Biological analysis devices and systems

Abstract

A biological analysis system can include an excitation module and an emission module. The excitation module can include a collimator element to receive excitation light from the excitation light source and transmit collimated excitation light in a first direction, and a plurality of excitation mirrors arranged along an excitation light path, each excitation mirror disposed at an acute angle relative to the first direction and configured to reflect collimated excitation light in a second direction. The emission module can be positioned to receive excitation light transmitted in the second direction and can include a sample block containing a plurality of sample receptacles positioned to receive collimated excitation light beams, and a plurality of photodetectors configured to receive emission light transmitted from a respective sample receptacle in a direction transverse to the second direction of the excitation light path.

Description

TECHNICAL FIELD

[0001] The present invention relates to the analysis of biological samples. More specifically, the present application relates to apparatuses, systems, and methods for the simultaneous analysis of multiple biological samples. BACKGROUND

[0002] Fluorescence is light emitted by a compound in response to its excitation by higher energy electromagnetic radiation, typically in the visible range. When the excited compound returns to its normal or baseline excited state, the excess energy is typically released in the form of light at a smaller wavelength than the wavelength energy used for excitation. In application, the emitted light signal produced during fluorescence can inform on the identity and / or concentration of certain compounds within a sample. A fluorometer is an example of an analytical instrument that uses excitation and emission spectra and intensities to analyze biological samples. Using a fluorometer, the presence and concentration of compounds such as nucleic acids and some proteins can be determined, either directly or as part of an analytical workflow for DNA, RNA, and proteins. Example applications include cloning, sequencing, transfection, qPCR, and protein assays.

[0003] In a traditional fluorometer, ultraviolet excitation light is produced by an excitation light source (e.g., a xenon or mercury lamp), which can provide a strong and sustained source of radiation, allowing for saturation of the excitable compounds. The excitation light can be collimated to improve excitation efficiency and then directed toward the biological sample of interest. The fluorescent sample or fluorescent reagent bound to a non-fluorescent sample is activated by exposure to the excitation light, causing the sample to fluoresce. This fluorescent emission light is received at a photodetector, and these measurements of the amount, intensity, and / or distribution of light can be used to identify and / or estimate the concentration of analytes within the sample.

[0004] Some fluorometers are configured to analyze a single sample at a time. The process of loading, taking measurements, and reloading samples is a time-consuming task for users who need to analyze and collect data about many samples. In such cases, the user trades the portability and lower cost of a single-sample device for extremely low throughput. However, additional benefits can be seen by performing single-sample analysis, including facilitating a reduction in excitation light contamination and noise and easier analysis of the emission light. These advantages are realized due to the single nature of the optical system component configuration. With only one sample being analyzed, only one set of optical components is needed to effectively excite and then capture and analyze the emission spectrum from the sample. Stray reflections of the excitation light and subsequent detection mixed with the desired emission light can be minimized.

[0005] Conversely, for multi-sample devices, stray excitation becomes more difficult to mitigate as the number of samples increases. This is because the configuration of the optical system becomes more complex with the number of samples, increasing the chance of sample optical path interference and cross-contamination between emitted and excitation light. This cross-contamination can reduce the effectiveness of activating fluorescent reagents and distort the amount of light received by the photodetector, thereby shifting the corresponding measured concentration of the analyte included in each sample.

[0006] Implementing multi-sample devices presents inherent challenges. The most common commercial multi-sample format is the multiwell plate. Commercially available well plates typically have standard geometries and dimensions, allowing them to be used across platforms (e.g., standard plate readers and centrifuges) without requiring custom machines or adapters to facilitate use. Incidentally, the (essentially) predefined volume of a standard well plate affects the volume of sample that can be processed in each well. Traditionally, the internal volume of the plate is divided into equally sized wells spaced equidistant from the nearest adjacent well; 6-well, 12-well, 24-well, 48-well, 96-well, 384-well, and 1536-well formats are common.

[0007] Because the entire volume of a plate is traditionally divided into the required number of wells, the working volume per well is inversely proportional to the total number of wells on the plate. For example, in a 6-well plate, the recommended working volume per well is 3 to 5 mL, while in a 24-well plate, the recommended working volume per well is even smaller—approximately 600 μL. Similarly, the recommended working volume for a 96-well plate is 200 μL / well, and for a 384-well plate and a 1536-well plate, it is 80 μL / well and 8 μL / well, respectively.

[0008] If users choose to forgo single-sample fluorescence assays and instead wish to perform multi-sample fluorescence assays, there is a lack of multi-sample systems or formats that utilize small sample volumes similar to standard single-sample fluorescence assay systems. Instead, users are forced to use multi-well plates (e.g., 96-well plates) with sufficiently small working volumes. While multi-well plates enable automated, continuous analysis of tens to hundreds of samples, most users only use a fraction of the available sampling wells for analysis, resulting in excessive throughput. In cases requiring sterile equipment, generally accepted aseptic techniques necessitate discarding a portion of the used plate after assay, and the majority of unused wells on the discarded plates contribute to increased operating costs.

[0009] Furthermore, while commercially available fluorometers can be used to analyze multi-well plates (fluorometers configured to accept and process these types of multi-sample plates), these systems are generally bulkier and more expensive than single-sample fluorometers. Single-sample fluorometers are also typically much smaller than their multi-well plate read counterparts, which can be several cubic feet in volume. Space constraints are a significant factor in most laboratories where bench space is often limited. Therefore, smaller multi-sample fluorometers are needed that can analyze multiple small-volume samples without the need for dedicated disposable supplies (tubes, plates, etc.).

[0010] Therefore, there are many problems and drawbacks in the field of analyzing biological samples using optical systems. Consequently, there is a need for bioanalytical devices, such as fluorometers, that can address at least some of these problems. Summary of the Invention

[0011] The various embodiments disclosed herein relate to apparatuses, methods, and systems for use in optical systems configured for bioanalysis. Such embodiments advantageously improve optical systems, particularly those used in fluorescence assay devices, by enabling efficient multi-sample analysis.

[0012] A first aspect provides a bioanalytical system comprising (i) an excitation module and (ii) an emission module. The excitation module includes: a collimator element configured to receive excitation light from at least one excitation source and to transmit collimated excitation light along an excitation optical path in a first direction; and a plurality of excitation mirrors arranged along the excitation optical path, wherein each excitation mirror is positioned at an acute angle relative to the first direction and configured to reflect a corresponding collimated excitation beam along a second direction of the excitation optical path. The emission module is positioned to receive the excitation light transmitted along the second direction of the excitation optical path, and the emission module includes a sample block and a plurality of photodetectors. The sample block includes a plurality of sample assemblies, each sample assembly positioned to receive a corresponding collimated excitation beam transmitted along the second direction of the excitation optical path, and each photodetector is configured to receive emitted light transmitted upwards in a third direction from a corresponding sample assembly. In one aspect, the third direction is transverse to the second direction of the excitation optical path.

[0013] In one aspect, the excitation module additionally includes a plurality of excitation lenses arranged such that each excitation lens is positioned in a second direction of the excitation optical path and configured to focus a corresponding reflected collimated beam into a corresponding focused excitation beam for reception at a corresponding sample container of the emission module. In one aspect, each photodetector is oriented toward the corresponding sample container in a third direction. In one aspect, the third direction is generally orthogonal to the second direction of the excitation optical path.

[0014] In one aspect, the emitting module additionally includes a plurality of emitting lenses configured to focus emitted light transmitted upwards onto a plurality of photodetectors. In another aspect, the emitting module additionally includes a plurality of emitting filters corresponding to the plurality of emitting lenses, the plurality of emitting filters being positioned downstream of the respective plurality of emitting lenses and configured to allow emitted light to pass through the emitting filters and substantially block stray excitation light. In one aspect, the plurality of emitting filters comprises dual bandpass filters. In one aspect, each emitting lens comprises a curved lens.

[0015] In one aspect, the emission module also includes multiple emission windows, each associated with a corresponding sample container, and defines the area in which the emitted light is transmitted upwards to downstream components.

[0016] In one respect, at least one of the multiple excitation mirrors is independently adjustable.

[0017] In one aspect, a plurality of excitation mirrors are arranged in an alternating diagonal pattern, the alternating diagonal pattern being formed by the vertical and horizontal offset of the first center point of the first excitation lens and the second center point of the second excitation lens, and the acute angle of each excitation mirror in the alternating diagonal pattern being between 50° and 75° relative to the first direction.

[0018] Embodiments of this disclosure additionally include a bioanalytical system having (i) an excitation module and (ii) an emission module. The excitation module includes: an excitation source configured to emit excitation light in a first direction; an excitation mirror selectively movable between a plurality of predefined positions, each predefined position forming an acute angle with respect to the first direction and configured to reflect the excitation light along a second direction; and a plurality of excitation lenses arranged such that each excitation lens is positioned in the second direction and configured to receive the reflected excitation beam guided thereon by the excitation mirror positioned at the respective predefined position. The emission module includes: a plurality of sample assemblies positioned to receive focused reflected excitation beams from corresponding plurality of excitation lenses; and at least one photodetector configured to receive emitted light transmitted in a third direction from the plurality of sample assemblies. In one aspect, the third direction is transverse to the second direction.

[0019] In one aspect, the emitting module additionally includes a plurality of emitting lenses and a plurality of emitting filters configured to focus and filter the emitted light onto at least one photodetector. In another aspect, the at least one photodetector includes a plurality of photodetectors, each photodetector configured to receive emitted light from a corresponding sample container, the emitted light having been focused and filtered by the corresponding emitting lens and corresponding emitting filter before being received at each photodetector.

[0020] In one aspect, the system additionally includes a sample loading system configured to removably secure one or more sample containers within corresponding sample containers of a plurality of sample seats. In another aspect, the sample loading system includes a closing mechanism configured to apply a closing force to one or more sample containers within the corresponding sample seats and position them securely.

[0021] In one respect, the emitted light comprises fluorescent radiation from one or more stimulated fluorescent labels.

[0022] In one aspect, the system additionally includes a plurality of emission apertures, wherein each emission aperture is associated with a corresponding emission lens among a plurality of emission lenses, and wherein each emission aperture is aligned upwards in a third direction and defines an area through which emitted light is received from the sample container by the corresponding emission lens. In another aspect, the center point of the emission aperture is aligned with the optical center of the corresponding emission lens.

[0023] Embodiments of this disclosure additionally include a bioanalytical system having (i) at least two excitation sources emitting different excitation wavelengths; (ii) a collimator element configured to receive excitation light from the at least two excitation sources and transmit collimated excitation light along an excitation optical path in a first direction; (iii) a plurality of excitation mirrors arranged in an alternating diagonal pattern along the excitation optical path, wherein each excitation mirror is positioned at an acute angle relative to the first direction and configured to reflect a corresponding collimated excitation beam along a second direction of the excitation optical path; and (iv) a plurality of excitation lenses positioned in the second direction of the excitation optical path and configured to reflect the corresponding collimated beams. (v) a sample block forming a plurality of sample pods, wherein the plurality of sample pods are positioned to receive the corresponding focused excitation beam; and (vi) for each corresponding sample pod, the bioanalytical system includes at least the following components aligned in a third direction upward, the third direction being transverse to the second direction in one aspect: (a) an emission window defining the area through which the emitted light travels in the third direction upward, (b) a curved lens configured to focus the emitted light through the emission window, (c) a dual bandpass filter for substantially blocking stray excitation light, and (d) a photodetector configured to receive the focused filtered emitted light.

[0024] The purpose of this summary is to introduce, in a simplified form, the selection of concepts further described below in the detailed description. This summary is not intended to identify key or essential features of the claimed subject matter, nor is it intended to be used as an indication of the scope of the claimed subject matter.

[0025] Additional features and advantages of this disclosure will be set forth in the description which follows, and will be apparent in part from the description, or may be learned by practice of this disclosure. The features and advantages of this disclosure may be realized and obtained by means of the instruments and combinations particularly pointed out in the appended claims. These and other features of this disclosure will become more fully apparent from the following description and the appended claims, or may be learned by practice of this disclosure as set forth below. Attached Figure Description

[0026] Embodiments of the invention will be better understood and readily grasped by those skilled in the art through the following written description, which is by way of example only and in conjunction with the accompanying drawings, in which:

[0027] Figure 1 A schematic diagram of a bioanalytical apparatus according to an example embodiment is shown.

[0028] Figure 2 An example embodiment is shown. Figure 1 A schematic diagram of the excitation module of the bioanalytical device.

[0029] Figure 3 An example embodiment is shown. Figure 1 A schematic diagram of the excitation module of the bioanalytical device.

[0030] Figure 4A and Figure 4B A schematic diagram of a hypothetical optical device for comparison with an example embodiment is shown.

[0031] Figure 5 A schematic diagram of an excitation lens according to an example embodiment is shown.

[0032] Figure 6 The drawing is shown Figure 5 Operation of the excitation lens Figure 1 A partial cross-sectional view of the device.

[0033] Figure 7 A schematic diagram of a transmitting module according to an example embodiment is shown. Figure 1 A partial cross-sectional view of the device.

[0034] Figure 8 A schematic diagram of a sample loading system according to an example embodiment is shown. Figure 1 A partial cross-sectional view of the device.

[0035] Figure 9 A schematic diagram of a bioanalytical apparatus according to another example embodiment is shown.

[0036] Figure 10A schematic diagram of an example computer environment is shown, including a computing system configured to implement methods corresponding to the disclosed embodiments. Detailed Implementation

[0037] As used in the specification, unless otherwise implied or expressly understood or stated, a word appearing in the singular form encompasses its plural form, and a word appearing in the plural form encompasses its singular form. Furthermore, it should be understood that, for any given component or embodiment described herein, any possible candidates or alternatives listed for said component may generally be used alone or in combination with each other, unless otherwise implied or expressly understood or stated. Additionally, it will be understood that any list of such candidates or alternatives is illustrative only and not restrictive, unless otherwise implied or expressly understood or stated. Furthermore, unless otherwise specified, numbers expressing quantities, composition, distance, or other measures as used in the specification and claims should be understood to be modified by the term “about.”

[0038] Therefore, unless otherwise indicated, the numerical parameters set forth in the specification and appended claims are approximations that may be varied depending on the desired properties sought from the subject matter presented herein. To a minimum, and without attempting to limit the application of the equivalence principle to the scope of the claims, each numerical parameter should be interpreted at least according to the number of significant figures reported and by applying general rounding techniques. Although the numerical ranges and parameters set forth in the broad scope of the subject matter presented herein are approximations, the values ​​set forth in particular examples are reported as precisely as possible. However, any numerical value inherently contains some error, which is necessarily caused by the standard deviation found in its respective test measurement.

[0039] Furthermore, directional terms such as “top,” “bottom,” “left,” “right,” “upper,” “lower,” “upper part,” “lower part,” “near side,” “adjacent,” “far side,” as used in the specification and appended claims, are used only to indicate relative directions and are not intended to otherwise limit the scope of the specification or claims.

[0040] As mentioned above, single-sample fluorescence assays allow for a small footprint, low disposable waste, and are generally easier to configure for precise, accurate measurements. However, due to low throughput, the time required to sequentially analyze multiple samples becomes increasingly longer as more samples are measured. For this reason, many users opt for multi-well plate readers configured for fluorescence assays. However, these devices are large, expensive, generate more disposable waste, and require external mitigation (i.e., dedicated plates with opaque well walls) to ensure accurate, precise data measurements. Furthermore, as confirmed in user surveys, there is a significant market demand for fluorometers that can analyze more than one sample at a time without the high volume associated with multi-well plates.

[0041] The embodiments provided herein overcome one or more of the aforementioned problems in the art and relate to a bioanalytical system for the simultaneous analysis of multiple samples. For example, the system disclosed herein includes a uniquely designed excitation module and a corresponding emission module, which significantly reduces the footprint typically associated with multisample fluorometers. Furthermore, the components of the disclosed optical system can be independently adjustable to accommodate various and variable configurations of the sample loading system, such as different numbers of sample wells or the orientation of the sample wells relative to each other. Additionally, the disclosed system is designed to reduce the amount of stray excitation light observed by the sample sensor and can prevent light cross-contamination between samples, while maintaining a small footprint and eliminating the need for dedicated disposable products. In practice, the disclosed system can use the same sample containers (e.g., 500 μL thin-walled polypropylene tubes) as conventional single-sample fluorometers to receive and analyze biological samples.

[0042] Figure 1 A schematic diagram of a bioanalytical system 100 according to an exemplary embodiment is shown. Figure 1 The bioanalytical system 100 is described as a fluorometer having an optical system including an excitation module 102 and an emission module 104. The excitation module 102 excites one or more samples (or fluorescent labels within the samples) to generate emitted light, and the emission module 104 detects the emitted light for analysis.

[0043] The excitation module 102 includes: one or more excitation light sources (e.g., LED 106 and / or LED 108); a beam splitter 110 configured to guide one or more excitation beams generated by the light sources in a first direction (e.g., direction 114A); a collimator element 112; a plurality of excitation mirrors 116 configured to guide one or more excitation beams in a second direction (e.g., direction 114B) to a plurality of excitation lenses 118; and a plurality of sample containers 120 configured to receive sample containers whose excited contents emit radiation in a third direction (e.g., direction 114C) toward a plurality of emission lenses 122, a plurality of emission filters 124, and a plurality of photodetectors 126.

[0044] Excitation module 102 can utilize multiple excitation light sources, such as Figure 1 The illustration shows a blue light-emitting diode (LED) 106 and a red LED 108, but it will be understood that other types or numbers of excitation sources, including various excitation wavelengths, may be used. Additional or alternative excitation sources include, for example, lasers or mercury / xenon arc lamps. Excitation sources may be selected based on wavelength ranges associated with the visible light spectrum of violet, green, yellow, or orange and / or invisible light ranges (such as ultraviolet, near-infrared, or infrared light). In some embodiments, one or more excitation sources used in the excitation module are selected based on the intended identity of the analyte to be analyzed within the biological sample.

[0045] In some embodiments, the excitation light source (e.g., LEDs 106, 108) is specifically tuned to the excitation wavelength of a predetermined fluorophore. Figure 1 In the illustrated example, the wavelengths of the excitation light generated by the blue LED 106 and the red LED 108 are selected based on the excitation wavelength of the known fluorophore to be used in the analysis of the biological sample. Alternatively, a high-intensity light source, such as a xenon / mercury arc lamp, can be used as the excitation source. Such lamps generate both ultraviolet (UV) and visible light, making their implementation more practical for non-specific analyses where the exact excitation wavelength or wavelength range is unknown. A light source that generates a single excitation wavelength or a known excitation wavelength range can advantageously target known fluorophores, thereby preventing or reducing unintentional excitation of non-target molecules within the sample. In some embodiments, an excitation filter (e.g., a bandpass filter) can be positioned in front of the excitation source as needed to narrow the wavelength range of the excitation light.

[0046] like Figure 1As shown, beam splitter 110 is used to guide two excitation beams from LEDs 106 and 108 along the same optical path (e.g., direction 114A), thereby reducing the number of components and space required by excitation module 102. Alternatively, fiber bundle combiners or the like can be used instead of beam splitter 110. The illustrated configuration is highly advantageous because the size of the excitation module is reduced, resulting in a smaller overall footprint for the corresponding bioanalytical device. Furthermore, the ability to include one or more excitation sources allows for increased versatility and customizable configurations for analyzing different samples and / or various types of fluorophores, with different samples and / or various types of fluorophores corresponding to different ranges of excitation light.

[0047] The excitation beam, after passing through beam splitter 110, is collimated by collimator element 112 (e.g., collimator lens or concave / parabolic mirror). The collimated excitation beam is transmitted along a first direction 114A toward a plurality of excitation mirrors 116. The first direction 114A is generally parallel to the optical axis of collimator element 112. The excitation beam is reflected from mirror 116 in the form of a plurality of individually reflected beams toward corresponding plurality of excitation lenses 118. Each excitation lens 118 focuses a corresponding reflected excitation beam, generating a focused beam (e.g., a line-focused beam) to illuminate the sample received within sample container 120 of emission module 104. Phosphors within each sample are excited by the focused excitation beam and generate emitted light.

[0048] like Figure 1 As shown, individually reflected excitation beams are reflected from each corresponding excitation mirror and propagate in a second direction (e.g., direction 114B). In some embodiments, the second direction is not perpendicular to the first direction and forms an acute angle with the first direction, such that the reflected excitation beam propagates in the direction returning to the collimator element 112. Conversely, some conventional fluorometer optics are configured to guide the light path downwards, perpendicular to the light path, thus increasing the overall length of the optics compared to the illustrated staggered mirror configuration. Additionally, some conventional fluorometer optics do not include a reflecting excitation mirror, which allows the collimated light to continue along its initial trajectory before passing through any filter and reaching the target sample. Such embodiments result in a greater... Figure 1 The system depicted is much larger. Therefore, as... Figure 1 The staggered mirror configuration shown and described advantageously reduces the size of the optical system.

[0049] As mentioned above, multiple excitation lenses 118 generate a focused excitation beam that propagates from excitation module 102 to emission module 104. Emission module 104 includes a series of biological sample nacelles 120 formed as sample blocks. As shown, the multiple sample nacelles 120 are arranged in a series of uniformly spaced nacelles aligned along an axis approximately parallel to a first direction 114A of the collimated light.

[0050] Each container 120 is associated with a corresponding emitting lens 122, emitting filter 124, and photodetector 126 (e.g., photodiode, photomultiplier tube, CCD / CMOS sensor, etc.). The emitting module 104 is configured relative to the excitation module 102 such that each focused excitation beam generated by the excitation module 102 propagates to a single sample container arranged within the sample container 120 of the emitting module 104 and excites its contents.

[0051] Emitted light (e.g., emitted radiation, fluorescent radiation) from fluorescent labels or molecules within the sample housed in the reservoir 120 is collected by individual emission lenses among a plurality of emission lenses 122. Cross-contamination of emitted light from neighboring or multiple samples is ensured by focusing the emitted light along a third direction 114C onto a corresponding photodetector. The focused emitted light is then passed through a corresponding emission filter of a plurality of emission filters 124 for subsequent detection by a corresponding photodetector 126. In some embodiments, each photodetector 126 is advantageously positioned at a distance determined by the focal length of the corresponding emission lens 122 such that the emitted beam passing through the emission lens reaches the target photodetector when it is optimally focused as a line beam. This is advantageous in the event of slight misalignment of one or more components by ensuring that the emitted light reaches at least a portion of the surface of the photodetector lens.

[0052] The configuration of the optical components of excitation module 102 and emission module 104 facilitates the acquisition of emitted light in a direction different from the excitation light. It is necessary to acquire emitted light in the direction incident on the excitation light to avoid receiving direct excitation light at the emission light sensor (e.g., photodetector 126). Emitted radiation is emitted from the stimulated sample in all directions, and the majority of the excitation light remains guided in the second direction 114B. By placing the emission optics in a direction transverse to (e.g., orthogonal to) the second direction 114, a large portion of the emitted light can be observed even in the absence of the majority of the excitation light. Any low-energy excitation light reflected upwards by a third party can be filtered out by the emission filter 124 (e.g., a bandpass filter) before reaching the photodetector 126.

[0053] As discussed above, embodiments of this disclosure include an excitation module 102 having a plurality of excitation mirrors 116 that reflect collimated excitation light at acute angles toward a plurality of excitation lenses 118. Figure 2 and Figure 3 It shows Figure 1 Various alternative embodiments of the excitation module 102 of the bioanalytical system 100. In such embodiments, each of the excitation mirrors (e.g., excitation mirrors 202a to 202h and / or 302a to 302h) is positioned at an acute angle relative to the direction of the collimated excitation light transmitted from the collimator element 212. For example, in Figure 2In this configuration, multiple mirrors 202a to 202h are positioned at an angle of approximately 45° relative to the direction 204 of the collimating excitation light. Therefore, Figure 2 The reflected excitation beam is approximately perpendicular to the incident beam (i.e., collimated excitation beam). Therefore, in such embodiments, a plurality of sample containers 226a to 226h (where sample container 226a corresponds to excitation mirror 202a, sample container 226b corresponds to excitation mirror 202b, etc.) are arranged at intervals along a uniform axis, the interval positioning each sample container in the path of each reflected excitation beam reflected from each excitation mirror.

[0054] exist Figure 3 In this configuration, multiple mirrors 302a to 302h are positioned at an angle of approximately 67.5° relative to the direction 304 of the collimating excitation light (i.e., the collimating excitation light forms an angle of approximately 22.5° with the normal direction of the mirrors 302a to 302h). Therefore, Figure 3 In the embodiment, the reflected excitation beam is at approximately 45° to the incident beam (i.e., the collimated excitation beam). Therefore, the reflected excitation beam originates from the collimated excitation beam in the second direction (see also...). Figure 1 It propagates in the second direction 114B, which is usually parallel to the optical axis of collimator 312.

[0055] Figure 3 An optical system comprising multiple excitation lenses 318a to 318h corresponding to multiple excitation mirrors 302a to 302h is also shown. For example, excitation mirror 302a corresponds to excitation lens 318a, excitation mirror 302b corresponds to excitation lens 318b, and so on. As shown, each excitation lens 318a to 318h is positioned at an angle such that the reflected excitation beam reflected from each excitation mirror 302a to 302h is approximately parallel to (and aligned with) the optical axis of the excitation lenses 318a to 318h.

[0056] In some embodiments, at least one of the excitation mirrors 202a to 202h and 303a to 302h is independently adjustable to compensate for any optical errors caused by the collimator or positioning errors of the light source or beam splitter. For example, mirrors 202a and 202h can be positioned at slightly different angles compared to mirrors 202b to 202g because the excitation beam transmitted by the collimator can be less collimated at the outer edges compared to the center.

[0057] It should be understood that, although Figure 2 to Figure 3Each of the examples depicts eight excitation mirrors and eight corresponding excitation lenses. In alternative embodiments, the number of mirrors and lenses can vary depending on the design of the overall optical system and its excitation and emission components, the number of samples to be analyzed simultaneously by the bioanalytical system 100, or other factors. For example, a similar device configured to simultaneously analyze up to twenty samples could employ twenty sets of mirrors and lenses, which can address the needs of users with higher sample reuse requirements while still providing the benefits described herein, such as reduced overall device size and footprint. In another example, a similar device could be configured to analyze up to 12 samples, wherein the excitation module can then be adjusted by widening the collimated beam to ensure coverage of additional samples. Alternatively, additional optics can be used to split the collimated beam into one or more sub-beams while maintaining sufficient beam intensity for the desired application.

[0058] As mentioned above, many conventional multi-sample devices have a very large footprint, which is a result of the associated configuration of optical components and corresponding sample loading systems. For example, now referring to... Figure 4A When sample containers (e.g., sample containers 426a to 426h) are configured to receive microcentrifuge tubes (or the like), and the tube-to-tube distance (i.e., the distance between adjacent samples) is 9 mm, the total length (e.g., length 402) of the sample container strip corresponding to 8 tubes is approximately 70 mm. If the collimating excitation beam is to directly illuminate the strip of the 8 tubes, the size of the collimating beam (e.g., length 402) needs to be greater than 70 mm. Therefore, the collimator and associated optics, as well as the required space, will be quite large, such as... Figure 4A drawn.

[0059] Similarly, if a single excitation mirror (or multiple excitation mirrors aligned along a similar axis shown by the single excitation mirror) is placed at a 45° angle to the collimating beam to reflect the excitation light onto a strip of eight tubes, the collimator and associated optics, as well as the required space, will still be quite large, such as Figure 4B The illustration illustrates this. The increased space required is further emphasized when considering the separation of the excitation beam and the emitted radiation (i.e., the angles of propagation of each beam should be non-parallel to facilitate a reduction in stray excitation light received by the photodetector). Stray excitation light will adversely affect the photodetector's ability to accurately detect precise amounts of emitted radiation, and thus can deviate from the concentration calculation corresponding to the biological sample. Therefore, in such cases, any subsequent optical components will be positioned accordingly, increasing the width and / or length of the optical system, and thus increasing the width and / or length of the entire bioanalytical apparatus housing the optical system.

[0060] In contrast, the optical system of this disclosure utilizes multiple individual mirrors arranged in an alternating pattern along the diagonal axis (e.g., Figure 1 to Figure 3The eight mirrors in the non-limiting example depicted (i.e., each mirror is laterally offset from its neighboring mirrors) fold the optical path, as shown in the figure. Figure 2 to Figure 3 As shown.

[0061] For example, refer to Figure 3 If the angle between mirrors 302a to 303h and the direction 304 of the collimating excitation light is 67.5°, then the reflected beam from mirrors 302a to 302h propagates downwards (i.e., in a direction away from excitation mirrors 302a to 302h and towards excitation lenses 318a to 318h) and to the left (in a direction opposite to the direction of the excitation light path flowing out of collimator 312). Figure 3 In this arrangement, if the vertical center-to-center distance between adjacent mirrors is 2.772 mm and the horizontal center-to-center distance between adjacent mirrors is 6.228 mm, then the horizontal center-to-center distance of the adjacent reflected beam is 9 mm, which is the tube-to-tube distance. Using this arrangement, the width of the collimated excitation beam will be only approximately 2.772 mm × 8 ≈ 22.2 mm, which is much smaller than the aforementioned 70 mm. Due to the "Z" layout (see... Figure 1 The light direction is 114A to 114C), and the entire optical device is also compact. In one embodiment, with Figure 4A Compared to the layout shown, this allows for a reduction in overall size of over 80%.

[0062] Continue to refer to Figure 2 to Figure 3 The acute angle at which each excitation mirror is positioned can be between approximately 50° and 75° to form a “Z” layout. For example, if the angle is close to 90°, the angle between the incident beam and the reflected beam from the mirror is close to 0°, then all mirrors will be positioned much further away from the collimators (e.g., collimators 212, 312) to ensure that the excitation lenses (e.g., excitation lenses 318a to 318h) and the emission module can be placed outside the collimated beam. On the other hand, if the angle is close to 45°, for example close to... Figure 2 The arrangement of the tubes makes it difficult to accommodate the emission module in the tube-strip direction due to the very limited space between tubes. At the same time, it ensures that the angle between the direction of the excitation beam and the emission detection is 90 degrees to minimize the amount of excitation light in the emission detection direction, which helps to reduce the background signal and increase the detection sensitivity.

[0063] The path of the excitation light from collimator element 212 to the excitation mirror and into the multiple reflected beams follows a principle corresponding to the law of reflection. For example, the angle of incidence (i.e., the angle at which the collimated light strikes the excitation light) is equal to the angle of reflection (i.e., the angle at which the excitation light is reflected toward the sample container). Additionally, the angle of incidence is partly based on the direction of a fixed collimated light (e.g., direction 204 and / or a first direction 114A). When the position of the sample container is determined, the horizontal (“x”) distance and vertical (“y”) distance from the excitation mirror (e.g., the center point of the excitation mirror) are known. It should be understood that the acute angle at which the excitation mirror is positioned is equal to the angle of incidence of the collimated excitation light based on the geometric principle of consistent interior angles between one or more parallel lines. Assuming that the effect of the rotation of the excitation mirror on the known x and y distances between the excitation mirror and the sample container is negligible, the acute angle (θm) of rotating the excitation mirror is approximately based on the following equation:

[0064]

[0065] Therefore, the amount by which the subsequent excitation mirror corresponding to the subsequent sample container to be analyzed is offset from the previous excitation mirror should be proportional to the amount by which the subsequent sample container is offset vertically and / or horizontally from the previous sample container. The horizontal and vertical offsets then characterize the pattern of the staggered diagonal configuration of the excitation mirrors.

[0066] Alternatively, because the exact angles and offsets of the mirrors can be precisely calculated, a single excitation mirror—instead of an interleaved array—can be used, capable of rotating through a series of corresponding incident and reflection angles, such that the direction of the reflected excitation light (i.e., the second direction 114B) is continuously guided to the individual excitation lenses and / or sample containers within short time intervals. While embodiments of bioanalytical systems including multiple excitation mirrors allow for the simultaneous analysis of each biological sample, embodiments with a single movable mirror cannot analyze each sample simultaneously. However, given the smaller number of samples analyzed, the reduction in total analysis time is negligible.

[0067] Excitation lenses can focus excitation beams of any shape into line-focused beams. Figure 5 The following is illustrated as a suitable method for use according to an example embodiment. Figure 1 A schematic diagram of one of the excitation lenses 118 in the system 100, namely the excitation lens 500. Figure 6 The drawing is shown Figure 5 Operation of the excitation lens 500 Figure 1 A partial cross-sectional view of system 100.

[0068] In the illustrated example, the excitation lens 500 is a cylindrical lens that can substantially reduce the beam width in one direction while maintaining the beam width in another direction. In other words, the excitation lens 500 can manipulate the incident beam to produce a focal line rather than a focused beam. Now refer to Figure 6For example, when the excitation lens 600 (e.g., Figure 1 When the excitation lens 500 is installed vertically, the excitation lens 600 can focus the excitation beam into a horizontal line-focused beam 604, such as... Figure 6 As shown. Due to the line-focused beam, the interaction volume between the excitation beam and the liquid sample within the sample container 602 is less sensitive to tolerances and assembly errors. In other words, even if the sample container 602 is slightly offset from its normal or expected position, the line-focused beam 604 can still effectively excite the sample contained within the sample container 602. In systems capable of analyzing multiple fluorophores, such as... Figure 1 In System 100, the focal lengths of different excitation lenses can be selected independently, allowing the focal lengths to vary between channels in order to improve signal balance across channels.

[0069] In some embodiments, as illustrated, the line-focused beam 604 passes through the excitation window 606, which facilitates the reduction of stray excitation light, such as excitation light corresponding to one or more other excitation mirrors and / or lenses. In some cases, the excitation window is provided by a housing (e.g., Figure 8 The opening in the container 804 is defined. In some cases, the excitation window 606 is connected to the sample loading system (e.g., Figure 8 The internal components of the sample loading system 800 are integrally formed. In some cases, the excitation window 606 is an attachment component (e.g., an adjustable aperture stop) disposed between the excitation lens 600 and the sample container 602.

[0070] Passing through the excitation window 606 and in the second direction (e.g., Figure 1 After propagating in the second direction 114B), the excitation light irradiates the biological sample (i.e., the contents of the sample container within the corresponding seat). In some embodiments, the linear focal beam 604 of the excitation light strikes a barrier wall (e.g., wall 608) configured to absorb light and / or prevent stray excitation light from propagating to the outside of the sample container 602.

[0071] Figure 7 The illustration shows a transmitter module 700 suitable for use as a transmitter module 104, according to an example embodiment. Figure 1 A partial cross-sectional view of system 100. The emission module 700 includes multiple sets of optical elements, including: an emission window 710 formed by an emission flange 720, an emission lens 702, an emission filter 704, and a photodetector 706. Fluorescent radiation emitted by the stimulated fluorophore is allowed to pass through the emission window 710 and be transmitted from the sample holder 712 through a transparent region confined by the emission window 710. In some cases, the emission window 710 is formed by a holder (e.g., Figure 8The opening in the container 804 defines the sample container and is configured to removably secure it. In some cases, the launch window 710 is connected to the sample loading system (e.g., Figure 8 The internal components of the sample loading system 800 are integrally formed. In some cases, the emission window 710 is an attachment component (e.g., an adjustable aperture stop) disposed between the emission lens 702 and the sample container 712. In some embodiments, the emission module 700 does not include the emission window 710.

[0072] In some embodiments, each sample container 120 is advantageously positioned at a distance approximately determined by the focal length of the corresponding excitation lens 118. Alternatively, each sample container 120 is arranged such that it receives a width and / or height associated with the focused excitation beam, wherein the width and / or height corresponds to the width and / or height of the excitation window.

[0073] After passing through the emission window 710, the emitted radiation is focused by the emission lens 702 to improve the signal-to-noise ratio. The focused fluorescence radiation then passes through the emission filter 704, which blocks stray light transmitted by the emission lens 702. In one embodiment, the emission filter 704 is in the form of a first dual-bandpass filter 704a and a second dual-bandpass filter 704b, configured to block radiation corresponding to the excitation light. The use of dual-bandpass filters 704a, 704b can provide blocking of light within a selected wavelength range in a compact configuration. For example, if the excitation light is generated by a red or blue LED, each of the dual-bandpass filters 704a, 704b can block both red and blue light to minimize stray excitation light.

[0074] In some embodiments, the emitting lens 702 is equipped with an emitting flange 720, which is configured to prevent stray excitation light and / or unwanted emitted radiation from non-corresponding sample containers from reaching the photodetector 706. For example, as Figure 7 As illustrated, the emission flange 720 can form an emission aperture configured to define an area allowing emitted radiation generated by a biological sample contained in the sample container 712 to pass through and reach the emission lens 702. In some cases, the emission aperture serves as an emission window 710 (i.e., without a separate or embedded emission window). The emission flange 720 may also include a circumferential sidewall 724 configured to surround the corresponding emission lens 702, wherein the circumferential sidewall extends beyond the thickness of the emission lens 702. The sidewall 724 (or multiple sidewalls) of the emission flange 720 in a third direction (e.g., Figure 1 The third party extends toward the emission filters 704a, 704b and / or the photodetector 706 on 114C, and can form a channel to protect the emission lens from receiving stray light.

[0075] In some embodiments, the emitting flange 720 is advantageously arranged such that the center point of the emitting aperture / window is aligned with the axis defined by the optical center of the emitting lens 702 and the optical center of the photodetector 706. In some cases, the emitting flange 720 is angled, wherein the outer surface of the end of the emitting flange 720 forming the emitting aperture is flush with the outer surface of the sample container 712 and / or the emitting window 710. In some embodiments, the circumferential (e.g., cylindrical) sidewall 724 of the emitting flange 720 extends until it meets the outer perimeter of the emission filter 704 and / or one or more of the dual bandpass filters (704a, 704b) of the emission filter 704, so as to create an enclosed space through which emitted radiation can propagate and shield stray excitation light and / or emitted radiation from adjacent sample containers.

[0076] In some embodiments, the sample container 712 is arranged such that emitted radiation is confined to transmission through the emission window 710, wherein the path of emitted radiation is blocked by an emission wall 708 disposed on the opposite side of the emission window 710. In this way, the photodetector 706 "sees" the emitted radiation propagating from the sample container 712 through the aforementioned opening. In some embodiments, the emission wall 708 is an integrated component in the emission module 700.

[0077] The bioanalytical system 100 according to an example embodiment also includes a sample loading system suitable for multi-sample environments. Figure 8 An exemplary sample loading system 800 is shown (e.g., it can be adapted to use with...). Figure 1 A partial cross-sectional view of the system 100 used together. The sample loading system 800 includes a sample block 802 having a plurality of receptacles 804. The receptacles 804 can receive corresponding plurality of sample containers 806, wherein each sample container 806 contains a corresponding sample. In a non-limiting example, eight receptacles are arranged in a single straight row to receive strips of eight sample containers. It will be understood that in other embodiments, the receptacles may be arranged in different ways, such as alternating or wavy (see System 100 for use). Figure 9 Furthermore, the number of containers can vary depending on the number of samples to be analyzed simultaneously.

[0078] Each container 804 is also designed to position and fix the corresponding receiving sample container 806. For example... Figure 8 As shown, the bottom surface of each container 804 includes a recess 808 configured to receive the bottom tip portion 810 of the corresponding sample container 806. Furthermore, the container opening 812 of each container 804 is equipped with a gasket 814 (which also indicates...). Figure 7The gasket 814 engages with the cap 818 of the corresponding sample container 806. The gasket 814 can contain any suitable material, such as rubber or silicone. When the sample container 806 is fully inserted into the reservoir 804, the sample container 806 is effectively positioned by the recess 808 and the gasket 814, wherein the wall of the sample container 806 does not contact the wall of the reservoir 804.

[0079] The sample loading system 800 also includes a closure mechanism 816 capable of applying a closing force to a plurality of sample containers 806. In one embodiment, the closure mechanism 816 is configured to press against the caps 818 of the plurality of sample containers 806. For example, the closure mechanism 816 includes a plurality of biasing members, such as springs 820, which can operate independently of each other. In use, if a cap 818 is not fully closed, the corresponding spring 820 can act on the cap 818 to press it down, thereby preventing adjacent sample containers from being displaced. The springs 820 also help to further secure the sample containers 806 in the vertical direction. In an alternative embodiment, the closure mechanism 816 may include a sealing member configured to close the sample containers 806 when the closure mechanism 816 acts on them. Furthermore, alternative forms of biasing members include bellows-like structures made of elastic materials such as rubber.

[0080] As referenced above Figure 1 Some embodiments of the optical system of the described bioanalytical system include a plurality of mirrors uniformly spaced apart from each other and at uniform angles relative to each other. However, it is contemplated that in some embodiments, each of the plurality of excitation mirrors is independently adjustable to accommodate variable configurations and sizes of sample containers. Thus, by adjusting one or more excitation mirrors of the optical system, the bioanalytical device can facilitate measurements of the diversity of sample containers to be read simultaneously.

[0081] Now for reference Figure 9 Provided Figure 1An example embodiment of a bioanalytical system 100 is shown, in which similar components are illustrated, and in which alternative configurations of a plurality of excitation mirrors 916 and sample containers 920 are shown. As illustrated, the plurality of sample containers 920 are arranged in a staggered, alternating pattern. In some embodiments, this staggered, alternating pattern forms one or more rows of sample containers, which are arranged vertically and / or horizontally offset from each other. Thus, the plurality of excitation mirrors 916 are configured such that the optical path of the excitation light from the collimator element 912 reaches each of the sample containers of the plurality of sample containers 920 as a discrete beam of focused excitation light. As illustrated, the plurality of excitation mirrors are arranged in a staggered, alternating pattern along a diagonal axis. In some embodiments, this staggered, alternating pattern forms one or more rows (i.e., the excitation mirrors are arranged along one or more parallel diagonal axes that are arranged at acute angles to the direction of the collimated light). Each excitation mirror 916 is positioned vertically and / or horizontally offset from one or more of the closest excitation mirrors 916. It should be understood that Figure 1 , Figure 9 The interlaced patterns of the excitation mirrors in the and / or alternative embodiments are formed in multiple different configurations to accommodate variations in the sample container configuration.

[0082] Although Figure 9 Alternative embodiments of the sample loading system and corresponding configurations of the excitation mirror are described, but other optical system configurations are also possible, including the addition or omission of certain optical components. For example, in some embodiments, the optical system may include a 1:1:1:1 ratio between the excitation mirror, excitation lens, emission filter, and photodetector (e.g., Figure 1 and Figure 9 In some embodiments, a single emission filter and a single detector array are used without integrating an excitation mirror or excitation lens. Alternatively, in some embodiments, a scanning detection head including an emission lens, a light emission filter, and a photodetector is used to scan the sample.

[0083] As described above, the disclosed embodiments of the bioanalytical device include novel configurations of the optical system that achieve numerous advantages over conventional multi-sample fluorometers. In addition to the optical system and sample loading system, the device can also be configured as a computerized device. For example, now refer to… Figure 10 It illustrates the integration of bioanalytical devices (e.g.) Figure 1 System 100 and / or Figure 9The computing environment 1000 of the system 900. In some embodiments, the bioanalysis system 1100 includes the optical system and / or computing system 1200 as described above. As shown, the computing system 1200 includes one or more processors 1240 and one or more hardware storage devices 1220 storing computer-executable instructions (e.g., instructions 1220A to 1220D) that can be executed by the one or more processors to cause the computing system 1200 to perform various actions corresponding to the embodiments disclosed herein. In some embodiments, the computing system 1200 facilitates a user interface 1300a including the bioanalysis system 1100.

[0084] The embodiments disclosed or contemplated herein may include or utilize a special-purpose or general-purpose computer (e.g., computing system 1200), which includes computer hardware such as one or more processors, as discussed in more detail below. Embodiments may also include physical media and other computer-readable media for carrying or storing computer-executable instructions and / or data structures. Such computer-readable media may be any available media accessible by a general-purpose or special-purpose computer system. Computer-readable media storing computer-executable instructions (e.g., instructions 1220A to 1220D) are physical storage media. Computer-readable media carrying computer-executable instructions are transmission media. Thus, by way of example and not limitation, embodiments may include at least two distinctly different types of computer-readable media: computer storage media (e.g., hardware storage device 1220) and transmission media.

[0085] Computer storage media include RAM, ROM, EEPROM, CD-ROM or other optical disk storage devices, magnetic disk storage devices or other magnetic storage devices, or any other medium that can be used to store desired program code in the form of computer-executable instructions or data structures and that can be accessed by a general-purpose or special-purpose computer.

[0086] A “network” (e.g., network 1500) is defined as one or more data links that enable the transmission of electronic data between computer systems and / or modules and / or other electronic devices. When information is transmitted or provided to a computer via a network or other communication connection (hardwired, wireless, or a combination of hardwired and wireless), the computer appropriately regards the connection as a transmission medium. The transmission medium may include networks and / or data links that can be used to carry data or desired program code in the form of computer-executable instructions or data structures and can be accessed by a general-purpose or special-purpose computer. Combinations of the foregoing should also be included within the scope of computer-readable media.

[0087] Furthermore, upon arrival at various computer system components, program code in the form of computer-executable instructions or data structures can be automatically transferred from the transmission medium to the computer storage medium (and vice versa). For example, computer-executable instructions or data structures received via a network or data link can be buffered in the RAM within a network interface module (e.g., a "NIC") and then ultimately transferred to the computer system RAM and / or a less volatile computer storage medium on the computer system. Therefore, it should be understood that computer storage media can be included within computer system components that also (or even primarily) utilize the transmission medium.

[0088] Computer-executable instructions include, for example, instructions and data that cause a general-purpose computer, special-purpose computer, or special-purpose processing device to perform a function or a set of functions. Computer-executable instructions can be, for example, binary, intermediate format instructions (such as assembly language), or even source code. Although the subject matter has been described in language specific to structural features and / or methodological actions, it should be understood that the subject matter defined in the appended claims is not necessarily limited to the features or actions described above. Rather, the described features and actions are disclosed as examples of the claims.

[0089] Those skilled in the art will understand that embodiments can be practiced in network computing environments (e.g., computing environment 1000) with many types of computer system configurations, including personal computers, desktop computers, laptop computers, message processors, handheld devices, multiprocessor systems, microprocessor-based or programmable consumer electronics, network PCs, minicomputers, mainframe computers, tablet computers, smartphones, routers, switches, etc. Embodiments can be practiced in distributed system environments where both local and remote computer systems perform tasks via network links (via wired data links, wireless data links, or a combination of wired and wireless data links). In a distributed system environment, program modules can be located in local and remote memory storage devices. An entity's program modules can reside and / or run in another entity's data center or "cloud." In this specification and the appended claims, a computer system is also defined to include graphics systems (e.g., Figure 1 (Bioanalytical system 100).

[0090] In some embodiments, the bioanalytical system 1100 communicates with a server and / or computing system 1400 via a wired, wireless, and / or cloud network 1500. For example, the computing system 1400 includes one or more processors 1440 and one or more hardware storage devices 1420 storing one or more computer-executable instructions 1420A, 1420B, 1420C. Additionally or alternatively, the computing system includes a database 146 configured to store one or more datasets (e.g., data types 1460A, 1460B). In some cases, the computing system 1400 also includes a user interface 1300B. The computing environment 1000 is configured such that data collected by the bioanalytical system 1100 (e.g., photodetector signal data and / or other data) can be stored and / or processed via the computing system 1200. Additionally or alternatively, data from system 1100 is pushed to computing system 1400 via a network, wherein the data may be stored in database 1460 and / or processed by processor 1440 and pushed back to computing system 1200 for storage and / or further processing.

[0091] In some embodiments, the bioanalytical system is configured as an “intelligent” device capable of automatically performing bioanalytical techniques and data processing, and can communicate with other computing systems to automatically report and / or store data, including raw and processed runtime information, excitation and / or emission light wavelengths and intensities, etc.

[0092] The disclosed embodiments also relate to the use of bioanalytical devices as described herein (e.g., Figure 1 The system 100) is a method for analyzing biological samples. In some embodiments, the computer-implemented method for analyzing multiple biological samples includes one or more of the following steps:

[0093] 1. The detection is removably fixed in a multi-sample loading device (e.g., Figure 8 Multiple sample containers (e.g., in the sample loading system 800) within the sample loading system 800 Figure 1 (within the sample container 120).

[0094] 2. In response to the detection of the plurality of biological sample containers, the computing system activates an excitation source, wherein: the excitation light generated by the excitation source is directed to the plurality of sample containers as a plurality of excitation beams through at least a plurality of mirrors arranged in an interlaced diagonal pattern, each mirror being configured to direct one of the plurality of excitation beams to a corresponding sample container among the plurality of sample containers, and the excitation light being configured to cause the biological samples stored in the plurality of biological sample containers to emit radiation.

[0095] 3. The amount of emitted radiation from each of the biological samples is detected by multiple photodetectors.

[0096] 4. Determine the concentration of one or more bioanalytes included in each of the plurality of sample containers, based at least in part on the amount of emitted radiation detected.

[0097] In some embodiments, the computing system of the bioanalytical device (e.g., computing system 1200) is configured to perform one or more of the following additional and / or alternative steps:

[0098] 1. Detects the specific arrangement of the sample container and automatically adjusts the independently adjustable excitation mirror (e.g., Figure 1 The excitation mirror 116 is arranged to correspond to the detected sample container.

[0099] 2. The concentration of one or more bioanalytes is determined in part based on the amount of emitted radiation detected and in part based on one or more of the following variables: the assay type based on the expected bioanalyte identity associated with one or more biological samples, a calculated calibration curve generated from a dataset corresponding to a standard sample set, the amount of each sample volume stored in each sample container, the assay kit lot number, label or sample identification number, and / or samples with measurements determined to be out of range based on the calibration curve are ignored.

[0100] 3. Display the determined bioanalyte concentrations in digital and / or graphical formats via a user interface (UI) (e.g., UI 130a).

[0101] 4. Perform molar concentration and other conversions and / or calculations.

[0102] 5. Automatically adjust the excitation window (e.g., Figure 6 Excitation window 606), emission window (e.g., Figure 7 The emission window 710) and / or emission aperture (e.g., Figure 7 The aperture size of the emission port 722.

[0103] 6. Automatically transmit data in various formats and / or to another computing system (e.g., Figure 10 The computing system 1400 outputs data (e.g., determined concentration, analyte identity, assay identity).

[0104] In some embodiments, a user can input the various data segments as described above, wherein, in addition to storing and / or processing data collected by the computing system via a bioanalytical device, the computing system can also store and / or process data.

[0105] As described above, the bioanalytical system of this disclosure is capable of analyzing multiple samples simultaneously while having a compact shape factor. Sample loading and unloading are also simplified, while ensuring that the sample container is safely and correctly positioned.

[0106] Those skilled in the art will understand that various changes and / or modifications can be made to the invention as illustrated in the specific embodiments without departing from the scope of the invention as broadly described.

Claims

1. A bioanalytical system comprising: The activation module includes: A collimator element configured to receive excitation light from at least one excitation source and to transmit collimated excitation light along an excitation optical path in a first direction; as well as A plurality of excitation mirrors are arranged along the excitation optical path in an alternating diagonal pattern, wherein each excitation mirror is positioned at an acute angle relative to the first direction and configured to reflect a corresponding collimated excitation beam along a second direction of the excitation optical path; and A transmitting module, positioned to receive excitation light transmitted along the second direction of the excitation optical path, the transmitting module comprising: A sample block comprising multiple sample assemblies, each sample assembly being positioned to receive a corresponding collimated excitation beam propagating along the second direction of the excitation optical path; and Multiple photodetectors, each configured to receive emitted light propagating upwards in a third direction from a corresponding sample container, the third direction being transverse to the second direction of the excitation light path; and A plurality of excitation lenses are arranged such that each excitation lens is positioned in the second direction of the excitation optical path and configured to focus a corresponding reflected collimated beam into a corresponding focused excitation beam for reception at a corresponding sample holder of the emission module, wherein the staggered diagonal pattern is formed by vertical and horizontal offsets of a first center point of a first excitation lens and a second center point of a second excitation lens.

2. The bioanalytical system according to claim 1, wherein, Each photodetector is oriented toward the corresponding sample container in the third direction.

3. The bioanalytical system according to any one of claims 1 to 2, wherein, The third direction is generally orthogonal to the second direction of the excitation optical path.

4. The bioanalytical system according to claim 1, wherein, The transmitting module additionally includes a plurality of transmitting lenses configured to focus the emitted light transmitted upward from the third party onto the plurality of photodetectors.

5. The bioanalytical system according to claim 4, wherein, The emission module additionally includes a plurality of emission filters corresponding to the plurality of emission lenses, the plurality of emission filters being positioned downstream of the plurality of emission lenses and configured to allow emitted light to pass through the emission filters and substantially block stray excitation light.

6. The bioanalytical system according to claim 5, wherein, The plurality of transmit filters include dual bandpass filters.

7. The bioanalytical system according to any one of claims 4 to 6, wherein, Each emitting lens contains a curved lens.

8. The bioanalytical system according to any one of claims 1 to 2, wherein, The emission module further includes multiple emission windows, each associated with a corresponding sample container and defining the area in which the emitted light is transmitted upward to the downstream component.

9. The bioanalytical system according to any one of claims 1 to 2, wherein, At least one of the plurality of excitation mirrors is independently adjustable.

10. The bioanalytical system according to any one of claims 1 to 2, wherein, The acute angle of each excitation mirror in the interlaced diagonal pattern is between 50° and 75° relative to the first direction.

11. A bioanalytical system comprising: The activation module includes: An excitation source configured to emit excitation light in a first direction; An excitation mirror is selectively movable between a plurality of predefined positions arranged in an alternating diagonal pattern, each predefined position forming an acute angle relative to a first direction and configured to reflect the excitation light along a second direction; as well as A plurality of excitation lenses are arranged such that each excitation lens is positioned in the second direction and configured to receive a reflected excitation beam guided thereon by an excitation lens positioned at a corresponding predefined location, wherein the staggered diagonal pattern is formed by vertical and horizontal offsets of a first center point of a first excitation lens and a second center point of a second excitation lens; and The transmitting module includes: Multiple sample assemblies are positioned to receive focused reflected excitation beams from corresponding multiple excitation lenses; At least one photodetector, configured to receive emitted light transmitted in a third direction upwards from the plurality of sample assemblies, the third direction being transverse to the second direction; and A plurality of emitting lenses and a plurality of emitting filters are configured to focus and filter the emitted light onto the at least one photodetector.

12. The bioanalytical system according to claim 11, wherein, The at least one photodetector comprises a plurality of photodetectors, each photodetector being configured to receive emitted light from a corresponding sample container, the emitted light being focused and filtered by a corresponding emitting lens and a corresponding emitting filter before being received at each photodetector.

13. The bioanalytical system according to any one of claims 11 to 12, further comprising a sample loading system configured to removably secure one or more sample containers within corresponding sample containers of the plurality of sample containers.

14. The bioanalytical system according to claim 13, wherein, The sample loading system further includes a closing mechanism configured to apply a closing force to the one or more sample containers within the corresponding sample holder and fix them in a fixed position.

15. The bioanalytical system according to any one of claims 11 to 12, wherein, The emitted light comprises fluorescent radiation from one or more stimulated fluorescent labels.

16. The bioanalytical system according to any one of claims 11 to 12, further comprising a plurality of emission orifices, wherein, Each emission aperture is associated with a corresponding emission lens among the plurality of emission lenses, and wherein each emission aperture is aligned upwards on the third and defines an area through which emitted light is received from the sample container by the corresponding emission lens.

17. The bioanalytical system according to claim 16, wherein, The center point of the emission aperture is aligned with the optical center of the corresponding emission lens.

18. A bioanalytical system comprising: At least two excitation sources with different excitation wavelengths are emitted; A collimator element configured to receive excitation light from the at least two excitation sources and to transmit collimated excitation light along the excitation optical path in a first direction; A plurality of excitation mirrors are arranged in an alternating diagonal pattern along the excitation optical path, wherein each excitation mirror is positioned at an acute angle relative to the first direction and is configured to reflect the collimated excitation light into a plurality of reflected excitation beams along a second direction of the excitation optical path. A plurality of excitation lenses are positioned in the second direction of the excitation optical path and configured to focus a corresponding reflected collimated beam into a corresponding focused excitation beam, wherein the staggered diagonal pattern is formed by the vertical and horizontal offset of the first center point of the first excitation lens and the second center point of the second excitation lens. A sample block, the sample block forming a plurality of sample assemblies, wherein the plurality of sample assemblies are positioned to receive the corresponding focused excitation beams; and For each corresponding sample container, the bioanalytical system includes at least the following components aligned upwards in a third direction, the third direction being transverse to the second direction: A transmission window that defines the area through which the emitted light travels upwards in the third party; A curved lens, the curved lens being configured to focus the emitted light passing through the emission window; A two-pass filter, configured to block stray excitation light; and A photodetector configured to receive focused filtered emitted light.

19. The bioanalytical system according to claim 18, wherein, The sample block includes multiple containers configured to receive multiple sample containers, each sample container being configured to receive a sample.

20. The bioanalytical system according to claim 19, wherein, Each of the plurality of containers includes a container opening configured to receive a pad, and wherein the container opening is configured to allow engagement between the pad and the top portion of one of the plurality of sample containers.

21. The bioanalytical system of claim 19 or claim 20, further comprising a closure mechanism configured to apply a closing force to the plurality of sample containers.

22. The bioanalytical system according to claim 21, wherein, The closing mechanism includes multiple biasing components.

23. The bioanalytical system according to claim 22, wherein, Each of the plurality of biasing components is operable independently.

24. The bioanalytical system according to any one of claims 18 to 20, 22 to 23, wherein, The multiple seats are arranged in a single row.

25. The bioanalytical system according to any one of claims 18 to 20, 22 to 23, wherein, Each of the plurality of excitation lenses comprises a focal length, and each focal length is independently selectable.

26. The bioanalytical system according to any one of claims 18 to 20, 22 to 23, wherein, At least one of the plurality of excitation mirrors is independently adjustable.

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