and further includes a light source and / or a second optical cable configured to transmit light from the light source to a probe (e.g., as shown in FIG. 4 and / or FIG. 5). It is also possible for an instrument to have a design like that shown in one or more of FIG. 1-5, but lack a probe. In such an embodiment, the instrument may be configured to receive a probe. By way of example, in some embodiments, the instrument includes a housing that includes a component configured to receive a probe. FIG. 6 shows one non-limiting example of an instrument according to this design. In FIG. 6, the instrument 110 includes a support structure 310, an optical detector 410, and a housing 810. The housing 810 includes a component 910 configured to receive a probe. In such an instrument, the probe may be located within the housing during use of the instrument.

[0047] The probe can be received in a component of the housing in a variety of suitable ways. In some embodiments, the component configured to receive the probe can be an opening, and the probe can be inserted into the opening. Additionally or alternatively, the probe can also be mechanically coupled to the component (e.g., by using a clamp).

[0048] It is also possible for the devices described herein to include more than one set of a certain component. By way of example, in some embodiments, the instrument includes two or more probes (e.g., located at different locations from each other). In some such embodiments, two or more of the probes present in the instrument can be configured to be translated. The instrument can be configured to translate two or more probes independently of each other and / or to translate them together. As an example of the latter type of translation, two or more optical probes can be located at a fixed distance from each other, and both or all can be translated in such a manner that these fixed distances are maintained while the probes are moving. As an example of the former translation, two or more optical probes can be translated relative to each other such that the movement of one optical probe does not affect the movement of any other optical probe from which it is translated independently.

[0049] In addition, when present, two or more probes can be translated between different locations and / or different sets of locations. This can advantageously allow different optical probes to perform different assays and / or different parts of a single assay. This can advantageously increase throughput compared to instruments that include only a single probe or multiple probes that are translated between a common location or set of locations. However, it is also possible for an instrument to include two or more probes that are translated between a common location or set of locations. By way of example, in some embodiments, two or more probes with the same surface chemistry (e.g., the same reagents immobilized thereon) can be translated through the sample and / or between a common set of locations (at least one of which is in contact with the sample). This can advantageously allow multiple measurements of the same analyte and / or multiple replicates of the same assay to be performed on a common sample.

[0050] As described above, instruments that include two or more probes that perform two or more assays may be particularly suitable (e.g., sequentially, simultaneously, in overlapping time periods, non-overlapping time periods). In such embodiments, each probe may be configured to perform an assay independently of the other probes. The assays may be of the same type (e.g., performed on different samples) or different types (e.g., performed to determine two or more different properties of a single sample). In some such embodiments, two or more probes are contacted with a common sample to perform a multiplex assay on the sample and / or detect two or more different analytes in the sample.

[0051] Such an instrument can also be used to perform a single assay. In such embodiments, different probes can be used to perform different aspects of the assay. For example, one probe can be used to perform an assay on a sample, and one or more additional probes can be used to perform an assay on one or more standards. In some embodiments, the presence of two probes and / or two components configured to receive probes can allow for rapid exchange of probes and / or performance of an assay with another probe while one probe is loaded and / or prepared. In some embodiments, different probes can be used to perform replicates of the same assay.

[0052] It is also possible for an instrument to include more than one set of components other than probes. For example, an instrument may include more than one location in a housing configured to receive a probe therein, more than one support structure, more than one light source, and / or more than one light detector. As another example, in some embodiments, an instrument includes more than one of the instruments shown in Figures 1-6. When an instrument includes more than one probe and / or more than one location in a housing configured to receive a probe therein, it may be beneficial for the instrument to further include more than one light detector. Each light detector may be configured to detect light signals arising from chemical species associated with different probes (e.g., chemical species immobilized on the probe, chemical species generated from chemical species immobilized on the probe). In some such embodiments, a common light source may be used that is configured to provide light to all of the probes. This may be particularly suitable for instruments in which a single assay is performed at one time and / or multiple assays of a single type are performed at one time. It is also possible for an instrument that includes more than one probe and / or more than one location in a housing configured to receive a probe therein to include more than one light source (e.g., a light source associated with each probe). Such an instrument may be particularly suitable for embodiments in which the instrument is configured to perform two or more different types of assays simultaneously.

[0053] As described above, in some embodiments, the instrument comprises a housing that includes and / or is configured to receive a probe. The probe may serve as a substrate on which an assay may be performed and / or may aid in the detection of one or more optical signals generated during an assay.

[0054] In some embodiments, the instrument includes a probe that is an optical probe. For example, the instrument may include a probe that is part of one or more optical paths therein and / or is configured to transmit light. It is also possible for the instrument to include a probe that is not an optical probe. A probe that is not an optical probe may be located outside any optical paths present in the instrument and / or may transmit a very low amount (or zero) of light. For example, the instrument may include a first optical cable that transmits light from a location proximal to the support structure to a light detector, and a second optical cable that transmits light from a light source to a location proximal to the support structure. As another example, the instrument may include an optical cable that transmits light from a location proximal to the support structure to a light detector, and may lack a light source. In other words, in some embodiments, the probe is not an optical probe, and the transmission of light to and from a location proximal to the support structure is not performed and / or is achieved by a path that does not pass through the probe. As described in more detail elsewhere herein, some instruments may include two or more probes. In such embodiments, the instrument may include one or more optical probes, and / or one or more probes that are not optical probes. Similarly, the instrument may include exclusively optical probes, probes that are not exclusively optical probes, or both optical and non-optical probes.

[0055] As described above, in some embodiments, the probe is configured to transmit light. In such embodiments, the probe may transmit light in a manner that facilitates the analysis of the assay. For example, some probes may transmit light from a light source to a location proximal to the probe, such as where the immobilized species on the probe is located and / or to a fluid that is proximal to the probe. In such embodiments, the light may be light that is transmitted from a light source to the probe (e.g., by an optical cable). The light may be light that facilitates the formation of an optical signal. For example, the light may be light that is absorbed, transmitted, reflected, scattered (e.g., by Raman scattering), polarized, and / or excites fluorescence to generate an optical signal that can be detected by a photodetector.

[0056] In some embodiments, the probe transmits light from a location proximal to the probe to an optical cable. In such embodiments, the light can be transmitted by the optical cable to a light detector. As one example, the light can be light generated by a chemical species proximal to the probe (e.g., immobilized on the probe, present in a fluid in contact with the probe). As another example, the light can be light transmitted from a fluid located proximal to the probe to a detector. In such embodiments, the light can be light that forms an optical signal. For example, the light can be unabsorbed light, transmitted light, reflected light, scattered light (e.g., by Raman scattering), light generated by fluorescence, and / or light generated by luminescence (e.g., chemiluminescence).

[0057] The probe may have a variety of suitable designs. In some embodiments, the probe is a fiber optic probe and / or includes an optical fiber. It is also possible for the probe to include more than one optical fiber. For example, the probe may include an optical fiber bundle. In some embodiments, the probe includes one or more gaps through which light can be transmitted. For example, the probe may include multiple optical fibers, and the end of each optical fiber may serve as a gap through which light can be transmitted. When present, the gap may be located on the opposite side of the probe from the side on which any optical cable is located. In such embodiments, the probe may serve to transmit light from the optical cable to the gap and / or from the gap to the optical cable.

[0058] It is also possible for the probe to include additional optical elements (e.g., in addition to the optical fiber) that aid in the transmission of light. By way of example, the probe may include a lens and / or a pinhole. When present, these components may aid in near-field imaging. In some embodiments, the probe includes a lens configured to collect and transmit light to the probe and / or its components. By way of example, the lens may be configured to collect and transmit light to an axis along the center and / or optical axis of the probe, along the center and / or optical axis of the optical fiber present in the probe, and / or along the center and / or optical axis of the optical fiber bundle present in the probe.

[0059] In some embodiments, the probe can transmit and / or transmit multiple wavelengths of light (eg, visible wavelengths, infrared wavelengths).

[0060] As described above, some of the probes described herein may be suitable substrates for performing assays. Such probes may be configured to be positioned proximate to multiple portions of the support structure and / or object (e.g., fluid, object containing fluid) supported by the support structure. This may be accomplished by translating the probe (e.g., vertically, in a first horizontal direction, in a second horizontal direction perpendicular to the first horizontal direction, in a combination of two or three of the aforementioned directions) and / or by translating the support structure (e.g., vertically, in a first horizontal direction, in a second horizontal direction, in a combination of two or three of the aforementioned directions). In some embodiments, the instrument may be configured such that it translates the probe by a preset program, in which the probe is positioned in multiple locations over multiple times. It is also possible for the instrument to be configured such that the operator may translate the probe at will (e.g., the operator may input a desired location to which the probe is translated and / or may move the probe in real time by use of a controller). In addition, some instruments may be configured such that they are not configured to translate the probe, in such embodiments, the probe may be static or non-movable absent manual movement by the operator.

[0061] The preset program may include some or all of the following steps in sequence: translating the probe horizontally (e.g., in a first horizontal direction, in a second horizontal direction perpendicular to the first horizontal direction, in a combination of the two directions) until it is positioned above the vessel and / or part thereof (e.g., a well on a multi-well plate); either pausing the probe for a defined amount of time (during which the vessel may be raised such that any fluid in a part of the vessel such as a well therein contacts the probe) or lowering it until it contacts any fluid in the part of the vessel (e.g., a well); maintaining the probe in a position such that it contacts any fluid in the part of the vessel (e.g., a well) for a defined amount of time; and either pausing the probe for a defined amount of time (during which the vessel may be lowered such that any fluid in a part of the vessel such as a well no longer contacts the probe) or raising it until it is no longer in contact with any fluid in the part of the vessel (e.g., a well). The preset program may repeat some or all of the above sequential steps, with the probe sequentially contacting multiple fluids contained in multiple vessels and / or portions thereof (e.g., multiple wells on a multi-well plate). Further examples of steps that the preset program may include include pre-wetting (e.g., coating dissolution), start-up, calibration, referencing, and / or shutdown steps.

[0062] In some embodiments, the probe comprises a surface that is functionalized and / or has a surface chemistry that aids in performing the assay. The surface functionalization and / or chemistry can facilitate the formation of reaction products thereon that are typically generated during an assay. For example, the surface functionalization and / or chemistry can facilitate the binding of one or more chemical species generated during an assay thereto. In some embodiments, the probe comprises a surface on which one or more reagents are immobilized. The reagent(s) can be immobilized on the probe in a variety of suitable manners. By way of example, the reagent(s) can be bound to the probe. The binding can include covalent, ionic, polar, van der Waals, hydrophobic, and / or hydrogen bonds.

[0063] In some embodiments, one or more reagents may be immobilized on the probe in such a manner that they do not undergo significant (and / or any) removal from the probe during the performance of the assay. For example, the reagent(s) may be immobilized on the probe in such a manner that they are stable to water, aqueous solutions, buffers, acids, bases, and / or body fluids. However, it is also possible that one or more reagents are initially immobilized on the surface of the probe, which are then released from the surface of the probe during the performance of the assay. By way of example, the reagents initially immobilized on the surface of the probe may be configured to be released from the probe by exposure to a particular stimulus. The stimulus may be present in a fluid.

[0064] Additionally or alternatively, one or more reagent(s) can be immobilized on the probe in such a manner that the probe can be regenerated. It is also possible for the method to include regenerating the probe. Regeneration can include removing one or more reagent(s) from the probe. For example, in some embodiments, regeneration includes exposing the probe on which one or more reagent(s) are immobilized to a fluid (e.g., a buffer, such as an acidic buffer) that causes one or more of the reagent(s) to be removed from the probe. The probe can then be exposed to a fluid containing one or more new reagent(s) to be immobilized on the probe. Regenerating the probe can advantageously allow the probe to be used (e.g., as a non-consumable) during more than one assay. By way of example, a first reagent and / or set of reagents can be immobilized on the probe prior to performing a first assay. These reagents can be configured to undergo a chemical reaction with one or more chemical species potentially present in the assay. If this chemical reaction does occur, the probe may be unsuitable for performing another assay unless it is regenerated, because the chemical reaction may render the reagent(s) unsuitable for performing a further chemical reaction. Thus, after performing an assay, the probe may be regenerated to yield a probe onto which a new reagent and / or set of reagents may be immobilized, thus allowing the probe to be used in performing a further assay. The reagent and / or set of reagents may be the same reagent and / or set of reagents that was originally immobilized on the probe, or may differ in one or more respects (e.g., if an operator wishes to use the probe to perform a different assay).

[0065] It is also possible that some probes are not regenerated and / or cannot be regenerated. Such probes may be used as consumables.

[0066] A variety of suitable reagents can be immobilized on the surface of the probes described herein. Some reagents can be chemical species capable of undergoing one or more chemical reactions (e.g., one or more chemical reactions that can occur during an assay that the probe is used to facilitate). For example, a probe can include a reagent that can bind (e.g., covalently, ionically, by polar interactions, by van der Waals interactions, hydrophobically, by hydrogen bonding, by complexation) with another chemical species, absorb another chemical species, adsorb another chemical species, catalyze a reaction of another chemical species and / or between two or more chemical species, decompose (e.g., by exposure to another chemical species), undergo a conformational transition, and / or catalyze a reaction. In some embodiments, one or more of the chemical reactions described above can have a chemical species immobilized thereon with which the reagent reacts. Selected, non-limiting examples of suitable reagents include biomolecules (e.g., proteins, glycoproteins, peptides, nucleic acids (e.g., DNA), antibodies, antigens, polysaccharides, carbohydrates, hormones), ligands, small molecules, viruses, cells, inorganic compounds, sequestrant compounds, capsids, and bacteria.

[0067] In some embodiments, the reagent immobilized on the surface of the probe is suitable for performing a chemical and / or biological reaction involving binding. It is also possible that the probe is suitable for performing a chemical and / or biological reaction not involving binding. When present, binding may include a reaction between a target and a binding partner (e.g., an agent or molecule that specifically binds to the target) that specifically binds to the target. Binding may also include immobilizing the target on the binding partner. In some embodiments, the binding partner may specifically bind to an epitope on the target molecule. Non-limiting examples of specific pairs of binding partners and targets include antibodies and antigens, antibody fragments and antigens, antibodies and haptens, antibodies and peptides, antibodies and small molecules, antigens and fusion proteins, antibody fragments and haptens, enzymes and enzyme substrates, enzymes and inhibitors, enzymes and cofactors, binding proteins and substrates, carrier proteins and substrates, proteins and small molecules, lecithin and carbohydrates, receptors and hormones, receptors and effectors, complementary strands of nucleic acids, proteins in combination with nucleic acid repressors and inducers, ligands and cell surface receptors, viruses and ligands, and receptors and ligands.

[0068] Non-limiting examples of antibodies that may be binding partners or antibodies include intact (i.e., full-length) polyclonal and monoclonal antibodies, antigen-binding fragments of polyclonal and monoclonal antibodies (e.g., Fab, Fab', F(ab')2, or Fv), single chains (scFv), single chain variants, fusion proteins containing antibody portions, humanized antibodies, chimeric antibodies, diabodies, linear antibodies, single chain antibodies, multispecific antibodies (e.g., bispecific antibodies), and engineered configurations of immunoglobulin molecules that contain an antigen recognition site of the required specificity. Non-limiting examples of antibodies in the last category include glycosylation variants of antibodies, amino acid sequence variants of antibodies, and covalently modified antibodies. In addition, the binding partner may be an antibody of any class, such as IgD, IgE, IgG, IgA, or IgM (or subclasses thereof, such as IgG1, IgG2, IgG3, IgG4, IgA1, and / or IgA2.

[0069] An antigen can be a molecule or a portion of a molecule against which antibodies can be developed. Antigens can be peptides, polysaccharides, and / or lipids. Some antigens can originate from within the body ("self-antigens") and some antigens can originate from the external environment ("non-self-antigens").

[0070] In some embodiments, antibodies suitable for carrying out chemical and / or biological reactions specifically bind to epitopes on their target molecules. An epitope (which may also be referred to as an antigenic determinant) may be the portion of an antigen that is recognized (or bound) by an antibody. For example, an epitope may be the specific portion of an antigen to which an antibody binds. The portion of an antibody that binds to an epitope may be referred to as a paratope. An epitope may be a conformational epitope (composed of discontinuous amino acids or sections of an antigen) or a linear epitope (composed of consecutive amino acids). Some proteins may share segments of high sequence homology and / or structural similarity. These similar proteins may have common epitopes (in other words, epitopes on different antibodies may be bound by the same antibody). Furthermore, a differentially processed protein (e.g., a protein that has undergone further enzymatic processing) may share some, but not all, epitopes with its pre-processed form. Non-limiting examples of different epitopes that can be added or removed during processing include N-terminal signal peptides (e.g., as found on a pre-propeptide) and changes seen when an inactive protein (e.g., a propeptide) is converted to an active form by post-translational modification.

[0071] When an antibody specifically binds to an epitope, it can carry out a binding reaction that can distinguish between target and non-target molecules. For example, a binding partner can specifically bind to a target molecule with an affinity that is 2-fold or more greater than that of the non-target molecule, 4-fold or more, 5-fold or more, 6-fold or more, 7-fold or more, 8-fold or more, 9-fold or more, 10-fold or more, 20-fold or more, 25-fold or more, 50-fold or more, or 100-fold or more greater than that of the non-target molecule.

[0072] The binding affinity of an antibody is determined by its apparent association constant or K A It can be parameterized by K A is the dissociation constant (K D In some embodiments, the binding partners described herein have a reciprocal of 10 -5 M or above, 10 -6 M or above, 10 -7 M or above, 10 -8 M or above, 10 -9 M or more, or 10 -10 The dissociation constant (K D ) with increased binding affinity (K A ) is the reduced dissociation constant (K D ). Higher affinity binding of a binding partner (e.g., an antibody) to a first molecule relative to a second molecule corresponds to the K A (or a number K D ) higher than the K A (or a small number K D ). In such cases, the antibody has specificity for a first molecule (e.g., a protein or a mimic thereof in a first conformation) relative to a second molecule (e.g., the same protein or a mimic thereof in a second conformation, or a second protein). The difference in binding affinity (e.g., specificity) can be 1.5-fold or more, 2-fold or more, 3-fold or more, 4-fold or more, 5-fold or more, 10-fold or more, 15-fold or more, 20-fold or more, 37.5-fold or more, 50-fold or more, 70-fold or more, 80-fold or more, 90-fold or more, 100-fold or more, 500-fold or more, 1000-fold or more, 10,000-fold or more, 10 5 It could be more than double.

[0073] In some embodiments, the reagents can be immobilized on the surface of the probe via covalent bonds. Prior to such immobilization, the surface of the probe can be functionalized such that it contains multiple functional groups suitable for forming such covalent bonds. For example, the surface of the probe can be functionalized by reaction with a bifunctional reagent that contains a siloxane group that facilitates attachment to the probe and a functional group that facilitates the formation of a covalent bond with the reagent to be immobilized on the probe. As another example, the surface of the probe can be exposed to a plasma or other treatment that generates in situ functional groups that facilitate the formation of a covalent bond with the reagent to be immobilized on the probe. Non-limiting examples of suitable types of functional groups that facilitate the formation of a covalent bond with the reagent to be immobilized on the probe include hydroxyl, amine, and carboxyl.

[0074] The probes described herein can be formed from a variety of suitable materials. In some embodiments, the probes comprise glass and / or polymers. A non-limiting example of a suitable glass is SiO 2 and Ta 2 O 5 Non-limiting examples of suitable polymers include polystyrene and polyethylene.

[0075] As described above, in some embodiments, the device includes a support structure. The support structure may be configured to support one or more fluids and / or solids used in the assay and / or may be configured to support one or more fluid and / or solid containers used in the assay. By way of example, in some embodiments, the support structure is configured to support and / or receive a multi-well plate. As a further example, the support structure may be configured to support a microtiter plate, a glass slide, a droplet array, a vial, a microfluidic device, a microfluidic array, a microarray, and / or a digital microfluidic chip. In some embodiments, the fluid and / or solid containers are located on the support structure.

[0076] In some embodiments, the support structure is configured to be translated by the instrument of which it forms a part (e.g., vertically, in a first horizontal direction, in a second horizontal direction, in a combination of two or three of the aforementioned directions). In some embodiments, the instrument may be configured such that it translates the support structure by a preset program, in which the support structure is located in multiple locations over multiple times. The instrument may also be configured such that the operator may translate the support structure at will (e.g., the operator may input a desired location to which the probe is to be translated and / or may move the probe in real time by use of a controller). In addition, some instruments may be configured such that they are not configured to translate the support structure. In such embodiments, the support structure may be static or non-movable without manual movement by the operator.

[0077] As described above, in some embodiments, the instrument comprises a light detector. The light detector can be configured to detect light signals, and / or the method can include detecting light signals. The light signals can indicate the characteristics of the sample being assayed (e.g., the presence, concentration, or absence of one or more components therein), and can indicate the characteristics of the standard present in the assay (e.g., the presence, concentration, or absence of one or more components therein), a reference signal, a background signal, and / or a baseline signal.

[0078] The light signal may include light or the absence of light. As an example of the former, the presence, intensity, and / or polarization of light may convey information about the assay being performed. For example, some assays may result in the generation of light of a particular wavelength, within a particular wavelength range, of a particular combination of wavelengths, and / or with a particular polarization. The detection of such light may indicate that the assay was performed correctly, that the sample being assayed has a particular characteristic, and / or that the sample contains a particular component in a particular amount. The absence of such light may indicate that the assay was performed incorrectly, that the sample being assayed lacks a particular characteristic, and / or that the sample lacks a particular component.

[0079] The light present in the optical signal may include light emitted by fluorescence, luminescence (e.g., chemiluminescence), and / or scattering (e.g., Raman scattering). It is also possible for the light present in the optical signal to include reflected or transmitted light. In some embodiments, the light present in the optical signal includes polarized light.

[0080] The light signals can originate from various locations of the fluid or solid. For example, some light signals can originate from the surface (e.g., upper surface, lower surface, side surface) of the fluid or solid. As another example, some light signals can originate from the interior of the fluid or solid. In some embodiments, the light signals originate from the entirety of the fluid or solid.

[0081] In some embodiments, the absence of light can convey information about the assay being performed. The assay can result in the generation of chemical species that absorb light of a particular wavelength, within a particular wavelength range, and / or at a particular combination of wavelengths. The absence of such light can indicate that the assay was performed correctly, that the sample being assayed has a particular characteristic, and / or that the sample contains a particular component in a particular amount. The presence of such light can indicate that the assay was performed incorrectly, that the sample being assayed lacks a particular characteristic, and / or that the sample lacks a particular component.

[0082] The light that is missing and forms the light signal may include absorbed or reflected light, which may be perceived as a change in color of light impinging on the fluid of interest.

[0083] The light signal may include the presence or absence of light of various wavelengths and / or polarization. In some embodiments, the light may include visible light. The light may also include infrared light. In addition, the light may be polarized or unpolarized light.

[0084] Detecting the light signal may include detecting and / or determining various suitable characteristics thereof. In some embodiments, detecting the light signal includes detecting the presence or absence of light as described above. Detecting the light signal may also include detecting the intensity and / or polarization of light as described above. Such detection may be performed at one or more discrete time points or over a period of time. In addition, such detection may be performed in a manner that produces a single data point (e.g., an end point, an average intensity of light at a particular wavelength measured over a period of time, an average intensity of light at a particular wavelength calculated by averaging multiple measurements of light intensity, an intensity of light at a particular wavelength determined from a single measurement), multiple data points. Multiple data points may describe the variation of the light signal over time (e.g., in a kinetic measurement), the variation of the light signal as a function of position (e.g., between multiple positions in a single fluid such as a single sample or a single standard), and / or the variation of the light signal as a function of wavelength.

[0085] In some embodiments, the method includes detecting two or more light signals. These light signals may include light signals of the same type (e.g., they may include the same type of light detected in the same manner) and / or may include light signals that differ in one or more respects. The two or more light signals may originate from a single fluid or solid, may originate from more than one fluid or solid, and / or may include light signals that do not originate from any fluid or solid (e.g., light signals that are reference signals, background signals, and / or baseline signals). In some embodiments, the two or more light signals are associated with the same sample and / or associated with assays performed on the same sample (although in some embodiments, are associated with and / or originate from different probes and / or fluids and / or solids).

[0086] When present, the two or more optical signals may include at least two optical signals (of the same type and / or different types) detected by optical detectors located at different locations and / or optically coupled to different locations (e.g., proximal to different locations on a vessel supported by a support structure, such as different wells on a multi-well plate; proximal to different vessels). It is also possible that the two or more optical signals include at least two optical signals (of the same type and / or different types) detected by a single optical detector. Similarly, the two or more optical signals may include at least two optical signals (of the same type and / or different types) detected at different times (e.g., at separate times during an assay, over the course of a reaction occurring in the vessel) and / or at least two optical signals detected at a single time point.

[0087] When the method includes detecting two or more different types of light signals, the light signals can differ in various ways. Non-limiting examples of such differences include the manner in which the detected light is generated (e.g., one light signal can include light emitted by fluorescence and another can include light emitted by luminescence), the wavelength (or wavelength range) of the detected light (e.g., one light signal can include light emitted at a first wavelength and another can include light emitted at a second wavelength), and the wavelength (or wavelength range) or light that is absorbed (e.g., one light signal can include light absorbed at a first wavelength and another can include light absorbed at a second wavelength). It is also possible for the method to include detecting light signals that include different types of light (e.g., one light signal that includes emitted light and another light signal that includes scattered light) and / or the method to include detecting both light signals that include light (e.g., that is emitted, transmitted, reflected, scattered, and / or polarized) and light signals that include the absence of light (e.g., that is absorbed or reflected). One further specific example of a method that includes detecting two light signals of different types is a method that includes detecting two light signals that include light having different wavelengths, and further includes determining the ratio of these two wavelengths to one another.

[0088] One example of a method that includes detecting two optical signals (of the same or different types) is a method that includes detecting both (1) a first optical signal indicative of a characteristic of a first sample and (2) a second optical signal. The second optical signal can be any suitable type of optical signal. For example, in some embodiments, the second optical signal is indicative of a second sample. The second optical signal can also be indicative of a characteristic of a different type of fluid and / or solid, not originating from any fluid or solid (e.g., in the case of an optical signal that is a reference signal, background signal, and / or baseline signal), indicative of a different characteristic of the first sample, and / or indicative of the same characteristic of the first sample. As an example, in some embodiments, the second optical signal is indicative of a characteristic of a standard (e.g., it can be a reference signal originating from a reference standard). Such an optical signal can help calibrate an instrument and / or detect whether the instrument is functioning properly. It is also possible for the method to include comparing a signal indicative of a characteristic of the sample to a signal indicative of a characteristic of the standard. Such a comparison may be useful to subtract background noise and / or improve the reproducibility of measurements.

[0089] Other examples of methods that include detecting two light signals (of the same or different types) include methods in which no light signals arise from either sample. Such methods may be methods in which only a reference, background, and / or baseline light signal is detected. In such embodiments, the method may include calibrating the instrument, evaluating the functionality of the instrument, and / or generating a data set that can be used to normalize and / or calibrate data obtained from the sample.

[0090] As described above, in some embodiments, detecting the optical signal comprises detecting the location where the optical signal was generated, which may be accomplished by detecting the location of the probe that transmits the optical signal to the detector and / or by detecting the location of the detector that detects the optical signal.

[0091] A variety of suitable photodetectors can be used in the instruments described herein, including, but not limited to, suitable types of detectors, including photon counting devices, spectrophotometers, Raman spectrometers, infrared spectrometers, polarization detectors, photodiodes, CCD / CMOS sensors, and imaging sensors.

[0092] As described above, in some embodiments, the device includes a light source. The light source can serve as a source of light to stimulate the emission of a light signal.

[0093] In some embodiments, the light source provides light of multiple wavelengths. For example, the instrument may include a light source that includes an incandescent bulb. As a further example, the instrument may include a light source that includes a xenon lamp, a mercury lamp, and / or an arc lamp. When the instrument includes a light source and provides light of multiple wavelengths, the instrument may further include one or more optical filters and / or monochromators. Such optical filter(s) and / or monochromator(s) may be located between the light source and the location of the chemical species that generates the light signal, between the light source and the detector, between the detector and the location of the chemical species that generates the light signal, between the photodetector and the probe, between the light source and the probe, and / or between the photodetector and the optical cable. The former can be beneficial when the light emitted by the light source includes at least one wavelength that will overlap with the wavelength of the optical signal and / or when the light emitted by the light source includes at least one wavelength that will stimulate the generation of an optical signal, independently of whether the assay will produce a positive or negative result (e.g., in cases where light of that wavelength will always stimulate emission from various chemical species, including species that will be immobilized on the probe and / or present in the fluid in contact with the probe).

[0094] In some embodiments, the instrument includes a light source that emits light in a relatively narrow band of wavelengths. For example, the instrument may include a laser light source and / or an LED light source.

[0095] The light source described herein may also provide light of a single polarization and / or of multiple polarizations. When the light source provides light of multiple polarizations, the instrument may further include one or more polarizing filters. Such polarizing filter(s) may be located between the light source and the location of the species generating the light signal, between the light source and the detector, and / or between the photodetector and the optical cable. The former may be beneficial when the light emitted by the light source includes light of a polarization that will overlap with the wavelength of the light signal, and / or when the light emitted by the light source includes at least one polarization that will stimulate the generation of a light signal, independent of whether the assay will produce a positive or negative result (e.g., in cases where light of the relevant polarization will always stimulate emission from various chemical species, including chemical species that will be immobilized on the probe and / or present in the fluid in contact with the probe). The former may also be beneficial when the light signal includes light polarized by chemical species immobilized on the probe and / or chemical species generated from the chemical species immobilized on the probe.

[0096] As described elsewhere in this application, some instruments may be suitable for performing an assay, and some methods may include performing an assay (e.g., by using an instrument described herein). In some embodiments, a method of performing an assay includes providing a probe on which a reagent is immobilized and through which light is transmitted one or more gaps, providing one or more fluid containers, and detecting a light signal. The light signal may include light emitted, polarized, and / or scattered from a chemical species immobilized on the probe, light emitted, polarized, and / or scattered from a chemical species generated from a chemical species immobilized on the probe, a lack of light due to absorption of light by a chemical species immobilized on the probe, and / or a lack of light due to absorption of light by a chemical species generated from a chemical species immobilized on the probe. This method is illustrated in the flow chart of FIG. 7. In FIG. 7, the method 1012 includes steps 1112 of providing a probe, 1212 of providing one or more fluid containers, and 1312 of detecting a light signal. In some embodiments, performing an assay involves performing more steps than those shown in Figure 7, and in some embodiments, an assay may be performed that lacks one or more of the steps shown in Figure 7. Non-limiting examples of additional steps that may be performed are described in more detail below.

[0097] In some embodiments, the assay involves contacting a probe with one or more fluids (and, in some embodiments, subsequently removing the probe from contact therewith). The probe may be removed from contact with each fluid from the plurality of fluids with which it is in contact before contacting the next fluid from the plurality of fluids. In some embodiments, removing the probe from contact with the fluid stops a reaction from occurring (e.g., a reaction between a species immobilized on the probe and a species in the fluid from which the probe is removed). Stopping the reaction by removing the probe from contact with the fluid may be performed in response to an optical signal (e.g., an optical signal indicative of the fluid and / or sample with which the probe was in contact prior to contacting the fluid). It is also possible for the reaction to be stopped by removing the probe from contact with the fluid after a preset interval has passed and / or by manual action of an operator.

[0098] In some embodiments, performing an assay comprises sequentially contacting a probe with a plurality of fluids and detecting an optical signal. The sequential contact can be accomplished by translating the probe and / or the support structure. During the assay, an optical signal can be associated with a chemical species immobilized on the probe. As described elsewhere in this application, the optical signal can include light emitted, transmitted, reflected, scattered, polarized, and / or absorbed by a chemical species immobilized on the probe, and / or light emitted, transmitted, reflected, scattered, polarized, and / or absorbed by a chemical species originating from a chemical species immobilized on the probe. In some embodiments, the optical signal is detected while the probe is in contact with a fluid from a plurality of fluids. It is also possible that the optical signal is generated by the first contact between the probe and a fluid from a plurality of fluids.

[0099] Also, as described elsewhere in this application, some methods may include using two probes to perform a common assay and / or two probes to perform two separate assays (which may be of the same type and / or performed on the same sample). In such embodiments, the second probe may also be contacted sequentially with the second plurality of fluids, and a second optical signal (including, for example, emitted, transmitted, reflected, polarized, and / or scattered light, and / or the absence of absorbed and / or reflected light) may be detected. The probe may be removed from contact with each fluid from the second plurality of fluids with which it is in contact before contacting the next fluid from the second plurality of fluids. In some embodiments, the second optical signal is detected while the probe is in contact with a fluid from the second plurality of fluids. The second probe may be used to perform a second assay on the same sample on which the first probe performs an assay, may be used to perform the same assay on the same sample on which the first probe performs an assay, and / or may be used to perform an assay on a different sample (e.g., the same assay performed by the first probe, a different assay).

[0100] Some assays involve detecting one or more qualitative characteristics of a sample (e.g., the presence or absence of a species of interest, such as a protein). Some assays involve detecting one or more quantitative characteristics of a sample (e.g., the amount of a species of interest present in a sample, e.g., the amount of protein present in a sample). In some embodiments, the assay involves performing a kinetic measurement (e.g., the rate of binding of a species in a fluid, such as a sample, to a reagent immobilized on a probe) and / or a pulse measurement. In some embodiments, the assay involves performing a pulse measurement, such as a flash luminescence reaction and / or a measurement performed during a flash reaction. Some suitable flash luminescence reactions and flash reactions involve contacting a probe with a species immobilized thereon that is a catalyst for the reaction and then measuring a light signal associated with the species generated by the reaction.

[0101] A variety of suitable assays can be performed. Non-limiting examples of these include ELISA assays (e.g., direct ELISA assays, indirect ELISA assays, sandwich ELISA assays), whole cell assays, and biomolecular interaction assays. Some assays can include detecting cell surface proteins, empty capsids, and / or capsids containing nucleic acid.

[0102] In some embodiments, the assay is performed on a sample. In such embodiments, at least one of the plurality of fluids used during the assay may comprise a fluid that is a sample. The sample may be one of the plurality of fluids that the probe is contacted with and / or may be present (e.g., suspended, dissolved) in one of the plurality of fluids that the probe is contacted with. It is also possible for two or more (or each) of the plurality of fluids used in the assay to comprise a fluid that is a sample (e.g., in cases where performing the assay comprises using two or more probes, each for contacting its own plurality of samples). In some embodiments, performing the assay comprises contacting at least one probe with at least one of the plurality of fluids that is devoid of any fluid that is a sample.

[0103] Some samples may include bodily fluids and / or biological materials. By way of example, in some embodiments, the sample includes cells (e.g., living cells) and / or reagents (e.g., biomolecules). The sample may include some or all of the reagents described elsewhere in this application for reagents that may be immobilized on the surface of the probe, and / or may include reagents other than those so described. Non-limiting examples of some reagents that may be included in a sample suitable for analysis by the assay include proteins, glycoproteins, peptides, ligands, antibodies, antigens, hormones, nucleic acids (e.g., DNA), polysaccharides, carbohydrates, small molecules, inorganic compounds, sequestrant compounds, viruses, capsids, cells, and bacteria.

[0104] In some embodiments, the sample includes a component that is immobilized on the probe during the performance of the assay and / or is configured to be immobilized on the probe during the performance of the assay. For example, in some embodiments, the sample includes a component that is bound to the probe and / or is configured to be bound to the probe. The performance of the assay can also determine whether the sample includes such a component. For example, in some embodiments, the sample may include an antigen for which an antibody is immobilized on the probe. The performance of the assay can identify whether the sample does in fact include an antigen and / or the concentration of such an antigen in the sample. As a further example, as described above, a reagent suitable for performing a chemical and / or biological reaction involving binding may be immobilized on the surface of the probe, and the sample may include a binding partner and / or target for the reagent. For example, an antigen may be immobilized on the surface of the probe, and the sample may include an antibody for the antigen (e.g., an enzyme-linked antibody for the antigen).

[0105] It is also possible that the assay is performed against a standard. For example, in some embodiments, the assay is performed against a positive standard and / or a negative standard. The positive standard may be configured to always produce a light signal when the assay is performed correctly and / or to always produce a light signal of known intensity and / or polarization. Some positive standards include a known concentration of a reagent to be detected by the assay. The negative standard may be configured to always not produce a light signal when the assay is performed correctly. Some positive standards lack a reagent to be detected by the assay. Performing an assay against a positive standard and / or a negative standard may be useful to calibrate the results obtained from an assay performed on a sample and / or to confirm that an instrument is working properly. Some embodiments may include contacting a first probe with a plurality of fluids including a sample (and optionally lacking a standard) and a second probe with a plurality of fluids including a standard (and optionally lacking a sample). It is also possible for embodiments to include contacting two or more standards (e.g., with two or more probes in a manner such that each probe is contacted with a single standard), such as both positive and negative standards and / or two or more positive standards that contain different concentrations of reagents to be detected by the assay.

[0106] Fluids other than samples and standards that may be present during the performance of an assay include fluids that contain chemical species that aid in the performance of the assay. As an example, there may be fluids that contain one or more reagents (e.g., one or more reagents of the type described elsewhere in this application for the type of reagents that may be immobilized on the probe). Such fluids may be provided separately from any samples and / or standards (e.g., in separate wells on a multi-well plate). In addition, such fluids may contain reagents configured to be immobilized on the chemical species immobilized on the probe. As an example, such fluids may contain reagents configured to be immobilized on the chemical species immobilized on the probe initially. The reagents present in the fluid may be reagents configured to undergo a reaction with a chemical species that may be present in the sample. The reaction may include immobilizing the reagents present in the sample thereon (i.e., on the chemical species that are initially present in the fluid). As another example, the fluid may contain reagents configured to be immobilized on the reagents initially present in the sample. Such reagents may be immobilized on the probe via the reagents initially present in the sample. Such reagents may be configured to generate an optical signal and / or to react with additional reagents to generate an optical signal.

[0107] Non-limiting examples of reagents that may be present in the fluids described herein and / or configured to be immobilized on the chemical species immobilized on the probe include ligands (e.g., ligands for analytes present in the sample), binding partners and / or targets for analytes present in the sample, antibodies (e.g., antibodies for antigens present in the sample, enzyme-linked antibodies, enzyme-linked primary antibodies, enzyme-linked secondary antibodies, enzyme-linked antibodies for antigens present in the sample, antibodies comprising fluorophores), proteins, glycoproteins, peptides, nucleic acids, antigens, polysaccharides, carbohydrates, hormones, small molecules, viruses, cells, inorganic compounds, sequestrant compounds, capsids, and bacteria. In some embodiments, the reagents include and / or are bound to enzymes. Non-limiting examples of suitable enzymes include horseradish peroxidase and alkaline phosphatase.

[0108] In some embodiments, a fluid containing one or more reagents configured to generate an optical signal is present during the performance of the assay. Such a fluid may be provided separately from any sample, standard, and / or fluid containing chemical species that aid in the performance of the assay (e.g., in separate wells on a multi-well plate), one or more reagents, and / or fluid containing chemical species that aid in the performance of the assay. One example of such a fluid is a fluid containing a reagent configured to react with a reagent immobilized on a probe (e.g., a reagent initially present in the sample, a reagent immobilized on a reagent initially present in the sample). A reagent configured to react with a reagent immobilized on a probe may generate an optical signal by undergoing such a reaction. For example, the fluid may contain a reagent configured to undergo a reaction with a chemical species immobilized on a probe that absorbs light, transmits light, reflects light, fluoresces light, undergoes scattering (e.g., Raman scattering), is polarized, and / or undergoes luminescence (e.g., chemiluminescence). In some embodiments, the optical signal is detected while the probe is in contact with a fluid containing one or more reagents configured to generate an optical signal and / or upon initial contact with such a fluid.

[0109] Non-limiting examples of reagents that can be configured to generate a light signal include an enzyme substrate (e.g., for an enzyme-linked antibody). Some methods involve reacting an enzyme substrate with an enzyme (e.g., an enzyme-linked antibody). Such a reaction can result in the generation of products of an enzymatic reaction, one or more of which can be capable of and / or configured to generate a light signal.

[0110] In some embodiments, one or more washing fluids are present during the performance of the assay. The washing fluids can be provided separately from any samples, standards, fluids containing chemical species that aid in the performance of the assay, and / or fluids containing reagents configured to generate an optical signal (e.g., in separate wells on a multi-well plate), one or more standards, one or more reagents, fluids containing chemical species that aid in the performance of the assay, and / or fluids containing reagents configured to generate an optical signal. The washing fluid can be a fluid configured to remove chemical species that are weakly attached to the probe. Removing such chemical species from the probe can improve the reproducibility of the assay by removing signals from chemical species that are not immobilized thereon. In addition, removing such chemical species from the probe can reduce cross-contamination between different fluids present in the assay. One example of a suitable washing fluid is a washing buffer (e.g., glycine buffer, phosphate buffer).

[0111] In some embodiments, the assay is performed by sequentially contacting a probe having a reagent immobilized thereon with the following fluids: a sample including a first reagent configured to be immobilized on the probe, a fluid including a second reagent configured to be immobilized on the first reagent, and a fluid including a third reagent configured to react with the second reagent to generate a chemical species that generates an optical signal. As another example, the assay may include sequentially contacting a probe having a reagent immobilized thereon with the following fluids: a sample including a first reagent configured to be immobilized on the probe, a fluid including a second reagent configured to be immobilized on the first reagent, a fluid including a third reagent configured to be immobilized on the second reagent, and a fluid including a fourth reagent configured to react with the third reagent to generate a chemical species that generates an optical signal. It is also possible to perform a process in which the standard is the first fluid contacted with the probe, but the other steps are the same as in one of the two preceding sentences. In addition, some methods may include contacting the probe with a wash fluid (e.g., a wash buffer) between two or more of the pairs of steps described above.

[0112] The fluids used in the assays described herein may be contained in a variety of suitable containers. In some embodiments, some or all of such fluids are contained in one or more multi-well plates. In such embodiments, the fluids may be contained in separate wells. The wells may be in a single common row, a common set of rows, a single common column, or a common set of columns. In embodiments in which two or more plurality of fluids are contacted by two or more probes, each plurality of fluids may be positioned as described above (e.g., each plurality of fluids may be positioned in a single common row, a common set of rows, a single common column, or a common set of columns). In some embodiments, the method includes contacting a first probe with a first plurality of fluids positioned in a single column or row, and contacting a second probe with a second plurality of fluids positioned in a different row or column. It is also possible that the method includes contacting a probe with a plurality of fluids positioned in two or more columns or in two or more rows. It is also possible that the fluids are contained in other types of articles described elsewhere in this application. During the performance of an assay, the probe may be translated between one or more vessels containing multiple fluids, and / or the support structure on which one or more such vessels or vessels are supported may be translated relative to the probe. For example, in the case of a multi-well plate, the probe may be translated between multiple wells on the multi-well plate, some or all of which may contain fluids used to perform the assay. As another example, the support structure on which the multi-well plate is supported may be translated such that multiple wells (some or all of which contain fluids suitable for performing the assay) are sequentially positioned proximal to the probe.

[0113] The performance of the assay may also include one or more steps and / or periods during which both the support structure and the probe are static, all the points of the device are static, two or more points of the device are static with respect to each other, and / or two or more points of the device (albeit non-static with respect to each other) do not experience significant net displacement from each other. By way of example, in some embodiments, the method includes one or more periods during which the probe is incubated with a fluid. The incubation can occur while both the probe and the fluid (and possibly the vessel containing the fluid and / or the support structure supporting such vessel) are static. The incubation can also occur while either the fluid (and possibly the vessel containing the fluid and / or the support structure supporting such vessel) and / or the probe are shaking. In some embodiments, both the fluid (and possibly the vessel containing the fluid and / or the support structure supporting such vessel) and the probe are shaking together. In some embodiments, the incubation includes agitating the fluid (e.g., the sample) and / or mixing the fluid. Agitation and / or mixing may be achieved by stirring the fluid (eg, by a probe).

[0114] It is also possible that incubation includes adjusting and / or maintaining the temperature of the fluid. For example, incubation can include heating the fluid and / or cooling the fluid.

[0115] In some embodiments, the optical signal may be generated and / or detected during one or more steps and / or periods in which both the support structure and the probe are static, all points of the instrument are static, two or more points of the instrument are static with respect to each other, and / or two or more points of the instrument (albeit non-static with respect to each other) experience little net displacement from each other. Detection may occur during incubation and / or in the absence of incubation.

[0116] Although several embodiments of the invention have been described and illustrated herein, those skilled in the art will readily envision various other means and / or structures for performing the functions and / or obtaining one or more of the results and / or advantages described herein. Each such variation and / or modification is deemed to be within the scope of the present invention. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary, and that the actual parameters, dimensions, materials, and / or configurations will depend on the specific application(s) to which the teachings of the present invention are put. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Thus, it should be understood that the foregoing embodiments are presented by way of example only, and that within the scope of the appended claims and their equivalents, the invention may be practiced otherwise than as specifically described and claimed. The present invention is directed to each individual feature, system, article, material, kit, and / or method described herein. In addition, any combination of two or more such features, systems, articles, materials, kits, and / or methods is encompassed within the scope of the present invention, if such features, systems, articles, materials, kits, and / or methods are not mutually inconsistent.

[0117] All definitions provided and used in this application should be understood to take precedence over dictionary definitions, definitions in documents incorporated by reference, and / or ordinary meanings of the terms defined.

[0118] In this application, the indefinite articles "a" and "an," as used in the specification and claims, unless clearly indicated to the contrary, should be understood to mean "at least one."

[0119] The phrase "and / or" as used herein in the specification and claims should be understood to mean "either or both" of the elements so conjoined, i.e., elements that are conjunctive in some cases and disjunctive in other cases. Multiple elements listed with "and / or" should be construed in the same manner, i.e., "one or more" of the elements so conjoined. Other elements may optionally be present other than the elements specifically identified by the "and / or" clause, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, "A and / or B," when used in conjunction with open-ended language such as "comprising," may refer to A only (optionally including elements other than B) in one embodiment, B only (optionally including elements other than A) in another embodiment, both A and B (optionally including other elements) in yet another embodiment, and so forth.

[0120] "Or" as used in the specification and claims in this application shall be understood to have the same meaning as "and / or" as defined above. For example, when separating listed items, "or" or "and / or" shall be construed as being inclusive, i.e., the inclusion of at least one of any element or list of elements, but also including more than one and optionally additional unlisted items. Only terms clearly indicated to the contrary, such as "only one of" or "exactly one of," or "consisting of" when used in the claims, shall refer to the inclusion of exactly one element of any element or list of elements. In general, the term "or" as used in this application, when preceded by a term of exclusivity, such as "either," "one of," "only one of," or "exactly one of," shall be construed as indicating only exclusive alternatives (i.e., "one or the other, but not both"). "Consisting essentially of," when used in the claims, shall have its ordinary meaning as used in the field of patent law.

[0121] The phrase "at least one," as used herein in the specification and claims with reference to a list of one or more elements, should be understood to mean at least one element selected from any one or more of the elements from the list of elements, but does not necessarily include at least one of every element specifically listed in the list of elements, and does not exclude any combination of elements from the list of elements. This definition also allows for the optional presence of elements other than the specifically identified elements from the list of elements to which the phrase "at least one" refers, whether related or unrelated to those specifically identified elements. Thus, as a non-limiting example, "at least one of A and B" (or, equivalently, "at least one of A or B," or, equivalently, "at least one of A and / or B") can refer in one embodiment to no B (and optionally including elements other than B), at least one A, optionally including more than one, in another embodiment to no A (and optionally including elements other than A), at least one B, optionally including more than one, in yet another embodiment to at least one A, optionally including more than one, and at least one B, optionally including more than one (and optionally including other elements), etc.

[0122] It should also be understood that, unless expressly indicated to the contrary, in any method claimed in the present application that includes more than one step or act, the order of the method steps or acts is not necessarily limited to the order in which the method steps or acts are described.

[0123] In the claims and the above specification, all transitional phrases such as "comprise," "include," "carry," "have," "contain," "involve," "have," "composed of," and the like, are to be understood to be open, i.e., to mean inclusive but not exclusive. Only the transitional phrases "consisting of" and "consisting essentially of" shall be closed or semi-closed transitional phrases, respectively, as defined in the United States Patent Office Manual of Patent Examining Procedures, Section 2111.03.

Claims

1. An apparatus for performing an assay, comprising: a probe; a support structure positioned proximal to the probe, the support structure having one or more fluid containers positioned thereon; a photodetector configured to detect an optical signal; wherein a reagent is immobilized on the probe; the probe is configured to be translated by the apparatus between a plurality of locations where a plurality of fluids are positioned; the optical signal comprises light emitted and / or transmitted from a species immobilized on the probe; light emitted, transmitted, reflected, and / or scattered from a species generated from a species immobilized on the probe; an absence of light due to absorption of light by a species immobilized on the probe, and / or an absence of light due to absorption of light by a species generated from a species immobilized on the probe; the apparatus.

2. An apparatus for performing an assay, comprising: a housing; an optical cable; a photodetector configured to detect an optical signal; wherein the housing includes a component configured to receive a probe; the probe transmits light through one or more gaps; the housing includes a support structure positioned proximal to the component configured to receive the probe; the support structure is configured to receive one or more fluid containers; the apparatus is configured to translate the probe between a plurality of locations proximal to a plurality of locations on the container; the optical cable transmits light to the photodetector; the optical signal comprises light emitted and / or transmitted from a species immobilized on the probe; light emitted, transmitted, reflected, and / or scattered from a species generated from a species immobilized on the probe; an absence of light due to absorption of light by a species immobilized on the probe, and / or an absence of light due to absorption of light by a species generated from a species immobilized on the probe; the apparatus.

3. An apparatus for performing an assay, comprising: a probe; a support structure positioned proximal to the probe, the support structure having one or more fluid containers positioned thereon; a photodetector configured to detect an optical signal; wherein a reagent is immobilized on the probe; The support structure is configured to be translated by the device such that a plurality of portions of the support structure are successively positioned proximal to the probe. The optical signal is light emitted and / or transmitted from a chemical species immobilized on the probe, light emitted, transmitted, reflected, and / or scattered from a chemical species generated from a chemical species immobilized on the probe, a lack of light caused by absorption of light by a chemical species immobilized on the probe, and / or a lack of light caused by absorption of light by a chemical species generated from a chemical species immobilized on the probe, The device includes.

4. A method of performing an assay, comprising: successively contacting the probe with a plurality of fluids by translating the probe between a plurality of wells containing the plurality of fluids; detecting an optical signal; and a reagent is immobilized on the probe, The optical signal is: light emitted and / or transmitted from a chemical species immobilized on the probe, light emitted, transmitted, reflected, and / or scattered from a chemical species generated from a chemical species immobilized on the probe, a lack of light caused by absorption of light by a chemical species immobilized on the probe, and / or a lack of light caused by absorption of light by a chemical species generated from a chemical species immobilized on the probe, The method includes.

5. A device for performing an assay, comprising: a photodetector configured to detect an optical signal; a probe configured to transmit light from a light source to a fluid positioned proximal to the probe, the probe being configured to transmit light from an optical cable to a fluid positioned proximal to the probe, the probe being configured to transmit light from a fluid positioned proximal to the probe to the photodetector, and / or the probe being configured to transmit light from a fluid positioned proximal to the probe to the optical cable; and a support structure positioned proximal to the probe; and a reagent is immobilized on the probe, the probe is configured to be horizontally translated by the device between a plurality of locations where the plurality of fluids are positioned, The optical signal is light emitted and / or polarized from a chemical species immobilized on the probe Light emitted, polarized, and / or scattered from chemical species generated from chemical species immobilized on the probe Absence of light caused by absorption of light by chemical species immobilized on the probe, and / or Absence of light caused by absorption of light by chemical species generated from chemical species immobilized on the probe The device comprising the above **Claim 6** A device for performing an assay, comprising A photodetector configured to detect an optical signal, A housing, A probe configured to transmit light from a light source to a fluid positioned proximal to the probe, the probe configured to transmit light from an optical cable to a fluid positioned proximal to the probe, the probe configured to transmit light from a fluid positioned proximal to the probe to the photodetector, and / or the probe configured to transmit light from a fluid positioned proximal to the probe to the optical cable, said probe Including The housing includes a component configured to receive the probe, A reagent is immobilized on the probe, The housing includes a support structure positioned proximal to the component configured to receive the probe, The support structure is configured to receive one or more fluid containers, The device is configured to translate the probe horizontally between a plurality of locations proximal to a plurality of locations on the container, The optical signal is Light emitted and / or polarized from chemical species immobilized on the probe, Light emitted, polarized, and / or scattered from chemical species generated from chemical species immobilized on the probe, Absence of light caused by absorption of light by chemical species immobilized on the probe, and / or Absence of light caused by absorption of light by chemical species generated from chemical species immobilized on the probe The device comprising the above **Claim 7** A device for performing an assay, comprising A photodetector configured to detect an optical signal, A probe, the probe being configured to transmit light from a light source to a fluid positioned proximally to the probe, the probe being configured to transmit light from an optical cable to a fluid positioned proximally to the probe, the probe being configured to transmit light from a fluid positioned proximally to the probe to a photodetector, and / or the probe being configured to transmit light from a fluid positioned proximally to the probe to an optical cable, and a support structure positioned proximally to the probe, comprising, a reagent being immobilized on the probe, one or more fluid containers being positioned on the support structure, the support structure being configured to be translated horizontally by the apparatus such that a plurality of portions of the support structure are sequentially positioned proximally to the probe, the optical signal being: light emitted and / or polarized from a species immobilized on the probe, light emitted, polarized, and / or scattered from a species generated from a species immobilized on the probe, an absence of light caused by absorption of light by a species immobilized on the probe, and / or an absence of light caused by absorption of light by a species generated from a species immobilized on the probe, the apparatus comprising.

8. An apparatus for performing an assay, a photodetector configured to detect an optical signal, a housing, a probe, the probe being configured to transmit light from a light source to a fluid positioned proximally to the probe, the probe being configured to transmit light from an optical cable to a fluid positioned proximally to the probe, the probe being configured to transmit light from a fluid positioned proximally to the probe to a photodetector, and / or the probe being configured to transmit light from a fluid positioned proximally to the probe to an optical cable, the probe, comprising, a reagent being immobilized on the probe, the housing including a component configured to receive the probe, the housing including a support structure positioned proximally to the component configured to receive the probe, one or more fluid containers being positioned on the support structure, the support structure being configured to receive the container, The support structure is translatable by the device such that when the probe is positioned on the component, a plurality of locations on the container are sequentially positioned proximal to the probe. The optical signal is light emitted and / or polarized from a chemical species immobilized on the probe, is light emitted, transmitted, reflected, and / or scattered from a chemical species generated from a chemical species immobilized on the probe, is the absence of light caused by absorption of light by a chemical species immobilized on the probe, and / or is the absence of light caused by absorption of light by a chemical species generated from a chemical species immobilized on the probe, wherein the device includes the above.

9. A method for performing an assay, comprising: providing a probe; providing one or more fluid containers, wherein the containers are positioned on a support structure; detecting an optical signal; wherein a reagent is immobilized on the probe, light is transmitted through one or more gaps on the probe, wherein the optical signal is light emitted and / or polarized from a chemical species immobilized on the probe, is light emitted, polarized, and / or scattered from a chemical species generated from a chemical species immobilized on the probe, is the absence of light caused by absorption of light by a chemical species immobilized on the probe, and / or is the absence of light caused by absorption of light by a chemical species generated from a chemical species immobilized on the probe, wherein the method includes the above.

10. The device according to claim 1, wherein the probe transmits light through one or more gaps, the device includes an optical cable, and the one or more gaps are positioned on the side of the probe opposite to the optical cable.

11. The device according to claim 1, wherein the container of one or more fluids includes a multi-well plate.

12. The device according to claim 1, wherein the device further includes a second probe, and the second probe is configured to be translated independently of the probe.

13. The device according to claim 1, wherein the device further includes a second photodetector.

14. The method according to claim 9, further comprising sequentially contacting the probe with a second plurality of fluids.

15. The method includes exposing the probe to a first fluid, thereby removing the reagent from the probe. ​ Thereafter, exposing the probe to a second fluid containing a new reagent, thereby immobilizing the new reagent on the probe; The method according to claim 9, comprising:

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