Bacterial endotoxin reader verification plate and method of use

Abstract

Verification plates, i.e., temperature verification plates (TVPs) and optical verification plates (OVPs), for bacterial endotoxin readers are provided. A TVP has a body configured to be placed on and rotated by a spindle of the reader. The body has a temperature verification circuit having a temperature sensor and a temperature indicator. The temperature sensor is configured to measure a temperature of the body rotated by the spindle of the reader. The temperature indicator optically indicates a value of the temperature measured by the temperature sensor. The temperature indicator is readable by an optical stage of the reader. The OVP has a body having a plurality of holes positioned along a perimeter that align with the optical stage of the reader. Light generated by a light source of the reader can pass through the holes and the intensity is measured by a photodetector of the reader.

Description

[0001] Cross-reference to related applications

[0002] This application claims priority to U.S. Provisional Patent Application No. 62 / 936,883, filed November 18, 2019, the entire contents of which are incorporated herein by reference. Invention Field

[0003] This application pertains to the validation of bacterial endotoxin readers. More specifically, this application pertains to the temperature and / or optical validation of bacterial endotoxin readers. Background of the Invention

[0004] Bacterial endotoxin readers require regular validation of their optical readings and temperature measurement performance.

[0005] Brief overview of the invention

[0006] In one aspect of the invention, a temperature verification plate (TVP) for a bacterial endotoxin reader has: a body configured to be placed on and rotated by a spindle of the reader; the body having a temperature verification circuit including a temperature sensor and a temperature indicator; the temperature sensor being configured to measure the temperature of the body as it rotates by the spindle of the reader; and the temperature indicator being configured to optically represent the value of the temperature measured by the temperature sensor, wherein the temperature indicator can be read by the optical bench of the reader.

[0007] In another aspect of the invention, the temperature sensor may be an electronic temperature sensor, a thermistor, a thermocouple, and / or a resistance temperature detector. The temperature indicator is at least one light-emitting diode (LED) and / or at least one liquid crystal display (LCD). The temperature indicator represents the temperature value as a binary number.

[0008] In another aspect of the invention, a binary number determines the resolution of the temperature measured by the temperature sensor, wherein the binary number has two or more verification bits. The binary number may be 12 bits.

[0009] In another aspect of the invention, the temperature indicator may have various LED or LCD configurations, such as a single LED, 12 LEDs, 14 LEDs, a single LCD, 12 LCDs, or 14 LCDs.

[0010] In another aspect of the invention, the temperature verification circuit also includes a battery and a switch. The battery provides power to the temperature verification circuit. When the switch is in the "on" position, the switch allows current to flow from the battery, while when the switch is in the "off" position, the switch prevents current from flowing from the battery.

[0011] In another aspect of the invention, the temperature sensor acquires temperature measurements at a first recurring interval over a first predetermined time period. The temperature indicator outputs the average value of the temperature measurements.

[0012] The first predetermined time length can be approximately 5 seconds, and the first cycle interval can be approximately 0.1 seconds.

[0013] In another aspect of the invention, a method for verifying the temperature performance of a bacterial endotoxin reader includes: providing a reader and a temperature verification plate (TVP); placing the TVP on the spindle of the reader, rotating the TVP upward using the spindle, and activating the reader's heater to maintain the body temperature of the TVP at a predetermined temperature; obtaining a temperature measurement value of the TVP body from a temperature indicator of the TVP using the reader's optical stage; obtaining a temperature measurement value of the TVP body using a temperature measurement sensor of the reader; calculating and comparing the difference between the temperature measurement value obtained from the temperature indicator of the TVP and the temperature measurement value obtained from the temperature measurement sensor of the reader; and indicating a calibration error of the reader's temperature measurement sensor when the difference is greater than a predetermined temperature difference threshold.

[0014] In another aspect of the invention, the method further includes calculating a calibration factor based on the difference between the temperature measurement value obtained from the TVP and the temperature measurement value obtained from the reader's temperature sensor, and applying the calibration factor to the temperature measurement value obtained from the reader's temperature sensor. The predetermined temperature difference threshold may be approximately 1°C, approximately 0.5°C, or approximately 0.1°C. The difference may be calculated at two or more predetermined temperatures. The predetermined temperatures may be 22°C and / or 37°C.

[0015] In another aspect of the invention, the method further includes calculating a calibration factor based on the difference between temperature measurements obtained from the TVP at two or more predetermined temperatures and temperature measurements obtained from the reader's temperature sensor at two or more predetermined temperatures, and applying the calibration factor to the temperature measurements obtained from the reader's temperature sensor. The calibration factor can be determined using linear interpolation and / or mathematical regression.

[0016] In another aspect of the invention, an optical verification plate (OVP) for a bacterial endotoxin reader may include: a body having a plurality of holes positioned along the periphery of the body; the center of each hole being positioned at a first predetermined radial distance away from the center of the body, thereby allowing the hole to be aligned with the optical stage of the reader, such that light generated by a light source of the reader can pass through the hole and the intensity of the light can be measured by a photodetector of the reader; the holes consist of filtered holes and unfiltered holes; the filtered holes are spaced a second predetermined distance when traveling counterclockwise around the OVP.

[0017] In another aspect of the invention, the filter aperture may consist of one or more neutral density filter apertures and one or more wavelength filter apertures. The one or more wavelength filter apertures may consist of one or more short-pass filter apertures, one or more long-pass filter apertures, one or more band-pass filter apertures, and / or one or more stopband filter apertures. The filter aperture may consist of at least one wavelength filter aperture and a second neutral density filter aperture. At least one wavelength filter aperture may consist of one long-pass filter aperture and one short-pass filter aperture. One or more filters may be mounted on the OVP to form a first predetermined angle relative to the top surface of the OVP body, and / or one or more filters may be mounted on the OVP to form a first predetermined angle relative to the filter bed of the OVP body. The first predetermined angle may be approximately zero degrees, approximately 30 degrees, or between approximately zero degrees and approximately 45 degrees.

[0018] On the other hand, OVP may include an entrance aperture and / or a registration aperture. The entrance aperture may be located between the first filter aperture and the registration aperture. The registration aperture may be located between the entrance aperture and the final filter aperture.

[0019] In another aspect of the invention, a method for verifying the optical performance of an optical stage of a bacterial endotoxin reader includes: providing a reader and an optical verification plate (OVP); placing the OVP on the spindle of the reader and rotating the OVP upwards; identifying a registration pattern on the OVP using the optical stage of the reader; and measuring the intensity of light passing through the entrance aperture of the OVP using a photodetector of the reader, wherein the light is generated by a light source of the reader, and the measured value is used as the incident light (I0). i The light intensity is stored in the reader's memory; the intensity of light passing through at least one neutral density filter aperture is measured using the reader's photodetector, wherein the light is generated by the reader's light source, and the measured value is used as the intensity neutral measurement value (I). fN The data is stored in the reader's memory, where N increments once for each neutral density filter aperture, and the measurement is repeated for each neutral density filter aperture; using formula T... N = (I fN / I i ) Calculate the transmittance (T) of each neutral density filter aperture. N ) and store it in the reader's memory; using formula A mN = -log 10 (T) N ) Calculate the measured absorbance (A) of each neutral density filter aperture. mN ) and store it in the reader's memory; by using the formula AError N = (A mN - A pN ) / A pNCalculate the percentage error to determine the A value of each neutral density filter aperture. mN Compared with the predetermined absorbance value (A) pN The comparison is performed, and the percentage error of absorbance calculated for each neutral density filter aperture is stored in memory; AError is then set to... N Compare with the predetermined neutral density absorbance error threshold, and if AError N If the absorbance exceeds the predetermined neutral density absorbance error threshold, it indicates that the optical stage does not meet the specifications; the intensity of light passing through at least one wavelength filter aperture is measured using the reader's photodetector, where the light is generated by the reader's light source, and the measured value is used as the intensity wavelength measurement value (I). WN The value is stored in memory, where N increments once for each wavelength filter aperture, and the measurement is repeated for each wavelength filter aperture; this is achieved by using the formula WError. N= I WN / I i Evaluation of I for each wavelength filter aperture WN and I i The ratio is used to calculate the wavelength error (WError) of the optical stage. N ), and store it in memory; and will set the WError for each wavelength filter aperture. N Compare with a predetermined wavelength error threshold, and if WError N If the error exceeds the predetermined error wavelength threshold, it indicates that the optical stage does not meet the specifications.

[0020] In another aspect of the invention, the filter aperture may include one or more neutral density filter apertures and one or more wavelength filter apertures. The one or more wavelength filter apertures may include one or more short-pass filter apertures, one or more long-pass filter apertures, one or more band-pass filter apertures, and / or one or more stopband filter apertures. The filter aperture may include at least one wavelength filter aperture and a second neutral density filter aperture. The at least one wavelength filter aperture may include at least one long-pass filter aperture and one short-pass filter aperture.

[0021] In another aspect of the invention, one or more filters may be mounted on the OVP to form a first predetermined angle relative to the top surface of the OVP body, and / or one or more filters may be mounted on the OVP to form a first predetermined angle relative to the filter bed of the OVP body. The first predetermined angle may be approximately zero degrees, approximately 30 degrees, or between approximately zero degrees and approximately 45 degrees.

[0022] In another aspect of the invention, a bacterial endotoxin reader includes a control unit and a memory storing executable code that, when executed by the control unit, performs actions including: rotating an optical verification plate (OVP) placed on the reader's spindle upwards using the reader's spindle; identifying a registration pattern on the OVP using the reader's optical stage; measuring the intensity of light passing through an entrance aperture of the OVP using a photodetector of the reader, wherein the light is generated by a light source of the reader, and the measured value is stored as incident light (Ii) in the reader's memory; and measuring the intensity of light passing through at least one neutral density filter aperture using a photodetector of the reader, wherein the light is generated by a light source of the reader, and the measured value is stored as an intensity neutral measurement (Ii). fN The data is stored in the reader's memory, where N increments once for each neutral density filter aperture, and the measurement is repeated for each neutral density filter aperture; using formula T... N = (I fN / I i ) Calculate the transmittance (T) of each neutral density filter aperture. N ), and store it in the reader's memory; using formula A mN = -log 10 (T) N Calculate the measured absorbance (A) for each neutral density filter aperture. mN ) and store it in the reader's memory, and store it in the memory; by using the formula AError N = (A) mN -A pN ) / A pN Calculate the percentage error to determine the A value of each neutral density filter aperture. mN Compared with the predetermined absorbance value (A) pN The comparison is performed, and the percentage error of absorbance calculated for each neutral density filter aperture is stored in memory; AError is then set to... N Compare with the predetermined neutral density absorbance error threshold, and if AError N If the absorbance exceeds the predetermined neutral density absorbance error threshold, it indicates that the optical stage does not meet the specifications; the intensity of light passing through at least one wavelength filter aperture is measured using the reader's photodetector, where the light is generated by the reader's light source, and the measured value is used as the intensity wavelength measurement value (I). WN The data is stored in memory, where N increments once for each wavelength filter aperture, and the measurement is repeated for each wavelength filter aperture; this is done using the formula WError. N= I WN / I i Evaluate I for each wavelength filter aperture WN and I iThe ratio is used to calculate the wavelength error (WError) of the optical stage. N ), and store it in memory; and set the WError for each wavelength filter aperture. N Compare with a predetermined wavelength error threshold, and if WError N If the error exceeds the predetermined error wavelength threshold, it indicates that the optical stage does not meet the specifications.

[0023] In another aspect of the invention, a bacterial endotoxin reader includes: a control unit and a memory storing executable code, which, when executed by the control unit, performs actions including: rotating a temperature verification plate (TVP) placed on the spindle of the reader upward using the spindle of the reader; activating the heater of the reader to maintain the temperature of the body of the TVP at a predetermined temperature; obtaining a temperature measurement value of the body of the TVP from a temperature indicator of the TVP using the optical stage of the reader and storing the temperature measurement value in the memory; obtaining a temperature measurement value of the body of the TVP using a temperature measurement sensor of the reader and storing the temperature measurement value in the memory; calculating a difference between the temperature measurement value obtained from the temperature indicator of the TVP and the temperature measurement value obtained from the temperature measurement sensor of the reader, storing it in the memory, and comparing the difference; and indicating a calibration error of the temperature measurement sensor of the reader when the difference is greater than a predetermined temperature difference threshold.

[0024] In another aspect of the invention, when executed by the control unit, the code execution includes the additional action of applying a calibration factor to the temperature measurement value obtained from the temperature measurement sensor of the reader based on the difference between the temperature measurement value obtained from the TVP and the temperature measurement value obtained from the temperature sensor of the reader.

[0025] In another aspect of the invention, when executed by the control unit, the code execution includes the additional action of: calculating a calibration factor based on the difference between temperature measurements obtained from the TVP at two or more predetermined temperatures and temperature measurements obtained from the reader temperature sensor at two or more predetermined temperatures, and applying the calibration factor to the temperature measurements obtained from the reader temperature sensor.

[0026] In another aspect of the invention, when executed by the control unit, code execution includes additional actions such as determining calibration factors using linear interpolation and / or mathematical regression.

[0027] The advantages of the invention will become more apparent to those skilled in the art from the following description of embodiments of the invention (which have been shown and described by way of illustration). As will be appreciated, the invention is capable of having other and different embodiments, and its details can be modified in various respects.

[0028] Brief description of several views in the accompanying drawings

[0029] These and other features and advantages of the invention are specifically illustrated with reference to the accompanying schematic diagrams, which will now be described by way of example in embodiments of the invention:

[0030] Figure 1A This is an isometric view of an illustrative reader and verification board according to exemplary embodiments of the disclosed technology;

[0031] Figure 1B This is a block diagram of an illustrative reader according to exemplary embodiments of the disclosed technology;

[0032] Figure 2A This is a cross-section of an illustrative reader according to exemplary embodiments of the disclosed technology;

[0033] Figure 2B This is a cross-section of an illustrative reader according to exemplary embodiments of the disclosed technology;

[0034] Figure 2C This is a cross-section of an illustrative reader according to exemplary embodiments of the disclosed technology;

[0035] Figure 3 This is an isometric view of an illustrative temperature verification panel according to exemplary embodiments of the disclosed technology;

[0036] Figure 4 This is a top view of an illustrative temperature verification panel according to exemplary embodiments of the disclosed technology;

[0037] Figure 5 This is a block diagram of an illustrative temperature verification panel according to exemplary embodiments of the disclosed technology;

[0038] Figure 6 This is a flowchart of an example method for using a temperature verification plate according to an exemplary embodiment of the disclosed technology;

[0039] Figure 7 This is a flowchart of an example method for verifying reader temperature measurements using a temperature verification board according to an exemplary embodiment of the disclosed technology;

[0040] Figure 8A This is an isometric view of an illustrative reader and an optical verification plate according to exemplary embodiments of the disclosed technology;

[0041] Figure 8B This is a cross-section of an illustrative reader and an optical verification plate according to exemplary embodiments of the disclosed technology;

[0042] Figure 9AThis is a top view of an illustrative optical verification panel according to exemplary embodiments of the disclosed technology;

[0043] Figure 9B This is a cross-section of an illustrative optical verification plate according to exemplary embodiments of the disclosed technology;

[0044] Figure 9C This is a cross-section of an illustrative optical verification plate according to exemplary embodiments of the disclosed technology;

[0045] Figure 10 This is an illustrative graph of the transmittance versus wavelength for a short-pass filter and a long-pass filter according to exemplary embodiments of the disclosed technology; and

[0046] Figures 11A-11B This is a flowchart of an example method for verifying optical measurements of a reader using an optical verification board, according to an exemplary embodiment of the disclosed technology.

[0047] It should be noted that all the accompanying drawings are illustrative rather than to scale. For clarity and convenience, the relative dimensions and proportions of the parts in these drawings have been exaggerated or reduced. The same reference numerals are generally used to refer to corresponding or similar features in different embodiments. Accordingly, the drawings and descriptions are considered to be illustrative rather than restrictive in nature.

[0048] Detailed Description of Preferred Embodiments

[0049] The approximate language used throughout this specification and claims can be used to modify any quantity representations that allow for change without altering the underlying functionality associated with them. Therefore, values ​​modified by one or more terms (such as “approximately”) are not limited to specified exact values. In at least some cases, approximate language may correspond to the precision of the instrument used to measure the value. Range limitations can be combined and / or interchanged, and unless otherwise indicated by context or language, these ranges are identified and include all subranges described herein. Except in operational examples or where otherwise indicated, all numbers or expressions relating to amounts of ingredients, reaction conditions, etc., used in the specification and claims should be understood to be modified by the term “approximately” in all instances.

[0050] "Optional" or "optionally" means that the event or situation described below may or may not occur, or that the material identified below may or may not be present, and the description includes instances of the event or situation occurring or the material being present, as well as instances of the event or situation not occurring or the material not being present.

[0051] As used herein, the terms “comprises,” “comprising,” “includes,” “including,” “has,” “having,” or any other variation thereof are intended to cover non-exclusive inclusion. For example, a process, method, article, or apparatus that comprises a list of elements is not necessarily limited to those elements, but may include other elements not expressly listed or inherent to such process, method, article, or apparatus.

[0052] The singular forms “a”, “an”, and “the” include references to the plural unless the context clearly indicates otherwise.

[0053] As used herein, a "processor" processes signals and performs general computational and arithmetic functions. Signals processed by a processor can include digital signals, data signals, computer instructions, processor instructions, messages, bits, bit streams, or other means that can be received, transmitted, and / or detected. Typically, a processor can be a variety of different processor architectures, including multiple single-core and multi-core processors and coprocessors, as well as other single-core and multi-core processor and coprocessor architectures. A processor can include various modules that perform a variety of functions.

[0054] As used herein, "memory" can include volatile memory and / or non-volatile memory. Non-volatile memory can include, for example, ROM (Read-Only Memory), PROM (Programmable Read-Only Memory), EPROM (Erasable PROM), and EEPROM (Electrically Erasable PROM). Volatile memory can include, for example, RAM (Random Access Memory), Synchronous RAM (SRAM), Dynamic RAM (DRAM), Synchronous DRAM (SDRAM), Double Data Rate SDRAM (DDRSDRAM), and Direct RAM Bus RAM (DRRAM). Memory can also include drives (disks). Memory can store the operating system that controls or allocates resources of a computing device. Memory can also store data for use by the processor.

[0055] As used herein, "controller" can include various configurations (such as processors and memory). A controller can also include a microcontroller with onboard processors and memory.

[0056] As used herein, "drive" can refer to, for example, a magnetic drive, a solid-state drive, a floppy disk drive, a magnetic tape drive, a Zip drive, a flash memory card, and / or a memory stick. Furthermore, a drive can be a CD-ROM (optical disc ROM), a CD-R drive (recordable CD-RW drive), and / or a digital video ROM drive (DVD ROM). A drive can store an operating system and / or programs that control or allocate resources for a computing device.

[0057] Some parts of the following detailed description are presented based on algorithms and symbolic representations of operations on data bits within computer memory. These algorithmic descriptions and representations are means used by those skilled in the art of data processing to most effectively communicate the essence of their work to others skilled in the art. Algorithms are, and generally are, conceived herein as a self-consistent sequence of steps (instructions) leading to a desired result. These steps are those that require physical manipulation of physical quantities. Typically, though not necessarily, these quantities take the form of non-transitory electrical, magnetic, or optical signals that can be stored, transmitted, combined, compared, and otherwise manipulated. Primarily for general use, it is sometimes convenient to refer to these signals as bits, values, elements, symbols, characters, terms, numbers, etc. Furthermore, it is sometimes convenient to refer to certain arrangements of steps requiring physical manipulation or transformation of physical quantities or representation of physical quantities as modules or code devices, without loss of generality.

[0058] However, all these and similar terms are associated with appropriate physical quantities and are merely convenient labels applied to those quantities. Unless otherwise explicitly stated (as is apparent from the following discussion), it should be understood that throughout the description, discussions using terms such as “processing” or “computing” or “operation” or “determining” or “displaying” refer to the actions and processes of a computer system or similar electronic computing device (e.g., a particular computing machine), whose manipulation and transformation are represented as data of physical (electronic) quantities within the computer system’s memory or registers or other such information storage, transmission, or display devices.

[0059] Certain aspects of the embodiments described herein include processing steps and instructions described herein in algorithmic form. It should be noted that the processing steps and instructions of the embodiments may be embodied in software, firmware, or hardware, and when embodied in software, may be downloaded to reside on and operate from various platforms used by different operating systems. The embodiments may also be in a computer program product executable on a computing system.

[0060] The embodiments also relate to means for performing the operations described herein. This means may be specifically constructed for a purpose (e.g., a particular computer), or it may comprise a general-purpose computer selectively activated or reconfigured by a computer program stored in the computer. Such a computer program may be stored in a non-transitory computer-readable storage medium, such as, but not limited to, any type of drive, including floppy disk drives (disks), optical drives (disks), CD-ROMs, magneto-optical drives (disks), read-only memory (ROM), random access memory (RAM), EPROM, EEPROM, magnetic cards or optical cards, application-specific integrated circuits (ASICs), or any type of medium suitable for storing electronic instructions, and each medium is electrically connected to a computer system bus. Furthermore, the computer mentioned in the specification may include a single processor, or may be an architecture employing multiple processors to increase computing power.

[0061] The algorithms and displays presented herein are not inherently related to any particular computer or other device. Various general-purpose systems may also be used with the procedures described herein, or it may prove convenient to construct more specialized devices to perform the method steps. The structures of various such systems will be presented in the following description. Furthermore, the embodiments are described without reference to any particular programming language. It will be understood that the teachings of the embodiments described herein can be implemented using various programming languages, and any references to specific languages ​​below are provided for the purpose of enabling and best mode of the disclosed embodiments.

[0062] Furthermore, the language used in this specification has been chosen primarily for readability and instruction purposes and may not be construed as describing or limiting the subject matter of the invention. Therefore, the disclosure of the embodiments is intended to be illustrative and not to limit the scope of the embodiments set forth in the claims.

[0063] Go to Figures 1A-7 If the temperature measurement at the reaction well of the reaction disk within the bacterial endotoxin reader 100 is outside the specified range, the bacterial endotoxin reaction results may be negatively affected. Furthermore, if the light source 130 and / or photodetector 135 of the reader 100 are not operating within the specified range, the results may be negatively affected. The light source and sensors measure the optical response of the plate (disk) 103, which can be a reaction plate or a validation plate 200.

[0064] Verification of the temperature and / or optical performance of the reader 100 is performed using a verification board 200 (e.g., a temperature verification board (TVP) 300 and / or an optical verification board (OVP) 800) that is detachably mounted to the spindle 105 of the reader 100.

[0065] TVP 300 can wirelessly report the temperature at a specific location on the body 335 of TVP to reader 100. TVP 300 can be used to verify that the heater 110 and temperature sensor 115 of reader 100 are operating correctly. In an embodiment, temperature sensor 115 can be one or more infrared temperature sensors. In an embodiment, heater 110 of reader 100 can consist of an upper heater 110a and a lower heater 110b, and temperature sensor 115 of reader 100 can consist of an upper temperature sensor 115a and a lower temperature sensor 115b, for maintaining the temperature of reaction chamber 140 of reader 100 at a predetermined temperature, for example, measuring the temperature at a predetermined location on TVP 300 and maintaining the temperature at the predetermined location on TVP 300 at the predetermined temperature. Upper heater 110a heats the top surface 336 of TVP 300 at a predetermined location on TVP 300, and lower heater 110b heats the bottom surface 337 of TVP 300 at a predetermined location to maintain the predetermined temperature. In an embodiment, the predetermined temperature can be approximately 37°C. In some embodiments, when the TVP 300 rotates within the reader 100 during use, a predetermined temperature is maintained at a first predetermined radial distance away from the center of the spindle 105 on the TVP 300. This first predetermined radial distance can also be a radial distance away from the center of the spindle 105, where the temperature sensor 115 of the reader 100 measures the temperature of the TVP 300. This first predetermined radial distance... Figure 3 The distance between the center of the spindle 105 and the center of the aperture 125 of the optical stage 120 of the reader 100 is also equal to the first predetermined radial distance "A". This first predetermined radial distance can also be equal to the distance between the spindle 105 and the position of the reaction well on the reaction plate 103. In an exemplary embodiment, the first predetermined radial distance "A" is approximately 98 mm. In an exemplary embodiment, the aperture 125 may be a window that allows light to pass through but prevents dust and / or fluid intrusion into the optical stage 120.

[0066] In other words, since the goal of TVP 300 and OVP 800 is to verify the operation of the temperature control and optical measurement capabilities of the reader 100 at the location of the reaction well on the reaction plate, the radial distance "A" in the embodiment of the reader 100 can be equivalent to the radial distance between the center of the spindle 105 and the location of the reaction well on the reaction plate 103 when placed in the reader 100, the radial distance between the center of the spindle 105 and the location on the TVP 300 where a predetermined temperature is measured and maintained using temperature sensor 115 and heater 110, the radial distance between the center of the spindle 105 and the location of the TVP temperature sensor 315, the radial distance between the center of the spindle 105 and the location of the TVP temperature indicator 320, the radial distance between the center of the spindle 105 and the location of temperature sensor 115, the radial distance between the center of the spindle 105 and the location of heater 110, the radial distance between the center of the TVP 300 and the location on the TVP 300 where a predetermined temperature is measured and maintained using temperature sensor 115 and heater 110, and the radial distance between the center of the TVP 300 and the location on the TVP 300 where a predetermined temperature is measured and maintained using temperature sensor 115 and heater 110. The radial distance between the center of TVP 300 and the position of TVP temperature sensor 315, the radial distance between the center of TVP 300 and the position of TVP temperature indicator 320, the radial distance between the center of spindle 105 and the position on OVP 800 (at which the optical stage 120 of reader 100 uses light source 130 and photodetector 135 to output light to OVP 800 and measure the light passing through OVP 800), the radial distance between the center of spindle 105 and the hole 805 of OVP 800, the radial distance between the center of OVP 800 and the position on OVP 800 (at which the optical stage 120 of reader 100 uses light source 130 and photodetector 135 to output light to OVP 800 and measure the light passing through OVP 800), and the radial distance between the center of OVP 800 and the position on OVP 800. The radial distance between holes 805 of 800, and / or the radial distance between the center of spindle 105 and / or the position of light source 130 and photodetector 135 of optical stage 120.

[0067] The TVP 300 has a temperature verification circuit 301, which may include a TVP controller 305, a battery 310, a temperature sensor 315, and a temperature indicator 320. The TVP 300 may also include a switch 325, a counterweight 330 for balancing the TVP 300, a body 335, and a temperature sensor channel 316 in the body 335 containing the temperature sensor 315. The body 335 may be made of a material having the same emissivity as the reaction disk, such that the temperature sensor 115 of the reader 100 measures the temperature of both the reaction disk and the TVP 300 with the same accuracy. The body 335 may be made of the same material as the reaction disk body. The body 335 may be made of one or more of polystyrene, cyclic olefin copolymers, and / or ethylene glycol-modified polyethylene terephthalate, but is not limited thereto. In some embodiments, carbon may be added to the body 335 to blacken the polystyrene to aid in optical absorbance methods. Furthermore, one or more components of the temperature verification circuit 301 may be located below the top surface 336 of the body 335 and may have a cover, such as a battery 310, a temperature indicator 320, and a temperature sensor 315. The body 335 may also have a bottom surface 337 located on the body 335 opposite to the top surface 336.

[0068] The controller 305 has a memory 307 and a processor 306. The battery 310 provides power to the controller 305, temperature sensor 315, and temperature indicator 320 of the temperature verification circuit 301 of the TVP 300. The switch 325 turns the temperature verification circuit 301 on and off, for example, by controlling (starting and stopping) the current flow between the battery 310 and other components of the temperature verification circuit 301. The temperature sensor 315 measures the temperature and provides the measured value to the controller 305. The temperature sensor 315 can be an electronic temperature sensor, such as a thermistor, thermocouple, and / or resistance temperature detector. The radial distance between the center of the TVP 300 and the temperature sensor 315 can also be equal to a first predetermined radial distance “A”, which is the same distance between the center of the spindle 105 and the center of the hole 125 of the optical stage 120 of the reader 100. Therefore, in an exemplary embodiment, when the temperature sensor 115 of the reader 100 measures the temperature of the body 335 of the TVP 300, the temperature sensor 315 of the TVP 300 measures the temperature of the body 335 of the TVP 300 at a precise radial position at the same distance from the center of the TVP 300 (and the spindle 105). This is in Figure 2CAs shown, the field of view 117 of the reader temperature sensor 115 includes the travel path of the board temperature sensor 315. As can be seen, the upper field of view 117a of the upper reader temperature sensor 115a includes the travel path of the board temperature sensor 315. Furthermore, the lower field of view 117b of the lower reader temperature sensor 115b includes the travel path of the board temperature sensor 315.

[0069] The optical stage 120 includes a light source 130 and a photodetector 135 for measuring the optical response of a reaction occurring within a reaction well in a reaction dish (reaction plate). The photodetector 135 may include a printed circuit board having power supply circuitry for supplying power to the photodetector 135 and signal processing circuitry for digitizing the output of the photodetector 135 to provide a digital output from the photodetector 135. The light source 130 may include a printed circuit board having power supply circuitry for supplying power to the light source 130. The controller 305 uses a temperature indicator 320 to optically represent the temperature value measured by the temperature sensor 315. In an exemplary embodiment, the temperature indicator 320 may consist of at least one visual element 321 that can be state-changeable (on / off) to indicate "1" or "0". In an exemplary embodiment, the visual element 321 may be, for example,... Figure 2A The LED lights shown or such Figure 2B The LCD shown is an example. In other embodiments, the temperature indicator 320 may consist of at least one LED and / or an LCD. The temperature indicator 320 may be registered with the reader 100 so that the orientation of the TVP 300 is matched with the timing of the measurement performed by the photodetector 135. This allows the reader 100 to make accurate measurements as each visual element 321 of the temperature indicator 320 passes below the photodetector 135.

[0070] In an exemplary embodiment, the temperature indicator 320 may consist of at least one LED (e.g., a single LED or an array of LEDs) to optically represent the value. In an exemplary embodiment, the LED array may be a 12-LED array whose blinking represents the temperature measurement value of the temperature sensor 315 in binary form, which can be read by the photodetector 135 of the reader 100. In some embodiments, when the bit value of the temperature measurement is less than or equal to the number of LEDs available to represent the temperature on the temperature indicator 320, the temperature measurement value may be transmitted by the TVP 300 to the photodetector 135 of the reader 100 during a single rotation of the TVP 300. In other embodiments, when the temperature measurement value of the temperature sensor 315 is greater than a single bit and the temperature indicator 320 has one LED available to represent the temperature, the temperature measurement value may be transmitted by the TVP 300 to the photodetector 135 of the reader 100 at a rate of one bit per rotation of the TVP 300.

[0071] In some exemplary embodiments, when the temperature measurement value of the temperature sensor 315 is a 12-digit number and the temperature indicator 320 has 12 LEDs that can be used to indicate the temperature, the temperature measurement value can be transmitted by the TVP 300 to the photodetector 135 of the reader 100 during a single rotation of the TVP 300.

[0072] In other exemplary embodiments, when the temperature measurement value of the temperature sensor 315 is 12 digits and the temperature indicator 320 has an LED that can be used to indicate the temperature, the temperature measurement value can be transmitted by the TVP 300 to the photodetector 135 of the reader 100 after the TVP 300 rotates 12 times, wherein the TVP 300 transmits one bit for each rotation. In this embodiment, the rotation speed of the TVP 300 can be coordinated with the timing of the LED so that with each rotation, the next bit indicates ("on" or "off").

[0073] In other exemplary embodiments, a temperature indicator 320 having multiple LEDs that can be used to represent temperature measurements from a temperature sensor 315 can transmit the temperature measurement to a photodetector 135 of a reader 100 using more than one rotation of the TVP 300. For example, a 12-bit temperature measurement can be represented by 2, 3, 4, or 6 LEDs, for which the 12-bit binary number is then transmitted from the temperature indicator 320 to the photodetector 135 during 6, 4, 3, or 2 rotations of the TVP 300. Furthermore, the temperature indicator 320 can even transmit binary temperature measurements that are not divisible by the number of LEDs in the temperature indicator 320; for example, a 13-bit temperature measurement can be represented by 5 LEDs during three rotations of the TVP 300.

[0074] In an exemplary embodiment, the temperature indicator 320 may consist of at least one LCD (e.g., a single LCD or an array of 12 LCDs) to optically represent the value, with changes in the opacity of these LCDs representing the temperature measurement value of the temperature sensor 315 in binary form. Changes in the opacity of the LCDs allow light generated by the light source 130 to pass through the LCDs and illuminate the photodetector 135, which may represent a "1", or reduce the amount of light generated by the light source 130 illuminating the photodetector 135, or block light generated by the light source 130 from illuminating the photodetector 135, which may represent a "0". In some embodiments, when the bit value of the temperature measurement is less than or equal to the number of LCDs available to represent the temperature on the temperature indicator 320, the temperature measurement value may be transmitted by the TVP 300 to the photodetector 135 of the reader 100 during a single rotation of the TVP 300. In other embodiments, when the temperature measurement value of the temperature measuring sensor 315 is greater than a single digit and the temperature indicator 320 has an LCD that can be used to display the temperature, the temperature measurement value can be transmitted by the TVP 300 to the photodetector 135 of the reader 100 at a rate of one digit per rotation of the TVP 300.

[0075] In an exemplary embodiment, the temperature indicator 320 may consist of at least one LCD (e.g., a single LCD or an array of 12 LCDs) to optically represent the value. Changes in the opacity of these LCDs represent the temperature measurement value of the temperature sensor 315 in binary form. Changes in the LCD opacity allow light generated by the light source 130 to pass through the LCD and illuminate the photodetector 135, which may represent a "1", or reduce the amount of light generated by the light source 130 illuminating the photodetector 135, or block light generated by the light source 130 from illuminating the photodetector 135, which may represent a "0". When the temperature measurement value of the temperature sensor 315 is 12 digits and the temperature indicator 320 has 12 LCDs available for representing the temperature, the temperature measurement value can be transmitted from the TVP 300 to the photodetector 135 of the reader 100 during a single rotation of the TVP 300, thereby transmitting the temperature value from the TVP 300 to the reader 100. When the temperature measurement value of the temperature sensor 315 is 12 digits and the temperature indicator 320 has an LCD that can be used to display the temperature, the temperature measurement value can be transmitted from the TVP 300 to the photodetector 135 of the reader 100 after the TVP 300 rotates 12 times, thereby transmitting the temperature value from the TVP 300 to the reader 100. In this embodiment, the rotation speed of the TVP can be coordinated with the timing of the LCD so that with each rotation, the next digit indicates ("allow light to pass" or "block light").

[0076] In other exemplary embodiments, a temperature indicator 320 having multiple LCD lights for representing temperature measurements from a temperature sensor 315 can transmit the temperature measurement to a photodetector 135 of a reader 100 using more than one rotation of a TVP 300. For example, a 12-bit temperature measurement can be represented by 2, 3, 4, or 6 LCDs, for which the 12-bit binary number is then transmitted from the temperature indicator 320 to the photodetector 135 during 6, 4, 3, or 2 rotations of the TVP 300. Furthermore, the temperature indicator 320 can even transmit binary temperature measurements that are not divisible by the number of LCDs in the temperature indicator 320; for example, a 13-bit temperature measurement can be represented by 5 LCDs during three rotations of the TVP 300.

[0077] This method of using light instead of radio frequency to transmit temperature values ​​from the TVP 300 to the reader 100 allows the TVP 300 to be used in areas where radio frequency is highly tuned or where potential radio interference may exist. Furthermore, the TVP 300 design allows the use of existing optical stage 120, which also eliminates the need to integrate an RF receiver or transceiver into the reader 100.

[0078] Proceeding to method 600 for measuring temperature using TVP 300, in 601, the method proceeds to 605 when TVP 300 is activated. TVP 300 can be activated when switch 325 is moved to the "ON" position. In 605, TVP uses temperature sensor 315 to obtain at least one temperature measurement value over a first predetermined time length and sends the measurement value to controller 305. In an exemplary embodiment, at least one temperature measurement value can be obtained using temperature sensor 315 during the first predetermined time length, and the measurement value can be provided to controller 305. Furthermore, when more than one temperature measurement value is obtained and provided to controller 305, the measurement values ​​can be obtained at a first cycle interval during the first predetermined time length. When one or more temperature measurement values ​​are provided to controller 305 during the first predetermined time length, controller 305 can average the temperature measurement values ​​obtained during the first predetermined time length. In an exemplary embodiment, the first predetermined time length can be approximately 5 seconds, and the first cycle interval can be approximately 0.1 seconds.

[0079] In step 610, at least one temperature measurement value obtained in step 605 is output (transmitted) by the controller 305 of the TVP 300 using the temperature indicator 320 within a second predetermined time length. In an exemplary embodiment, the second predetermined time length may be approximately 0.4 seconds. This value may be the average of the temperature measurement values ​​obtained during the first predetermined time length. Before outputting, the controller 305 may convert the value from a numerical value to a binary value. In an exemplary embodiment, the numerical value may be converted to a 12-bit binary value and output using 12 LEDs of the temperature indicator 320. However, it is conceivable that the numerical value may be converted to different binary resolutions and may be output using different numbers of LEDs or an LCD on the temperature indicator 320. The temperature indicator 320 and the controller 305 may also output verification information that notifies the reader 100 that the measurement is valid. In an embodiment, the verification information may be an additional "1" bit at the beginning and end of the 12-bit number, for a total of 14 bits, where only the middle 12 bits indicate the temperature measurement value. In some embodiments where the temperature output is a 12-digit number plus an additional 2 digits for verification, the temperature indicator 320 may have 12 LEDs or an LCD to enable the transmission of measurement and verification information during a single rotation of the TVP, or a single LED or LCD may be used to enable the transmission of measurement and verification information over 14 rotations of the TVP 300. The method then returns to 601 and proceeds to 605 while the TVP 300 remains active. In an exemplary embodiment, the TVP 300 remains active while the switch 325 remains in the "on" position.

[0080] A block diagram of component 106 of reader 100 that interacts with reader controller 145 is shown in Figure 1BAs shown in the diagram, the controller 145 comprises a memory 119 and a CPU (processor) 118 that executes programs stored in the memory 119. The controller interfaces with a user interface 113, a spindle 105, a plate 103, an optical stage 120, and a reaction chamber augmenter 155. In some embodiments, the user interface 113 may also interact with the controller 145. In one embodiment, the housing 101 may have at least one reaction chamber augmenter, such as a heater 110 and / or a temperature sensor 115 for regulating the temperature within the reaction chamber 140 of the housing 101 and the plate 103. The plate 103 provides position information to the controller 145. The optical stage 120 provides the controller 145 with information about the intensity of light received by the photodetector 135. The reaction chamber augmenter 155 (e.g., the temperature sensor 115) provides the controller 145 with a measurement of the temperature of the plate 103 at the reaction well location on the reaction plate, and the controller 145 uses this information to determine whether the heater 110 should be activated within the housing 101. User interface 113 allows users to provide test parameters to controller 145 and allows controller 145 to display test results to users. The spindle 105 with a motor can provide position information to controller 145 and also allows controller 145 to adjust the rotation of plate 103 via user interface 113.

[0081] Proceeding to method 700 (temperature verification mode) for verifying the temperature measurement performance of reader 100, in 701, TVP 300 is activated, for example, by moving a switch to the "ON" position, and TVP 300 is placed in reader 100. TVP 300 measures and outputs the temperature at temperature sensor 115 according to method 600. As can be seen, TVP 300 measures the temperature of its body 335 as it rotates by spindle 105 of reader 100. In 705, reader 100 is placed in temperature verification mode via user interface 113. In 710, reader 100 rotates TVP 300 upward using spindle 105 and maintains this rotation in temperature verification mode. The rotation of TVP 300 allows reader temperature sensor 115 and heater 110 to be tested under the same conditions when a reaction plate is present in reader 100. In 715, the heater 110 and the reader temperature sensor 115 are activated by the reader controller 145 to heat the body 335 of the TVP 300 and maintain it at a predetermined temperature.

[0082] In step 720, once the body of the TVP is maintained at a predetermined temperature for at least a first predetermined time length, the reader 100 uses the reader temperature sensor 115 to obtain a temperature measurement of the body of the TVP 300. The TVP 300 obtains and outputs the temperature measurement using the temperature indicator 320 according to method 600, and the reader 100 receives the temperature measurement of the TVP 300 and optionally a verification bit using the optical stage 120. In an exemplary embodiment, the reader 100 may obtain temperature measurements of the bottom surface 337 and / or the top surface 336 on the body 335. In an exemplary embodiment, the temperature measurement may be output from the TVP 300 in a 12-bit binary format. Optionally, the temperature measurement from the TVP 300 may be converted from binary to decimal and scaled for the measurement range of the temperature verification circuit 301 of the TVP 300, for example, by using the following formula:

[0083] ,in:

[0084] N = 12-bit temperature received from TVP 300 (in degrees Celsius);

[0085] UT = TVP 300, the upper limit of temperature measurement (in degrees Celsius);

[0086] LT = TVP 300 lower limit of temperature measurement (in degrees Celsius).

[0087] In step 725, reader 100 calculates and compares the difference between the temperature measurement obtained from TVP 300 (also known as the TVP temperature measurement) and the temperature measurement obtained from reader temperature sensor 115 (also known as the reader temperature measurement). In step 730, if the difference between the TVP temperature measurement and the reader temperature measurement is less than or equal to a predetermined temperature difference threshold, the calibration of reader temperature sensor 115 is verified, and the user is notified via user interface 113. If the difference between the TVP temperature measurement and the reader temperature measurement is greater than the predetermined temperature difference threshold, the calibration of temperature sensor 115 is not verified, and the user is notified of the temperature sensor calibration error via user interface 113. In one embodiment, the predetermined temperature difference threshold may be approximately 1°C. In another embodiment, the predetermined temperature difference threshold may be approximately 0.5°C. In yet another embodiment, the predetermined temperature difference threshold may be approximately 0.1°C.

[0088] In some embodiments, steps 715-725 may be repeated to obtain the temperature difference between TVP 300 and reader 100 at an additional predetermined temperature point. For example, the temperature difference between TVP 300 and reader 100 may be evaluated at both 22°C and 37°C.

[0089] In optional step 730, a calibration factor can be applied to the value of the reader temperature sensor 115's output (e.g., via user interface 113) to return the temperature sensor 115 to calibration. When using only a single predetermined temperature point, a single-point offset can be used to obtain the calibration factor for calibrating the temperature sensor 115. When using two predetermined temperature points, linear interpolation can be performed to obtain the calibration factor for calibrating the temperature sensor 115. When using three or more predetermined temperature points, other interpolation methods (e.g., mathematical regression) can be used to obtain the calibration factor for calibrating the temperature sensor 115. In an exemplary embodiment, mathematical regression can be multinomial regression.

[0090] Go to Figures 1A-2C and Figures 8A-11B The Optical Verification Plate (OVP) 800 can be used to verify whether the optical stage 120 of the reader is operating correctly. The OVP 800 has a plurality of holes 805 positioned along the periphery of the body 801 of the OVP 800. The center of each hole 805 is located at a first predetermined radial distance “A” away from the center of the body 801 of the OVP 800, which allows the hole 805 to be aligned with the light source 130 and the photodetector 135 of the optical stage 120, such that light generated by the photodetector 135 can pass through the hole 805 and the intensity of the light can be measured by the photodetector 135. In an embodiment, the plurality of apertures 805 may be filter apertures 806, some of which have a neutral density filter 810 (neutral density filter aperture 811), and one or more apertures have a wavelength filter (wavelength filter aperture 850), which may include at least one of a short-pass filter 815 (short-pass filter aperture 816), a long-pass filter 820 (long-pass filter aperture 821), a band-pass filter (band-pass filter aperture), and / or a stopband filter (stopband filter aperture).

[0091] In an exemplary embodiment, the filter aperture 806 of the OVP 800 may consist of at least one wavelength filter aperture 850 and seven (7) neutral density filter apertures 811. In an exemplary embodiment, each of the seven neutral density filter apertures of the OVP 800 may have a different optical density (darkness) value. In an exemplary embodiment, the neutral density filter optical density value may be between approximately 0.01 and 3. In another exemplary embodiment, the neutral density filter optical density value may be between approximately 0.01 and 2. In yet another exemplary embodiment, the neutral density filter optical density value may be between approximately 0.1 and 1.2. In yet another exemplary embodiment, the neutral density filter optical density value may be between approximately 0.1 and 1.15. When traveling counterclockwise around the OVP 800, the filter apertures 806 may be spaced apart by a second predetermined distance “B”.

[0092] In an exemplary embodiment, at least one wavelength filter aperture 850 may consist of a long-pass filter aperture 821 and a short-pass filter aperture 815. In an exemplary embodiment, the short-pass filter 815 may have a cutoff of approximately 400 nm, while the long-pass filter 820 may have a cutoff of approximately 410 nm. In an exemplary embodiment, the light source 130 of the optical stage may output light with a wavelength of approximately 405 nm + / - 5 nm. By examining the output of the light source 130 passing through at least one wavelength filter aperture 850 (e.g., short-pass filter 815 and / or long-pass filter 820) using a photodetector 135, the reader 100 may determine whether the spectrum of the light output by the light source 130 is within the specified range or has drifted.

[0093] The spectral transmittance curves of short-pass filter 815 and long-pass filter 820 are shown in Figure 10 As shown in the diagram, the short-pass filter 815 and the long-pass filter 820 have very narrow transition bands (the band between the stopband and the passband). Therefore, it is anticipated that some embodiments of the OVP 800 may replace both the short-pass filter 815 and the long-pass filter 820 with a single stopband or bandpass filter having a sufficiently narrow transition band.

[0094] In one embodiment, one or more filters 807 may be mounted on the OVP 800 to form a zero (0) degree angle with respect to the top surface 835 of the OVP 800. In other words, one or more filters 807 may be flat on the top surface 835 of the OVP 800. Thus, one or more filters 807 may be perpendicular (90°) to the direction of light traveling from the light source 130 to the photodetector 135 of the optical stage 120.

[0095] In other embodiments, one or more filters 807 may be installed such that the filters 807 form a first predetermined angle "F" relative to the top surface 835 of the OVP 800. In an exemplary embodiment, the first predetermined angle "F" may be between approximately 0 degrees and approximately 30 degrees. In another exemplary embodiment, the first predetermined angle "F" may be approximately 30 degrees.

[0096] In another embodiment, one or more filters 807 may be mounted below the top surface 835 of the OVP 800 on the filter bed 808. One or more filters may be mounted to the OVP 800 such that they form a zero (0) degree angle relative to the filter bed 808 of the OVP 800. Thus, one or more filters 807 may be perpendicular (90°) to the direction of light traveling from the light source 130 to the photodetector 135 of the optical stage 120.

[0097] In other embodiments, one or more filters 807 may be installed such that the filters 807 form a first predetermined angle "F" relative to the filter bed 808 of the OVP 800. In an exemplary embodiment, the first predetermined angle "F" may be between approximately 0 degrees and approximately 45 degrees. In another exemplary embodiment, the first predetermined angle "F" may be approximately 30 degrees.

[0098] The OVP 800 may also have an entrance aperture 825 and a registration aperture 830, both of which are unfiltered. All apertures 805 may have the same radius, except for the registration aperture 830, which may have a smaller radius. In an exemplary embodiment, the entrance aperture 825 may be located between the first filter aperture 806a and the registration aperture 830. Furthermore, in an exemplary embodiment, the registration aperture 830 may be located between the entrance aperture 825 and the final filter aperture 806b. The distance between the first filter aperture 806a and the entrance aperture 825 may be a second predetermined distance "C". The distance between the entrance aperture 825 and the registration aperture 830 may be a third predetermined distance "D". The distance between the registration aperture 830 and the final filter aperture 806b may be a fourth predetermined distance "E". In an exemplary embodiment, the second predetermined distance may be approximately 16 mm, the third predetermined distance may be approximately 4 mm, and the fourth predetermined distance may be approximately 74 mm. It is contemplated that in some embodiments, the reader 100 may use the registration pattern 845 to determine the rotation angle of the OVP 800. In an exemplary embodiment, the registration pattern 845 may include a registration aperture 830. In another exemplary embodiment, the registration pattern 845 may include both a registration aperture 830 and an entrance aperture 825.

[0099] In an exemplary embodiment, the reader 100 can be programmed to identify the registration pattern 845 rotating through the optical stage 120, and then know that a predetermined number of filter apertures 806 will be the next aperture 805 to pass through the optical stage. The filter values ​​and sequences of the filter apertures 806 can be programmed into the reader 100, thereby allowing the processor 118 of the reader 100 to analyze the performance of the optical stage 120 and output the results to the user via the user interface 113.

[0100] In some exemplary embodiments, the OVP 800 may have a balancer 840 for balancing the OVP 800 as it rotates within the reader 100. The balancer 840 may include, but is limited to, one or more of a counterweight, a weight-reducing groove, and / or a weight-reducing cavity.

[0101] Figures 11A-11BAn exemplary method 1100 is shown for measuring and verifying the optical performance (measurement of absorbance or optical density and error) of the optical stage 120 of the reader 100 using an OVP 800. In block 1101, the OVP 800 is placed in the reader 100, and the reader 100 rotates the OVP 800. In block 1105, the reader 100 uses the optical stage 120 to identify a registration pattern 845 on the OVP. This registration allows the reader 100 to time the sampling of the optical stage 120 at a precise moment when the aperture 805 passes through the optical stage. In block 1110, the reader uses a light source 130 to pass light through an entrance aperture 825 and measures the intensity of the light received by a photodetector 135. This measurement is taken as the incident light (I0). i It is stored in memory 119.

[0102] In frame 1115, the reader uses light source 130 to pass light through at least one neutral density filter aperture 811 and measures the intensity of the light received by photodetector 135. The value of this intensity measurement (I...) fN The values ​​are stored in memory 119, where N increments once for each neutral density filter aperture 811. The action of box 1115 can be repeated until the value of each neutral density filter aperture 811 has been measured and stored in memory 119.

[0103] In frame 1120, for at least one neutral density pore 811, the transmittance (T) N Processor 118 uses formula T N =(I fN / I i The transmittance values ​​of each neutral density filter aperture 811 are calculated by the processor 118 and stored in the memory 119. The operation of box 1120 can be repeated until the transmittance value of each neutral density filter aperture 811 has been calculated by the processor 118 and stored in the memory 119.

[0104] In box 1125, the absorbance (A) is measured for at least one neutral density filter aperture 811. mN Processor 118 uses formula A mN = -log 10 (T) N The calculation is performed and stored in memory 119, where the effective T... N The value is between 0 and 1. The action of box 1125 can be repeated until the measured absorbance value of each neutral density filter aperture 811 has been calculated by processor 118 and stored in memory 119.

[0105] In box 1130, absorbance (A) is measured for at least one neutral density filter aperture 811. mN ) and the predetermined absorbance value (A pNThe comparison was performed using processor 118 with the formula AError. N = (A) mN -A pN ) / A pN The percentage error is calculated and stored in memory 119. In an exemplary embodiment, the predetermined absorbance value may be the actual certified absorbance of the neutral density filter at the neutral density filter aperture 811. The operation of block 1130 may be repeated until the absorbance percentage error value for each neutral density filter aperture 811 is calculated by processor 118 and stored in memory 119.

[0106] In box 1135, the processor 118 calculates the percentage error (AError) of at least one neutral density filter aperture absorbance measurement 811. N The error threshold (AError) between the measured absorbance and the predetermined neutral density absorbance threshold. p The comparison is performed. If a predetermined neutral density error threshold is exceeded, the processor 118 can notify the user, indicating that the optical stage 120 of the reader 100 does not meet the specifications. The processor 118 can notify the user via the user interface 113. In an exemplary embodiment, the predetermined neutral density error threshold may be approximately 5%. The operation of block 1135 can be repeated until the comparison for each neutral density filter aperture 811 has been completed by the processor 118, and the result is stored in the memory 119 and output to the user via the user interface 113.

[0107] In frame 1140, the reader uses light source 130 to pass light through at least one wavelength filter aperture 850 and measures the intensity of the light received by photodetector 135. This measured value is stored as an intensity wavelength measurement value I. WN For each wavelength filter aperture 850, N increments once. The action of box 1140 can be repeated until the value of each wavelength filter aperture 850 has been measured and stored in memory 119.

[0108] In box 1145, the wavelength error (WError) of the optical stage. N The processor 118 uses the formula WError N= I WN / I i By evaluating at least one measurement (I) of the intensity of incident light passing through wavelength filter aperture 850. WN The measured values ​​of the intensity of incident light passing through the incident aperture 825 (I) iThe wavelength error is calculated using the ratio of the wavelength of the optical stage to the wavelength of the filter aperture 850. This wavelength error is stored in memory 119. The operation of box 1145 can be repeated until the wavelength error value of each wavelength filter aperture 850 has been calculated by processor 118 and stored in memory 119.

[0109] In block 1150, processor 118 compares the wavelength error of each wavelength filter aperture 850 with a predetermined wavelength error threshold and, if the predetermined wavelength threshold has been exceeded, notifies the user, thereby indicating that the optical stage 120 of reader 100 does not meet specifications. The predetermined error threshold may be a predetermined total wavelength error threshold or a predetermined single wavelength error threshold. The processor may notify the user via user interface 113. In an exemplary embodiment, the sum of wavelength errors must not exceed approximately (or be greater than) 5%, in other words, the predetermined total wavelength error threshold may be approximately 5%. In another embodiment, any single wavelength error threshold may be approximately 2.5%, in other words, the predetermined single wavelength error threshold may be approximately 2.5%. In another embodiment, the predetermined wavelength error threshold may correspond to the output of light source 130 having a wavelength greater than approximately 410 nm and / or less than approximately 400 nm. The operation of block 1150 may be repeated until the comparison for each wavelength filter aperture 850 has been completed by processor 118, the result is stored in memory 119, and output to the user via user interface 113.

[0110] Although the present invention has been described in conjunction with the specific embodiments described above, it will be apparent to those skilled in the art that many alternatives, combinations, modifications, and variations will be apparent. Therefore, the preferred embodiments of the invention described above are intended to be illustrative only and not restrictive. Various changes can be made without departing from the spirit and scope of the invention. After studying the above description, combinations of the above embodiments and other embodiments will be apparent to those skilled in the art and are intended to be included therein. Therefore, the scope of the invention is defined by the appended claims, and all devices, processes, and methods within the meaning of the claims (whether literal or equivalent) are intended to be included therein.

Claims

1. A temperature verification plate (TVP) for a bacterial endotoxin reader, comprising: a body configured to be placed on and rotated by a spindle of the reader; the body defining a temperature sensor channel and having a temperature verification circuit comprising a temperature sensor and a temperature indicator within the temperature sensor channel; the temperature sensor configured to measure a temperature of the body at a predetermined location on the TVP as it is rotated by the spindle of the reader; the temperature indicator configured to optically represent a value of the temperature measured by the temperature sensor at the predetermined location on the TVP, wherein the temperature indicator is readable by an optical stage of the reader; wherein a difference between a temperature measurement obtained from the temperature sensor and a temperature value obtained from the temperature indicator is calculated and compared to a predetermined temperature difference threshold; and when the difference is greater than the predetermined temperature difference threshold, indicating a reader temperature measurement sensor calibration error.

2. The TVP of claim 1, wherein, the temperature sensor is an electronic temperature sensor, a thermistor, a thermocouple, and / or a resistance temperature detector, the temperature sensor being placed at a first predetermined radial distance from a center of the spindle, wherein the first predetermined radial distance is equal to a distance between the spindle and a location of a reaction well on a reaction plate in the reader.

3. The TVP of claim 1, wherein, the temperature indicator is at least one light emitting diode (LED) and / or at least one liquid crystal display (LCD); wherein the temperature indicator represents the value of the temperature as a binary number.

4. The TVP of claim 3, wherein, the binary number determines a resolution of the temperature measured by the temperature sensor, wherein the binary number has two or more verification bits.

5. The TVP of claim 4, wherein, the binary number is a 12-bit number.

6. The TVP of claim 4, wherein, the temperature indicator is a single LED, 12 LEDs, 14 LEDs, a single LCD, 12 LCDs, or 14 LCDs.

7. The TVP of claim 1, wherein, the temperature verification circuit further comprises a battery and a switch; the battery provides power to the temperature verification circuit; the switch allows current to flow out of the battery when the switch is in an "on" position and prevents current from flowing out of the battery when the switch is in an "off" position.

8. The TVP of claim 1, wherein, the temperature sensor obtains temperature measurements at a first cyclic interval during a first predetermined length of time; the temperature indicator outputs an average of the temperature measurements.

9. The TVP of claim 8, wherein, the first predetermined length of time is about 5 seconds and the first cyclic interval is about 0.1 seconds.

10. A method of verifying temperature performance of a bacterial endotoxin reader, comprising: providing a reader and a temperature verification plate (TVP); placing the TVP on a spindle of the reader, rotating the TVP upward using the spindle, and activating a heater of the reader to maintain a temperature of a body of the TVP at a predetermined temperature; obtaining a temperature measurement of the body of the TVP from a temperature indicator of the TVP using an optical stage of the reader; obtaining a temperature measurement of the body of the TVP using a temperature measurement sensor of the reader; computing a difference between the temperature measurement obtained from the temperature indicator of the TVP and the temperature measurement obtained from the temperature measurement sensor of the reader, and comparing the difference to a predetermined temperature difference threshold; and indicating a reader temperature measurement sensor calibration error when the difference is greater than the predetermined temperature difference threshold.

11. The method of claim 10, further comprising: computing a calibration factor based on the difference between the temperature measurement obtained from the TVP and the temperature measurement obtained from the temperature measurement sensor of the reader and applying the calibration factor to the temperature measurement obtained from the temperature measurement sensor of the reader.

12. The method of claim 10, wherein, the predetermined temperature difference threshold is about 1 °C, about 0.5 °C, or about 0.1 °C.

13. The method of claim 10, wherein, the difference is computed at two or more predetermined temperatures.

14. The method of claim 13, wherein, the predetermined temperatures are 22 °C and / or 37 °C.

15. The method of claim 13, further comprising: computing a calibration factor based on the difference between the temperature measurement obtained from the TVP at two or more predetermined temperatures and the temperature measurement obtained from the temperature measurement sensor of the reader at the two or more predetermined temperatures and applying the calibration factor to the temperature measurement obtained from the temperature measurement sensor of the reader.

16. The method of claim 15, wherein, the calibration factor is determined using linear interpolation and / or mathematical regression.

17. A bacterial endotoxin reader comprising: a control unit; and a memory storing executable code that, when executed by the control unit, performs actions including: spinning a temperature verification plate (TVP) placed on a spindle of the reader using the spindle of the reader; activating a heater of the reader to maintain a temperature of a body of the TVP at a predetermined temperature; obtaining a temperature measurement of the body of the TVP from a temperature indicator of the TVP using an optical stage of the reader and storing the temperature measurement in a memory; obtaining a temperature measurement of the body of the TVP using a temperature measurement sensor of the reader and storing the temperature measurement in the memory; computing a difference between the temperature measurement obtained from the temperature indicator of the TVP and the temperature measurement obtained from the temperature measurement sensor of the reader, storing the difference in the memory, and comparing the difference to a predetermined temperature difference threshold; and indicating a reader temperature measurement sensor calibration error when the difference is greater than the predetermined temperature difference threshold.

18. The bacterial endotoxin reader of claim 17, wherein, the code, when executed by the control unit, performs additional actions including: applying a calibration factor to the temperature measurement obtained from the temperature measurement sensor of the reader based on the difference between the temperature measurement obtained from the TVP and the temperature measurement obtained from the temperature measurement sensor of the reader.

19. The bacterial endotoxin reader of claim 17, wherein, the code, when executed by the control unit, performs additional actions including: Based on the difference between the temperature measurements obtained from the TVP at two or more predetermined temperatures and the temperature measurements obtained from the temperature measurement sensor of the reader at the two or more predetermined temperatures, a calibration factor is calculated and applied to the temperature measurements obtained from the temperature measurement sensor of the reader.

20. The bacterial endotoxin reader of claim 19, wherein, The code, when executed by the control unit, performs additional actions comprising: using linear interpolation and / or mathematical regression to determine the calibration factor.

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