Self-tuning bubble detector assembly for diagnostic analyzers, calibration method and computer program product

Abstract

A self-tuning optical bubble detector assembly for a diagnostic analyzer. The bubble detector assembly has a light emitter that operates in a plurality of inputs (i.e., generates a plurality of light intensities) for a dry supply line conduit (i.e., without liquid) and for a wet supply line conduit (i.e., with liquid therein). A plurality of outputs representative of light detected through the dry supply line conduit and the wet supply line conduit are generated. Based on the received output, a final calibration setting (e.g., a% duty cycle setting or ILED) and a threshold value are determined at which it is accurately and repeatedly determined whether liquid or air is present in the supply line conduit. Methods and computer program products for a self-tuning optical bubble detector for diagnostic analyzers are further provided, as are other aspects.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 375,851, filed on September 15, 2022, entitled “SELF-TUNING BUBBLE DETECTOR ASSEMBLIES, CALIBRATION METHODS, AND COMPUTER PROGRAM PRODUCTS FOR DIAGNOSTIC ANALYZERS,” the disclosure of which is hereby incorporated by reference in its entirety for all purposes. Technical Field

[0003] The present disclosure relates to diagnostic analyzers, and more particularly to bubble detector assemblies and methods for use in such diagnostic analyzers. Background Art

[0004] Various medical diagnostic analyzers (e.g., chemical analyzers and immunoassay instruments) are used to analyze patient samples, such as, for example, whole blood, serum or plasma, cerebrospinal fluid, interstitial fluid, urine, semen, sputum, saliva, and the like. These diagnostic analyzers typically use one or more liquid reagents, cleaning liquids, or other process liquids combined with the processing of such patient samples. In order to obtain accurate diagnostic results, it may be necessary to transfer a very precise amount of liquid reagents and possibly one or more other liquids from a location (e.g., a storage container or liquid supply) to a receptacle where a chemical reaction can occur, or vice versa. In many cases, liquid transfer is performed by a probe (pipette) coupled to a length of flexible supply line tubing. Although bubble detectors are used to detect the presence of liquid in a pipeline, such liquid detection may have certain performance disadvantages. Summary of the invention

[0005] According to some embodiments, the present disclosure provides an optical bubble detector assembly, including a controller configured to: operate a light emitter that projects light into a supply line conduit and detects, by 33, the transmitted light through the conduit at multiple light intensities corresponding to multiple inputs; receive a first plurality of outputs from a light detector of the optical bubble detector, the first plurality of outputs corresponding to the multiple inputs, each of the first plurality of outputs representing an amount of light detected through the supply line conduit without liquid therein; receive a second plurality of outputs from the light detector, the second plurality of outputs corresponding to the multiple inputs, each of the second plurality of outputs representing an amount of light detected through the supply line conduit with liquid therein; and select a specific one of the multiple inputs as a final calibration setting based on a selected output from the first and second plurality of outputs.

[0006] According to a second embodiment, the present disclosure describes a method for calibrating an optical bubble detector. The method includes receiving a first plurality of outputs, each of the first plurality of outputs representing an amount of light detected through a supply line conduit without liquid therein, the first plurality of outputs corresponding to a plurality of inputs of a light emitter, respectively; receiving a second plurality of outputs, each of the second plurality of outputs representing an amount of light detected through a supply line conduit with liquid therein, the second plurality of outputs corresponding to a plurality of inputs of the light emitter, respectively; and selecting a specific one of the plurality of inputs as a final calibration setting based on a selected output of the first and second plurality of outputs.

[0007] According to a third aspect, a computer program product is provided. The computer program product includes a computer-readable non-transitory medium having a computer program code configured to: receive a first plurality of outputs, each of the first plurality of outputs representing an amount of light transmitted through a supply line conduit without liquid therein for a corresponding plurality of inputs of a light emitter; receive a second plurality of outputs, each of the second plurality of outputs representing an amount of light transmitted through a supply line conduit with liquid therein for a corresponding plurality of inputs; and set a final calibration setting based on a selected output of the first plurality of outputs and the second plurality of outputs.

[0008] Other aspects, features and advantages of the present disclosure may be readily apparent from the following detailed description, in which a number of example embodiments are described and illustrated, including the best mode for carrying out the present disclosure as contemplated. The present disclosure may also be capable of other and different embodiments, and its several details may be modified in various aspects, all without departing from the scope of the present disclosure. Therefore, the drawings and description are to be considered illustrative in nature, and not restrictive. The present disclosure covers all modifications, equivalents and substitutes that fall within the scope of the claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0009] The drawings described below are for illustration purposes only and are not necessarily drawn to scale. The drawings are not intended to limit the scope of the present disclosure in any way.

[0010] Figure 1 A perspective view of a bubble detector assembly according to a first embodiment is illustrated.

[0011] Figure 2 A detailed schematic diagram of a first self-tuning bubble detector assembly configured to read a bubble detector according to an embodiment is illustrated.

[0012] Figure 3A Illustrated is a schematic overview of a second self-tuning bubble detector assembly configured to read a bubble detector according to an embodiment.

[0013] Figure 3B A detailed schematic diagram of a second self-tuning bubble detector assembly configured to read a bubble detector according to an embodiment is illustrated.

[0014] Figure 4A A first graph of output voltage from a light detector versus a % duty setting provided to drive a light emitter of a first embodiment of a bubble detector assembly according to an embodiment is illustrated.

[0015] Figure 4B A second graph of current to a light emitter versus a reference voltage output from a light detector for a second embodiment of a bubble detector assembly according to an embodiment is illustrated.

[0016] Figure 5 A general flow chart of a method of calibrating an optical bubble detector according to an embodiment is illustrated.

[0017] Fig. 6A A flow chart of a general self-calibration method for calibrating an optical bubble detector (eg, first and second optical bubble detectors of first and second optical bubble detector assemblies) according to an embodiment is illustrated.

[0018] Figure 6B A flow chart of a first self-calibration method of calibrating a first optical bubble detector according to an embodiment is illustrated.

[0019] Figure 6C A flow chart of a second self-calibration method for calibrating a second optical bubble detector according to an embodiment is illustrated.

[0020] Fig.6D A flow chart of a method of generating dry and wet calibration data for dry (DRY) and wet (WET) calibration curves of a second bubble detector calibration method according to an embodiment is illustrated.

[0021] Fig. 6EA flow chart of a method of finding I_LED_Final (final calibration setting) of the second bubble detector method according to an embodiment is illustrated.

[0022] Fig. 6F A flow chart of a method of determining V_Ref_Final of the second bubble detector method according to an embodiment is illustrated.

[0023] Figure 7 Illustrated is a diagram of a Manchester auto-calibration command waveform that may be used by a bubble detector assembly according to an embodiment.

[0024] Fig. 8A and 8B Illustrated are zoomed-in and zoomed-out views, respectively, of an auto-calibration command waveform that may be used by a second self-tuning bubble detector assembly according to an embodiment.

[0025] Figures 9A to 9F Various views of a second bubble detector assembly and its components are illustrated according to an embodiment. DETAILED DESCRIPTION

[0026] Reference will now be made in detail to example embodiments of the present disclosure, which are illustrated in the accompanying drawings. Wherever possible, the same reference numerals will be used throughout the drawings to refer to the same or like parts.

[0027] When managing the flow of liquid, devices such as bubble detectors are often used to ensure that the expected volume of liquid has actually moved from one location to another. This is often performed using non-contact techniques that may include optical techniques. Basic and regulated optical liquid / air sensors (referred to herein as "bubble detectors") are known, but they may have limited performance in diagnostic analyzers for medical applications. Specifically, there is a need to provide an optical bubble detector assembly and / or a calibration method for an optical bubble detector that can accurately and repeatedly detect the presence of certain liquids or air in a supply line conduit. As used herein, a supply line conduit means any conduit used to transfer liquid from one location to another. In some embodiments, the precise amount of a small volume of liquid in a supply line conduit used in such a medical diagnostic analyzer can be measured. In other applications, the presence or absence of liquid at certain locations along the supply line conduit can be determined, that is, whether it is wet (containing liquid) or dry (mainly containing air).

[0028] In such medical diagnostic analyzer, a probe (e.g., pipette) coupled to a robot and movable by the robot is generally used to aspirate a liquid, such as a patient sample liquid and / or a reagent liquid, and the sample and / or the reagent liquid are transferred to another position, and then (one or more) liquids are dispensed in a receiver, such as a cuvette. After this, the liquid can undergo further processing and / or cultivation (incubation). After transferring and distributing (one or more) liquids, the probe can be cleaned in some cases to reduce (one or more) liquids and carry over to the next diagnostic test. In certain embodiments, cleaning can be accomplished by lowering the probe at a cleaning station with a receiver or well that contains cleaning liquid and aspirating the cleaning liquid into the probe.

[0029] In another application, such as at the cleaning station of a diagnostic analyzer, the cleaning station probe can be used to complete the cleaning of the magnetic beads (magneticbead) contained in the vessel as part of the culture process occurring on the diagnostic analyzer. The cleaning operation can occur at the cleaning station, such as, for example, occurring on the cleaning or culture loop of the diagnostic analyzer. In some embodiments, more than one such cleaning station can be provided on the diagnostic analyzer. In some embodiments, the cleaning liquid can be distributed from the probe through the supply line pipeline. In other embodiments, the process and / or the cleaning liquid can be aspirated into the probe and the supply line pipeline. In each case, in order to ensure that the distribution, suction and / or cleaning operation have indeed occurred, the inventor has included a bubble detector assembly in this article, which is positioned along a certain length of supply line pipeline coupled to the probe and coupled to the supply line pipeline of the certain length. Such a bubble detector assembly can be located at a position where liquid or air is determined or measured, such as near or even directly adjacent to the probe or other places along the supply line pipeline. Therefore, the bubble detector assembly according to the embodiment described herein can be configured to ensure that the suction and / or distribution of liquid (cleaning liquid, liquid reagent or even sample) has successfully occurred.

[0030] Thus, embodiments of the bubble detector assemblies, self-calibration electronic circuits, self-calibration methods, and computer program products disclosed herein can improve the performance of such bubble detector assemblies, making them much more practical for use in demanding fluid flow monitoring applications, and particularly for use in medical diagnostic analyzer applications, especially in detecting subtle transitions between very clear liquids and passing air.

[0031] Particularly, in the reagent liquid dispensing operation, it is desirable that the liquid reagent of accurate amount is transferred from the storage container to the receptor (for example, cuvette) where chemical reaction will take place, promotes the specific analyte or the material contained in the sample to be quantitatively measured. In the cleaning operation, one or more cleaning liquids can be introduced into the fluid manifold and / or the supply line pipeline, so that the magnetic beads contained in the cuvette are carried out cleaning operation. Such cleaning operation can remove process and / or cleaning liquid by the supply line pipeline, and / or all wetting surfaces of cleaning reagent probe or cleaning probe. This can minimize or avoid the legacy influence from one test to another test, and / or promote cleaning process. In one aspect, the present method and assembly can detect that cleaning operation has been successfully carried out indeed.

[0032] In certain embodiments, pumps such as diluter pumps can be used to transfer (e.g., aspirate and then dispense) amounts of these liquid reagents as small as 100 μL or even smaller. Due to the medical significance of these assays and chemical tests performed by the diagnostic analyzer, in certain embodiments, the delivery of reagents of known volumes should be repeated without significant errors. For this reason, the diagnostic analyzer may not only rely on the ability of the pump to dispense or aspirate known volume reagents via open-loop control. On the contrary, each distribution or aspiration of reagents should be checked for the correctness of volume by a combination of one or more additional sensors, signal conditioning electronics and / or firmware and / or software methods.

[0033] Some known medical diagnostic analyzers, such as the CENTAUR XP system available from SIEMENS HEALTHINEERS, use optical sensors to confirm that reagent is correctly transported through the supply line pipeline of the system. For reagent probes, i.e., probes for aspirating and dispensing liquid reagents, bubble detectors with light emitter / photodetector pairs have been used, which enable software to ascertain that the correct volume is aspirated from the reagent container of the analyzer by the reagent probe and then be assigned to a receiver (e.g., a cuvette) for cultivation and analysis. Diagnostic analyzers can use any suitable analyte or component detection method, such as using chemiluminescence, absorbance or the like. For the reagent aspiration of this type, the group reagent can be clamped with the air gap in front and the air gap in the back around a group (slug) of reagent in the supply line pipe.

[0034] Since the software is instructing the pump to draw and / or dispense the liquid reagent into and / or out of the reagent probe at specific time intervals, there is an expected timeframe in which the bubble detector will see air, followed by liquid, and then followed by air. In this way, the software can detect whether the correct aliquot of the liquid reagent is indeed dispensed, and if not, a mark is generated to indicate that something went wrong in the process. Potential causes of such a mark may be that the reagent runs out, there is a blockage in the supply line pipeline, and / or bubbles are detected.

[0035] In the bulk fluid area of ​​the diagnostic analyzer, a bubble detector with a light emitter / light detector pair can also be used to detect the presence of one of the reagents. For example, a bubble detector can be used to detect that a reagent container (e.g., a bottle) has run out and a supply line tubing has gone dry.

[0036] However, in the systems of these prior art, the calibration process that enables the distinction between dry supply line pipes (dry) and wet supply line pipes (wet) containing liquids (e.g., reagents or cleaning liquids) is set automatically or manually by adjusting the operation. And although it is sufficient to some extent, the calibration systems and methods of the prior art are not very robust and may take a lot of experiments to make them correctly calibrated. In particular, since each component may contain different structures and / or materials, or may change over time, it is desirable that such a system is self-calibrated with minimal manual input to each slightly different component. In addition, for systems that pump and / or dispense very clear liquids, such as in diagnostic analyzer applications, improved calibration is needed because the optical difference between such clear liquids and air is slight.

[0037] like Figure 1, a first embodiment of a bubble detector assembly 100 according to the present disclosure is shown. The bubble detector assembly 100 may have a channel 102, which is configured to receive a supply line conduit 105 (shown in dotted lines) therein. The bubble detector assembly 100 may have a light emitter on one of the sides 104 or 106, which may be an LED (light emitting diode), and may have a light detector on the other of the sides 104 or 106, which may be a photodetector. When a new container (e.g., a bottle or other suitable storage) of a reagent liquid is installed on the diagnostic analyzer, a software counter may be set to a value corresponding to the number of suctions available for the container volume. For each suction, the counter may be decremented by one. Once the counter reaches zero, the operating software may not allow further tests to be run, and may prompt the operator to replace or refill the reagent container via, for example, a computer monitor. The present disclosure includes a bubble detector assembly 100 including a light emitter / light detector pair at sides 104 and 106 that can act as a failsafe mechanism to the software counter method to ensure that the diagnostic test of the diagnostic analyzer is not run unless the appropriate amount of reagent liquid is actually present. Thus, the bubble detector 100 can provide a safety feedback mechanism above and beyond the software counter by detecting whether the reagent liquid is actually present in the supply line conduit 105. Other suitable uses of the bubble detector assembly 100 in a diagnostic analyzer may include, but are not limited to, determining the presence or absence of a large amount of reagent, the presence or absence of a cleaning liquid, the presence or absence of a process liquid, and / or liquid measurement.

[0038] In the above applications (e.g., bulk reagent container applications), light may be transmitted laterally (crosswise) through the supply line conduit from one side and detected by a light detector (e.g., a photodiode) on the other side of the supply line conduit 105. In some embodiments, the light emitter (e.g., an LED) and the light detector (e.g., a photodetector) may be positioned on opposite sides of the same axis of the supply line conduit 105. In other embodiments described herein, the light emitter (e.g., an LED) and the light detector (e.g., a photodetector) may be positioned on one side of the conduit axis and may include a reflective surface on the opposite side of the conduit axis.

[0039] According to the present disclosure, the signal conditioning circuit system configured to receive the analog signal from the light detector should be configured to be able to distinguish between dry supply line pipe (dry) and wet supply line pipe (wet) containing liquid (e.g., reagent, process or cleaning liquid). The detected output can be a function of such variables, such as, for example, the optical alignment of the light emitter (e.g., LED) and the light detector (e.g., photodetector), the optical properties of the pipe due to pigmentation and size, the turbidity or color of the liquid passing through the supply line pipe 105, and possible other factors. Note that the bubble detector alignment may and usually does vary from bubble detector to bubble detector due to at least the mechanical misalignment of the light emitter and the light detector. The thickness and / or opacity of the pipe may also vary at various locations along a section of the supply line pipe 105. These variations may shift the wet state and dry state output voltages by as much as half a volt. Therefore, a robust calibration method is needed that can be used to correctly calibrate each individual bubble detector assembly as described herein.

[0040] Some known bubble detectors may have some degree of self-calibration, but it is generally too limited for use with at least some diagnostic analyzers. Such prior art self-calibration capabilities may simply establish a fixed operating output based on experience with the bubble detector. On-board circuitry may implement intensity control of the light emitter using an adjustable current source. During calibration, the microcontroller may incrementally adjust the intensity of the light from the light emitter and read the emission voltage of the light detector. In this way, the firmware looks for a current from one of the input settings that is capable of driving the light emitter to the desired set point. The calibrated settings may be saved in the microcontroller's memory so that any time it is powered on thereafter, it will resume operation with the calibrated settings. This single case calibration may be useful in some applications, but is generally insufficient for diagnostic analyzer applications involving very clear liquids.

[0041] Furthermore, however, this prior art approach does not take into account the relationship between measured voltages indicative of dry and wet pipes, which is important for bubble detection in a diagnostic analyzer that determines the presence of a particular liquid in the supply line tubing 105, or otherwise quantifies the amount of liquid that has been aspirated and / or dispensed. In particular, a need exists for an improved calibration method in these applications because liquids (e.g., reagents and wash liquids) tend to be very clear, and thus the optical difference between wet and dry readings can be very small and very difficult to detect.

[0042] Figure 2A first embodiment of a bubble detector assembly 100 including a self-tuning circuit according to an embodiment of the present disclosure is shown. According to one or more embodiments herein, the bubble detector assembly 100 can be operated to optimize circuit performance (tuning) for its bubble detector 202, such as, for example, an OPTEK OPB350W250Z bubble detector. The bubble detector assembly 100, which can include one or more printed circuit board assemblies, can be used with a probe (pipette) that aspirates liquids, such as when the liquid is a liquid reagent or a cleaning liquid, but can be used in any analyzer (assay instrument or chemical analyzer) where it is desired to determine the presence or absence of a liquid at a location along a supply line conduit 105.

[0043] Given the above variability, it is desirable to tune each individual bubble detector 202. Self-tuning utilizing the bubble detector assembly 100 described herein may include the use of a calibration LED 204 and a dry / wet pipe indicator 206 (e.g., LEDs) that are operable to display the calibration status and condition (e.g., wet or dry) in the supply line pipe 105, respectively. To facilitate self-calibration, one or more button inputs (e.g., button 208) and one or more calibration outputs (e.g., LEDs) 204, 206 may be used. Fig. 6A and Figure 6B , the bubble detector assembly 200 may perform a calibration / self-tuning process according to an embodiment of the present disclosure.

[0044] In a first embodiment, the calibration / self-tuning method can begin with the supply line tubing 105 in a dry state. A section of the supply line tubing 105 (shown in dashed lines) passes through the bubble detector 202. The supply line tubing 105 can be coupled to a pipette and optionally to a reagent or waste container. When a dry "calibration" sequence is initiated, the controller 210 (which can be A microcontroller, such as, for example, a PIC16F876 from Microchip Technology, can step through a full range of % duty cycle settings supplied as input to the light emitter circuitry. For example, the input can be a pulse width modulated (PWM) signal (or waveform) in input line 215.

[0045] For example, the LED intensity of light emitter 211 can be controlled by three stages of electronics. The first stage can be a PWM input from controller 210. This input signal in line 215 can drive an RC circuit (stage 2) that converts the PWM output into a voltage. This voltage can drive an OP-AMP 218 / transistor 219 pair (stage 3), resulting in an adjustable current sink from the cathode terminal of light emitter 211. The anode terminal of light emitter 211 can be connected to the positive circuit power supply of the circuit. In this way, each % duty cycle setting of the PWM signal generated by controller 210 corresponds to a different steady-state current and therefore a different intensity level emitted from light emitter 211 (e.g., a light emitting diode (LED)).

[0046] The PWM signal input in line 215 is injected into the regulating portion of the circuit of the bubble detector assembly 100 to generate a DC voltage at the input of OP-AMP 218. For example, OP-AMP 218 can be a TS922 rail-to-rail dual BiCMOS operational amplifier. The signal can drive transistor 219, which can be a bipolar junction transistor (BJT) that creates a current sink for the light emitter 211. For example, transistor 219 can be a 2N222 NPN bipolar junction transistor. Each % duty cycle of the PWM waveform is associated with a specific sink current of the light emitter 211. The light signal passing through the supply line conduit 105 is converted into a DC voltage at the output pin of the light detector 212. This detector output voltage in line 217 can be digitized with an A / D converter and stored in the memory 210M of the controller 210. Dry calibration involves injecting increasing % duty cycle settings of the PWM signal to generate a series of different light intensity levels. Each output (e.g., voltage) in output line 217 can correspond to a corresponding input of the % duty cycle setting of the PWM signal.

[0047] Next, the supply line tubing 105 may be wetted and a wet "calibration" sequence may be initiated, such as by pressing button 208. The wet "calibration" injects the same set of % duty cycle settings of the PWM signal into the circuit as performed during the dry "calibration" routine to generate corresponding intensity levels of the light emitter 211, as will be explained below. The data forming the dry and wet "calibration" curves (see 404A, 402A) are presented in Figure 4A These curves are different due to the altered light scattering that occurs between the dry and wet calibration sequences due to the presence or absence of liquid in the tube at the location of the bubble detector 202.

[0048] The supply line conduit 105 can be wetted by any suitable pump or vacuum supply coupled or interconnected to the supply line conduit 105, and any suitable pump or vacuum supply provides liquid to the area of ​​the supply line conduit 105 that receives the light signal from the light emitter 211. In the case of reagent aspiration and dispensing, the supply line conduit 105 is wetted by aspirating a desired amount of reagent liquid so that the reagent liquid is present between the light emitter 211 and the light detector 212. In the case of a single cleaning operation, the cleaning liquid can be aspirated from the cleaning reservoir into a pipette immersed therein. The cleaning liquid can be aspirated by operation of the pump until the cleaning liquid occupies a portion of the supply line conduit 105 located between the light emitter 211 and the light detector 212. In another cleaning embodiment, a cleaning probe can be lowered into a receptacle (e.g., a cuvette) and used to aspirate process liquid, and / or wash magnetic beads with cleaning liquid, wherein the light emitter 211 and the light detector 212 can be positioned at a point along the supply line conduit 105 to determine whether the liquid has been aspirated and / or dispensed into the supply line conduit 105. The light emitter 211 and light detector 212 of the bubble detector 202 may be positioned directly adjacent to the probe or at another location along the supply line conduit 105 .

[0049] In each embodiment, the controller 210 may again walk through the same full range of the same % duty cycle settings for the PWM signal as previously input for the dry condition in input line 215. As previously described, the measured output (e.g., voltage) in output line 217 from the photodetector 212 may be digitized at the output of the controller 210. The digitized output voltage values ​​resulting from each injected % duty cycle setting may be stored in the memory 210M and / or sent to an external computer for analysis.

[0050] According to an embodiment, the bubble detector assembly 100 then performs an analysis to determine which of the particular % duty cycle settings (hereinafter referred to as the "final calibration setting") achieves superior signal separation. In particular, it is desirable to achieve the maximum separation difference between the output voltages in the wet and dry conditions (see Figure 4A In some embodiments, the final calibration setting 407 may be a % duty cycle setting input value that provides the maximum amount (maximum) voltage difference between the recorded outputs (eg, voltages) of the wet calibration sub-method and the dry calibration sub-method.

[0051] For example, in a so-called "maximum separation" embodiment (first embodiment), the controller 210 may calculate the Vwet-Vdry voltage spread for each % duty cycle setting provided as input in line 215, and further search for a particular one of the % duty cycle settings (hereinafter referred to as the "final calibration setting") that provides the greatest amount (maximum 408) of voltage spread. Curve 406 is a plot of the output voltage difference in line 217 for each corresponding % duty cycle setting. Curve 402A is a plot of the wet output voltage in line 217 for wet calibration. Curve 404A is a plot of the dry output voltage in line 217 for dry calibration. This particular final calibration setting 407 may be stored in a memory 210M such as NVRAM (non-volatile random access memory). Looking ahead, the final calibration setting 407 may be used to drive the optical emitter 211 for excellent signal separation. The optical emitter 211 may be any suitable light emitting device, such as a light emitting diode (LED). The optical detector 212 may be any suitable photodetector.

[0052] In this embodiment, the midpoint voltage 409 between Vdry and Vwet at the final calibration setting 407 can be calculated and stored in the memory 210M. The midpoint voltage 409 can be used as a firmware comparator reference (i.e., voltage threshold (V TH )) to determine whether the supply line conduit 105 is wet, i.e., contains liquid, or dry, i.e., contains no liquid. When V at line 409 is met or exceeded TH , the dry / wet pipe indicator 206 may illuminate, thereby signaling the detection of a wet pipe condition, such as Figure 4A . More practically, the output signal 217 to the controller 210 can be used to drive the digital I / O lines of an external electronic circuit, microcontroller or computer. The calculation can be performed by the controller 210 and / or the external electronic circuit, microcontroller or computer or a combination thereof. These methods and components can respond to the detected wet or dry bubble detector state, such as by providing an error that can alert the operator. The marked error can indicate that an incorrect state has been output for a specific operating stage of the ongoing process, such as, for example, the aspiration or dispensing of a liquid reagent or the aspiration or dispensing of a cleaning liquid.

[0053] exist Figure 2In detail, the bubble detector assembly 100 may include an operational amplifier 218 coupled to receive an input in an input line 215 from the controller 210, which may be a pulse width modulated (PWM) signal. The operational amplifier 218, together with the transistor 219, may be configured to convert the PWM drive signal into an adjustable current and provide a current drive signal to the light emitter 211, which is responsive to the input in the input line 215. This supplies a variable current input to the light emitter 211, thereby controlling the intensity of the light emitted by the light emitter 211, which may be varied during wet and dry calibrations (e.g., in step increments). After calibration, the input value corresponding to the final calibration setting is used to illuminate the light emitter 211. Note that, as used herein, each "% duty cycle setting" is an input proportional to the intensity level (e.g., magnitude) of the light emitted by the light emitter 211. For example, a 30% duty cycle setting of the PWM signal may correspond to an intensity level of 30% of the maximum intensity of the light emitter 211. The maximum separation calibration method described herein includes selecting a % duty cycle setting for the PWM signal supplied from the controller 210 and then selecting a comparator reference V for maximum wet-dry output signal separation. TH , the comparator reference V TH Can be tuned to create the most "centered" setting.

[0054] Figure 4A Graph 400A illustrates example calibration data for a calibration run that seeks maximum separation of wet and dry signals according to a first embodiment. Figure 4B Graph 400B illustrates example calibration data for a calibration run according to a second embodiment that seeks maximum separation of wet and dry signals by examining the maximum and minimum recorded values ​​(the so-called 1 / 2 max-min embodiment) described herein below.

[0055] Figure 4AThe test data in includes the output voltage of the photodetector 212 relative to the % duty cycle setting of the PWM input, which corresponds to the intensity of the light emitter 211 for dry pipe (Vwet data curve 402A) and wet pipe (Vdry data curve 404A). The calibration data also illustrates the voltage difference between the corresponding voltages for wet and dry pipe conditions for each % duty cycle setting (see ΔV=Vwet-Vdry data curve 406). In this example, 20 different % duty cycle settings ranging from 0% to 40% duty cycle were used to obtain corresponding multiple Vdry and Vwet output voltages, resulting in Vwet data curve 402A and Vdry data curve 404A. In other embodiments, other numbers and ranges of % duty cycle settings may be used as inputs. For example, at least ten% of duty cycle settings ranging from 10% to 90% may be used. In this example, the % duty cycle setting that produces the maximum Vwet-Vdry signal separation is approximately 34%, as indicated by point 408 on the ΔV=Vwet-Vdry data curve 406 .

[0056] like Figure 4A As shown in FIG. 4 , at this % duty cycle setting (final calibration setting) on ​​line 407, the midpoint voltage between the Vwet and Vdry voltages is approximately 2.85 volts (see line 409). In some embodiments, this midpoint voltage can be set to a threshold voltage V TH , is used to determine whether the pipeline condition is wet or dry during the actual non-calibration operation time, that is, as a trigger point, below which the supply line pipeline 105 is determined to be dry, and equal to or above which the supply line pipeline 105 is determined to be wet. In other embodiments, the threshold voltage V TH It may be set to a voltage other than the midpoint between the Vwet and Vdry voltages where the maximum voltage difference ΔV occurs, such as slightly above or below the midpoint (eg, + / - 5%).

[0057] In some embodiments, the bubble detector assembly 100 and its firmware may include a small circuit board 132 to which the bubble sensor 202 is mounted (e.g., in a manner similar to known sensors). In other embodiments, if the bubble detector location on the supply line conduit 105 does not provide sufficient space for the bubble detector assembly 100, the bubble detector assembly 100 and firmware may be placed on one or more separate circuit boards.

[0058] Figure 5 According to one or more embodiments disclosed herein, such as Figure 2 and Figure 3A-3B Flowchart of a method 500 for calibrating an optical bubble detector according to an embodiment of the present invention. At process block 502, the method 500 may include receiving a first plurality of outputs (eg, Figure 2 (First embodiment) the dry voltage 404A or the dry output in line 317, which can be Figure 4B (i.e., dry calibration mode), each of the first plurality of outputs represents the amount of light detected through a supply line conduit (e.g., supply line conduit 105) without liquid therein, and the first plurality of outputs respectively correspond to a plurality of inputs to a light emitter (e.g., light emitters 211, 311). For example, for Figure 2 Embodiment (first embodiment), the input is the % duty cycle setting of the PWM signal in input line 215, and for Figure 3B In the embodiment (second embodiment), the input is the input in line 315 to DAC 320 (scanning the current until the comparator voltage of comparator 319 is equal to each V_Ref value).

[0059] Reference again Figure 5 At process block 504, method 500 may include receiving a second plurality of outputs (eg, Figure 2 (First Embodiment) wet voltage 402A or wet output voltage in line 317 (with Figure 3B (i.e., wet calibration mode), each of the second plurality of outputs represents an amount of light detected by a supply line conduit (e.g., supply line conduit 105) having a liquid (e.g., a liquid reagent or a cleaning liquid) therein, and the second plurality of outputs respectively correspond to a plurality of inputs to a light emitter (e.g., light emitters 211, 311). For example, for Figure 2 In the embodiment of (first embodiment), the input can be the % duty cycle setting in input line 215, and the input in line 315 that controls the current to the optical transmitter 311 via DAC 320. Here, for Figure 3B In an embodiment of the present invention (second embodiment), the state machine 310 may sweep the current to the optical transmitter 311 until the comparator voltage at the comparator 319 is equal to the V_Ref value). For clarity, the same input is used for both dry calibration and wet calibration.

[0060] At process block 506, method 500 may include selecting a "final calibration setting" based on a selected output from the first and second plurality of outputs. The selected outputs may be selected from a pair of corresponding dry outputs and wet outputs such that they achieve maximum signal separation. For example, in a first embodiment, Figure 2 A particular one of the plurality of % duty cycle setting inputs of input line 215 is connected to Figure 2 (See also Figure 4A) is related to a specific output (pair) among the multiple outputs (output voltage pairs for wet and dry cases). The selected output can be the corresponding output of the pair of dry and wet voltage values ​​at a specific % duty cycle setting (final calibration setting). Similarly, in the second embodiment, Figure 3B A particular one of the plurality of voltage inputs in the input line 315 and a particular output of the plurality of voltage outputs (corresponding to a pair of I_LED values ​​for dry and wet conditions - see Figure 4B ) is related. The controller 210, 310 can be configured to operate the light emitter 211, 311 at a final calibration setting during operation to detect whether the supply line conduit 105 contains liquid (e.g., liquid reagent or cleaning liquid), that is, (wet) or does not contain liquid (dry). Figure 2 In the embodiment (first embodiment), the selected final calibration setting can be selected based on achieving the maximum difference ΔV between the wet output and the dry output. Figure 3A-3B The final calibration setting selected may be based on Figure 4B The minimum value for the dry curve and the maximum value for the wet curve in .

[0061] At process block 508, method 500 may further include setting a threshold (e.g., V TH The threshold value may be selected to be between the wet output level and the dry output level of the final calibration setting (e.g., between Figure 2 between the first voltage 404A and the second voltage 402A and between Figure 3B In one example, for the first embodiment, the threshold voltage 409 can be set at a point where a maximum voltage difference (ΔVMax) occurs between the first and second plurality of voltages (i.e., at Figure 4A The maximum difference at 408 in the voltage value.

[0062] In another embodiment, the controller (state machine) 310 and the method 500 may be operable, as in Figure 3B and Figure 4B , to select a maximum current (I_LED_Max) corresponding to the first plurality of outputs, and to select a minimum current (I_LED_Min) corresponding to the second plurality of outputs, and then to set the final calibration setting 409 to a current value between the maximum current (I_LED_Max) and the minimum current (I_LED_Min). Figure 4BAs shown in , the final calibration setting 409 may include a current I_LED setting that is approximately midway (50%) between the maximum current (I_LED_Max) and the minimum current (I_LED_Min). The order of running the dry calibration and the wet calibration may be reversed.

[0063] exist Figure 4B In an embodiment of the present invention, method 500 may include, via operation of controller (state machine) 310, setting a light emitter (e.g., light emitter 311) to operate at a selected final calibration setting (e.g., final calibration setting 409). In particular, final calibration setting 409 may correspond to a setting that may occur halfway (50%) between I_LED_Max and I_LED_Min.

[0064] The method 500 may further include setting a comparator threshold (eg, V_Ref_Final 409) based on the selected output of the first and second outputs. In particular, the method 500 may set the threshold voltage (eg, V TH ) is set to a voltage value equal to V_Ref_Final. In other embodiments, V TH It can be set to a voltage value slightly higher or lower than V_Ref_Final, such as + / - 1V_Ref division. Figure 3A and Figure 4B Example V TH It may be set based on a midpoint between intersection points E and F between the final calibration setting line 409 and each of the wet curve 404B and the dry curve 402B.

[0065] The magnitude of the respective plurality of V_Ref inputs of the second embodiment may vary from a minimum value to a maximum value (e.g., from 0 to 15 V_Ref increments). The plurality of inputs of each embodiment may include at least 10 different input settings (e.g., % duty cycle settings or V_Ref settings) that generate a variable light source current that is a steady state once finalized. Then, in each embodiment, V may be selected for the final calibration setting. TH , resulting in maximum signal separation ( Figure 4A and Figure 4B ).

[0066] For the second embodiment, a 2-step process can be used (see Figure 4B). Here, the light emitter 311 may be pulsed at a 12.5% ​​duty cycle setting, but the current may be provided as a 10-bit variable signal from 3 mA to 85 mA (always at this fixed % duty cycle setting of PWM). I_LED_FINAL 409 is provided based on V_REF_FINAL 407, which is carefully selected from a selection of multiple discrete levels (e.g., 16 discrete levels from 1 to 15) to allow utilization of the comparator threshold V TH The comparator threshold V TH Approximately centered in the possible operating band between I_LED_Max and I_LED_Min. Both embodiments achieve this by separating the wet and dry outputs as much as possible and by maximizing V TH The settings are centered, achieving the same end goal of achieving maximum noise immunity.

[0067] Once calibration has been performed for individual supply line conduits 105, positioning, and liquid contained (wet) and non-liquid contained (dry) modes, then the light emitter 311 may be operated at an intensity corresponding to a final calibration setting (e.g., final calibration setting 407) to accurately detect supply line conduits 105 without liquid therein and supply line conduits 105 with liquid therein. If the output from the light detector 312 in the output line 317 is equal to or above a threshold, the supply line conduit 105 is determined by the controller (state machine) 310 to be wet (having liquid therein), and if the output from the light detector 312 in the output line 317 is below the threshold, the supply line conduit 105 is determined to be dry (not having liquid therein).

[0068] In each embodiment, the method may include storing in the non-volatile memory 310M of the controller 210, 310 a value representing a threshold value (eg, a voltage V TH ). The threshold value may be used in conjunction with a generated operating parameter (e.g., voltage 409 or I_LED 409) that is: 1) at a maximum voltage difference (ΔV_Max) between the first plurality of voltages 404A and the second plurality of voltages 402A for the first embodiment, or 2) in conjunction with an I_LED 409 selected (V_Ref) that is between a maximum current input (I_LED_Max) and a minimum current input (I_LED_Min) of the first plurality of currents 404B and the second plurality of currents 402B, respectively, for the second embodiment.

[0069] Some of the above process blocks of method 500 may be performed or carried out in an order or sequence that is not limited to the order and sequence shown and described. For example, in some embodiments, process block 504 may be performed before process block 502.

[0070] Fig. 6A A flow chart illustrating a general method 600A for calibrating an optical bubble detector (e.g., bubble detector 202, 302) in accordance with one or more embodiments of the present disclosure is illustrated in greater detail. The method 600A begins at process block 601 by turning the unit (e.g., bubble detector assembly 100, 300) on. At decision block 603, the desired calibration mode (wet calibration mode or dry calibration mode) is selected. For example, the calibration mode may be selected by actuating (e.g., holding down) a calibration button (e.g., calibration button 308), which may be any suitable switch. Optionally, once a calibration start (calibration) command is received, it may occur in an automatic sequence (e.g., dry then wet calibration), or vice versa. When the bubble detector assembly (e.g., bubble detector assembly 100) performs the calibration / self-tuning method 500, a calibration LED (e.g., calibration LED 204) may illuminate. Other mechanisms or methods for initiating dry and wet calibrations may be used.

[0071] The start of a wet or dry calibration mode can be optionally confirmed in either of process blocks 605 by receiving a signal on output line 217 or 317. For each corresponding input (e.g., % duty cycle setting or other input value) supplied on input lines 215, 315, when performing a dry calibration mode, the output obtained can be a calibration data (Cal Data) value in block 607D, or a wet calibration data (Cal Data) value in block 607W. In a first embodiment, the input can be a PWM signal with different % duty cycle settings. For example, the on-duty time of various supplied % duty cycle settings can be increased in increments of 1% or 2% from 0% to a maximum % in a desired range. Other suitable increments can be used. The output data can be a plurality of voltages, each of which represents the amount of light detected by the supply line conduit 105 with no liquid therein (i.e., dry) and then with liquid therein (i.e., wet). Each dry calibration value and wet calibration value in the output lines 217 , 317 corresponds to an input in the plurality of inputs to the optical transmitter 311 provided in the input lines 215 , 315 , respectively.

[0072] Each of the wet calibration mode values ​​and the dry calibration mode values ​​may be stored in a memory 210M, 310M such as an NVRAM or other suitable memory type, and / or may be forwarded to an external processor, microprocessor, or computer (e.g., computer 316). Once the dry and wet cal data points are acquired in blocks 607D, 607W, the method 600A may then optionally confirm to the user in process block 609 that each of the dry and wet data collections have been completed individually. Process block 611 (if optionally used) may further verify that the collected calibration data points are, for example, monotonically increasing, and that both dry and wet calibrations have been completed. If increasing the input of the % duty cycle setting (first embodiment) or increasing I_LED (second embodiment) does not produce an increased output in line 217, 317, something is wrong and the entire routine may be aborted.

[0073] The method 600A, via the controller 210, 310 (or other computer connected thereto (e.g., computer 316)), can then perform an analysis on the dry and wet cal data points acquired and stored in memory (e.g., memory 210M or other memory) in process block 613. The analysis involves determining which of the multiple inputs in the lines 215, 315 provides the best signal separation between wet and dry. For the first embodiment, the input 407 that results in the maximum voltage separation (ΔV_Max between the dry data 404A and the wet data 402A) is sought. In the second embodiment, a particular V_Ref value 407 is sought that results in finding an equal voltage difference between I_LED_Max for the wet data and I_LED_Min for the dry data.

[0074] After the analysis in block 613 is complete, the method 600A may perform an optional data check in block 615 to inquire whether the collected data is sufficient. This may test whether the maximum voltage separation (ΔV_Max) is above a preselected value, or whether the input (I_LED_Min) is above a preselected minimum value. For example, a maximum voltage separation of at least 100 mV may be desired, or a minimum current (I_LED_Min) of 10 mA may be desired. If the data is insufficient (N), there may be insufficient signal strength to keep the signal-to-noise ratio high or to establish an appropriate comparator reference. When the data is sufficient (Y), in block 621, the specific input settings ("final calibration settings") that resulted in the desired output are stored in the memory 210M, 310M and included in the bubble detector assembly 100, 300 of the bubble detector 202, 302 that is advanced in the operating mode for wet and dry discrimination (after the self-calibration method 500 is completed).

[0075] Additionally, in block 621, a threshold may be selected as a comparator threshold that determines whether a wet or dry condition exists when going into a run mode (non-calibration mode). For example, in some embodiments, the selection may be determined as V TH For example, in the first embodiment, the threshold V TH can be the midpoint of the maximum voltage separation (ΔV_Max) and is used as the comparator threshold V for advancing in the run mode. TH The comparator threshold V TH Can be saved to the memory 210M. In some embodiments, the comparator threshold V TH is a carefully chosen V_Ref_Final setting from the preselected settings. Here again, this value may be chosen as close as possible to the midpoint between the intersections E and F of line 409 with the wet and dry data of curves 404B, 402B, resulting in a value of 407. Different thresholds other than these midpoint values ​​may be used.

[0076] As shown in block 623, the bubble detector assembly 100, 300 including the bubble detector 202, 302 is now calibrated and can be operated in the run mode. For example, the dry / wet pipe indicator 306 can now be "on" for a dry condition in the supply line pipe 105 and "off" for a wet condition in the supply line pipe 105 (or vice versa). Other mechanisms for marking a wet or dry condition can be used, such as sending a wet or dry signal to a computer (e.g., computer 316) interconnected with the bubble detector assembly 100, 300.

[0077] Figure 6B The diagram shows that the calibration according to the present disclosure includes the following steps: Figure 2 Flowchart of method 600B of bubble detector assembly 100 of bubble detector 202 shown in . As previously described, method 600B begins at process box 601 by turning on the unit (e.g., bubble detector assembly 100). At decision box 603, the desired calibration mode (dry calibration mode or wet calibration mode) can be selected. For example, the calibration mode can be selected by actuating (e.g., pressing) calibration button 208, which can be any suitable switch. When bubble detector assembly 100 performs calibration method 600B, calibration LED 204 can be illuminated. For example, 1 flash of LED 204 can indicate that dry calibration will be performed, while 2 flashes can indicate that wet calibration will be performed. Calibration button 208 can be released immediately after the desired mode (wet or dry) is indicated. In one example, one periodic slow flash can indicate that dry calibration mode is being entered, while two periodic slow flashes can indicate that wet calibration mode is being entered. Other suitable indications can be used.

[0078] Assuming that the first calibration mode entered is the dry calibration mode, the pressing of the button 208 may initiate the issuance of a plurality of inputs as % duty cycle settings from the controller 210, and the acquisition of the resulting associated output voltage from the light detector 212. In block 607D, the output voltage may be provided to the controller 210 as an A / D input. All of these digitized dry calibration values ​​may be stored in an array internal to the controller 210 (e.g., a microcontroller). When dry calibration is performed for each corresponding setting in the % duty cycle settings of the PWM signal supplied in the input line 215, each PWM signal having a different % duty cycle setting, the voltage value acquired may be the V_DRY value in block 607D. The V_DRY value may be referred to herein as a first plurality of voltages, wherein each voltage represents the amount of light detected through the supply line conduit 105 without liquid therein (i.e., dry). Each V_DRY data value in the output line 217 corresponds to an input of a plurality of % duty cycle settings from the input line 215 to the light emitter 211, respectively.

[0079] When the second entered calibration mode is a wet calibration mode, the same plurality of inputs of % duty cycle settings are issued from the controller 210. However, now the acquired V_WET output voltage in 607W lies on a different curve because the medium inside the supply line conduit 105 will have changed, thus providing a relatively different refractive index. All of these digitized wet calibration values ​​may be stored in an array internal to the controller 210. For example, the V_WET value in the output line 217 may be a second plurality of voltages.

[0080] Prior to acquiring calibration data in each of the dry and wet cases, the passage of air or liquid may optionally be confirmed by the operator or by other suitable means in either process block 605. Once the V_DRY and V_WET data (calibration data) have been acquired, the method 600B may then optionally separately confirm to the user in process block 609 that the dry and wet data collection has been completed separately via flashing (e.g., three flashes) of the calibration LED 204 or other suitable means. The method 600B may then determine in process block 611 that both the dry calibration and the wet calibration (CAL) have been completed.

[0081] Once completed, the method 600B can then perform analysis on the V_DRY and V_WET data in process block 613 via the controller 210 or an external controller (e.g., an external processor, microprocessor, or computer) interconnected with the controller 210. The V_DRY and V_WET data can be stored in the memory 210M and / or forwarded and analyzed by the controller 210, or sent to an external controller (e.g., an external processor or computer) for analysis. In some embodiments, some portions of the analysis can be performed by the controller 210, while other portions can be performed by the external controller.

[0082] In this first embodiment (the "maximum difference" embodiment), the analysis may include determining which of the multiple inputs of % duty cycle settings provided in line 215 causes the maximum voltage separation (the maximum difference between V_WET and V_DRY). This may involve calculating the difference between the outputs of V_WET and V_DRY (ΔV=V_WET-V_DRY) for each input of the PWM signal having a different % duty cycle setting. Each difference ΔV is then analyzed and compared to select the maximum difference ΔV_Max between the corresponding wet and dry data pairs. The output of the photodetector 212 may be connected to an analog input pin of the controller 210, where the signal may be digitized and read into a maximum difference determination routine configured to derive ΔV_Max. The maximum difference seeking routine may be a routine executed locally on the controller 210 or external to a suitable controller (e.g., a processor, microprocessor, or computer).

[0083] After the analysis in block 613 is complete, method 600B may optionally query whether there is sufficient voltage separation (ΔV_Max) to calculate the maximum separation in block 615. For example, a voltage separation ΔV_Max of at least 100 mV may be desired. If there is optionally sufficient voltage separation ΔV_Max (Y), three flashes (e.g., periodic slow flashes) or other suitable indication may be sent to calibration LED 204 to indicate and confirm this. If the optional query of voltage separation ΔV_Max is not sufficient (N), continuous fast flashes or another suitable indication may be sent to calibration LED 204 to indicate the error condition. When the voltage separation (ΔV) is not sufficient (N), there may be insufficient signal strength to keep the signal-to-noise ratio high or to establish a suitable comparator reference.

[0084] When the voltage separation ΔV_Max is sufficient (Y), in box 621, the specific % duty cycle setting (“final calibration setting”), i.e., the specific % duty cycle setting that causes the maximum difference ΔV_Max, can be stored in the memory 210M and can then be used as an input for the wet and dry determination of the bubble detector assembly 100 including the bubble detector 202 that advances in the operating mode after the self-calibration method 600B.

[0085] Additionally, in block 621, a threshold voltage may be selected. For example, the selection may be calculated as the midpoint of the maximum voltage separation (ΔV_Max) and used as the comparator threshold V TH reference, advances to determine the trigger point between wet determination and dry determination. The comparator threshold V TH Can be saved to memory 210M. Other comparator thresholds V other than midpoint can be used TH For example, the comparator threshold V THIt can be 0.48x midpoint, or another fraction of ΔV_Max, such as + / - 5% of midpoint. This midpoint voltage as a comparator threshold can be used as the comparator threshold V in the firmware program. TH , used to set its output status LED to an "on" state for dry or an "off" state for wet (or vice versa).

[0086] As shown in block 623, the bubble detector assembly 100 including the bubble detector 202 is now calibrated and operable in the run mode. Figure 4A If any measured voltage is equal to or higher than the threshold voltage V TH (line 409), it is determined as a wet condition in the supply line conduit 105, while below line 409 it is determined as a dry condition.

[0087] Figure 6C A flow chart of a second method 600C for calibrating the optical bubble assembly 300 is illustrated in more detail. The method 600C is referred to herein as the 1 / 2 maximum-minimum method. The second method 600C may be performed by Figure 3A-3B and Figures 9A-9F In this method embodiment, the reflective bubble detector 302 is used to optically sense the difference between the dry condition of the supply line pipe 105 (without liquid therein) and the wet condition of the supply line pipe 105 (with liquid therein).

[0088] The second method 600C is initiated at process block 601 by turning on the unit (e.g., the bubble detector assembly 300) as before. At decision block 603, the desired calibration mode (dry calibration mode or wet calibration mode) is selected. For example, the calibration mode may be selected by sending a calibration command (calibration) to the bubble detector assembly 300, or other suitable initiation method, such as through the basic I / O board 303 from the interconnected external computer 316. Optionally, once the calibration start command is received, the selection order may occur in an automatic sequence (e.g., dry then wet calibration), or vice versa, in some embodiments. Once the bubble detector assembly (e.g., the bubble detector assembly 300) successfully completes the calibration method 600C, a confirmation signal in block 605 may be received, such as through the basic I / O board 303.

[0089] The start of the wet calibration mode or the dry calibration mode includes passing air or liquid (e.g., liquid reagent, cleaning liquid, or process liquid) through the supply line conduit 105 at the location of the bubble detector 302. The optional confirmation in box 605 can be completed by receiving a test signal, such as by measuring the supply line pressure, or other suitable means. For each of the dry calibration mode and the wet calibration mode, I_LED data is acquired in boxes 607D and 607W. When the dry calibration mode is performed for each of the corresponding inputs supplied on the input line 315, the acquired output can be the calibration data (Cal Data) value in box 607D. For example, the V_Ref value can vary from a low voltage to a high voltage (e.g., from 245mV to 676mV). The drive current to the light emitter 311 can vary, for example, from about 3mA to about 85mA. In this method 600C, calibration is performed at each reference voltage (V_Ref) value available for use. In this way, a multi-point method is provided that scans across the available reference voltage inputs to generate voltage output data that constitute wet and dry calibration curves.

[0090] As shown, 15 different V_Ref levels are provided for use as comparator voltage values, which are incremented in magnitude from the lowest value to the highest value in approximately equal increments during each calibration mode (wet and dry calibration). Each V_Ref setting is used as a target voltage by the controller (state machine) 310 as the current is ramped from 3mA to 85mA during each calibration. The optical receiver 312 receives the reflected light and provides voltage feedback to the controller 310 via the output line 317 and the comparator 318. Once the ramping feedback output voltage at the output line 317 reaches the target voltage V_Ref value for that increment, the associated I_LED is recorded.

[0091] The output data in output line 317 may be a plurality of voltages (or currents), wherein each output represents the amount of light detected through supply line conduit 105 at each V_Ref setting when there is no liquid therein (i.e., dry calibration) or when there is liquid therein (i.e., wet calibration). Each dry calibration value in output line 317 may be a first plurality of outputs corresponding to a plurality of inputs from input line 315 to light emitter 311, respectively.

[0092] The wet calibration values ​​in output line 317 may be a second plurality of outputs, each of which represents the amount of light detected through the supply line conduit 105 with liquid (i.e., wet calibration) therein. Each Cal Data value obtained as an output in block 607W corresponds to a plurality of inputs from input line 315 to light emitter 311, respectively. Each of the wet calibration mode values ​​and the dry calibration mode values ​​may be stored in memory 310M, such as NVRAM or other suitable memory type, and / or sent to computer 316.

[0093] Once the dry and wet cal data points are acquired in blocks 607D, 607W, method 600C may then optionally individually confirm that each of the dry and wet data sets are complete in process block 609. Method 600C may then determine in process block 611 that both dry and wet calibrations have been completed.

[0094] The method 600C via the controller 310 or computer 316 may then be executed in process block 613 and perform an analysis of the dry and wet cal data points acquired and stored in memory (e.g., memory 310M or a memory of computer 316). The analysis may be performed in computer 316 or controller 310 to determine which of the multiple inputs in line 315 provides the best signal separation between wet and dry conditions. For example, in this embodiment, once the final calibration setting I_LED_FINAL is determined, the maximum V_Ref separation between the dry data and the wet data may be determined (e.g., Figure 4B ).

[0095] After the analysis in block 613 is complete, method 600C may then perform an optional data check in block 615 to inquire whether the collected data is sufficient. This may test whether I_LED_Min is above a preselected minimum current. For example, a minimum current (I_LED_Min) of 100 mA may be desired. If the data range is not sufficient (N), there may be insufficient signal strength to keep the signal-to-noise ratio high or to establish a suitable comparator reference.

[0096] When the data is sufficient (Y), in block 621, the final calibration setting (I_LED_Final) that results in the desired output is stored in the memory 310M and used as the current supplied to the light emitter 311 for wet and dry determinations by the bubble detector assembly 300 including the bubble detector 302 proceeding after self-calibration. As discussed herein, I_LED_Final can be calculated to be equal to (I_LED_Max+I_LED_Min) / 2. From I_LED_Final, the corresponding V_Ref can be estimated.

[0097] Additionally, in block 621, a comparator threshold may be selected that determines whether a wet or dry condition exists when going into a run mode (non-calibration mode). For example, in some embodiments, this selection may be determined as V TH For example, V THV_REF_Final may be equal to V_REF_Final. V_REF_Final may be the midpoint of the measured voltage separation 407 (V_REF_Final = (WetVrefIntercept + DryVrefIntercept) / 2) and is used as the comparator threshold V for advancing in the run mode. TH The comparator threshold V TH It can be saved in the memory 310M or other suitable memory. Figure 4B As shown above, the comparator threshold V TH Can be set at a voltage midway between WetVrefIntercept E and DryVrefIntercept F. Other comparator thresholds V other than the midpoint value can be used TH , such as some other fraction of V_Ref_Final. The selected V_REF_Final value may be the V_Ref increment that is closest to the midpoint value.

[0098] As shown in block 623, the bubble detector assembly 300 including the bubble detector 302 is now calibrated and can now operate in the run mode. The dry / wet pipe indicator 306 can now be "on" for a dry condition detected in the supply line pipe 105 and "off" for a wet condition detected in the supply line pipe 105 in the run mode (or vice versa). Other mechanisms for marking a wet or dry condition can be used, such as sending a wet or dry signal to a base I / O board 303 or other controller (e.g., a microprocessor, processor, or computer 316) interconnected with the bubble detector assembly 300.

[0099] Figures 9A-9E Various views of an embodiment of a bubble detector assembly 300 including an optical bubble detector 302 and its components are illustrated in accordance with one or more embodiments. Fig. 9A , 9E 9F for illustrative purposes) are disposed at a defined position relative to the bubble detector 302, as will be described herein. The bubble detector assembly 300 may include a calibration LED to indicate when calibration is in progress and / or a wet / dry indicator (e.g., Figure 3B 306). Optionally, all status indications and data compilations can be provided to the base I / O board 303 through the SPP interface circuitry 301. The base I / O board 303 can be part of a computer 316 or a peripheral thereof, which can be used to receive data and perform analysis and can also provide input instructions and calibration commands to the bubble detector assembly 300 via the SPP interface circuitry 301.

[0100] Method 600C may be performed by Figure 3A and 3B as well as Figures 9A-9F As described above, method 600C is operable to test (e.g., scan) a bubble detector (e.g., bubble detector 302) across a range of reference voltages input to light emitter 311 and record the corresponding automatically calculated I_LED level determined to be necessary to drive light detector 312 to achieve the desired V_Ref value, which is Figure 4B . The automatic calculation of the I_LED current for each V_Ref input setting is a process by which I_LED is ramped from 3mA to 85mA until the photodiode output feeding the plus input of the comparator 319 is equal to the reference voltage (Vref) feeding the “-” input of the comparator. Once the output of the photodetector 312 reaches the level of V_Ref, the comparator output switches from low to high. The I_LED for that particular V_Ref is then latched into an NVRAM register or otherwise saved. The method is performed at each V_Ref setting while all 16 V_Ref values ​​(including zero) are tested, with liquid or air always inside the supply line conduit. These (V_Ref, I_LED) data pairs can be saved in the controller 310 and / or computer 316, and can then be analyzed in box 613 to determine the final calibration setting and comparator threshold V TH , thereby achieving excellent signal separation for the particular bubble detector 302 used; note that each such bubble detector 302 may be slightly different from each other.

[0101] Once this analysis in block 613 is complete, the values ​​for I_LED_Final and V_REF_Final may be written to a memory (e.g., flash memory such as EEPROM 310M or other memory type) that may be part of the bubble detector assembly 300. Optionally, the data and analysis that determine such values ​​for I_LED_Final and V_REF_Final may be written to a memory card interconnected to the base I / O board 303 ( Figure 3B ) and is implemented by a controller (e.g., a microprocessor, processor, or computer 316) external to the bubble detector assembly 300. The bubble detector assembly 300 may include, for example, an OPB9000 reflective optical sensor integrated circuit available from TT ELECTRONICS / OPTEKTECHNOLOGY as an adaptive sensor integrated circuit 307 (hereinafter referred to as "ASIC 307").

[0102] The bubble detector assembly 300 (and the bubble detector 302) can be configured to operate with an optically transparent or translucent tube, such as a fluorinated ethylene propylene (FEP) material, as the supply line conduit 105 or the like. The supply line conduit 105 can have dimensions such as an outer diameter of 2.54 mm, an inner diameter of 1.52 mm, and can have a wall thickness of 0.51 mm. However, the bubble detector 302 can be adapted to use other conduit sizes and types. The supply line conduit 105 can be fluidly connected to the probe 945 at one end by a connector 940, such as Fig. 9A The other end of the supply line conduit 105 (shown as truncated between the connector 940 and the bubble detector assembly 300 for illustrative purposes) can be connected to a liquid coupling 942, which can be connected to a dispenser, valve and / or pump, which in turn is coupled to a reservoir 943.

[0103] Depending on the application, the reservoir 943 may be a waste container (which may be held under vacuum), and when a valve is opened or a pump is operated, waste liquid may be drawn from a receptacle 944 (e.g., a cuvette) through a probe 945. In the depicted embodiment, a connector 940 at the end of the supply line conduit 105 is connected to a probe 945, which may be movable by a robot 946 (e.g., including a stepper motor or the like) configured to control the movement of the probe 945, such as by lowering the probe 945 into the receptacle 944 to drain the liquid 944L therein. The liquid may be a cleaning liquid and / or a process liquid.

[0104] In some embodiments, a connector 942 at the other end of the supply line tubing 105 can be connected to a flexible / collapsible tubing (e.g., silicone-rubber tubing) that can be squeezed closed with a pinch valve 946. The tubing travels forward from the pinch valve 946 to a reservoir 943 (e.g., a waste bottle) that can be maintained under a vacuum (e.g., negative pressure) to pull liquid 944L into and out of the probe 945 when the pinch valve 946 is opened.

[0105] In other embodiments, the system can be configured to dispense a liquid (e.g., a liquid reagent, a wash liquid, or the like) into a receptacle such as a cuvette 944. During such a dispensing operation, the bubble detector assembly 300 can be positioned directly adjacent to a probe such as probe 945 to minimize the distance between the bubble detector 302 and the probe.

[0106] In more detail, the bubble detector assembly 300 is configured to provide a wet / dry output signal to determine the presence (wet) or absence (dry) of liquid in the supply line conduit 105 at a location along the supply line conduit 105 where such a determination is desired. The output may be provided at J1 of the interface circuit 301 (see Figure 3A ) and can be carried by the interface cable 303C connected to the SPP interface 303I.

[0107] In some applications as discussed above, the bubble detector assembly 300 is designed to, for example, provide confirmation that a cleaning liquid has been aspirated and / or dispensed by the probe 945 located at the cleaning station. The probe 945 and the cleaning station may be part of a cleaning loop assembly of a diagnostic analyzer (e.g., an immunoassay instrument or a chemical analyzer). In other embodiments, the probe (e.g., Fig. 9A The probe 945) can be part of a probe assembly and robot that dispenses liquid reagents into a culture receptacle (e.g., a cuvette or cup) residing in a culture loop.

[0108] In more detail, the bubble detector assembly 300 can be equipped with a highly integrated optical reflective bubble detector 302 that is capable of detecting moving liquid and air masses in the supply line conduit 105. For example, the bubble detector 302 can have a very low (e.g., 6 μS) response time. As will be apparent from the following, the bubble detector assembly 300 operates to automatically calibrate the supply line conduit 105 used, which is constrained in a specially designed mounting assembly, such as Figures 9A-9F Best shown.

[0109] The backing member 936 ( Fig. 9A and 9B ) and standoff 930( Figures 9E-9F ) helps keep the supply line conduit 105 properly positioned and fixed from moving relative to the bubble detector assembly 300, and further provides a highly reflective surface 302R of the plate 933 attached to the rear of the supply line conduit 105 to provide maximum light reflection to the light detector 312. The supplied light can be infrared (IR) light from the light emitter 311. The detected light can be amplified and compared to a determined threshold to provide a discrete comparator output. In this way, the bubble detector assembly 300 can distinguish between wet or dry conditions inside the supply line conduit 105 in the operating mode after calibration.

[0110] like Figure 3B As shown in FIG. 3 , the functional operation of the bubble detector assembly 300 can be broken down into the following functional blocks:

[0111] 1) Serial Peripheral Port (SPP) interface circuitry 301 including ID EPROM 313,

[0112] 2) Local voltage regulation 305, and

[0113] 3)ASIC 307.

[0114] Reference again Figure 3B , a simplified functional diagram of the bubble detector assembly 300 may include an SPP interface 301 designed to interface with an SPP port 303I of a base I / O board 303, which may interface with a computer 316. The SPP interface 301 may operate to expand the functional features of the ASIC 307. Figure 3A J1 is the SPP interface connection to the ASIC 307, which can provide power and control to it. The basic I / O board 303 and the bubble detector board 932 ( Fig. 9A )Shared SPP interface 303I.

[0115] The basic I / O board can manage high-level bubble detector functions through the SPP interface 303I. Low-level functions such as automatic calculation of I_LED for a given V_Ref can be managed by the ASIC 307. As described herein, the ASIC 307 can have a discrete light emitter 311 (e.g., an IRLED) and a discrete IR light detector 312 (e.g., a photodiode) mounted therein. Sensor sampling rates of 1 Hz to 1 KHz can be used. The bubble detector 302 includes an IR photoelectric pair (e.g., a light emitter 311 and a light detector 312) aimed at the supply line conduit 105. A reflective surface or membrane 302R ( Figure 9C-9D ) may be positioned on the opposite side of the supply line conduit 105 from the light emitter 311 and the light detector 312. As shown, the reflective surface 302R may be appropriately mounted to the back of the backing member 936 and accessed through a hole 936H formed therein. The plotting of the wet and dry calibration curves and the subsequent calculations performed on the data to determine I_LED_Final and V_REF_Final may be performed by the controller 310 and / or the computer 316. The computer 316 may send commands such as SET_CONFIG, GET_CONFIG, READ_OUTPUT, and CALIBRATE to the ASIC 307 via the SPP interface circuit 301.

[0116] The output signal from the light detector 312 in output line 317 is a signal proportional to the reflected IR light, which changes intensity level based on whether air (dry) or liquid (wet) is contained in the supply line conduit 105. Power can be supplied from the basic I / O board 303. The bubble detector assembly 300 can provide 3.3V push-pull compatible logic or open-drain output. The discrete output logic can be configured to generate a high (HIGH) for dry and a low (LOW) for wet, or vice versa. The definitions for the SPP interface 301 pins are shown in Table 1 below herein.

[0117] Table 1. SPP interface pin explanation

[0118]

[0119] As shown in Table 1 above, the signal directions supplied are relative to the basic SPP 303I. Utilizing a combination of the SPI serial protocol and the basic I / O polling method, communication with the bubble detector assembly 300 may be achieved through the SPP interface circuitry 301. While communication with the SPI EEPROM 310M may follow the SPI protocol, communication with the controller 310 (e.g., the state machine shown) of the ASIC 307 may use a 1-wire interface and the Manchester protocol. Figure 7 An example encoding of a calibration request is shown, and in particular a Manchester encoding of a calibration command.

[0120] Communication with the registers of ASIC 307 can be accomplished through this interface. EEPROM 310M can be a type of non-volatile memory that can be used to store calibration data and can allow erasure and reprogramming of individual bytes. It can also be used to store the identity and revision level of the PCA. The state machine of controller 310 is hardware that can execute a behavioral model and output a number of states. The model can include a finite number of states and is therefore also referred to as a finite state machine (FSM). Based on the current state and a given input, the state machine performs a state transition and generates an output.

[0121] The SPP interface circuit 301 provides power to the ASIC 307 and also provides digital communication lines. +5.3V power enters the SPP interface circuit 301, which can be immediately converted to +3.3V by a low dropout voltage regulator (LDO) 309. The LDO 309 is a type of power supply integrated circuit that can output a stable voltage from a supply input voltage that may have some variability. The ASIC 307 can consume approximately 16mA of current in operation.

[0122] Marked as Figure 3BThe SPI communication and SPI_GEN lines of the SPP interface circuitry 301 are used to communicate with the ASIC 307 and with the ID EEPROM 313. The SPI_CS_Flash is dedicated to the ID EEPROM 313. The SPI_GENL is used to direct data to and from the ASIC 307. To understand the basic functionality, the ASIC 307 is explained in detail below.

[0123] ASIC 307 is an integrated circuit (IC) packaged in a surface mount device (SMD) package. Its function is to detect the presence or absence of an object via optical reflection. Figure 3B As shown in , when powered and equipped with pull-up resistors attached to its OUT and Cal-Stat lines, ASIC 307 can provide a high (HI) or low (LOW) discrete output signal (from the OUT pin) depending on whether a reflective surface of a reflective target is directly in front of it or not. In the diagnostic equipment application described herein, ASIC 307 can be configured for push / pull mode versus open drain mode. All logic levels for I / O with ASIC 307 are referenced to +3.3V.

[0124] While the ASIC 307 can operate as-is off the shelf for basic operation with robust reflective target items, the use of the ASIC 307 for less reflective surfaces, such as for detecting the presence of a typically clear liquid in a supply line conduit 105, benefits from the special calibration provided by the inventive methods described herein. All communication with the ASIC 307 is through two digital pins, OUT and Cal-Stat. While the ASIC 307 operates most of the time as a sensor, with a discrete output from the OUT pin, it also allows access to internal registers via the Cal-Stat and OUT pins.

[0125] In most cases, serial commands are sent to the ASIC 307 via the Cal-Stat pin and received serially from the ASIC 307 via the OUT pin. When the ASIC 307 is not processing any commands, the OUT pin provides the function of enabling the output of the status of the bubble detection function, i.e., high for air and low for water. However, when sending commands and accessing the internal registers of the ASIC 307, the Cal-Stat pin receives write, read, and calibration commands. When a read command is issued, the register contents can be dumped via the OUT pin. For calibration commands, the ASIC 307 can generate a reply on the same pin, so this pin can be bidirectional.

[0126] By using multiple SPP digital control lines, tri-state buffers (TSBs), and analog multiplexers, these complex communication scenarios can be handled. Due to the serial nature of the incoming commands and outgoing data of the ASIC 307, intandem, the SPI_DOUT controller line can be used to transmit data to the Cal-Stat pin and the SPI_DIN controller line can receive data from the OUT pin.

[0127] In some embodiments, this steering can be achieved using a tri-state buffer IC (TSB) at the input to the Cal-Stat pin and an analog multiplexer IC at the output of the OUT pin. The SPI_GENL_chip select line can be used to manage the steering of these paths. When SPI_GENL is low, the SPI line is connected to the ASIC 307 to support the transmission of all serial commands to the ASIC 307 and to receive data from the ASIC 307 during the read command. When SPI_GENL is high, then the calibration confirmation data can be transmitted back to the controller 310 from the Cal-Stat pin via the SPI_IO line and the wet / dry status data can be transmitted from the OUT pin to the SER_B line. For example, the latter condition can be set by the controller 310. During normal operation, the only path in operation is the path created from the OUT pin to the SER_B line for the transmission of the wet / dry status. In this same signal steering state, the controller 310 samples the SPI-IO input to detect the calibration confirmation pulse.

[0128] In the "auto-calibration mode" of operation, the SPI_GENL line can be strobed low via a signal from the base I / O board 303 and the auto-calibration command can be transmitted over the Cal-Stat line via SPI_DOUT to the ASIC 307. The SPI_GENL low assertion also directs the OUT signal to the SPI_DIN pin, but in this auto-calibration mode of operation, it is ignored by the base I / O board 303. Once the calibration command transmission 824 (FIG. 8) is complete, the SPI_GENL line can be de-asserted high to let the base I / O board 303 read back the acknowledge pulse via SPI_DIN.

[0129] In "manual programming mode", commands can be sent to set the current level, amplifier gain level, and output pin behavior of the optical transmitter 311. In this manual programming mode, SPI_GENL can be asserted low, and both the Cal-Stat and OUT signals on the ASIC 307 can be simultaneously routed to the SPI_DOUT and SPI_DIN pins, respectively. SPI_GENL remains low for both the transmission of a specific manual programming command and any ensuing response from the ASIC 307.

[0130] The SER_A pin is another SPP pin that can be used by the basic I / O board 303 for serial communication. However, here, it can be used as a digital output. This digital output can allow power to be switched on or off for the entire board. When SER_A is high, the board is powered on. When SER_A is low, the board is powered off.

[0131] SPI_CS_FLASH may be used when the microcontroller on the basic I / O board 303 communicates with the ID EEPROM 313. The ID EEPROM 313 may contain board identification information including the board type and version number. This may be queried by the microcontroller of the basic I / O board 303 at initialization and used to make decisions based on the hardware features supported by a particular version number.

[0132] A microchip (e.g., a 1K-bit SPI serial EEPROM) can be used as the ID EEPROM 313. The ID EEPROM 313 can be pre-programmed with a unique board type ID and board type ID revision. A specific diagnostic analyzer can use the board ID to confirm that the expected hardware configuration has been installed. The memory contents of the ID EEPROM 313 can be accessed via a simple SPI interface that is controlled using the SPI_CLK, SPI_DIN, SPI_DOUT, and SPI_CS_FLSH signals.

[0133] Various measures may be used to minimize noise, crosstalk, and surge immunity issues. For example, the +5.3V power may pass through a power inductor before accessing the LDO 309 to improve power line immunity. Likewise, all I / O lines may have low pass filters in place (not shown). Finally, there may be transient voltage suppression (also not shown) applied to each I / O line to mitigate electrostatic discharge events.

[0134] In the case of ASIC 307, by using the methods herein, a fully integrated, high precision on-board circuit system can distinguish between slightly different levels of reflected light. For this dry / wet application, ASIC 307 can be used to distinguish between light reflected from a supply line conduit 105 that is filled with liquid (wet) or filled with air (dry).

[0135] ASIC 307 (e.g., OPB9000) may have features including an optical signal amplifier (which may be included in analog front end 318), an output comparator 319, and a finite state machine (as a state machine operated by controller 310) to control the input to DAC 320 and receive the output from light detector 312 to assist in running the automatic calibration method 600C described herein. OPB9000 may also incorporate other features such as light modulation for ambient light immunity and LED temperature compensation.

[0136] As discussed above, the ASIC 307 can communicate using the Manchester serial communication protocol, which can be a 1-wire protocol that uses a single line for clock and data. There are basically only 3 commands, one of which allows passing parameters (arguments), such as read (READ), write (WRITE), and calibration (CALIBRATE). Writes can include sequencing nibbles and parameters that can be passed during write commands. The read command has no parameters because it dumps the contents of all registers. The calibration command also has no parameters. Fig. 8A An example of an encoded command for a calibration request is shown in FIG.

[0137] ASIC 307 may include four non-volatile registers: BANK1, BANK2, BANK3, and RESERVED. BANK3 and the RESERVED register have 11 bits and 7 bits that are not recorded, respectively. BANK2 has 6 bits, all of which are writable. The format for writing to this register is 1101-10-bbbbbb. The bit level definition here is: [sync nibble][detect nibble]-[command nibble]-[REF0][REF1][REF2][REF3][DS][OP]. 4 bits of this register are allocated to maintain reference levels (REF0:REF3). The remaining two bits can be drain select (DS) and output polarity (OP), which can set the behavior of discrete output pins. For drain select, 0 is set for open drain and 1 is set for push-pull operation. For output polarity, 0 is set for non-inverting and 1 is set for inverting.

[0138] BANK1 has 13 bits, 12 of which are writable. The format for writing to this register is 1101-01-bbbbbbbbbbbb. The bit level definition here is: [Sync nibble] [Detect nibble] - [Command nibble] - [CA bit] [AGC-LSB] [AGC-MSB]

[0139] [LED0][LED1][LED2][LED3][LED4][LED5][LED6][LED7][LED8][LED9]. Bank 1 has 10 bits allocated to the LED current level, 2 bits allocated for automatic gain control (AGC) of the detected light, and 1 bit allocated for confirmation that the calibration was successful (1=successful). AGC=00 sets the gain to 1, AGC=01 sets the gain to 4, and AGC=10 sets the gain to 8. At a 50% duty cycle setting, the programmed communication rate for the write command can be a maximum of 100kbit / s. At a 50% duty cycle setting, the programmed communication rate for the read command can be 100kbit / s±5kbit / s.

[0140] Figure 8B Illustrated is a zoomed out view (lower trace) of an auto-calibration command 823 that may be issued on a Cal-Stat line to initiate the auto-calibration method 600C described herein. Fig. 8A 824 is shown as a zoomed in view (upper trace) of a calibration request 824 sent from the microcontroller to the Cal_Stat pin of the ASIC 307 during a calibration command 823. Upon receiving this automatic calibration command 823 including the calibration request 824, the pulsed LED driver may ramp up its current at a pre-set V_Ref setting in the range of 3 mA to 85 mA. The resulting I_LED for each V_Ref may be recorded in the memory 310M (e.g., EEPROM) of the ASIC 307 as shown in FIG. Figure 4B The automatic calibration method 600C may take less than one second. If the method passes, a 13ms low pulse 825 may be transmitted from the Cal-Stat pin. The CA bit in BANK1 may also be set high.

[0141] In more detail, the multi-point self-calibration method 600C is Figure 6C-6F600C. The method 600C herein operates to achieve calibration with improved wet / dry signal separation. As previously described, this is particularly important because when attempting to detect clear or slightly clear liquids, such as in a diagnostic analyzer, the signal difference between the wet reading and the dry reading is very slight. In order to improve the separation of the wet signal from the dry signal and achieve excellent noise immunity, the self-calibration method 600C generates a multi-point wet calibration curve 404B (e.g., a 16-point wet calibration curve) and a multi-point dry calibration curve 402B (e.g., a 16-point dry calibration curve), such as Figure 4B as shown in .

[0142] like Figure 6C As shown in FIG. 6 , method 600C involves turning on circuit 300B at block 601. This can be accomplished by powering bubble detector assembly 300 via power from base I / O board 303. Next, calibration mode is selected at block 603. This can be done automatically, such as running a dry calibration and then a wet calibration, or vice versa. Additionally, a calibration signal can be provided from base I / O board 303, such as via an SPI_DOUT pin ( Figure 3B ) to initiate calibration.

[0143] The method 600C then passes liquid (e.g., liquid reagent, cleaning liquid, or the like) or air through the supply line conduit 105 so that the liquid or air is present at the location of the bubble detector 302. The passage of the liquid or air may optionally be confirmed in block 605. For example, the confirmation may be performed by monitoring the pump or otherwise monitoring the pressure in the supply line conduit 105.

[0144] For each mode (wet calibration mode and dry calibration mode), calibration data is acquired. In blocks 607D and 607W, I_LED data is obtained based on the delta voltage input, such as Figure 4B The acquired data may be stored locally and / or may be transferred to the base I / O board 303 and ultimately further transferred to the computer 316 where the data may be plotted and / or analyzed. Figure 4B A graphical display of the acquired data (V_Ref versus I_LED) is shown in FIG. 4. The data for the dry and wet curves 402B, 404B may be generated by ramping up I_LED via the voltage input to the DAC 320 in line 315 at each V_Ref setting until the detected and amplified light signal from the light detector 311 reaches each V_Ref level ( Figure 4B). During calibration, the pulsed LED drive signal from DAC 320 is ramped up to cause a current to the light emitter 311 from about 3 mA to about 85 mA. The total ramping period can be about 17 mS. The V_Ref value for performing the calibration process can be varied from 245 mV to 676 mV in equally spaced increments, for example, represented by settings from 0 to 15. However, other numbers of increments and ramp periods can be used.

[0145] During calibration mode, the Cal-Stat pin may initially be asserted high from the SPI_DOUT pin. Calibration is initiated via a calibration command routed from the SPP interface 301 to the Cal-Stat pin, which is facilitated by setting SPI_GENL=0. In this mode, the tri-state buffer TSB may drive command data from SPI_DOUT onto the Cal-Stat pin of the ASIC 307. Once the command transmission is complete, the tri-state buffer TSB is set to HI-Z mode. This allows for the ASIC 307 to drive the Cal-Stat pin. After a successful calibration, which may last for approximately 17ms, the Cal-Stat pin will transition to a low state for 13ms. An unsuccessful calibration may occur if the reflective surface 302R is not present or there is insufficient reflected light received by the light detector 312 during calibration. The DAC 320 used may be a 12-bit current control circuit that may sink the cathode of the LED to ground. The thick arrow labeled 315 from the control logic (state machine) of controller 310 into DAC 320 may represent the 10 current control + 2 gain control digital lines passing from controller 310 to DAC 320 to control the ramp up of current to optical transmitter 311. The pulse digital lines (thinner lines) passing from controller 310A to DAC 320 are the gate drives that modulate the on and off of DAC 320. When this digitally controlled gate drive is in its prescribed ON-duty phase, it issues a current sink level selected by DAC 320. In its off-duty phase, no current sink occurs.

[0146] The current to the light emitter 311 (LED) can be pulsed at 500KHz, 12.5% ​​duty cycle. In this embodiment, the variability of the intensity of the light emitter 311 (eg, LED) is not as large as in Figure 2 Rather than being controlled by a PWM signal as in the embodiment of FIG. 1 , the optical emitter 311 is independently controlled by opening or closing a channel of the driver to permit or limit current flow to the optical emitter 311 .

[0147] The remaining unscattered light from the light emitter 311 is received by the light detector 312, which may be any suitable photodiode, after passing through the supply line conduit 105 for the first time, being reflected off the reflective surface 320R, and passing through the supply line conduit 105 for the second time. For any given V_Ref applied, increasing this voltage may provide an increase in current to the light emitter 311 and thus cause an increase in voltage from the light detector 312.

[0148] Fig.6D A flow chart of a method of generating a dry or wet calibration curve for calibration of the second bubble detector assembly 300 is illustrated. In this method, calibration is performed at each reference voltage value (V_Ref) available for use. In this way, a multi-point method is provided that scans across the available reference voltage inputs and feeds into the internal comparator 319 of the optical bubble detector assembly 300 according to an embodiment. In particular, Fig.6D One method is illustrated of how the I_LED value may be obtained in blocks 607D and 607W.

[0149] In block 608, at the start of the scan, the value of V_Ref is set to zero. In block 610, calibration is performed by sweeping V_Ref from a minimum value V_Ref_Min=0 to a maximum value V_Ref_Max. The value of V_Ref may be an integer value. V_Ref_Max may be an integer, such as 15. Thus, in this example, V_Ref is swept by the DAC 320 and incremented from 0 to 15 in increments of one, where each number is Figure 3B 319. As V_Ref is scanned, the I_LED value generated from the current received from the light detector 312 in the output line 317 is recorded in block 612, which is necessary to match each V_Ref value, as determined by the comparator 319. For example, the resulting I_LED value corresponding to each V_Ref increment can be stored in local memory. Alternatively or additionally, the data can be sent to the base I / O board 303 and the computer 316.

[0150] The analog front end 318 may receive the output in line 317 from the photodetector 312 corresponding to each increment V_Ref provided as an input to the comparator 319. The analog front end 318 may be bandpass filtered to phase lock the photodetector circuitry to the LED driver circuitry. Thus the output signal in 317 is received only during the time interval when the gate drive signal of the DAC 320 is enabled. In this way, any constant light signal (like ambient light) or other noise artifacts occurring at other frequencies (e.g., 60 Hz noise) may be ignored. The analog front end 318 may also include suitable amplification.

[0151] When V_Ref equals V_Ref_Max in block 614, then the increment stop for both the dry calibration mode and the wet calibration mode can be repeated for the wet calibration mode. Fig.6D In other embodiments, wet calibration may occur before dry calibration.

[0152] Reference again Figure 6C Once completed Fig.6D , the self-calibration method 600C may optionally implement a confirmation in block 609 to ensure that sufficient data has been generated for the wet and dry calibrations. This confirmation may be achieved by the controller 310 evaluating that there are a desired number (e.g., 15) of successful calibrations in the row, one for each V_Ref input. Next, in block 613, the self-calibration method 600C may perform an analysis of the data points that make up the wet and dry calibration curves 404B, 402B, which are obtained from implementing Fig.6D 404B and the dry calibration curve 402B. In some embodiments, the I_LED_Final value may be obtained and stored by a method of , so as to obtain the final values ​​of I_LED_Final and V_Ref_Final. As a precursor to the analysis, or concurrently with the analysis, an optional data check may be performed in box 615 to see if the received data will be sufficient for the analysis. For example, the data may be checked to see that the received maximum I_LED has at least met a minimum pre-established current level, such as 10 mA, or to evaluate the difference between the V_Ref value at the intersection with the I_LED line 409 and a pre-established voltage delta value (ΔV). In particular, at I_LED_Final 409, the pre-established voltage delta value (ΔV) should be 3.50 or more complete V_REF division between the wet calibration curve 404B and the dry calibration curve 402B. Additionally or alternatively, the I_DRY / I_WET current ratio (C1 / C2) at V_Ref_Final on line 407 should be C1 / C1 ≥ 1.15.

[0153] As shown in block 621, the analysis of method 600C in block 613 ultimately results in the determination of I_LED_Final, which is a current value that can be stored in EEPROM 310M. In short, the analysis in block 613 finds the final calibration setting 409, i.e., the current setting, which results in an I_LED current to the light emitter 311 that allows for suitable operation within the valid region of both the wet (404B) and dry (402B) calibration data curves.

[0154] To assist in understanding how the final calibration settings 409 may be selected in this embodiment, Figure 4B and Fig. 6E For reference. Fig. 6EThe calibrated I_LED_Final setting method 613I shown in FIG. 613 includes, in block 620, finding I_LED_Max as the maximum current value on the wet curve 404B. In block 622, method 613I includes finding I_LED_Min as the minimum current value on the dry curve 402B. In block 624, the I_LED_Final value, i.e., the final calibration setting, is determined. This I_LED_Final value is used for the wet / dry detection going forward, as shown in block 621 ( Figure 6C ). For example, the I_LED_Final value may be calculated as: (I_LED_Max+I_LED_Min) / 2. The I_LED_Final value may be rounded to the nearest whole number corresponding to the V_Ref value that the DAC 320 is capable of outputting.

[0155] According to method 600C, analysis of the V_DRY and V_WET data in block 613 may further determine a final reference value V_Ref_Final, which is a comparator threshold value that is advanced when determining a wet or dry determination of the supply line pipe 105. In one embodiment, the threshold determination method 613T for determining V_Ref_Final is Fig. 6F Shown in.

[0156] from Fig. 6E Given I_LED_Final from the previous flow chart, V_Ref_Final can now be determined. I_LED_Final can be rounded to the nearest value. According to method 613T, in block 626, calculate Figure 4B , and in block 628, the DryV_RefIntercept (point F) is calculated. This involves identifying the wet straddle points (A and B) and the dry straddle points C and D. The wet straddle points, referred to herein as WetHighEdge (point A) and WetLowEdge (point B), straddle either side of the WetV_RefIntercept (point E), as shown in FIG. Figure 4B Similarly, the dry spanning points referred to herein as DryHighEdge (point C) and DryLowEdge (point D) straddle either side of the DryV_RefIntercept (point F), as shown in FIG. Figure 4B The span points may be points just above and just below the intersection points E and F.

[0157] In block 630, V_Ref_Final is determined. V_Ref_Final may be determined by determining WetV_RefIntercept and DryV_RefIntercept in any order as follows:

[0158] As shown in block 626, WetV_RefIntercept (point E) is calculated using the following calculations and definitions:

[0159] WetHighEdge = the wet calibration current value that is closest to and greater than or equal to the final I_LED_Final at point A.

[0160] WetHighV_Ref=V_Ref value corresponding to WetHighEdge current at point A.

[0161] WetLowEdge = the wet calibration current value closest to and less than or equal to I_LED_Final at point B.

[0162] WetLowV_Ref=V_Ref value corresponding to the WetLowEdge current at point B.

[0163] WetYIntercept=the Y intercept of the straight line passing through the points (WetHighV_Ref, WetHighEdge) and (WetLowV_Ref, WetLowEdge), that is, passing through points A and B.

[0164] WetSlope=the slope of the line passing through the points (WetHighV_Ref, WetHighEdge) and (WetLowV_Ref, WetLowEdge), that is, the slope of the line passing through points A and B.

[0165] WetV_RefIntercept=the point where the I_LED_Final current value intersects the wet calibration curve 404B.

[0166] WetSlope = (WetHighEdge - WetLowEdge) / (WetHighV_Ref - WetLowV_Ref) = WetHighEdge - WetLowEdge / 1 = WetHighEdge - WetLowEdge (Note that ΔV_Ref is always equal to 1)

[0167] WetYIntercept=WetLowEdge-(WetLowV_Ref*(WetHighEdge-WetLowEdge))

[0168] WetV_RefIntercept (point E) = (I_LED_Final–WetYIntercept) / (WetHighEdge-WetLowEdge)

[0169] If the I_LED_Final current intersects the wet calibration curve 404B directly at a calibration point (eg, one of points 1-15), then WetV_RefIntercept is equal to the V_Ref value at that calibration point.

[0170] As shown in block 628, DryV_RefIntercept (point F) is calculated using the following calculations and definitions:

[0171] DryHighEdge=the dry calibration current value that is closest to and greater than or equal to the I_LED_Final current at point C.

[0172] DryHighV_Ref=V_Ref value corresponding to the DryHighEdge current at point C.

[0173] DryLowEdge = the dry calibration current value that is closest to and less than or equal to the I_LED_Final current at point D.

[0174] DryLowvRef=V_Ref value corresponding to the DryLowEdge current at point D.

[0175] DryYIntercept = the Y intercept of the straight line that will pass through the points (WetHighV_Ref, WetHighEdge) and (WetLowV_Ref, WetLowEdge), that is, through points C and D.

[0176] DrySlope=the slope of the line passing through the points (DryHighV_Ref, DryHighEdge) and (DryLowV_Ref, DryLowEdge), ie, the slope of the line passing through points C and D.

[0177] DryV_RefIntercept=V_Ref point where the I_LED_Final current value intersects the wet calibration curve 404B.

[0178] Wet Slope = (DryHighEdge - DryLowEdge) / (DryHighV_Ref - DryLowV_Ref) = (DryHighEdge - DryLowEdge) / 1 = (DryHighEdge - DryLowEdge). (Note that ΔVref is always equal to 1)

[0179] DryYIntercept=DryLowV_Ref*(DryHighEdge–DryLowEdge)

[0180] DryV_RefIntercept(F)=(I_LED_Final–DryYIntercept) / (DryHighEdge–DryLowEdge).

[0181] If the I_LED_Final current 409 intersects the dry calibration curve 402B at a calibration point, then DryV_RefIntercept is equal to the V_Ref value at that calibration point.

[0182] In block 630, method 613T may optionally perform a pass / fail DeltaV_Ref test. This optional test may analyze the V_Ref values ​​at points E and F. This test may involve calculating a DeltaV_Ref value, where:

[0183] DeltaV_Ref=WetV_RefIntercept-DryV_RefIntercept.

[0184] The pass / fail criteria may be a DeltaV_Ref value that is a 3.50 or more complete V_Ref division between the intersection of the wet calibration curve 404B and the dry calibration curve 402B at I_LED_Final 409 (point E - point F).

[0185] In some embodiments, a current ratio (CR) test may also be optionally performed in block 632, where:

[0186] C1 = the dry calibration current value on the dry curve 402B corresponding to V_Ref_Final, and

[0187] C2 =wet calibration current value on wet curve 404B corresponding to V_Ref_Final.

[0188] The current ratio is defined as: CR = C1 / C2. For example, the pass / fail criteria may be that CR at V_REF_Final must be ≥ 1.5.

[0189] After WetV_RefIntercept and DryV_RefIntercept are determined in blocks 626 and 628, the V_Ref_Final value may be calculated in block 634 as follows:

[0190] V_RefFinal= <WetV_RefIntercept+DryV_RefIntercept) / 2。

[0191] The V_Ref_Final value can be rounded to the nearest V_Ref integer. The V_Ref_Final value can be used as the comparator threshold V TH. Comparator threshold V TH Can be used as the demarcation (trigger) point between wet and dry determinations.As should be appreciated, the resulting value of V_Ref_Final is the reference voltage setting that achieves the highest level of signal separation between wet and dry states.

[0192] These two final parameters (I_LED_Final and V_Ref_Final) can be written and stored in the EEPROM 310M. Figure 6C This calibration method 600C allows finding the perfect trip points for signaling dry and wet conditions in ongoing use.

[0193] Reference again Figures 9A-9F , the ASIC 307 of the bubble detector assembly 300 may include a support 930, such as a cylinder (e.g., a metal cylinder) that may be coupled to a printed circuit board 932, the support 930 operating to contact and position the supply line conduit 105 at a defined distance away from the light emitter 311 and the light detector 312 ( Fig.9E ). For example, the defined distance between the light emitter 311 (or light detector 312) and the nearest portion of the supply line conduit 105 may be approximately 2.09 mm. However, other suitable distances may be used. On the other side of the supply line conduit 105, a reflective surface 302R is provided. The reflective surface 302R may be formed of any suitable reflective material such as a reflective film 934. The reflective film 934 may be a 3M TM SCOTCHLITE TM Reflective graphic film 680-10 or the like. Reflective film 934 can be attached to a surface, such as a flat surface 935 of a support member 933. For example, reflective film 934 can be wrapped around and secured to support member 933. Support member 933 can be a rigid block, such as, for example, an aluminum block.

[0194] The support member 933 having the reflective surface 302R can be coupled to the backing member 936, such as by using a Fig. 9B and 9D 936 or another suitable attachment mechanism. The backing member 936 may include a groove 938 along its length that is configured to receive the supply line conduit 105 therein. When the backing member 933 is assembled to the printed circuit board 932, as shown in FIG. Fig. 9A, the bottom of the groove 938 makes contact with the supply line conduit 105 along its length, as does the support 930, and thus the position of the supply line conduit 105 relative to both the light emitter 311 and the light detector 312, and further relative to the reflective surface 302R, can be precisely controlled. The reflective surface 302R can be configured to be approximately 2.5 mm away from the nearest portion of the supply line conduit 105. However, other suitable distances can be used.

[0195] As shown, the supply line conduit 105 can be further secured by a bracket 947 coupled to the backing member 936. Attachment fasteners 949 can be part of the bubble detector assembly 300 and used to secure the bubble detector assembly 300 to a structure. For example, in some embodiments, the bubble detector assembly 300 can be mounted to a frame of a diagnostic analyzer, the probe 945 itself, a structure attached to the probe 945 (not shown), a part of a robot (not shown) that operates to move the probe 945, or a cleaning station.

[0196] In another embodiment, a computer program product is provided. The computer program product includes a computer-readable non-transitory medium having a computer program code configured to: receive a first plurality of outputs, each of the first plurality of outputs representing an amount of light detected through a supply line conduit without liquid therein for a corresponding plurality of inputs to a light emitter; receive a second plurality of outputs, each of the second plurality of outputs representing an amount of light detected through a supply line conduit with liquid therein for a corresponding plurality of inputs; and set a threshold based on a selected output of the first plurality of outputs and the second plurality of outputs.

[0197] In one embodiment, the computer program code of the computer program product may be configured to select one of the corresponding plurality of inputs where the largest difference occurs between the corresponding pairs of the first and second pluralities of outputs, and determine the threshold value based on the corresponding pair of the first and second pluralities of outputs where the largest difference occurs. In another embodiment, the computer program code of the computer program product may be configured to select the operational input (I_LED_Final) based on the minimum I_LED value (I_LED_Min) and the maximum I_LED value (I_LED_Max). The threshold value may be located midway between I_LED_Final and the intersection of the wet and dry I_LED pair V_Ref curves.

[0198] Those skilled in the art should readily appreciate that the disclosure described herein has broad utility and application is a diagnostic analyzer. Without departing from the spirit or scope of the present disclosure, many embodiments and adaptations of the disclosed embodiments and many variations, modifications and equivalent arrangements in addition to those described herein will become clear or reasonably suggested from the disclosure and detailed description herein.

[0199] For example, although described in conjunction with a particular liquid bubble detector, one or more embodiments of the present disclosure may be used with other types of liquid bubble detectors. Therefore, although the present disclosure has been described in detail herein with respect to particular embodiments, it should be understood that the present disclosure is merely illustrative, presents examples of the present disclosure, and is intended only to provide a complete and enabling disclosure. The present disclosure is not intended to limit the invention to the particular apparatus, device, component, system, or method disclosed herein, but on the contrary, is intended to cover all modifications, equivalents, and alternatives falling within the scope of the claims.

Claims

1. An optical bubble detector assembly, comprising: The controller is configured as: operating a light emitter to project light into a supply line conduit of the optical bubble detector at a plurality of light intensities corresponding to the plurality of inputs; receiving a first plurality of outputs from a light detector of the optical bubble detector, the first plurality of outputs corresponding respectively to the plurality of inputs, each of the first plurality of outputs representing an amount of light detected through the supply line conduit without liquid therein; receiving a second plurality of outputs from the light detector, the second plurality of outputs corresponding respectively to the plurality of inputs, each of the second plurality of outputs representing an amount of light detected through the supply line conduit having liquid therein; and Based on the selected output from the first and second pluralities of outputs, a particular one of the plurality of inputs is selected as a final calibration setting.

2. The assembly according to claim 1, wherein The controller is further configured to determine a threshold based on a selected output of the first and second pluralities of outputs.

3. The assembly according to claim 1, wherein: The controller is configured to operate the light emitter at the final calibration setting when detecting whether the supply line conduit contains the liquid or air.

4. The assembly according to claim 1, wherein: The controller is further configured to: selecting a maximum current based on the first plurality of outputs; selecting a minimum current based on the second plurality of outputs; and The final calibration setting is determined to be between the maximum current and the minimum current.

5. The assembly according to claim 4, wherein: The final calibration setting includes a value approximately midway between the maximum current and the minimum current.

6. The assembly according to claim 1, wherein: The controller is configured to: The threshold value is selected as the voltage value at which a maximum voltage difference occurs between corresponding pairs of the first and second pluralities of voltages.

7. The assembly according to claim 6, wherein: The threshold comprises an operating voltage midway between respective pairs of the first and second pluralities of voltages where the maximum voltage difference occurs.

8. The assembly of claim 1, wherein: The controller is configured to calculate a voltage difference between each corresponding pair of the first and second pluralities of outputs for each of a plurality of duty cycle periods.

9. The assembly of claim 1, further comprising an operational amplifier coupled to receive a pulse width modulation input from the controller and configured to provide a current input to the optical emitter in response thereto.

10. The assembly of claim 1, wherein: The controller is configured to store a plurality of stored values ​​representing the first and second pluralities of outputs in a non-volatile memory.

11. The assembly according to claim 1, wherein: The controller is configured to operate the light emitting device at the final calibration setting and determine whether the supply line conduit has liquid or air based on a threshold value.

12. The assembly of claim 1, wherein: The supply line conduit is held between the backing member and the support to space the light emitter and light detector from the supply line conduit.

13. The assembly of claim 12, wherein: The supply line conduit is retained in a groove formed in the backing member.

14. A method for calibrating an optical bubble detector, comprising: receiving a first plurality of outputs, each of the first plurality of outputs representing an amount of light detected through a supply line conduit without liquid therein, the first plurality of outputs respectively corresponding to a plurality of inputs to a light emitter; receiving a second plurality of outputs, each of the second plurality of outputs representing an amount of light detected through the supply line conduit having liquid therein, the second plurality of outputs respectively corresponding to the plurality of inputs to the light emitter; and Based on the selected output from the first and second pluralities of outputs, a particular one of the plurality of inputs is selected as a final calibration setting.

15. The method of claim 14, further comprising setting a threshold based on a selected output of the first and second pluralities of outputs.

16. The method according to claim 15, wherein: The controller is operable to: selecting a minimum current based on the first plurality of outputs; selecting a maximum current based on the second plurality of outputs; and The final calibration setting between the maximum current and the minimum current is determined.

17. The method according to claim 16, wherein: The final calibration setting is midway between the maximum current and the minimum current.

18. The method of claim 14, further comprising setting the optical transmitter to operate at a final calibration setting corresponding to a position where a maximum voltage difference occurs between corresponding pairs of the first and second pluralities of outputs.

19. The method of claim 14, further comprising setting a threshold based on the corresponding pairs of the first plurality of outputs and the second plurality of outputs.

20. The method of claim 14, further comprising calculating, with a controller, a difference between each corresponding pair of the first plurality of outputs and the second plurality of outputs for each corresponding plurality of inputs.

21. The method according to claim 14, wherein: The multiple inputs are % duty cycle settings ranging from 10% to 40% of maximum output.

22. The method according to claim 14, wherein: The plurality of inputs includes at least 10 different inputs.

23. The method of claim 14, further comprising operating the light emitter in the final calibration setting to detect the supply line conduit with no liquid therein or with liquid therein.

24. The method of claim 14, further comprising storing in a non-volatile memory a value representing a threshold value, the threshold value corresponding to an operational output between the first plurality of outputs and the second plurality of outputs.

25. A computer program product comprising: A computer readable non-transitory medium having a computer program code configured to: receiving a first plurality of outputs, each of the first plurality of outputs representing an amount of light detected through a supply line conduit without liquid therein for a corresponding plurality of inputs to the light emitters; receiving a second plurality of outputs, each of the second plurality of outputs representing an amount of light detected through the supply line conduit having liquid therein for a corresponding plurality of inputs; and Final calibration settings are set based on selected outputs of the first plurality of outputs and the second plurality of outputs.

26. The computer program product of claim 25, wherein: The computer program code is configured to: selecting one of the corresponding plurality of inputs for which a maximum difference occurs between corresponding pairs of the first and second pluralities of outputs; and The final calibration settings are determined based on the corresponding pairs of the first and second pluralities of outputs where the maximum differences occur.

27. The computer program product of claim 25, wherein: The computer program code is configured to: determining a minimum I_LED based on the first plurality of outputs; determining a maximum I_LED based on the second plurality of outputs; and The final calibration setting is selected between the maximum I_LED and the minimum I_LED.

28. The computer program product of claim 27, wherein: Thresholds are determined based on the intersection of the final calibration setting with the wet and dry curves.

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