System and method for calibrating an instrument that measures temperature and microbial growth in blood culture bottles - Patents.com

Abstract

Calibrator bottles and methods of calibration. The calibrator bottles include a plastic material doped or blended with a fluorogenic material system that fluoresces in a target range and can be used to calibrate blood culture instruments that measure the fluorescence of a sample to determine whether the bottle is positive or negative. Also described herein are systems and methods for controlling the temperature of a sample in a blood culture instrument using a resistance temperature detector (RTD) device that measures the temperature of the sample. The sample readings are correlated with the environmental temperature to determine an environmental temperature that provides a target bottle contents temperature.

Description

[Technical field]

[0001] Described herein is a blood culture instrument and method of operation, including standards for calibrating the instrument to test a sample in a container by detecting a fluorescent signal, and a method of operating the instrument to obtain accurate temperature measurements for blood cultures.

[0002] [CROSS REFERENCE TO RELATED APPLICATIONS] This application claims priority to and the benefit of U.S. Provisional Patent Application No. 63 / 306,797, filed February 4, 2022, and incorporated herein by reference in its entirety. [Background technology]

[0003] Fluorescence detection devices are commonly used in the fields of analytical chemistry and cytometry, and for these applications, methods of calibration are well developed and well known to those skilled in the art. For example, U.S. Patent Nos. 5,233,339, 5,296,282, 5,363,133, and many other patents and publications disclose methods for calibrating flow cytometers and fluorescence microscopes. The devices and methods described herein are used in the field of diagnostics of biological samples, particularly for the detection of microbial growth in blood samples, culture media, and sample bottles that contain indicators that reflect changes in the sample that are indicative of microbial growth. For example, such indicators fluoresce in response to changes in the oxygen content of the sample, or changes in the carbon dioxide content of the sample, or changes in the pH of the sample, such changes being indicative of microbial growth in the sample.

[0004] Patent document 4 describes a fluorescence verification plate for calibrating an instrument that optically tests a sample to observe changes in fluorescence over time. Patent document 4 describes a fluorescence verification material having a first layer selected from a fluorescent layer or a reflective layer and a second layer for light attenuation, which may be continuous or have separate attenuating and non-attenuating regions. According to Patent document 4, the advantage of using a second layer for light attenuation together with a fluorescent layer or a reflective layer is that the function of the fluorescence verification material can be changed simply by changing the aspect of the second layer for light attenuation. In a multifunctional fluorescence verification plate, all wells can use the same fluorescent material as well as wells that require different functions using different second material layers. According to Patent document 4, fluorescent and reflective materials are available but are not suitable for fluorescence verification purposes because the characteristics of the emitted light (e.g., intensity, spectrum, and polarization state) are not precisely controlled or the emitted light is too bright, especially in terms of intensity, and is outside the range of the detector. These materials can be made suitable for fluorescence verification purposes by adding a suitable and precise optical verification material such as a second layer for light attenuation.

[0005] Calibration of the instrument is necessary to provide accurate readings from the containers from the raw readings. Calibration is required to address and correct for aspects of the system that may adversely affect the accuracy of the raw readings. Understanding the difference in readings due to the sample and distinguishing that from differences in readings due to variations in the operation of the system on which the test is being performed is important to making the system operate accurately and effectively.

[0006] Certain instruments (such as the BACTEC 9050 Blood Culture System available from Becton Dickinson, Franklin Lakes, NJ) use special calibrator bottles whose fluorescence output is within a certain tolerance of the target value and that have rotational stability relative to the measurement system (fluorescence output does not change when rotated in the measurement station). To facilitate repeated use, calibrators are required to have a consistent fluorescence output over time to ensure consistency of results. Calibrators that are not very consistent in fluorescence output over time or do not maintain a highly consistent fluorescence output over time are less desirable.

[0007] The purpose of the calibration process is to calculate adjustment parameters that, when used to normalize raw readings from the calibrator at various sample stations (sample stations that are rack positions inspected by the sensors), the normalized readings become standard values. For the purposes of this analysis, the calibrators are referred to as instrument (INST) calibrators, although the analysis is not specific to instrument calibrators.

[0008] The BACTEC 9050 has a drum-shaped rack with bottle receptacles arranged in rows around its periphery. Each row is called a ring. If both the sample station (i.e., a rack receptacle that can hold an instrument calibrator to be tested by the sensor) and the control station (i.e., a reference receptacle that holds a specially prepared calibrator bottle) contain calibrator bottles, any variation in the raw readings of two values ​​from two bottles in different receptacles is assumed to be proportional to the raw readings, and the ratio of the raw readings from the two receptacles is assumed to be constant.

[0009] In calibration mode, normal (NORM) values ​​are calculated using data collected during a calibration process in which an instrument calibrator is placed in the instrument's sample station. Raw readings are collected from the instrument calibrator and a calibration standard provided in sample station 0 of each rack (sample station zero is simply the reference position in the rack) and input into the following formula: JPEG2025507314000002.jpg9170It is important to note that in the rack configured as a multi-row drum, the multiple sensors are all in one column. Each sensor in a column is aligned with one row in the multi-row rack. Because sample station 0 for each row is aligned in a single column, all calibration bottles / devices in sample station 0 in each row of the rack are read simultaneously.

[0010] To illustrate the calibration using the instrument calibration standards, assume that the standardized calibrator value represents a reading of 0.792 V on the analog-to-digital (A / D) scale in the measurement electronics. This is the measurement for the instrument calibrator bottle when measured in the sample station.

[0011] The calibrator bottles in the reference station (Station 0) for each rack row in each ring are considered part of the instrument measurement system and therefore the NORM values ​​are corrected when calculated with the raw readings from the instrument calibrator.

[0012] The STD value is a multiplier included in the NORM calculation so that the NORM value can be stored as an integer, otherwise the NORM value will be a floating point number close to 1 due to the closeness of the instrument calibrator and REF values. When the NORM value is used to normalize the readings, it is divided by the STD value to recover the actual ratio of INST to REF.

[0013] The normalized value for the bottles in the sample station is calculated as follows: Replace JPEG2025507314000003.jpg9170NORM with that expression: JPEG2025507314000004.jpg13170This reduces to: JPEG2025507314000005.jpg9170 which can be rewritten as: JPEG2025507314000006.jpg11170

[0014] JPEG2025507314000007.jpg26170

[0015] JPEG2025507314000008.jpg53170

[0016] With respect to heating (i.e., culturing) of the bottles within the device to promote microbial growth, the blood culture device incubates a sample bottle, and the sample bottle is moved past a sensor (or the sensor is moved past the sample bottle) to monitor an indicator within the bottle that indicates microbial growth. The sensor is used to test the sample to see if microbial growth has occurred within the sample container. The user of the blood culture device is also required to check the temperature of the blood culture bottle by placing an independent temperature probe within the incubation chamber near the blood culture bottle and periodically manually reading the independent temperature probe. These quality control checks must be recorded by the user. Currently, there is no mechanism to accurately determine the temperature of the sample within the blood culture bottle using measurements of the environmental temperature within the blood culture device. Although an offset between the air temperature within the housing and the temperature within the culture bottle can be determined, these offsets may change over time. Thus, a need continues to exist for a method to determine the temperature of the blood culture within the sample container (i.e., bottle).

[0017] In summary, laboratory instrument calibration is complex, and because there are many system variables, the laboratory instrument's operation must be adaptable to changes in the laboratory instrument's internal environment and provide readings that are standardized and do not drift as operating conditions change. [Prior art documents] [Patent documents]

[0018] [Patent Document 1] U.S. Pat. No. 5,414,258 [Patent Document 2] U.S. Pat. No. 5,093,234 [Patent Document 3] U.S. Pat. No. 4,868,126 [Patent Document 4] US Patent Application Publication No. 2005 / 0287040 Summary of the Invention

[0019] Described herein is a calibration device formed from a plastic doped or blended or injected with a dye or pigment or compound that fluoresces in a desired or predetermined wavelength range. The fluorescent dye or pigment or compound or fluorescent dye / pigment / compound combination is referred to herein as a fluorescent material system. In one embodiment, the plastic containing the fluorescent material system is one or more injection molded sheets containing a fluorescent material system that fluoresces when excited with light. The molded sheets are provided with one or more fluorescent dyes / pigments / compounds for selection so that their excitation and emission spectra can be selected for the particular instrument in which the calibration device is to be used. In one embodiment, the fluorescent dye is an organic fluorescent dye.

[0020] In another embodiment, the fluorescent organic dye is added to / compounded with a plastic material to form a fluorescent plastic material that is used to form the calibration device. In one embodiment, the calibration device takes the shape of a container used in the system to be calibrated. In one embodiment, the calibration device is a bottle formed from a fluorescent plastic material.

[0021] For example, if the instrument to be calibrated is one that incubates and optically tests blood culture bottles for signs of microbial growth therein, the calibration device is molded similarly to a blood culture bottle so that it can be received in a rack receptacle sized to receive a blood culture bottle for testing. The amount of dye added into the plastic forming the calibration device instrument bottle is a matter of design choice. The amount of dye and its wavelength range of emission are selected based on the sensor to be calibrated. One skilled in the art can select a dye with target absorption characteristics that result in the desired fluorescence.

[0022] In one embodiment, the instrument has multiple detectors since the sample containers (typically bottles) are detected in a fly-by manner. Thus, a row of multiple sensors is provided, with each sensor aligned with a row of racks holding sample containers with samples therein. As the racks are moved, the sample containers pass the sensor (i.e., the containers "fly-by" the sensor), and the sensor inspects the sample bottles and reads their fluorescence. Since the device has multiple sensors, the device requires multiple calibrators. The calibrators are required to be free of variation and have uniform characteristics so that any differences in sensor readings are not due to variation in the calibration standards.

[0023] For example, in a system in which containers are stored in a rack and read by a sensor in a fly-by manner, changes in the distance between the container and the sensor can cause variations in the intensity readings from the sensor that are not due to the sample in the container (and its effect on the indicator in the container), but rather due to variations in the sensitivity of the system itself.

[0024] In one embodiment, a sleeve can be placed over the calibration device (e.g., a bottle). Such a sleeve restricts the fluorescent output to the area of ​​the bottle that is aligned with the sensor. In a blood culture instrument, the bottom of the bottle is aligned with the sensor. The sleeve can also have a feature that aligns with a receptacle in the rack in which the bottle is received, providing the bottle with a target orientation within the receptacle. This provides target alignment in an embodiment of the invention where a one bottle receptacle has a light pipe that indicates its interior is occupied by a bottle.

[0025] In one embodiment, the bottle material is polycarbonate.

[0026] In one embodiment, the instrument includes a rack that receives a plurality of containers for fluorescence detection. The rack has an array of rows and columns to process a large number of containers. In one embodiment, the rack is drum-shaped and each row is circular. A plurality of sensors are positioned in a column adjacent to the outer surface of the drum. Each sensor in the column of sensors is aligned with a row in the rack such that one sensor is positioned to detect the fluorescence of each bottle in the row as each bottle rotates past a sensor (i.e., the fly-by configuration described above).

[0027] For calibration, the rack has one row designated to receive a reference calibrator device (e.g., a calibrator bottle). The calibrator bottle is placed in the other row. The sensor reads the raw fluorescence values ​​from the calibrator and reference bottles. These values ​​are then used to assess the accuracy of the instrument in reading the fluorescence of the blood culture bottles.

[0028] If the calibrator bottle readings deviate significantly from expected values, this may indicate that the drum and sensor are not in their proper relative positions. In a correction, the relative positions of the drum and sensor are adjusted to achieve the target readings from the calibrator bottles. If readings within range are obtained for at least some of the calibrator bottles, the bottles with out-of-range readings are replaced and the calibration process is repeated until all of the calibrator bottle readings are within range.

[0029] In another aspect, the present specification describes a method for calibrating an instrument for detecting fluorescence of a sample. According to the method, a calibration device is provided. The calibration device includes a plastic material, into which a fluorescent material system having at least one dye or pigment or compound having a fluorescence emission spectrum in a first predetermined wavelength range when excited by light in a second predetermined wavelength range is added, compounded, or injected. The calibration device is placed in the instrument having a sensor. The calibration device is then aligned with the sensor, after which light is directed from a light source, which emits light in the second predetermined wavelength range to generate fluorescence in the first predetermined wavelength range. Then, it is determined whether the sensor detects fluorescence in the first predetermined wavelength range.

[0030] Also described herein are temperature sensors, such as resistance temperature detectors (RTDs), located within instruments that process biological samples, such as blood culture samples, where temperature control is required to ensure that the biological samples are incubated at the correct temperature.

[0031] In one embodiment, described herein is an instrument for blood culture. The instrument includes a housing and a rack disposed within the housing. The rack includes a plurality of rack receptacles for receiving a plurality of blood culture sample containers. At least one rack receptacle is configured to receive a temperature measuring device. The temperature measuring device may include a resistance temperature detector. In one embodiment, the instrument is configured to read a temperature recorded by the resistance temperature detector and estimate a temperature of a blood culture within a sample container within the instrument from the temperature. In a further embodiment, the instrument may include a controller. Upon receiving a temperature from the temperature measuring device, the controller compares the received temperature to a set temperature and controls the temperature within the housing based on the comparison.

[0032] In one embodiment, the rack receptacle can have a light pipe and the receptacle configured to receive the temperature measuring device can have a temperature embedded within the light pipe. In a further embodiment, the receptacle configured to receive the temperature measuring device can have thermal grease or a thermally conductive pad disposed thereon. In a further embodiment, the resistance temperature detector can be electrically coupled to a cable that includes a power line, a ground line, and a serial communication line. In a further embodiment, the cable can be coupled to a slip connector.

[0033] In a further aspect, the temperature measurement device is in the form of a container configured to be received by a receptacle configured to receive the temperature measurement device. According to this aspect, the resistance temperature detector can be submerged in the liquid in the container-shaped measurement device and coupled to a cable having a plurality of contacts configured to electrically connect to a slip connector adjacent the receptacle configured to receive the temperature measurement device. In one aspect, the contacts are contact rings.

[0034] In another aspect, a plurality of contacts are spaced apart on a surface of the temperature measurement device. In a further aspect, the resistance temperature detector is coupled to a cable including a contact strip having contacts configured to electrically connect to corresponding spring contacts in electrical communication with a microprocessor. Optionally, the temperature measurement device further includes a transmitter and a power source and is rechargeable. [Brief description of the drawings]

[0035] [Figure 1] FIG. 1 shows the emission spectra of different doped plastics. [Diagram 2] FIG. 1 illustrates a calibrator device assembly according to one embodiment of the present disclosure. [Diagram 3] FIG. 3 is an end view of the calibrator device assembly of FIG. 2. [Figure 4] FIG. 3 is a side view of the assembled calibrator device assembly of FIG. 2. [Diagram 5] FIG. 1 shows a blood culture bottle. [Figure 6A] FIG. 13 shows a comparison of fly-by readings obtained from a plastic bottle with the sensor as a calibrator and a plastic bottle with fluorescent dye added. [Figure 6B] FIG. 6B shows the transmittance of the neutral density filter used to obtain the readings in FIG. 6A. [Figure 7] FIG. 14 shows the fluorescence emission spectra for different dye-loaded bottle materials demonstrating the feasibility of using dye-loaded bottles as calibrator bottles. [Figure 8] FIG. 1 is a top view of the interior of an incubator having a circular rack for receiving blood culture bottles. [Figure 9] FIG. 1 illustrates a rack receptacle having a temperature probe. [Figure 10] FIG. 2 is an exploded view of the bottle and its receptacle. [Figure 11] FIG. 1 is a side view of a slip connection on a light pipe (rack receptacle). [Figure 12](A) is a perspective view of a blood culture bottle with an RTD device submerged in the fluid within the bottle, and (B) is an end view of the neck of the blood culture bottle shown in FIG. 12(A). [Figure 13] FIG. 2 is a schematic diagram of an exemplary wiring connection for an RTD device. [Figure 14] 14(A) is a perspective view of an RTD device disposed within a bottle according to a different embodiment, and (B) is an end view of the neck of the blood culture bottle shown in FIG. 14(A). [Figure 15] FIG. 1 is a schematic diagram of a docking station for a bottle-shaped RTD device. [Figure 16] FIG. 1 shows a bottle with a temperature sensor disposed therein to provide the temperature of the solution within the bottle. [Figure 17] FIG. 13 is a side view of a calibration bottle having an RTD device configured to communicate with an RTD reading device according to an alternative embodiment of the apparatus described herein. [Figure 18] FIG. 1 illustrates one embodiment of an RTD reader using gripper fingers. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0036] The embodiments of the present disclosure will be described in detail with reference to the drawings in which like reference numerals identify similar or identical elements. It should be understood that the disclosed embodiments are merely examples of the present disclosure, which can be embodied in various forms. Known functions or structures are not described in detail to avoid obscuring the present disclosure in unnecessary detail. Therefore, specific structural and functional details disclosed herein should not be interpreted as limiting, but merely as a basis for claims and as a representative basis for teaching those skilled in the art to variously employ the present disclosure in substantially any suitable detailed structure.

[0037] Currently, BACTEC™ instruments are calibrated using specially prepared BACTEC™ calibrator glass bottles. These calibrator glass bottles contain a multi-component chemical formulation that produces a fluorescent signal at a specific wavelength and emission intensity. The calibrator bottles are manufactured separately from the BACTEC™ sensor bottles, and once manufactured, the calibrator bottles require a dedicated manufacturing line and storage location.

[0038] Described herein is a calibrator device in which a plastic is impregnated or blended or mixed or doped with one or more dyes and / or one or more pigments that fluoresce in response to an external light source. The one or more dyes and / or one or more pigments are referred to herein as fluorescent material systems. In one embodiment, the calibrator device is molded from the doped / blended plastic material. In another embodiment, the calibrator device receives doped plastic parts that fluoresce when stimulated by an external light source. In one embodiment, the instrument being calibrated is a blood culture instrument. Such an instrument has a rack with multiple receptacles. Each receptacle is sized to receive a blood culture container (hereinafter "bottle"). During calibration of the instrument, the receptacles receive the calibrator device. Thus, the calibrator device has a size and configuration that allows it to be received by the rack receptacle. In one embodiment, the calibrator bottles are shaped similarly to the bottles received by the rack. The bottle material itself is used to calibrate the instrument, thereby eliminating the need for a calibrator bottle that holds specially manufactured liquid standards inside that may be used for calibration. The calibrator bottle retains its fluorescent properties (i.e., its fluorescent spectral response to light) for very long periods of time.

[0039] Referring to FIG. 1, a number of injection molded sheets are shown, each of which contains a fluorescent material system having at least one dye that fluoresces when excited by a particular wavelength of light (i.e., the excitation wavelength). Shown in FIG. 1 are sheets 110, 111, 112, and 113 that are doped with different organic dyes that cause the doped plastic to fluoresce in the blue, red, green, and yellow ranges, respectively. As shown in FIG. 1, the wavelength ranges are about 400 nm to about 500 nm (blue range, 120), 550 nm to about 750 nm (red range, 121), about 450 nm to about 650 nm (green range 122), and about 475 nm to about 750 nm (yellow range 123), respectively. Although there is a wide range of wavelength overlap, the peak wavelength ranges for each wavelength shown in FIG. 1 do not overlap. Conventional dyes are used as additives for plastic sheets. For example, Texas Red dye (rhodamine dye) is added to the plastic sheet to fluoresce in the red spectrum. Those skilled in the art will recognize that rhodamine dyes are actually a group of dyes with absorption and emission spectra in the visible to near infrared (NIR) region of the spectrum. Those skilled in the art will be able to select a fluorescent material system that will aid in the calibration of the sensor of the instrument being calculated. Those skilled in the art will recognize that the absorption and fluorescence spectroscopic properties are a function of the molecular properties of the particular dye. See Maeda, H. et al. "Absorption and Fluorescence Spectroscopic Properties of 1- and 1,4-Silyl-Substituted Napthalene Derivatives", Molecules 17, pp 5108-5125 (2012), which is incorporated herein by reference. Dyes and dye loadings for fluorescence in specific spectra are well known to those skilled in the art and will not be described in detail herein.

[0040] For example, if one wishes to use a fluorescent material system that has a fluorescence emission spectrum of about 360 nm when excited using a light source that has a maximum excitation wavelength of about 300 nm, one would review the list of potential dyes / additives / pigments to identify a dye / additive / pigment or dye / additive / pigment combination that provides a fluorescent material system with the target excitation and emission spectra. For example, referring to Table 1 below, naphthalene or p-terphenyl may be suitable because the characteristic characteristic fluorescence emission spectral range for either includes 360 nm and its peak excitation wavelength is very close to 300 nm.

[0041] The concentration of the fluorescent compound or fluorescent material system is then controlled to provide the desired fluorescent emission intensity. One skilled in the art can evaluate different concentrations of the fluorescent compound or different concentrations of the components of the fluorescent material system that provide the desired fluorescent emission intensity. In another aspect, the fluorescent dye concentration or different concentrations of the components of the fluorescent material system are selected by utilizing the fluorescence quantum yield value for the candidate fluorescent material.

[0042] for example: Quantum yield = molar concentration of fluorescent emission / molar concentration of fluorescent compound added to plastic material (6)

[0043] The fluorescence quantum yields of compounds are reported in published books or scientific journal articles, such as Berlman, I., "Handbook of Fluorescent Spectra of Aromatic Molecules" (1971). As reported in Berlman, the fluorescence quantum yields for naphthalene and p-terphenyl are 0.23 and 0.93, respectively.

[0044] To provide a fluorescent material system having a fluorescent emission of about 475 nm when excited using a light source with a maximum excitation wavelength of 350 nm, referring to Table 1 below, a suitable candidate fluorescent compound may be either ovalene or tetraphenylbutadiene, since the characteristic excitation and fluorescence emission spectral range for either includes 475 nm and its peak excitation wavelength is very close to 350 nm.

[0045] Once the fluorescent compound or fluorescent dye / pigment combination is selected, the concentration of the fluorescent compound or fluorescent dye / pigment combination is selected to provide the target fluorescent emission intensity. One skilled in the art can select the concentration by evaluating formulations with various concentrations of the fluorescent components. In another embodiment, the concentration of the fluorescent compound or fluorescent dye / pigment combination can be selected by utilizing the fluorescence quantum yield value for the candidate fluorescent material. A summary of fluorescence excitation and emission data is provided in Bio Rad's Fluorophore Reference Guide, downloaded from the Internet on January 30, 2022 at www.bio-rad.com / webroot / web / pdf / lsr / literature / Bulletin_2421.pdf.

[0046] Those skilled in the art know that fluorescence intensity also depends on molar concentration. For fluorescence measurements, the molar concentration is typically low, as reported in Table 1 below. See Fonin, A., et al., "Fluorescence of Dyes in Solutions with High Absorbance Inner Filter Effect Correction", PLoS One 9(7)(2014).

[0047] Examples of suitable dyes and their concentrations and emission ranges are given in the table below.

[0048] [Table 1]

[0049] The calibrators described herein have a fluorophore dye or pigment or fluorophore material system embedded in plastic, so the dye or pigment is more stable over a longer period of time than if it were incorporated into a liquid standard.

[0050] As mentioned above, in one embodiment, the calibrator can include plastic parts doped or compounded to include a fluorescent dye or pigment. With reference to FIG. 2, a calibrator device 130 is assembled from such molded parts. The molded part shown is a base 131 having an opening 132 therein. Inserted into the opening are, in order from the opening, a neutral density filter 133, a fluorescent plastic 134, a backing plate 135, a foam holder 136, and an assembly top 137. The fluorescent plastic can be a thermoplastic material such as, for example, polycarbonate doped or compounded with a fluorescent compound, such as one or more of the fluorescent dyes listed above. The thermoplastic material is selected based on its stability (oxidative, hydrolytic, and photochemical). In addition, the thermoplastic material is selected so that its inherent light absorption or emission properties do not overlap or compete with the absorption and emission ranges of the fluorescent compound or fluorescent material system. In addition, the fluorescent compound can be a fluorescent pigment. FIG. 3 is a bottom view of the calibrator device with a neutral density filter 133 visible through the opening 132. FIG. 4 is a side view of calibrator device 130.

[0051] Those skilled in the art will appreciate that neutral density filters are used to reduce or modify the intensity of all wavelengths. A neutral density filter is used in this calibrator device because the intensity of the fluorescent signal would be too great if it were not modulated.

[0052] In one embodiment, the calibrator device is a polycarbonate bottle formed from a plastic material doped with at least one dye / pigment or fluorescent material system, the fluorescent plastic material described above. In this embodiment, a neutral density filter is not required. Such a bottle 200 is shown in FIG. 5. Previously, calibrator bottles have been provided in which the calibrator material is fixed to the bottom 210 of the bottle 200. A problem with such previous approaches was that the calibrator material was not sufficiently stable over time, requiring frequent replacement. Other plastics that may be doped with one or more dyes / pigments / compounds to be used as a calibrator device as contemplated herein include nylon 6 and polymethylmethacrylate (PMMA). The solid polymethylmethacrylate matrix provides a stable environment for the fluorescent compounds. The incorporated dye / additive is not in the form of a solvent and therefore does not evaporate upon incorporation into the matrix. Thus, the dye is stable in the polymer matrix in its incorporated state.

[0053] In practice, excitation of a calibrator bottle made from a plastic material doped with a fluorescent material system as shown in FIG. 5 can excite not only the area of ​​the bottle where the excitation light directly falls, but also other areas of the bottle as the excitation light penetrates the plastic material doped with the fluorescent material system. As a result, the resulting fluorescence emission can be a combination of fluorescence from the area where the excitation light directly falls (i.e., first transmission) and fluorescence from other areas of the bottle where the excitation light penetrates through the plastic bottle material doped with the fluorescent material system (i.e., second transmission). In mitigation, it may be desirable to control the measured fluorescence emission by eliminating any transmission of the excitation light through the plastic bottle doped with the fluorescent material system so that there is only fluorescence from the first transmission. A simple way to avoid unwanted secondary transmission from the calibrator bottle is to coat the inner surface of the plastic bottle with a material system layer that blocks the excitation light transmission resulting in secondary transmission. The material system layer can contain a pigment or dye system or a combination of these that blocks the excitation light transmission. Alternatively, the material system layer can be a highly reflective material. In addition to blocking the transmission of excitation light through the thickness of the bottle, it is expected that the coating on the inside surface of the bottle should be able to block any transmission (other than first order transmission) of fluorescent light from areas of the bottle exposed to the excitation light.

[0054] FIG. 6A provides a comparison of readings using two different calibrators to demonstrate the effectiveness of neutral density filters. Because neutral density filters filter light, they are typically formed as a film or other semi-transparent material. As described above, the plastic bottles were placed in a drum-shaped rack. Three different neutral density (ND) filter systems were evaluated. The blue curve was obtained using an ND3 filter with a nominal transmission of about 50%. The orange curve was obtained using an ND6 filter with a nominal transmission of about 40%. The gray curve was obtained using a 2xND3 filter (i.e., two ND3 filters placed one on top of the other), each with a nominal transmission of about 50% and a total nominal transmission of about 25%. FIG. 6B shows the transmission of the neutral density filters used to obtain the data in FIG. 6A over a range of wavelengths. The average transmission increases slightly with increasing wavelength.

[0055] These filters or a combination of the two filters were placed in a calibrator device as shown in FIG. 3 with components as shown in FIG. 2. The reading 140 on the left is for a conventional calibrator with a sensor calibrator (such as the curing liquid formulation described above) placed in a container. The reading 141 on the right was taken using the calibrator device 130 shown in FIGS. 3 and 4. The spectral reading 141 demonstrates that the different neutral density filters can be used to tune / modulate the fluorescent emission of the device by adjusting the amount of incident light that excites the doped plastic component 134. Comparing the emission spectra between 140 and 141, the peak defined at 141 provides a higher quality signal than the signal from the conventional calibrator.

[0056] FIG. 7 shows the spectrum of a calibration system using a series of fluorescent plastic materials with different emission spectra. Thus, the series of fluorescent plastic materials from which the emission spectra shown in FIG. 6 were derived cover a wide spectral range from about 260 nm to about 600 nm, and an emission range from about 370 nm to about 630 nm. This wide spectral range allows the user to select from a series of calibrators the calibrator whose spectral characteristics correspond most closely to the spectral characteristics of the analyte to be tested by the sensor. This allows the calibrator to be tested by the sensor without adjustments to the device (e.g., changing parameters such as the width of the slit through which the sensor signal is projected onto the calibrator device, or changing the wavelength settings from those used to read the sample).

[0057] The calibration device described herein is used to calibrate the sensors in the instrument during a calibration cycle (i.e., during system setup) and also during a test cycle (i.e., when the system is in use). The amplitude of the readings from the calibration device in the calibration device receptacle in the rack (i.e., Station 0) is constant over some period of time, but this can be high enough to minimize the signal-to-noise ratio on the scale of the analog-to-digital converter. Note that the same calibration device can be used for calibration during a test cycle and for calibration during a calibration cycle. The ratio of the readings obtained from the calibration device during the test cycle to the readings from the same calibration device during the calibration procedure is the same, regardless of the absolute fluorescence output from the calibration device readings. The calibration device used in the calibration station (also called Station 0) of each row of receptacles in the three rings of the incubator (i.e., each rack row) does not need to be expensive to manufacture to be reliable and provide good results over time. Thus, the fluorescent plastic materials described herein provide an economical alternative to other calibration devices used to calibrate systems such as BACTEC, which optically inspect samples to detect fluorescence indicative of positive blood cultures.

[0058] As described above, the system described herein is calibrated initially and during use. In one embodiment, the calibration device used to initially calibrate the system is different from the calibration device that is part of the instrument and is used for routine operation. Also, the calibration device used to initially calibrate the system is used to calibrate the calibration device that is part of the instrument.

[0059] Temperature Calibration / Control Blood culture instruments are designed to maintain the media and blood in the blood culture bottles being processed near a specific temperature set point as configured by the user. To do this, the blood culture bottles are processed in an incubation chamber, and the air in the chamber is controlled to the configured temperature using heaters and blowers to transfer heat into the incubation chamber. A controlled temperature probe is used to measure the amount of heat transferred into the chamber.

[0060] The temperature control probe used to control the incubation system is typically placed somewhere in the heated air path through the incubation chamber. Generally, the control temperature probe is placed in the air path just after the heater. At this location, the control probe measures the maximum temperature of the air in the air path. As the heated air follows its air path through the incubation chamber, it loses heat to the bottles and other components in the incubation chamber, and then returns to the blower and heater at its lowest temperature.

[0061] Referring to FIG. 8, a top view of an example of a rolling bottle rack for blood cultures is shown. The rolling bottle rack is a drum-shaped rack 240 disposed within a housing 224. The module further includes a blower and heater 225 to keep the bottles 230 warm. The drum-shaped rack 240 has receptacles for holding the culture bottles 230. Positioned on the inner surface of the housing are measurement electronics 250 and culture bottle / indicator electronics 260. Such electronics can be located on the inner surface of the drum (as shown) or can be located along the outer surface of the drum (i.e., between the drum-shaped rack 240 and the housing 224). A drive motor 270 is provided to rotate the drum-shaped rack 240. As shown, the housing 224 of the drum 240 has six panels 221 that define six drum sectors (222A-222F). As shown, approximately one-sixth of the drum's capacity (assuming the drum is at its full capacity) is accessible at any one time since the extent of one sector is approximately the same as the extent of the opening in the housing through which bottles are added to or removed from the drum 240. The culture bottles 230 can be positioned with their necks oriented inward or with their necks oriented outward. In FIG. 7, the bottles are positioned with their necks oriented outward, so that the sensors etc. are positioned inside the drum-shaped rack 240. If the bottles are positioned with their necks oriented inward, the sensors etc. are positioned along the exterior surface of the drum-shaped rack 240. The motor 270 is a reliable and simple direct drive motor with high torque, little or no hysteresis, low noise.

[0062] The air path taken by the heated air in the blood culture vessel is around the blood culture bottles housed in drum-shaped racks within the incubation chamber, and the temperature of the air as it passes around the blood culture bottles is somewhere between the high temperature of the air as it leaves the heater and the low temperature of the air as it completes the air path and enters the blower.

[0063] The contents of the blood culture bottle are generally not at the temperature reported by the control probe located in the housing. The contents of the blood culture bottle are generally at a lower temperature than that reported by the control probe. To adjust, an offset is added to the configured temperature setpoint and the temperature at the control probe is increased to raise the average bottle temperature to the target or setpoint temperature. The offset is the difference between the temperature measured by the control probe and the temperature of the blood culture bottle when the system is at steady state. For example, in a system that targets a bottle temperature of 35° C., if at steady state the control probe reads 35° C. and the blood culture bottle is at 34.5° C., an offset of 0.5° C. is established for the culture system. The heater is then controlled such that the control probe measures the air temperature of the setpoint plus the offset (35° C. + 0.5° C. = 35.5° C.), and the blood culture bottle then reaches the configured setpoint temperature of 35° C. because the probe's setpoint temperature was 0.5° C. higher than required.

[0064] The offset required by the culture system depends on several factors, such as the location of the control probe in the air path, the rate at which heat is lost from the culture chamber at each point in the air path, the location of the blood culture bottle in the air path, the environmental temperature around the culture chamber, and many other factors. The offset is determined empirically during development of the system by measuring the temperature difference between the control probe and the contents of the blood culture bottle at the extremes of the operating environment in which the system is intended to operate. The offset is then selected to accommodate all conditions while maintaining the blood culture bottle within its specified temperature range.

[0065] During operation of the system, the operator of the blood culture instrument must verify the temperature of the blood culture bottles by placing an independent temperature probe in the incubation chamber near the blood culture bottles and must periodically manually read the independent temperature probe. These quality control checks must be recorded by the operator.

[0066] As an alternative to using a generic offset value to control the temperature of the contents of the blood culture bottle, methods and apparatus are disclosed herein that use a resistance temperature detector to determine the temperature offset between the probe temperature measurement and the temperature of the contents of the blood culture bottle. Also, the methods and apparatus disclosed herein allow for run-time adjustment of the culture offset to adjust for changes in environmental operating conditions. As used herein, environment refers to the environment within the housing of the device.

[0067] Referring to FIG. 9, the temperature probe is contained within a light pipe 417 of the bottle holder 220 in the drum that holds the reference bottle 230. Assuming a drum-shaped rack has 10 rows, there are rows of 10 reference bottles arranged in each drum arranged in a single column of the drum. As with the calibration device described above, the reference temperature bottles are arranged in a single column, with each receptacle being station 0 for each row. Also, the reference temperature bottle 230 can contain a piece of plastic doped with a fluorescent dye / pigment / compound with a neutral density filter as described above, or can be formed from a plastic material doped / blended / injected with a fluorescent material system as described above. In an alternative embodiment, the reference temperature bottle can be an existing empty bottle without an indicator dye sensor.

[0068] 10 and 11, there is an exploded assembly 500 of the bottle 230 received by the light pipe 417. The light pipe 417 indicates the status of the bottle in the receptacle (e.g., positive, negative, needs resolution). As shown, the light pipe has an internally embedded resistance temperature detector (RTD) that makes direct contact with the reference bottle 230 when the reference bottle 230 is placed on the light pipe 417. RTDs are well known to those skilled in the art and will not be described in detail herein. A thermal grease 502 or other conductive material may be placed in the light pipe 417 between the RTD and the bottle 230 to improve the efficiency of heat transfer from the bottle to the RTD. The end of the light pipe 417 has an electrical wire 503 that leads to a slip connector elsewhere in the instrument. Three electrical wires 504 may be connected to the electrical wire that leads to the RTD embedded in the light pipe 417. In one embodiment, power, ground and serial communications contact strips 505 are attached to the wires (end view of light pipe 417). Referring to Figure 12(A), connections 533 run between the slip connector contacts 512 in the RTD receptacle and the control microprocessor electronics interface.

[0069] 12(A) and 12(B), in an alternative embodiment, the reference bottle 230 can hold a volume of sealed liquid 509 in its interior 231 in which the RTD 501 is immersed. The cable tail 504 of the RTD (with the three wires mentioned above) can be sealed as it exits the reference bottle 230. As shown in FIG. 12(B), which is an end view of the bottle 230 shown in FIG. 12(A), the three wires (power (P), ground (G), and serial communications (S)) are formed as a contact ring 510 to be received in a complementary receptacle 512 in a cap slip connector 511. The slip connector 511 is formed as a cap into which the neck 241 of the bottle-shaped container 230 can be placed. The contacts in the slip connector 550 can be any conventional contacts, such as pogo pins, leaf contacts, etc. In an alternative embodiment, contacts 513 (P), (G), and (S) are formed on the bottle and connected to cable 242.

[0070] 13 shows a cable from an RTD 501 that is embedded in or placed on a light pipe 417. At the end of the light pipe is a contact strip 505 that can be electrically connected to a spring contact 506. As mentioned above, there are three wires and three contacts for power (P), ground (G), and serial communications (S) wires. The contacts 506 can be mounted on a circuit board 507. An LED 508 is provided to illuminate the light pipe.

[0071] 16, the RTD device 235 can have a sealed connector 234 on one side of the reference bottle 230. In an alternative embodiment, a cable tail 233 can be connected to the light pipe 417 interface described above. The cable tail 233 can further be connected to a slip connector 511. The RTD has an extension 232 so that the RTD reaches almost to the bottom of the bottle interior 231 to ensure that a portion of the RTD device is located in the liquid as described elsewhere herein. The RTD is shown in cross section with the cut surface hatched.

[0072] 17, in an alternative embodiment, described herein is a bottle-shaped RTD reading device having electrical wire connections 514 to contacts 513 via spring-loaded conductors 515. A bottle detector 536 and indicator LED 520 are located at the neck end 525 of the bottle-shaped RTD device 230. As described above, the bottle-shaped receptacle securely contains the fluid in which the RTD device is placed. The spring-loaded connections 515 are brought into contact with the bottle contacts 513 when the bottle 230 is received by the rack receptacle 240. In addition to contacts for power, ground, and serial communications, there are three contacts 513 shown that connect to the RTD in the reference bottle holder 220 (which holds the proximal end of the bottle 230) with light pipes 417. The electrical wires 514 are also connected to a microprocessor 543 or other control electronics.

[0073] 14(A) and 14(B), a rechargeable RTD device 501 is shown disposed in a liquid 509 in a bottle-shaped receptacle 230. The bottle 230 has a seal 551 that keeps the liquid within the portion of the bottle 230 in which the RTD 501 is disposed. Also disposed on the dry side of the bottle 230 is electronics 552 for an RTD reader 560 with a power source as shown in FIG. 14(A). Examples of suitable electronics 552 include a circuit board memory and / or transmitter with an antenna. The RTD reader 560 charges an internal power source 553 when connected to a docking station via a recharging wire 554 electrically connected to a contact ring 555 as shown in FIG. 14(B). In one embodiment, an ultracapacitor-based power source is used due to its long life.

[0074] FIG. 15 shows the RTD reader 560 received by the docking station 570. The charging contacts 556 provide power to the mobile power source 553 shown in FIG. 14(A). The capacity of the mobile power source 553 can be low because the RTD reader only requires battery power for a short period of time while it is away from its docking station 570. In addition to charging, the RTD reader can communicate with the control microprocessor wirelessly or wired via a serial communication line. From the control microprocessor, the RTD can receive the following commands, listed by way of example and not limitation: i) set real-time clock, ii) clear RTD reading memory, iii) upload RTD reading memory, and iv) sense the connection of the RTD to the three RTD lines in the slip connector.

[0075] The RTD reader assembly 560 of FIG. 14(A) can be combined with the calibrator bottle 130 shown in FIG. 3. Such a combination can reduce the number of bottle receptacle stations filled with non-patient samples, thereby freeing up more receptacles in the rack to receive sample containers. This in turn increases the capacity of the instrument to process more samples. The calibrator bottle and the combined wireless RTD reader bottle can be placed in column 0 in the drum assembly as described above. Alternatively, if the RTD reader assembly is designed as a separate part from the calibration bottle assembly, one or more RTD assemblies can be placed in the drum receptacle at the target location. Typically, the robotic arm assembly responsible for inserting and removing the patient sample bottles in the drum assembly can be used to return the RTD bottle assembly to the docking station(s).

[0076] The reader reads the temperature for any connected RTD and cooperates with a memory to store the time-stamped RTD readings. The memory can have any capacity.

[0077] A single RTD reader serves up to four different blood culture modules, each with its own housing and incubation and reading environment. Additional data storage capacity is included to prevent overwriting of current values ​​when multiple readings for a single RTD occur.

[0078] The RTD data storage can be a circular buffer where each new reading overwrites the oldest stored reading. However, the RTD data storage is a design choice. Those skilled in the art can select RTD data storage that suits their operational objectives. The system described herein is not limited to any particular type of data storage.

[0079] In one embodiment, the system described herein can include a command center. The command center can track the time to command the robot to move the RTD reading device to the reference bottle location. The command center can also manage the workflow, the movement of the robot, etc. The command center is configured to associate the time when a particular RTD was read with a timestamp stored by the RTD reading device along with the RTD reading. The controller can then detect when an RTD was not detected and read by the RTD reading device, preventing erroneous association of an RTD temperature with an inaccurate reference bottle location.

[0080] As discussed above, the RTD device can have a slip connector and a cap portion configured for easy interconnection with other components interconnected to the RTD device to receive data from the RTD device. Described above is a ring connector that easily electrically engages the RTD device with other devices in an instrument for measurement and control of the system.

[0081] In one embodiment, the RTD reader is oriented so that it can electrically engage with the electrical connectors on the reference bottle holder and docking station.

[0082] The RTD reader docking station has a form factor similar to that of a bottle holder in a drum-shaped rack. The RTD reader docking station requires access to power and a serial interface. With reference to FIG. 15, the docking station form factor is configured to receive a particular calibrator device configuration. Although not specifically shown, the illustrated docking station 570 may include a clip, tray, or other structure that removably holds the calibration device within the docking station. Such structures are well known and are described in International Publication No. WO 2021 / 026272, published February 11, 2021, and incorporated herein by reference.

[0083] In one embodiment, a robot is used to insert and remove the RTD reader from the docking station. For efficiency, the robot can use the same motions to insert and remove the RTD reader from the docking station that the robot uses to insert and remove bottles from the drum-shaped rack.

[0084] As described above, the docking station can have a slip connector similar to the slip connector for the RTD device on the reference bottle holder described above. Such a slip connector can be mounted horizontally inside the bottle holder of the docking station. The slip connector on the USB reader engages with the USB reader when it is inserted into the docking station. In one embodiment, the RTD reader can also be shaped to wrap around the light pipe 417 such that the forces holding the RTD reader against the stop orient the RTD reader to rotate.

[0085] In one embodiment, the reference bottle temperatures are collected based on instructions from a controller that stops a drum-shaped rack in a position where the reference row of bottles is accessible, for example, by a robotic mechanism that loads and unloads bottles from the rack.

[0086] The controller opens a door in the housing and sets the time in the RTD reader via a microprocessor or other controller that communicates with a command center for the instrument. Such control components are well known to those skilled in the art and will not be described in detail herein.

[0087] The robot then picks up the RTD readers and moves them to a drum-shaped rack. At each row of the drum, the robot moves the RTD readers into contact with the slip connectors for the RTD receptacles in that row.

[0088] The RTD reader senses contact with the slip connector, measures the temperature from the RTD, timestamps the temperature data and stores it in an RTD reading buffer. The controller saves the time the row temperature was collected and associates this with the module and row that the robot is accessing.

[0089] Once temperatures from all rows in the drum-shaped rack of a module have been collected, the controller then begins collecting temperatures from the RTDs in another module. With the current module completing temperature collection, the robot is moved to the RTD reader docking station. The robot inserts the RTD reader into the docking station, after which the robot can perform other tasks in the module (i.e., loading and unloading sample bottles).

[0090] The controller can call up the temperature data from the RTD reader from the microprocessor or other controller. In response, the RTD reader transfers all time-stamped temperature readings to the controller via the VIS. The controller analyzes the temperature data for each module and determines if the culture offset for that module needs to be updated. If an update is required, a new culture offset is sent to the module.

[0091] Adjusting the culture offset In one embodiment, the temperature measured from the reference bottle may not be used directly to control the air temperature in the culture chamber. The reference bottle temperature probe, which is placed in the liquid in the reference bottle, may not respond quickly enough for proper air temperature control. The reference bottle temperature may be used to periodically adjust the offset used for air temperature control.

[0092] In one embodiment, the module can determine its culture offset for each culture chamber during final testing after manufacture. Since the culture offset is most sensitive to the environmental temperature in which the device is operating, the initial culture offset will be for the environmental conditions experienced during manufacture. Each culture system can store and use its individual culture offset.

[0093] For any particular environmental condition, the incubation offset can be kept constant, so that all adjustments to the incubation offset are made gradually. The reference bottle temperature can be read and averaged periodically (e.g., once an hour, or once a day, etc.), and the incubation offset is only allowed to change by some small increment at each update. This protocol avoids substantial changes in the offset, and thus substantial changes in the bottle temperature, that could adversely affect the fluorescence readings measured by the measurement system.

[0094] In one embodiment, the modular instrument is operated at steady state for some period of time (e.g., to achieve stable heater output) before the reference bottle temperature can be used to update the incubation offset. The heater output is continuously monitored and no changes to the incubation offset may be necessary until a significant change in heater output occurs, indicating a change relative to the environmental temperature.

[0095] Charging the RTD Reader As noted above, the RTD reader is charged whenever it is in its docking station via the slip connector. In one embodiment, the power supply in the RTD reader is configured to have a long life and be replaceable by the user as needed. In other words, the RTD reader is a critical tool for the module and must be maintained in good and reliable working condition.

[0096] In one embodiment, the culture offset is selected during development of the culture system (i.e., pre-manufacturing) by measuring the temperature of the liquid in the operating medium bottles of the module at the extremes of the culture temperatures used during system operation. The culture offset is selected such that the full range of bottle medium temperatures is within temperature specifications for all environmental temperature conditions. Collecting the temperature of the liquid contents of the operating medium bottles requires special equipment that may only be used during equipment development.

[0097] As described above, the culture offset established during the development of the device remains substantially constant over the life of the product for all subsequently manufactured devices operating in all conditions except for small incremental changes in the offset. However, if an RTD device is used in the module, it is possible to access the reference bottle temperature in the drum during operation of the module. This allows the module to directly determine the culture offset, allowing the culture system to account for the actual ambient environment of the culture system. Such an RTD device allows the system to more accurately control the temperature of the blood culture bottles in the culture chamber.

[0098] Environmental temperature control is more difficult at low environmental temperatures than at high environmental temperatures. At low environmental temperatures, heat is lost from the incubation chamber faster than at high environmental temperatures. As a result, when the instrument is operating at low environmental temperatures, the average bottle temperature tends to be lower because the average air temperature in the module is lower. When the incubation offset is determined during development, there is a trade-off between the average bottle temperature at low environmental temperatures and the average bottle temperature at high environmental temperatures, since the offset may be different at the upper and lower parts of the environmental temperature range. When the RTD device described herein is used, the actual average of the bottle temperature can be calculated at the environmental temperature, and the incubation offset can be adjusted appropriately for the particular environmental temperature.

[0099] When the RTD device described herein is used, the module is provided with a tool to adjust the incubation offset during operation of the module. Therefore, a generic offset does not need to be designed into the module. The design can be to provide a temperature range for the bottles to be incubated, and the offset is determined when the module is operated. As mentioned above, the coarse control of the bottle temperature is the air flow and air path in the module, as well as the temperature of the heated air in the module. The average temperature of the bottles to be incubated is controlled by the change in air temperature as the air moves through the incubation chamber. The RTD provides fine control to obtain a higher accuracy in heating the bottle contents to the set temperature, without relying on a generic offset that may not achieve the set temperature in all circumstances.

[0100] 18, in a different embodiment, instead of using an RTD reader to collect the temperature from the reference bottle and send it to a microprocessor that communicates with the command center described above, the RTD reader 660 can be a connector that includes power, ground, and serial communication lines 605, as well as contacts 606 included in gripper fingers 612. The electronics of the RTD reader 660 can be located in the gripper fingers 612 of a robot that is used to grip and release the bottle 230 as it is inserted and removed from a bottle rack in the module. The contacts 606 can connect to contacts 610 of an RTD device 601 located in the reference bottle holder (e.g., light pipe 617) when the robot grips the reference bottle. The electronics can be connected via an interface such that the measured temperature is recorded and used, as described above.

[0101] In one embodiment, the connector 606 on the robot finger can be a spring loaded pin (e.g., a pogo pin) that engages with a corresponding contact 610 on the light pipe 617 of the reference bottle holder. As mentioned above, in one embodiment, there are three contacts 610 for connection to the RTD. The connector can be mounted on a small board that is attached to the outer surface of one of the gripper fingers 612. The gripper finger 612 containing the RTD reader 660 can be molded such that the board is recessed within the finger 612, reducing the chance of interference with the object the gripper finger 612 is to move around. In a further embodiment, the small board containing the RTD connection 610 also houses the electronics that read the RTD in the light pipe 617. If the electronics are located on this board, there is no need to run the RTD analog signal through longer wires that run through the robot wire guide 605 to a microprocessor that receives temperature information for the RTD device. This improves the accuracy of the RTD reading.

[0102] Typical workflow: The control device (referred to herein as the command center) requests the module to stop rotating its drum-shaped rack having a row of reference bottles accessible by the bottle robot. The command center then causes the module hatch to open so that the robot can access the bottles placed in the rack. The command center then controls the movement of the robot to the drum. At each row of the drum, the command center instructs the robot to grab the reference bottle for that row. The command center then verifies that the necessary connections are made such that the electronics of the RTD are connected to collect temperatures from the currently connected RTDs. After the measurements are verified, the command center instructs the robot to release the reference bottle. Once temperatures have been collected from the reference bottles in all rows in the drum-shaped rack of the module, the robot is moved away from the drum and then the command center causes the module hatch to close. The command center then releases control of the drum-shaped rack of the module to the module. The command center then releases the robot for other workflows. The command center then analyzes the temperature data for each module to determine if the incubation offset for that module needs to be updated, and if so, a new incubation offset is provided to the module.

[0103] Direct Wiring of RTD to Command Center In another embodiment, the RTD temperatures measured from the reference bottles are collected periodically when the drum is stopped. In this embodiment, the bottom of the drum has a multi-pin slip connector (several pads) that connects back to each reference bottle. In a further embodiment, temperatures from only some of the bottles in the drum-shaped rack row are collected. For example, in one embodiment, temperatures from the top row, bottom row, and middle row are collected.

[0104] In one embodiment, while the drum is in the parked position, a series of pogo pins on the floor of the module can be extended upward via a motor-driven slide rail (or similar mechanism that automates the upward translation) to contact pads located on the bottle-shaped RTD device. A wire harness can extend from the pogo pins and connect them to a controller or microprocessor that records the temperature of the bottle contents and correlates the temperature with the rack position for the bottle associated with the temperature measurement. This data can be fed to a command center, which can use it to determine a temperature offset.

[0105] Wireless connection of RTD to command center In a further embodiment, the wires and connectors can be avoided by using a wireless connection. In this embodiment, the RTD data is transmitted using typical low power transmission hardware for common wireless protocols such as IOT protocols, Bluetooth, WiFi, and RFID with EEPROM. The wireless interface device has a power source. In one embodiment, the power source can be a battery mounted on a frame for the drum-shaped rack. Alternatively, a bottle-shaped rechargeable battery can be provided to provide power. As the rechargeable battery requires recharging, the module is configured to allow the rechargeable battery to be removed and replaced. In one embodiment, the robot removes and replaces the rechargeable battery. The module or system (in case of multiple modules) can store additional rechargeable batteries for use as needed.

[0106] The term "about" as used herein indicates that there is some variation in the ranges and values ​​represented. Those skilled in the art will appreciate such variation and the degree of variation associated with each value. Typically, such variation is 25% or less of the represented value, and may be 20% or less, 15% or less, 10% or less, 5% or less of the represented value.

[0107] Described herein is a calibration device made from a plastic material, to which at least one dye or pigment or compound is added or blended or infused, having a fluorescent emission spectrum in a first predetermined wavelength range when excited by light in a second predetermined wavelength range. In one embodiment, the plastic material does not absorb light in either the first predetermined wavelength range or the second predetermined wavelength range. In another embodiment, the calibration device is a bottle formed from a plastic material, which can be polycarbonate. The calibration device can have an inspection area formed as an opening in the calibration device, into which the plastic material is inserted. A neutral density filter can be disposed on the plastic material. In one embodiment, the neutral density filter includes a plurality of neutral density filters, which can be formed into a stack. In one embodiment, the at least one dye or pigment or compound is provided as a fluorescent material system selected to provide a fluorescent emission spectrum, and can be an organic dye.

[0108] Described herein is a method of calibrating an instrument that detects fluorescence of a sample in a calibration device having a plastic material, the plastic material being doped, blended or infused with at least one dye or pigment or compound that has a fluorescence emission spectrum in a first predetermined wavelength range when excited by light in a second predetermined wavelength range, and the plastic material being disposed in an instrument having a sensor. The calibration device and the sensor are aligned. Light is directed to the calibration device from a light source, the light source emitting light in the second predetermined wavelength range to generate fluorescence in the first predetermined wavelength range. It is then determined whether the sensor detects fluorescence in the first predetermined wavelength range. If the sensor does not detect fluorescence in the first predetermined wavelength range, the instrument is adjusted and recalibrated by aligning the calibration device with the sensor. Again, the light source directs light to the calibration device, the light source emitting light in the second predetermined wavelength range to generate fluorescence in the first predetermined wavelength range. It is then determined whether the sensor detects fluorescence in the first predetermined wavelength range. In one embodiment, the plastic material does not absorb light in either the first predetermined wavelength range or the second predetermined wavelength range. In one embodiment, the calibration device is a bottle formed from a plastic material, which can be polycarbonate. In one embodiment, the calibration device has an inspection area formed as an opening in the calibration device, and the plastic material is inserted into the opening of the calibration device. In one embodiment, a neutral density filter is placed on top of the plastic material. The neutral density filter can be a plurality of neutral density filters that can be formed into a stack. In one embodiment of the above method, at least one dye or pigment or compound is provided as a fluorescent material system selected to provide a fluorescent emission spectrum, and the dye can be an organic dye.

[0109] Also described is a blood culture instrument having a housing and a rack disposed within the housing, the rack including a plurality of rack receptacles for receiving a plurality of blood culture sample containers. In one embodiment, at least one rack receptacle is configured to receive a temperature measuring device. The temperature measuring device can have a resistance temperature detector, and the instrument can be configured to read a temperature recorded by the resistance temperature detector and estimate a temperature of the blood culture in the sample container from the temperature. In one embodiment, the instrument can have a controller, and upon receiving a temperature from the temperature measuring device, the controller can compare such temperature to a set temperature and control a temperature in the housing based on the comparison. In a further embodiment, the rack receptacle can have a light pipe, and the receptacle can be configured to receive a temperature measuring device embedded within the light pipe. In a further embodiment, the receptacle configured to receive the temperature measuring device has thermal grease or a thermally conductive pad disposed thereon. In another embodiment, the resistance temperature detector is electrically coupled to a cable having a power line, a ground line, and a serial communication line. In one embodiment, the cable is coupled to a slip connector. In a further aspect of the device, the temperature measuring device can be in the shape of a container, the shape being configured to be received by a receptacle configured to receive the temperature measuring device. In a further aspect, the resistance temperature detector can be immersed in the liquid in the measuring device in the shape of a container and coupled to a cable having a plurality of contacts configured to electrically connect to a slip connector adjacent to the receptacle configured to receive the temperature measuring device. In one aspect, the contacts are contact rings, and the plurality of contacts can be spaced apart on a surface of the temperature measuring device. In a further aspect of the device, the resistance temperature detector can be coupled to a cable including a contact strip, the contact strip having a plurality of contacts configured to electrically connect to corresponding spring contacts in electrical communication with a microprocessor. In one aspect, the temperature measuring device can include a transmitter and a power source. In one aspect, the temperature measuring device can be rechargeable.In a further embodiment of the device, the container-shaped temperature measuring device is formed from a plastic material, which may be doped, blended or injected with at least one dye or pigment or compound having a fluorescence emission spectrum in a first predetermined wavelength range when excited by light in a second predetermined wavelength range. In all the above embodiments, the container-shaped temperature measuring device may be bottle-shaped. In a further embodiment, the plastic material does not absorb light in either the first or second predetermined wavelength range and may be polycarbonate. The plastic material may be doped, blended or injected with at least one dye or pigment or compound and is provided as an insert in an opening formed in the container-shaped temperature measuring device. In one embodiment, the container-shaped measuring device may be formed from a plastic material, which may be doped, blended or injected with at least one dye or pigment or compound.

[0110] From the foregoing and with reference to the various drawings, those skilled in the art will appreciate that certain modifications may be made to the present disclosure without departing from the scope of the present disclosure. While several embodiments of the present disclosure have been shown in the drawings, it is not intended that the disclosure be limited thereto, but rather that the disclosure be as broad as the art will permit, and that the specification be read in the same manner. Therefore, the above description should not be construed as limiting, but merely as exemplifications of certain embodiments. Those skilled in the art will envision other modifications within the scope and spirit of the claims appended hereto.

Claims

1. 1. A calibration device comprising: Contains plastic materials, A calibration device in which at least one dye, pigment, or compound having a fluorescent emission spectrum within a first predetermined wavelength range when excited by light within a second predetermined wavelength range is added, blended, or injected into the plastic material.

2. 2. The calibration device of claim 1, wherein the plastic material does not absorb light in either the first predetermined wavelength range or the second predetermined wavelength range.

3. 2. The calibration device of claim 1, wherein the calibration device is a bottle formed from the plastic material.

4. 4. The calibration device of claim 3, wherein the plastic material is polycarbonate.

5. 3. A calibration device according to claim 1 or 2, wherein the calibration device includes a test area formed as an opening in the calibration device, the plastic material being inserted into the opening in the calibration device.

6. 6. The calibration device of claim 5, wherein a neutral density filter is disposed over the plastic material.

7. The calibration device of claim 6 , wherein the neutral density filter comprises a plurality of neutral density filters.

8. The calibration device of claim 7 , wherein the plurality of neutral density filters are formed in a stack.

9. 6. The calibration device of claim 5, wherein the plastic material is polycarbonate.

10. A calibration device according to any one of claims 1 to 4, wherein the at least one dye or pigment or compound is provided as a fluorescent material system selected to provide the fluorescent emission spectrum.

11. The calibration device of claim 10 , wherein the dye is an organic dye.

12. 1. A method of calibrating an instrument for detecting fluorescence of a sample, comprising: providing a calibration device comprising a plastic material, wherein the plastic material has added to it, blended with it, or impregnated with it at least one dye, pigment, or compound that has a fluorescence emission spectrum within a first predetermined wavelength range when excited by light within a second predetermined wavelength range; placing the calibration device in an instrument having a sensor; aligning the calibration device with the sensor; directing light from a light source, the light source emitting light in the second predetermined wavelength range to produce fluorescence in the first predetermined wavelength range; determining whether the sensor detects the fluorescent light in the first predetermined wavelength range; A method comprising:

13. If the sensor does not detect the fluorescent light in the first predetermined wavelength range, the method further comprises: adjusting and recalibrating the instrument by aligning the calibration device with the sensor; directing light from a light source, the light source emitting light in the second predetermined wavelength range to produce fluorescence in the first predetermined wavelength range; determining whether the sensor detects the fluorescent light in the first predetermined wavelength range; Further comprising: The method of claim 12.

14. The method of claim 12 , wherein the plastic material does not absorb light in either the first predetermined wavelength range or the second predetermined wavelength range.

15. The method of claim 12, wherein the calibration device is a bottle formed from the plastic material.

16. 16. The method of claim 15, wherein the plastic material is polycarbonate.

17. 14. The method of claim 12 or 13, wherein the calibration device includes an inspection area formed as an opening in the calibration device, and the plastic material is inserted into the opening in the calibration device.

18. 18. The method of claim 17, wherein a neutral density filter is disposed over the plastic material.

19. The method of claim 18 , wherein the neutral density filter comprises a plurality of neutral density filters.

20. The method of claim 19 , wherein the plurality of neutral density filters are formed in a stack.

21. 18. The method of claim 17, wherein the plastic material is polycarbonate.

22. 17. A method according to any one of claims 12 to 16, wherein said at least one dye or pigment or compound is provided as a fluorescent material system selected to provide said fluorescent emission spectrum.

23. 23. The method of claim 22, wherein the dye is an organic dye.

24. 1. An instrument for blood culture, said instrument comprising: Housing and a rack disposed within the housing, the rack including a plurality of rack receptacles for receiving a plurality of blood culture sample containers; at least one rack receptacle configured to receive a temperature measurement device; Equipped with the temperature measurement device includes a resistance temperature detector, and the instrument is configured to read the temperature recorded by the resistance temperature detector and estimate the temperature of the blood culture in the sample container therefrom; device.

25. 25. The device of claim 24, wherein the device further includes a controller that, upon receiving a temperature from the temperature measurement device, compares the received temperature with a set temperature and controls the temperature within the housing based on the comparison.

26. 25. The apparatus of claim 24, wherein the rack receptacle includes a light pipe, and the receptacle configured to receive the temperature measurement device has the temperature embedded within the light pipe.

27. 27. The apparatus of claim 26, wherein the receptacle configured to receive the temperature measurement device has thermal grease or a thermally conductive pad disposed thereon.

28. 27. The apparatus of claim 26, wherein the resistance temperature detector is electrically coupled to a cable that includes a power line, a ground line, and a serial communication line.

29. 30. The device of claim 28, wherein the cable is coupled to a slip connector.

30. 25. The apparatus of claim 24, wherein the temperature measurement device is in the shape of a container configured to be received by the receptacle configured to receive the temperature measurement device.

31. 31. The apparatus of claim 30, wherein the resistance temperature detector is immersed in a liquid within the container-shaped measuring device.

32. 32. The apparatus of claim 31 , wherein the resistance temperature detector is coupled to a cable having a plurality of contacts configured to electrically connect to a slip connector adjacent the receptacle configured to receive the temperature measurement device.

33. 33. The device of claim 32, wherein the contact is a contact ring.

34. 33. The apparatus of claim 32, wherein a plurality of said contacts are spaced apart on a surface of said temperature measuring device.

35. 32. The instrument of claim 31, wherein the resistance temperature detector is coupled to a cable including a contact strip having contacts configured to electrically connect to corresponding spring contacts in electrical communication with a microprocessor.

36. 32. The apparatus of claim 31, wherein the temperature measurement device further includes a transmitter and a power source.

37. 37. The apparatus of claim 36, wherein the temperature measurement device is rechargeable.

38. 31. The apparatus of claim 30, wherein the temperature measuring device in the form of a container further comprises a plastic material doped, blended or infused with at least one dye or pigment or compound having a fluorescence emission spectrum within a first predetermined wavelength range when excited by light in a second predetermined wavelength range.

39. 39. The apparatus of claim 38, wherein the temperature measuring device in the shape of a container has a bottle shape.

40. 39. The device of claim 38, wherein the plastic material does not absorb light in either the first predetermined wavelength range or the second predetermined wavelength range.

41. 41. The device of claim 40, wherein the plastic material comprises polycarbonate.

42. 42. The apparatus of claim 41, wherein the plastic material to which the at least one dye or pigment or compound has been added or compounded or injected is provided as an insert in an opening formed in the temperature measuring device in the form of a container.

43. 42. The apparatus of claim 41, wherein said temperature measuring device in the form of a container is formed from said plastic material into which said at least one dye or pigment or compound has been added or blended or injected.

Images