Patent Application
20250020509
Disclosed embodiments are related to spectrophotometers.
Spectrophotometers generally comprise a light source and a detector, which are used to emit light and measure the intensity of transmitted light at various wavelengths, respectively. Accordingly, spectrophotometers leverage the light emitted from the light source by transmitting it through a sample and directing it towards the detector. In such schemes, any changes in the intensity of the emitted light measured at the detector may provide information regarding the sample, such as sample concentration, composition, and/or optical properties.
In some embodiments, a spectrophotometer includes a first printed circuit board; a second printed circuit board; a cavity disposed between the first printed circuit board and the second printed circuit board, where the cavity is configured to receive a sample cartridge disposed therein with one or more sample wells in fluid communication with one or more sample channels formed therein; one or more integrated photodiode modules disposed on the first printed circuit board; and a first set of one or more light sources disposed on the second printed circuit board. The first set of one or more light sources are configured to direct light towards the one or more integrated photodiode modules through the one or more sample wells when the sample cartridge is disposed in the cavity.
In some embodiments, a method for performing spectrophotometry on a sample includes: inserting a sample cartridge into a cavity disposed between the first printed circuit board and a second printed circuit board; aligning one or more sample wells of the sample cartridge between one or more integrated photodiode modules disposed on the first printed circuit board and a first set of one or more light sources disposed on the second printed circuit board; transmitting light from the first set of one or more light sources to the one or more integrated photodiode modules through the one or more sample wells; sensing the transmitted light with the one or more integrated photodiode modules; and determining one or more sample parameters based on the sensed transmitted light.
In some embodiments, a spectrophotometer includes: a first printed circuit board; a second printed circuit board; a heater block disposed between the first printed circuit board and the second printed circuit board; a cavity formed in the heater block, where the cavity is configured to receive a sample cartridge disposed therein with one or more sample wells in fluid communication with one or more sample channels formed therein; a heater thermally coupled to the heater block; a first temperature sensor disposed on the first printed circuit board, where the first temperature sensor is compressed against a first surface of the heater block; and a second temperature sensor disposed on the second printed circuit board. The second temperature sensor is compressed against a second surface of the heater block opposite from the first surface.
In some embodiments, a method for performing spectrophotometry on a sample includes: inserting a sample cartridge into a cavity disposed within a heater block between the first printed circuit board and a second printed circuit board; heating the heater block using a heater that is thermally coupled to the heater block; sensing a temperature of the heater block with a first temperature sensor disposed on the first printed circuit board and compressed against a first surface of the heater block and a second temperature sensor disposed on the second printed circuit board and compressed against a second surface of the heater block opposite from the first surface.
In some embodiments, a spectrophotometer includes: a first printed circuit board; a second printed circuit board; a cavity disposed between the first printed circuit board and the second printed circuit board, wherein the cavity is configured to receive a sample cartridge disposed therein with one or more sample wells in fluid communication with one or more sample channels formed therein; and a pump. The pump includes: a motor; and one or more pistons operatively connected to the motor. The one or more pistons are configured to apply suction to the one or more sample wells when the sample cartridge is disposed in the cavity and the spectrophotometer is operated. One or more processors are configured to control operation of the motor, and where when a current of the motor is greater than or equal to a threshold current, the one or more processors are configured to stop operation of the motor.
In some embodiments, a method for performing spectrophotometry on a sample includes: inserting a sample cartridge into a cavity disposed within a heater block between the first printed circuit board and a second printed circuit board; pumping fluid through the one or more sample channels to the one or more sample wells of the sample cartridge using a pump; and stopping operation of the pump when a current of the motor is greater than or equal to a threshold current.
It should be appreciated that the foregoing concepts, and additional concepts discussed below, may be arranged in any suitable combination, as the present disclosure is not limited in this respect. Further, other advantages and novel features of the present disclosure will become apparent from the following detailed description of various non-limiting embodiments when considered in conjunction with the accompanying figures.
The accompanying drawings are not intended to be drawn to scale. In the drawings, each identical or nearly identical component that is illustrated in various figures may be represented by a like numeral. For purposes of clarity, not every component may be labeled in every drawing. In the drawings:
The Inventors have recognized that optical sensing is widely used due to the variety of parameters that may be sensed using optics based sensing methods. Moreover, many optical sensing schemes are relatively simple and offer relatively high sensitivity for measuring absorbance and/or transmittance of light through a sample (e.g., with a spectrophotometer). Accordingly, optical sensing is often desirable and is widely used across various applications such as biochemical assays, chemical synthesis, and materials science. For example, optical sensing may be used with fluidic system for characterization of fluid based samples. This may include sensing applications in millifluidic and/or microfluidic systems.
The Inventors have also recognized that in most optical sensing systems, it is desirable to have extreme sensitivity for low limits of detection and/or for providing large dynamic sensing ranges. However, this may lead to the use of overengineered, expensive optical sensing systems that may also be fragile and require frequent calibration and/or maintenance to maintain appropriate operation of the system. For example, analog circuitry including separately engineered high performance photodiodes, amplifiers, and/or analog-to-digital converters are oftentimes used in such systems. However, these separately engineered and installed components are relatively expensive, may be complex to integrate in the system, and may be prone to failure. Additionally, for certain types of optical applications including, for example, spectrophotometers as disclosed herein, these types of photosensitive detection circuits may exhibit sensitivities that are magnitudes greater than may be needed to provide a desired sensitivity for sensing certain types of parameters (e.g., absorption of a transmitted light signal exceeding a threshold absorbance). In some instances, the complexity and expense of these overengineered and complex components on a printed circuit board may be further exacerbated by the integration of on-board controllers that provide on board computation and/or data processing. Specifically, the use of these integrated on-board controllers may again lead to increased complexity and may also result in a less reliable and more expensive system. Moreover, in previous systems, the designs did not account for the differing relative lifetimes of each component, where these components are typically included on a single board. Thus, the failure of a single component with a relatively short lifetime may necessitate the replacement of an entire circuit board comprising a number of other, potentially costly, components which may exhibit different expected lifetimes.
In view of the above, the Inventors recognized a need for more cost-effective, less complex, quicker performing, more robust, and/or more easily maintained optical sensing systems. Embodiments which may exhibit one or more of the above benefits, and/or other potential benefits different from those noted above, are detailed further below.
Some aspects of the present disclosure are related to using one or more integrated photodiode modules on-board (e.g., on the circuit boards) of spectrophotometers. Integrated photodiode modules, according to some embodiments, are robust, low-cost, and relatively lower-resolution sensors that may be inappropriate for use in most optical sensing applications, such as diagnostic sensors that need high accuracy sensors for correspondingly accurate measurements. Moreover, the wavelength range that may be sensed by integrated photodiode modules may be relatively limited, which may not be suitable in some optical sensing applications. However, the inventors have recognized in the context of the present disclosure that such integrated photodiode modules may be suitable for threshold sensing, wherein a relative change in a signal is being sensed, as opposed to conventional diagnostic sensing where an accurate absolute signal must be sensed to determine a desired parameter. This may be advantageous because the integration of robust, low-cost sensors may prove cost-effective and/or improve the lifetime of a system including the one or more integrated photodiode modules.
In view of the above, in some embodiments, a spectrophotometer comprising a first printed circuit board, a second printed circuit board, with a cavity disposed between the first printed circuit board and the second printed circuit board are described. In some cases, the cavity is configured to receive a sample cartridge disposed therein with one or more sample wells in fluid communication with one or more sample channels formed therein. The spectrophotometer may further comprise one or more integrated photodiode modules disposed on the first printed circuit board and a first set of one or more light sources disposed on the second printed circuit board, in accordance with some embodiments. The first set of one or more light sources are configured to direct light towards the one or more integrated photodiode modules through the one or more sample wells when the sample cartridge is disposed in the cavity. Thus, the one or more integrated photodiode modules may be used to perform spectrophotometry sensing of fluid samples introduced into the sample cartridges.
When using the above system, a sample cartridge may be inserted into the cavity between the first and second printed circuit boards. In some embodiments, the one or more sample wells of the sample cartridge may be aligned between the one or more integrated photodiode modules disposed on the first printed circuit board and the first set of one or more light sources disposed on the second printed circuit board. According to some embodiments, the spectrophotometry may further comprise transmitting light from the first set of one or more light sources to the one or more integrated photodiode modules through the one or more sample wells and sensing the transmitted light with one or more integrated photodiode modules. Any changes in the light intensity transmitted through the sample wells between the one or more light sources and the one or more integrated photodiode modules over a desired time period may be used to sense a desired sample parameter as elaborated on further below. For example, as described in more detail elsewhere herein, the time needed for an absorbance measured in a sample well to cross a threshold absorbance value may be correlated with a concentration of a target within a fluid sample.
Some aspects of the present disclosure are generally directed to spectrophotometers configured to be coupled to microfluidic sample cartridges. In some embodiments, it may be advantageous to use a spectrophotometer comprising less complex circuitry compared to previous generations of optical sensing devices, which may lead to more robust functionality and/or reduced cost of the system while maintaining a desired optical sensing performance of the system. According to some embodiments, control of the spectrophotometer may be relocated off-board, which may facilitate the simplification of on-board components and also facilitate the interface between the spectrophotometer and one or more remote processors (e.g., in an associated computer, a remotely located server, a smart device such as a smart phone or tablet, or other appropriate computing device). In some such cases, the one or more remote processors may comprise significantly more computer processing power than is feasible to introduce on-board the spectrophotometer, and may provide for quick control and/or data analysis. In some cases, improved temperature sensors and/or heating block arrangements with the spectrophotometer are used. In accordance with some embodiments, the components of the circuit boards of the spectrophotometer may be arranged such that the relative lifetime and/or costs of components on each circuit board are similar such that the failure of a single component may lead to a more cost-effective replacement of the relevant circuit board where a board including lower cost components with expected lifetimes that are shorter than those found on another circuit board may be easily replaced rather than needing to repair a circuit board that also includes expensive components with different lifetimes.
In some embodiments, a relevant process may be heated in order to facilitate and/or speed the reaction (e.g., catalytic reaction, cleavage reaction, etc.). However, previous systems provided a pin sensor positioned loosely in a correspondingly shaped hole formed in a heater block. The pin-in-hole sensors provided relatively low accuracy readings and need relatively frequent calibration. Improving the accuracy of the temperature readings and reducing the frequency of calibration are both desirable for improving temperature control and thus reaction control within the sensing system.
To provide the desired improved heating and/or thermal sensing, in some embodiments, a spectrophotometer may include a heater block disposed between the first and second printed circuit boards, where a cavity is formed in the heater block. The cavity may be sized and shaped to receive a sample cartridge as elaborated on further below. The heater block may be thermally connected to a heater, a first temperature sensor disposed on the first printed circuit board, and a second temperature sensor disposed on the second printed circuit board. The temperature sensors disclosed herein may correspond to any appropriate type of temperature sensor including, but not limited to, thermocouples, resistive temperature detectors (RTD), a semiconductor based temperature sensor, and/or any other appropriate type of temperature sensor. Thus, the heating block may be used to heat the sample cartridge when it is disposed in the cavity of the heating block. The first and second temperature sensors may be compressed against a first and second surface of the heater block opposite from the first surface by the associated first and second printed circuit boards disposed against the opposing first and second surfaces of the heater block. Such an arrangement may also compress the heater block between the first and second printed circuit boards. In some embodiments, the first and second temperature sensors may optionally be aligned with each other such that an axis perpendicular to both the first and second surfaces of the heater block may pass through both sensors, though instances in which the sensors are not aligned are also contemplated.
In some embodiments, the first and second temperature sensors in any of the embodiments described herein are board mounted temperatures sensors. As used herein, a board mounted component (e.g., sensor, processor, etc.) may refer to a surface mounted components that include electrical contacts that are soldered to corresponding electrical contacts on a surface of the printed circuit board without extending through the printed circuit board as may occur with pin-through-hole components where a pin extends through a hole and is soldered within a hole extending through the printed circuit board. Board mounting of the temperature sensors to the first and/or second printed circuit boards may help with a cost of the sensors and improve an ability of the sensors to be compressed against the heater block without causing cracking or other increased modes of failure. This may help to improve both the reliability and the accuracy of the temperature readings obtained using the temperature sensors, which may improve the temperature control of the spectrophotometer.
Performing spectrophotometry using a spectrometer including the above described thermal system and temperature sensors may include inserting a sample cartridge comprising one or more sample wells into the cavity disposed within the heater block between the first printed circuit board and a second printed circuit board and heating the heater block using a heater that is thermally coupled to the heater block. In some cases, a temperature of the heater block may be sensed with the first temperature sensor disposed on the first printed circuit board and compressed against the first surface of the heater block and the second temperature sensor disposed on the second printed circuit board and compressed against the second surface of the heater block opposite from the first surface. This use of sensors compressed against a surface of the heater block, rather than a single pin sensor floating within a hole filled with thermal grease as has been used in earlier systems, may provide more accurate temperature signals of the heater block and thus of the sample cartridge disposed therein. These temperature signals may be used to at least partially control operation of the heaters using any appropriate method including, for example, appropriate temperature feedback control loops. In some embodiments, the improved heating systems described herein may be used to heat the sample cartridge before and/or after aliquots of solution comprising a sample of interest is inserted into one or more inlets of a sample cartridge.
As noted above, certain aspects of the current disclosure are generally related to simplifying the components of the spectrophotometer present on-board (e.g., components physically present on the circuit boards of the spectrophotometer), for example, by remotely controlling the spectrophotometer by using one or more off-board processors. For instance, the sensors, one or more heaters, light sources, and other components may be configured to execute received commands and/or control signals. However, processing of these signals and active control of these systems may be performed by one or more processes that are remotely located from the one or more printed circuit board of the disclosed spectrophotometers. For example, a wired or wireless communication protocol may be used to connect the remotely located one or more processors with the associated components of any one of the embodiments of a spectrophotometer disclosed herein. In some specific embodiments, a pump including a motor may be configured to be controlled by one or more off-board processes that may send a commanded encoder position for a stepper motor, or other appropriate pump control parameter, to the pump. Moving control and analysis of the different signals and operations for a spectrophotometer off-board may be desirable for any of a variety of reasons. In some cases, off-board processing and control may facilitate the use of less complex circuitry which may be more cost effective, streamline performance of the circuitry, and/or provide more reliable operation of the system as there is no need to have a full onboard operating system for doing all these processes. Additionally, in some embodiments, off-board control may facilitate the use of more one or more processors which may exhibit increased computational power for device operation and/or data analysis.
As also noted above, the positioning of certain components on different printed circuit boards based on various considerations such as cost, lifetime, ease of replacement, and/or other considerations may be taken into account in any of the embodiments disclosed herein. For example, in some embodiments, less expensive components that may also be more prone to failure may be included on a first circuit board, while the remaining, more expensive and/or more reliable components may be included on a second circuit board. For example, less reliable components with shorter average lifetimes such as light sources (e.g., LEDs or other light sources), and optionally their associated control circuits may be located on a first circuit board. Correspondingly, the more reliable and/or expensive components, such as corresponding photosensitive detectors (e.g., photodiodes, integrated photodiode modules, or other appropriate types of photosensitive detectors), may exhibit longer average lifetimes and may be located on the associated second printed circuit board. In some such cases, grouping components that are prone to failure (e.g., exhibit a lower average lifetime) on the first circuit board may be desirable for easier and/or more cost-effective replacement and/or maintenance. That is, in previous systems, the failure of one component on a large printed circuit board including all of the necessary components with different average lifetimes necessitated the replacement and/or maintenance of the whole circuit board, which could entail high costs and/or long delays associated with either fixing and/or replacing the damaged circuit board. This problem is circumvented by the spectrophotometers described herein.
The systems and methods described herein may offer a number of different benefits. This may include reduced costs, increased reliability, and reduced system sizes as compared to earlier systems. Additionally, the systems and methods described herein are suitable for use in any of a variety of applications where an optical signal may be measured. For example, in some cases, the system and/or methods may be used to measure the progress and/or result of a biochemical and/or biomedical assay or general chemical reactions (e.g., cleavage reaction, precipitation reaction, synthesis, or the like). Thus, it should be understood that the various embodiments disclosed herein are not limited to any particular type of sensing application.
The sample cartridges disclosed herein may comprise one or more sample inlets in fluid communication with one or more sample wells formed in the sample cartridge. The sample inlets and wells may be fluidically connected via one or more corresponding sample channels extending therebetween. These one or more sample channels may in some instances also be connected to one or more corresponding outlets which may be configured to be connected to a vacuum source such as one or more pumps. For example, as described in more detail elsewhere herein, the one or more outlets of a sample cartridge may be configured to be fluidically connected with tubing and/or a pump of a spectrophotometer. The one or more outlets may be located downstream from sample wells along the one or more sample channels relative to the corresponding inlets. The sample channels may correspond to any appropriate size and, in some embodiments, may be microfluidic or millifluidic channels. Sample channels, fluid channels, and other similar terms may be understood as generally referring to a structure configured to direct the flow of fluid along a desired flow path and may either be partially open, fully enclosed, or exhibit any desired type of structure capable of being used with the systems and methods disclosed herein.
The one or more sample inlets, one or more sample wells, and one or more sample channels, in some cases, may be a plurality of sample inlets, a plurality of sample wells, and a plurality of sample channels, wherein each of the plurality of sample channels flow parallel to each other, as described in more detail elsewhere herein. In some embodiments, it may be desirable to have at least two sample inlets, at least two sample wells, and at least two sample channels in the sample cartridge to facilitate the analysis of a plurality of separate samples with a corresponding plurality of light sources and photosensitive detectors as described herein.
Each sample channel and/or sample well in the various embodiments described herein may have any of a variety of heights or widths. In some cases, the height and/or width of each of the one or more sample channels may be less than or equal to 2 mm, less than or equal to 1 mm, less than or equal to 750 microns, less than or equal to 500 microns, less than or equal to 300 microns, less than or equal to 200 microns, less than or equal to 100 microns, less than or equal to 50 microns, or less than or equal to 10 microns. According to some embodiments, the height and/or width of each of the one or more sample channels may be greater than or equal to 1 micron, greater than or equal to 10 microns, greater than or equal to 50 microns, greater than or equal to 100 microns, greater than or equal to 200 microns, greater than or equal to 300 microns, greater than or equal to 500 microns, greater than or equal to 750 microns, or greater than or equal to 1 mm. Combinations of the foregoing ranges are possible (e.g., greater than or equal to 1 micron and less than or equal to 2 mm). Other ranges are also possible. It should be understood that in some embodiments, the height and width of a channel may correspond to the in plane width which is contained with a plane in which the channels extend and out of plane height which may be perpendicular to the plane in which the channels extend. The height and width may be directed in directions that are perpendicular to each other and may also be perpendicular to a longitudinal axis of the channels extending along a length of the channels within the portion of the channel the height and width are referenced to.
Each sample channel may have any of a variety of lengths. In some cases, the length of each of the one or more sample channels may be less than or equal to 10 cm, less than or equal to 8 cm, less than or equal to 6 cm, less than or equal to 4 cm, or less than or equal to 2 cm. In some embodiments, the length of each of the one or more samples channels may be greater than or equal to 1 cm, greater than or equal to 2 cm, greater than or equal to 4 cm, greater than or equal to 6 cm, or greater than or equal to 8 cm. Combinations of the foregoing ranges are possible (e.g., greater than or equal to 1 cm and less than or equal to 10 cm). Other ranges are also possible.
The one or more sample wells of a sample cartridge may have any appropriate volume to accommodate an expected sample volume therein for testing purposes. Appropriate volumes of a sample well may be greater than or equal to 0.01 milliliter (mL), 0.05 mL, 0.1 mL, 0.2 mL, or any other appropriate volume. The sample well volume may also be less than or equal to 0.3 mL, 0.2 mL, 0.1 mL, or any other appropriate volume. Combinations of the forgoing are contemplated including, for example, a sample well volume may be between or equal to 0.01 mL and 0.3 mL. Other sample well volumes are also possible.
It should be understood that a sample cartridge may have any appropriate size and/or shape for accommodating the presence of the one or more sample inlets, channels, and wells formed therein. Thus, the sample cartridges and corresponding structures configured to receive the sample cartridges (e.g., a cavity configured to receive the sample cartridge within a spectrophotometer) are not limited to any specific size and/or shape as the disclosure is not limited in this fashion.
The integrated photodiode modules and/or infrared light sensors in any one of the various embodiments of a spectrophotometer disclosed herein may be used for threshold sensing in some instances, and as described elsewhere herein. In some such embodiments, the threshold value may be a threshold absorbance for light transmitted through the sample between a light source and corresponding photosensitive detector. This may be detected using relative changes in light intensity from an initial light intensity, a measured light intensity relative to an expected or reference light intensity, a change in magnitude of a measured light intensity, a measured light signal falling below a threshold light signal, or other appropriate threshold related to determining a threshold light absorbance being exceeded. In one such embodiment, the absorbance is described relative to a number extending between 0 and 1 where 0 is pure transmission with no absorbance (i.e., no sample present) and 1 is total absorbance of a light signal by a sample with no transmission. Depending on the application the absorbance threshold may be greater than or equal to 0.1, greater than or equal to 0.2, greater than or equal to 0.3, or greater than or equal to 0.5, or greater than or equal to 0.8. In some embodiments, the absorbance threshold may be less than or equal to 1, less than or equal to 0.8, less than or equal to 0.5, less than or equal to 0.3, or less than or equal to 0.2,. Combinations of the foregoing ranges are possible (e.g., greater than or equal to 0.1 and less than or equal to 0.8). According to some embodiments, when a threshold absorbance is measured at the infrared light sensors, the threshold absorbance represents the presence of a solution in the corresponding sample channels. In some cases, a threshold value measured at the integrated photodiode modules may be used to determine a sample parameter, for example, the presence and/or the concentration of a compound, particles, and/or other target species in the sample.
As used herein, integrated photodiode modules used with any one of the embodiments described herein may correspond to a semiconducting device corresponding to a single piece of semiconducting material that includes multiple electrical components that are formed in and/or disposed on and electrically connected to the components formed in the semiconducting material. Thus, in some embodiments, an integrated photodiode module may include components such as a photodiode, amplifier, and analog to digital converter that are formed in and/or attached to a single semiconducting substrate. The integrated photodiode modules used with the various embodiments described herein may be mounted to corresponding electrical contacts on an associated printed circuit board the integrated photodiode modules are attached to. This may include board mounting of the one or more integrated photodiode modules. As noted previously, a board mounted component may refer to a surface mounted components that include electrical contacts that are soldered to corresponding electrical contacts on a surface of the printed circuit board without extending through the printed circuit board. This is in contrast to pin-through-hole components where a pin extends through a hole and is soldered within the hole extending through the printed circuit board.
In accordance with some embodiments, the integrated photodiode modules used with any one of the embodiments described herein may have a relatively low resolution when compared with sensors used in conventional diagnostic sensors. Again, such sensors are not appropriate for use with conventional diagnostic sensors due to the high resolution requirements of those systems, and as such are not commonly used in optical sensing of fluid samples. For example, conventional systems use optical sensors with a resolution of greater than or equal to 24 bits, and may be up to 32 bits, in order to provide high accuracy measurements which are necessary for these high accuracy diagnostic tests. In contrast, the integrated photodiode modules used herein may have relatively lower resolutions because the threshold sensing described elsewhere herein does not need such precise measurements to determine the presence and/or concentration of the species of interest. For instance, in some cases, the resolution of the integrated photodiode modules may be greater than or equal to 12 bits, greater than or equal to 14 bits, or greater than or equal to 16 bits. In some embodiments, the integrated photodiode modules may have a resolution of less than or equal to 18 bits, less than or equal to 16 bits, or less than or equal to 14 bits. Combinations of the above are contemplated including an integrated photodiode module with a 12 bit to 18 bit resolution. In some embodiments, it may be desirable to use a 16 bit integrated photodiode module because they are widely commercially available.
Integrated photodiode modules may be smaller and/or more compact than equivalent separately formed analog circuits. In comparison to conventional sensors used for diagnostic devices, integrated photodiode modules are relatively cost-effective due to their use in cellular devices and the corresponding push to provide sufficient supply. Likewise, due to their use in cellular devices rather than diagnostic devices, though integrated photodiode modules have lower resolution than conventionally used sensors, and thus one of ordinary skill would not consider using integrated photodiodes for such a sensing application. However, the inventors have recognized in the context of the present disclosure that the resolution afforded by integrated photodiode modules may be sufficient for certain sensing applications while also offering increased reliability, decreased cost, and reduced design complexity.
As noted above, in any one of the embodiments described herein, some and/or all of the components of the spectrophotometer may be controlled off-board. Generally, off-board control is a configuration where computational tasks and/or data processing are performed off-board by one or more remotely located processors (e.g., an adjacent computer, tablet, smartphone, separate control system, a remotely located server, and/or any other computing device capable of controlling a spectrophotometer to perform any one of the methods disclosed herein). That is, computational tasks related to the analysis and control of the various components may occur on the one more remotely located processors. In some cases, for examples, commands for the various components may be transmitted via an off-board computational system and relayed to the on-board components. After receiving the commands from off-board, the components may perform corresponding actions and relay subsequently collected information (e.g., signals from the one or more sensors) back to the one or more off-board computer processors. Any received signals may then be processed by the off-board computer processor as detailed further herein.
Configuring the spectrophotometer for off-board control may be desirable for any of a variety of reasons. For example, this may facilitate the use of more powerful computational resources and/or storage capacity than may otherwise by achievable on-board without excessive costs, increased complexity, and/or decreased reliability. Moreover, off-board control may facilitate the simplification of the components of the spectrophotometer, which may again be desirable for the above noted reasons. Note that, in some embodiments, the on-board control of the spectrophotometric process may still be possible.
It should be understood that the above descriptions of various components as well as the specific ranges for different parameters may be used with any one of the embodiments of a spectrophotometer as described herein. Further, these various components and ranges may either be used individually and/or together in any desired combination with the various embodiments of a spectrophotometer described herein.
The spectrophotometers described herein may be suitable for sensing any of a variety of sample parameters, as long as the spectrophotometer is capable of measuring the sample parameter. That is, the spectrophotometer can be used to sense any of a variety of optical signals, for example, the attenuation of light transmitted through a sample. The attenuation may be attributed to the absorbance of the light by the sample. In some cases, any changes in the absorbance as a function of time may be correlated to reaction rates and/or concentrations of a target species (e.g., compounds, particles, bound or cleaved dye, etc.) within a sample. Depending on the application, the signal may either be constant with time, or it may vary with time as elaborated on further below.
In one exemplary embodiment, the spectrophotometers disclosed herein may be used to determine the presence and/or concentration of a chromogenic endotoxin. When a sample comprising the chromogenic endotoxin is spiked with an enzyme that reacts with the chromogenic endotoxin, the absorbance of the chromogenic endotoxin may change.
Accordingly, the spectrophotometer may measure the absorbance of the sample as a function of time after introducing the enzyme that reacts with the chromogenic endotoxin. In some embodiments, as described in more detail elsewhere, the spectrophotometer may sense the changing absorbance of light transmitted through the system (e.g., by sensing the corresponding change in transmission of light through the sample) using threshold based sensing. In such an exemplary embodiment, if the absorbance threshold is exceeded, the presence of the chromogenic endotoxin is confirmed, whereas the time it takes to sense the signal exceeding the absorbance threshold may be correlated with the concentration of the chromogenic endotoxin.
Generally, the spectrophotometers described herein may be used in any of a variety of sensing schemes involving optical signals, wherein the optical signal may be large enough to measure with threshold based sensing. Exemplary systems include cleavable dyes, wherein once a co-reactant is introduced, the concentration of the cleavable dye changes. In some such cases, the measure absorbance of the sample may increase as the cleavable dye reacts, whereas in other such cases, the measured absorbance of the sample dye may decrease as the cleavable dye reacts. In some embodiments, the spectrophotometer may be used to measure contamination of biological and/or biomedical samples. Measuring the occurrence and/or progress of other chemical reactions are also possible, in accordance with some embodiments, such as precipitation reactions, catalytic reactions that generate light absorbing compounds, and/or changes in pH in the presence of pH dependent light absorbers.
Turning to the figures, specific non-limiting embodiments are described in further detail. It should be understood that the various systems, components, features, and methods described relative to these embodiments may be used either individually and/or in any desired combination as the disclosure is not limited to only the specific embodiments described herein.
The above noted arrangement of one or more temperature sensors, and preferably two temperature sensors located on opposing sides of a heater block, which are compressed against a heater block may offer improved accuracy relative to other temperature sensing arrangements. For example, in some embodiments, a sensed temperature, which may correspond to an average of the temperatures sensed by the separate temperature sensors, may have an offset from an actual temperature of the heater block that is less than or equal to 0.5° C., 0.4° C., 0.3° C., 0.2° C., or another appropriately low temperature offset. Due to the compression of the temperature sensors against the heater block surfaces, such an arrangement may exhibit little to no drift over time and may be much more accurate as compared to other prior methods of measuring a temperature of the heater block such that calibrations of the temperature sensors may be less frequent and/or unnecessary in some embodiments as compared to the earlier designs described above.
Schematic diagrams of one embodiment of a pump 124 that may be used in any one of the spectrophotometers disclosed herein are shown in
While a piston based pump is described above, it should be understood that any appropriate type of pump or other suction source capable of causing a sample to flow through a sample cartridge may be used as the disclosure is not so limited. This may include, but is not limited to, positive displacement pumps such as peristaltic pumps, though any appropriate type of suction source may be used.
In this exemplary embodiment, the sample cartridge 190 is configured to be inserted into a spectrophotometer, where an aliquot of solution comprising a sample may be inserted into each of the sample inlets 192 of the sample cartridge. A pump 124 may then be operated to pump liquid from each of the sample inlets through each of the sample channel 198 to each of the sample wells 196. As the liquid is pumped through the sample channels, the second set of one or more light sources 120, see
The second printed circuit board 200 in
The light sources 205 and 215 may be configured to emit light of any suitable wavelength as described elsewhere herein. Additionally, when the second printed circuit board is assembled in a spectrophotometer, the emitted light may be directed through a sample cartridge when present and towards the first printed circuit board. Note that, as configured, spectrophotometric components with relatively short lifetimes are all grouped on the second printed circuit board. As disclosed elsewhere herein, this may be desirable because it may reduce maintenance times and/or minimize cost when there is a need to replace a component on the second circuit board, as the components on the second printed circuit board may be replaced more frequently on average (i.e., they have a shorter average lifespan) then the components located on the first printed circuit board.
The first printed circuit board 202 depicted in
In accordance with some embodiments, it may be desirable to control operation of the first and/or second sets of light sources 205 and 215 using a pulse width modulation (PWM) controller (e.g., a PWM driver circuit) as the driver 225 which may be used to control an intensity of the first and/or second light sources to emit light with a desired intensity. In some instances, a single PWM driver may be used to control operation of both the first and/or the second set of one or more light sources which may offer benefits related to cost, simplified design, and reliability. However, according to other embodiments, there may be separate individual PWM drivers associated with each light source of the first and/or second set of one or more light sources. Alternatively, in other embodiments, there may be a single PWM driver for the first one or more light sources and a separate single PWM driver for the second set of one or more light sources. Regardless of the number and arrangement of the PWM drivers, or other light source controllers, a control frequency of the PWM may be selected to be significantly greater than a sampling rate of a corresponding sensor (e.g., at least twice as fast or other appropriate frequency) such as an infrared light sensor and/or the integrated photodiode module.
In accordance with some embodiments, the light emitted from the first and/or second set of one or more light sources may be modulated at a rate of greater than or equal to 10 kHz, greater than or equal to 20 kHz, greater than or equal to 50 kHz, greater than or equal to 100 kHz, or greater than or equal to 150 kHz. According to some embodiments, the emitted light may be modulated at higher frequencies, but this may not be cost effective for point of care sensing. In some cases, the emitted light may be modulated at a rate of less than or equal to 200 kHz, less than or equal to 150 kHz, less than or equal to 100 kHz, less than or equal to 50 kHz, or less than or equal to 20 kHz. Combinations of the foregoing ranges are possible (e.g., greater than or equal to 10 kHz and less than or equal to 200 kHz). Other ranges are also possible.
As noted previously, the first set of one or more light sources may be configured to emit UV-Visible light, or other appropriate spectrum of light, associated with detecting a desired sample parameter (e.g., cleavage of a dye, presence of an absorbing and/or scattering particles and/or compounds within the sample, or other appropriate type of parameter capable of being sensed with a spectrophotometer). In some cases, the emitted light from the first set of one or more light sources may have a wavelength of greater than or equal to 300 nanometers, greater than or equal to 390 nm, greater than or equal to 400 nm, greater than or equal to 500 nm, or greater than or equal to 600 nm. In some embodiments, the emitted light from the first set of one or more light sources may have a wavelength of less than or equal to 700 nm, less than or equal to 600 nm, less than or equal to 500 nm, less than or equal to 400 nm, or less than or equal to 390 nm. Combinations of the foregoing ranges are possible (e.g., greater than or equal to the 300 nm and less than or equal to 700 nm, greater than or equal to 400 nm and less than or equal to 700 nm, greater than or equal to 390 nm and less than or equal to 400 nm). Other ranges are also possible.
As also noted previously, the second set of one or more light sources may be configured to sense the presence of a sample within a sample channel. Thus, in some instances, the second set of light sources may be configured to emit infrared (IR) light or other appropriate spectrum of light that may be used to determine the presence of a sample within the sample channels. In some cases, the emitted light from the second set of one or more light sources may have a wavelength of greater than or equal to 900 nm, greater than or equal to 950 nm, greater than or equal to 1000 nm, greater than or equal to 1050 nm. In some embodiments, the emitted light from the second set of one or more light sources may have a wavelength of less than or equal to 1100 nm, less than or equal to 1050 nm, less than or equal to 1000 nm, less than or equal to 950 nm. Combinations of the foregoing ranges are possible (e.g., greater than or equal to the 900 nm and less than or equal to 1000 nm). Other ranges are also possible.
In some embodiments, the integrated photodiode modules and the infrared light sensors may be configured to sense light having a wavelength that corresponds to the light emitted from the first and second set of one or more light sources, respectively. In some cases, the integrated photodiode modules and/or the infrared light sensors may be capable of detecting ranges of wavelengths of light that are broader than the light emitted from the first and/or second set of one or more light sources. In some such cases, this ensures the integrated photodiode modules and/or infrared light sensors sense the light emitted from the light sources. However, embodiments, in which the various photosensitive detectors, such as the integrated photodiode modules and/or the infrared light sensors, only sense a portion of the light emitted from an associated light source are also contemplated.
The sampling rate of the integrated photodiode modules and/or the infrared light sensors may be any of a variety of suitable values, in accordance with some embodiments. The sampling rate of the sensors may be selected based on the application. For example, a relatively low sampling rate may be chosen the monitor the progress of a relatively slow reaction, in some embodiments. Alternatively, in some cases, a relatively fast sampling rate may be chosen to monitor the progress of a relatively fast reaction. According to some embodiments, the sampling rate of the integrated photodiode modules and/or the infrared light sensors may be greater than or equal to 10 Hz, greater than or equal to 50 Hz, greater than or equal to 100 Hz, greater than or equal to 250 Hz, greater than or equal to 500 Hz, or greater than or equal to 750 Hz. In some embodiments, the sampling rate of the sensor may be less than or equal to 1 kHz, less than or equal to 750 Hz, less than or equal to 500 Hz, less than or equal to 250 Hz, less than or equal to 100 Hz, or less than or equal to 50 Hz. Combinations of the foregoing ranges are possible (e.g., greater than or equal to 10 Hz and less than or equal to 100 Hz). Other ranges are also possible.
As mentioned above, the second and first circuit board 200 and 202 may be interconnected connected to each other by electrical connectors 245 and 246. As noted previously, during operation a cavity disposed between the first and second circuit board may be configured to receive a sample cartridge therein, and the IR LEDs 205 may be aligned to transmit light through the one or more sample channels of the sample cartridge towards the infrared light sensors 210. In some cases, a change in transmitted light intensity measured at the infrared light sensors may indicate that there is a sample present in one or more sample channels of the sample cartridge.
Before or after the indication that the sample is present in the sample cartridge, the microcontroller 250 may control the motor driver and to begin driving the motor. The motor may be operatively connected to a pump (e.g., as described previously above), which may be fluidically connected to the sample cartridge. This pump operation may draw fluid from the one or more sample inlets through the one or more sample channels to the one or more sample wells of the sample cartridge. As the solution comprising the sample reaches the one or more sample wells, the first set of light sources (e.g., UV-Visible LEDs) 215 may be aligned to transmit light through the sample wells towards the integrated photodiode modules 220. As disclosed elsewhere herein, changes in the transmitted light may be indicative, for example, of the presence and/or concentration of a species of interest.
Throughout the above-described process, the temperature sensors 235 and 236 on the second printed circuit board 200 and first printed circuit board 202 have been described as being configured to measure the temperature of the heater block, as shown in
Signaler 270 may produce any of a variety of signals, in accordance with some embodiments. Non limiting examples of signals include optical signals (e.g., a flashing LED) or audible signal (e.g., a sound). Signaler 270 may produce a signal when a sample is inserted in the sample inlets of the sample cartridge when present in the spectrophotometer, in some cases. According to some embodiments, signaler 270 may produce a signal when a sample is detected by the spectrophotometer. Additionally, the signaler 270 may produce signals for other reasons, as this disclosure is not so limited.
The remaining components of the first printed circuit board 202 include cartridge switches 272 and 274, a fan connector 276, a USB connector 278, and a power conditioning connector and/or communication system 280. The fan connector may be used to connect a fan, which in some embodiments, may cool the circuitry of the spectrophotometer. In some cases, USB connector and/or other communication system 278 may facilitate off-board control, as described elsewhere herein. Power conditioning connector 280 may be used to provide external power to the spectrophotometer for operation, according to some embodiments.
As alluded to above, the components of the first printed circuit board are generally more expensive and have longer lifetimes compared to the components on the second printed circuit board. Accordingly, grouping the components as illustrated in
As noted above, a threshold absorbance of a transmitted light signal from a light source to a corresponding sensor may be used to determine either the presence of a sample within a sample channel (e.g., as the sample flows into the channel) and/or the presence of a desired species within a sample disposed in a sample well (e.g., as a reaction progresses over time).
Various methods for using the spectrophotometers described herein are possible.
The solution comprising the sample may be flowed from the one or more sample inlets to the one or more sample wells through the one or more sample channels of the sample cartridge at 450. As described elsewhere herein, this may be accomplished by use of a pump or other appropriate source of suction. According to some embodiments, the sample cartridge may be heated by using a heater integrated with or in thermal communication with a heater block at 460 where the sample cartridge is disposed in a cavity formed in the heater block such that a temperature of the sample cartridge may be controlled by the heater an heater block. The temperature of the sample cartridge may be controlled using signals from one or more temperature sensors compressed against one or more surfaces of the heater block, as described elsewhere herein. For example, an average of a temperature sensed by a first temperature sensor compressed against a first surface of the heater block and a second temperature sensed by a second temperature sensor compressed against a second surface of the heater block may be used to control operation of the heater. For example, the measurements from the temperature sensors may be used as feedback to increase or decrease the amount of heat applied by the heater and heater block to the sample cartridge to maintain a desired temperature of the sample cartridge during operation.
Performing spectrophotometry may further comprise transmitting light from the first set of one or more light sources through the one or more sample wells 470. As mentioned above, the first set of one or more light sources may be aligned to transmit light through the one or more sample wells towards the one or more integrated photodiode modules. The integrated photodiode modules may sense the transmitted light from the first set of one or more light sources at 480. The sensed, transmitted light may be used to determine one or more sample parameters at 490. In some cases, it may be desirable to use UV-Visible LEDs as the first set of one or more light sources, to probe the optical properties of the sample in the UV-visible spectrum. As noted previously above, and as elaborated on relative to the examples, this may correspond to determining a time for a detected signal from the integrated photodiode modules to exceed a predetermined threshold absorbance (e.g., a threshold intensity change, a light intensity less than a threshold light intensity, or other appropriate parameter related to absorbance) though other methods of performing spectrophotometry with the disclosed systems may be implemented as well as the disclosure is not so limited.
The above method may be implemented by one or more controllers including at least one processor operatively coupled to the various controllable portions of a spectrophotometer as disclosed herein. The method may be embodied as computer readable instructions stored on non-transitory computer readable memory associated with the at least one processor such that when executed by the at least one processor, the spectrophotometer may perform any of the actions related to the methods disclosed herein. Additionally, it should be understood that the disclosed order of the steps is exemplary and that the disclosed steps may be performed in a different order, simultaneously, and/or may include one or more additional intermediate steps not shown as the disclosure is not so limited.
The following describes an exemplary test using an spectrophotometer similar to that described above relative to
The above-described embodiments of the technology described herein can be implemented in any of numerous ways. For example, the embodiments may be implemented using hardware, software or a combination thereof. When implemented in software, the software code can be executed on any suitable processor or collection of processors, whether provided in a single computing device or distributed among multiple computing devices. Such processors may be implemented as integrated circuits, with one or more processors in an integrated circuit component, including commercially available integrated circuit components known in the art by names such as CPU chips, GPU chips, microprocessor, microcontroller, or co-processor. Alternatively, a processor may be implemented in custom circuitry, such as an ASIC, or semicustom circuitry resulting from configuring a programmable logic device. As yet a further alternative, a processor may be a portion of a larger circuit or semiconductor device, whether commercially available, semi-custom or custom. As a specific example, some commercially available microprocessors have multiple cores such that one or a subset of those cores may constitute a processor. Though, a processor may be implemented using circuitry in any suitable format.
Further, it should be appreciated that a computing device including one or more processors may be embodied in any of a number of forms, such as a rack-mounted computer, a desktop computer, a laptop computer, or a tablet computer. Additionally, a computing device may be embedded in a device not generally regarded as a computing device but with suitable processing capabilities, including a Personal Digital Assistant (PDA), a smart phone, tablet, or any other suitable portable or fixed electronic device.
Also, a computing device may have one or more input and output devices. These devices can be used, among other things, to present a user interface. Examples of output devices that can be used to provide a user interface include display screens for visual presentation of output and speakers or other sound generating devices for audible presentation of output. Examples of input devices that can be used for a user interface include keyboards, individual buttons, and pointing devices, such as mice, touch pads, and digitizing tablets. As another example, a computing device may receive input information through speech recognition or in other audible format.
Such computing devices may be interconnected by one or more networks in any suitable form, including as a local area network or a wide area network, such as an enterprise network or the Internet. Such networks may be based on any suitable technology and may operate according to any suitable protocol and may include wireless networks, wired networks or fiber optic networks.
Also, the various methods or processes outlined herein may be coded as software that is executable on one or more processors that employ any one of a variety of operating systems or platforms. Additionally, such software may be written using any of a number of suitable programming languages and/or programming or scripting tools, and also may be compiled as executable machine language code or intermediate code that is executed on a framework or virtual machine.
In this respect, the embodiments described herein may be embodied as a computer readable storage medium (or multiple computer readable media) (e.g., a computer memory, one or more floppy discs, compact discs (CD), optical discs, digital video disks (DVD), magnetic tapes, flash memories, RAM, ROM, EEPROM, circuit configurations in Field Programmable Gate Arrays or other semiconductor devices, or other tangible computer storage medium) encoded with one or more programs that, when executed on one or more computers or other processors, perform methods that implement the various embodiments discussed above. As is apparent from the foregoing examples, a computer readable storage medium may retain information for a sufficient time to provide computer-executable instructions in a non-transitory form. Such a computer readable storage medium or media can be transportable, such that the program or programs stored thereon can be loaded onto one or more different computing devices or other processors to implement various aspects of the present disclosure as discussed above. As used herein, the term “computer-readable storage medium” encompasses only a non-transitory computer-readable medium that can be considered to be a manufacture (i.e., article of manufacture) or a machine. Alternatively or additionally, the disclosure may be embodied as a computer readable medium other than a computer-readable storage medium, such as a propagating signal.
The terms “program” or “software” are used herein in a generic sense to refer to any type of computer code or set of computer-executable instructions that can be employed to program a computing device or other processor to implement various aspects of the present disclosure as discussed above. Additionally, it should be appreciated that according to one aspect of this embodiment, one or more computer programs that when executed perform methods of the present disclosure need not reside on a single computing device or processor, but may be distributed in a modular fashion amongst a number of different computers or processors to implement various aspects of the present disclosure.
Computer-executable instructions may be in many forms, such as program modules, executed by one or more computers or other devices. Generally, program modules include routines, programs, objects, components, data structures, etc. that perform particular tasks or implement particular abstract data types. Typically the functionality of the program modules may be combined or distributed as desired in various embodiments.
The embodiments described herein may be embodied as a method, of which an example has been provided. The acts performed as part of the method may be ordered in any suitable way. Accordingly, embodiments may be constructed in which acts are performed in an order different than illustrated, which may include performing some acts simultaneously, even though shown as sequential acts in illustrative embodiments.
Further, some actions are described as taken by a “user.” It should be appreciated that a “user” need not be a single individual, and that in some embodiments, actions attributable to a “user” may be performed by a team of individuals and/or an individual in combination with computer-assisted tools or other mechanisms.
While several embodiments of the present invention have been described and illustrated herein, those of ordinary skill in the art will readily envision a variety of other means and/or structures for performing the functions and/or obtaining the results and/or one or more of the advantages described herein, and each of such variations and/or modifications is deemed to be within the scope of the present invention. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and/or configurations will depend upon the specific application or applications for which the teachings of the present invention is/are used. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. It is, therefore, to be understood that the foregoing embodiments are presented by way of example only and that, within the scope of the appended claims and equivalents thereto, the invention may be practiced otherwise than as specifically described and claimed. The present invention is directed to each individual feature, system, article, material, kit, and/or method described herein. In addition, any combination of two or more such features, systems, articles, materials, kits, and/or methods, if such features, systems, articles, materials, kits, and/or methods are not mutually inconsistent, is included within the scope of the present invention.
This Application claims the benefit of priority under 35 U.S.C. § 119(e) of U.S. Provisional Application Ser. No. 63/513,528, filed Jul. 13, 2023, the disclosure of which is incorporated herein by reference in its entirety.
| Number | Date | Country | |
|---|---|---|---|
| 63513528 | Jul 2023 | US |
