Patent Description:
Chromatography is a set of techniques for separating a mixture into its constituents. For instance, in a liquid chromatography system, a pump takes in and delivers a mixture of liquid solvents to a sample manager, where an injected sample awaits its arrival. The mobile phase, comprised of a sample dissolved in a mixture of solvents, passes to a column, referred to as the stationary phase. By passing the mixture through the column, the various components in the sample separate from each other at different rates and thus elute from the column at different times. A detector receives the elution from the column and produces an output from which the identity and quantity of the analysis may be determined.

Prior to being provided into the liquid chromatography system, the sample may be provided to a sample organizer and/or a sample manager. The sample organizer and/or a sample manager may be configured to store the sample in conditions that prevent the sample from degrading or becoming otherwise damaged. The sample organizer and/or sample manager may be configured to provide the sample into the liquid chromatography system. The sample organizer and/or sample manager may be configured to store a plurality of samples prior to analysis by the liquid chromatography system.

Sample managers and/or sample organizers often include thermal chambers with the need of very accurate temperature control at temperatures at or close to freezing point of water. Temperature control may include incorporating a heat sink running at temperatures below <NUM>. However, heat sinks running at such temperatures are known to condense liquid and eventually freeze. When ice has built up the performance of the engine controlling the temperature decreases and the temperature within the thermal chamber will undesirably rise. Furthermore, sometimes engines that control thermal chambers of these systems fail unexpectedly.

Thus, liquid chromatography thermal systems, or liquid chromatography sample managers and/or organizers, with associated systems and methods for detecting the status of thermal chambers therein, would be well received in the art.

<CIT> discloses a sample manager of a liquid chromatography system that implements a thermal system that uses a dual-loop feedback control system to control temperature within a thermal chamber. The sample manager includes an external heatsink disposed externally to the thermal chamber, an internal heatsink disposed within the thermal chamber, and one or more thermoelectric devices thermally coupled to the external and internal heatsinks to transfer heat therebetween in response to a pulse-width modulated power signal. A first temperature sensor disposed within the thermal chamber continuously measures a chamber temperature. A second temperature sensor coupled to the internal heatsink within the thermal chamber continuously measures temperature at the internal heatsink. A feedback control system controls a duty cycle of the pulse-width modulated power signal in response to a target chamber temperature and real-time temperature measurements produced by the first and second temperature sensors.

<CIT> discloses an apparatus that includes a heater block assembly having a heater block made of thermally conductive material to heat a flowing liquid. The heater block assembly has a tube inlet, a tube outlet, and a tube path between the tube inlet and tube outlet. Tubing extends through the tube path from the tube inlet to the tube outlet. The tubing is in thermal communication with the heater block. A heater cartridge, in thermal communication with the heater block, is configured to provide heat to the heater block for transfer to liquid flowing through the tubing between the tube inlet and the tube outlet of the heater block assembly. Circuitry is in electrical communication with the heater cartridge to control a temperature of the heater block by controlling operation of the heater cartridge.

<CIT> discloses a sample cooling device capable of effectively removing moisture in the air inside an accommodating chamber where a sample container is accommodated, and of preventing a problem caused by occurrence of frost, an autosampler provided with the same, and a sample cooling method. A first driving process of setting a set temperature of a dehumidifier section to at or below the freezing point, and a second driving process of stopping driving of the dehumidifier section or of raising the set temperature of the dehumidifier section to above the freezing point after the first driving process is performed over a predetermined period of time are performed. Thus, the set temperature of the dehumidifier section may be made to at or below the freezing point by the first driving process, and moisture in the air inside the accommodating chamber may be made to temporarily attach to the dehumidifier section as frost and then be melted by the second driving process and be collected as water. <CIT> discloses a power compensation differential scanning calorimeter that uses one absolute temperature measurement, two differential temperature measurements, a differential power measurement, and a five-term heat flow equation to measure the sample heat flow. The calorimeter is calibrated by running two sequential calibration experiments. In a preferred embodiment, the first calibration experiment uses empty sample and reference pans, and the second calibration experiment uses sapphire specimens in the sample and reference holders. In an alternate embodiment, sapphire calibration specimens are used in both the first and second calibration experiments. This document further discloses a method for calculating sample heat flow in a Differential Scanning Calorimeter in which the effect of heat storage in the sample pans and the difference in heating rate between sample and reference are included. Accounting for heat flow associated with the pans and the difference between sample and reference heating rate gives a more accurate sample heat flow measurement and improves resolution, which is the ability to separate closely spaced thermal events in the heat flow result.

<CIT> discloses methods, systems, and products for monitoring the temperature of a high powered computing component. The high powered computing component has a thermal sensor and the high powered computing component in thermal communication with a liquid cooled heatsink. Embodiments include determining, by a thermal monitoring module, a temperature of the thermal sensor; determining, by the thermal monitoring module, a temperature of the heatsink; determining, by the thermal monitoring module, a power delivered to the high powered computing component; and calculating, by the thermal monitoring module, a thermal value in dependence upon the temperature of the thermal sensor, the temperature of the heatsink, and the power delivered to the high powered computing component.

In one embodiment, a method for determining a status of a thermal chamber in a liquid chromatography system comprises: receiving, by a computer system, a first temperature measurement from a first temperature sensor configured to sense the temperature of a heat sink (<NUM>) located in the thermal chamber; receiving, by the computer system, a second temperature measurement from a second temperature sensor configured to sense the temperature of the thermal chamber (<NUM>); receiving, by the computer system, power information related to power utilized by a temperature control engine configured to maintain the temperature of the thermal chamber (<NUM>); analyzing, by one or more processors of the computer system, the first and second temperature measurements and the power information; and determining, by the one or more processors, the status of the thermal chamber (<NUM>) by determining the efficiency of the temperature control engine (<NUM>) or determining whether ice has formed on the heat sink in the thermal chamber.

In another embodiment, a liquid chromatography sample manager comprises: a sample delivery system configured to provide a sample to a liquid chromatography column located downstream from the sample delivery system; a thermal chamber housing the sample delivery system; a temperature control engine configured to control the temperature in the thermal chamber; a heatsink operably connected to the temperature control engine and arranged within the thermal chamber; a first temperature sensor configured to sense the temperature of the heat sink; a second temperature sensor configured to sense the temperature of the thermal chamber; a computer system configured to receive temperature information from each of the first and second temperature sensors and power information related to power utilized by the temperature control engine, the computer system comprising: one or more processors; one or more memory devices coupled to the one or more processors; and one or more computer readable storage devices coupled to the one or more processors, wherein the one or more storage devices contain program code executable by the one or more processors via the one or more memory devices to implement a method for controlling temperature in the thermal chamber, the method comprising: receiving, by the computer system: a first temperature measurement from the first temperature sensor, a second temperature measurement from the second temperature sensor, and by the computer system, power information related to power utilized by the temperature control engine; analyzing, by the one or more processors, the first and second temperature measurements and the power information; and determining, by the one or more processors, a status of the thermal chamber by determining the efficiency of the temperature control engine or determining whether ice has formed on the heatsink in the thermal chamber based on the analysis.

In another embodiment, a liquid chromatography system comprises: a solvent delivery system; the sample manager of the previous embodiment; the liquid chromatography column located downstream from the solvent delivery system and the sample manager; a detector located downstream from the liquid chromatography column.

The present teaching will now be described in more detail with reference to exemplary embodiments thereof as shown in the accompanying drawings. While the present teaching is described in conjunction with various embodiments and examples, it is not intended that the present teaching be limited to such embodiments. On the contrary, the present teaching encompasses various alternatives, modifications and equivalents, as will be appreciated by those of skill in the art. Those of ordinary skill having access to the teaching herein will recognize additional implementations, modifications and embodiments, as well as other fields of use, which are within the scope of the present disclosure as described herein.

<FIG> shows an embodiment of a liquid chromatography system <NUM> for separating a mixture into its constituents. The liquid chromatography system <NUM> includes a solvent delivery system <NUM> in fluidic communication with a sample manager <NUM> (also called an injector or an autosampler) through tubing <NUM>. The sample manager <NUM> is in fluidic communication with a chromatographic column <NUM> and in mechanical communication with a sample organizer <NUM>. The sample organizer <NUM> may be configured to store samples and provide stored samples to the sample manager <NUM> using an automated, robotic, or other mechanical moving process. A detector <NUM> for example, a mass spectrometer, is in fluidic communication with the column <NUM> to receive the elution.

The solvent delivery system <NUM> includes a pumping system <NUM> in fluidic communication with solvent reservoirs <NUM> from which the pumping system <NUM> draws solvents (liquid) through tubing <NUM>. In one embodiment, the pumping system <NUM> is embodied by a low-pressure mixing gradient pumping system having two pumps fluidically connected in series. In the low-pressure gradient pumping system, the mixing of solvents occurs before the pump, and the solvent delivery system <NUM> has a mixer <NUM> in fluidic communication with the solvent reservoirs <NUM> to receive various solvents in metered proportions. This mixing of solvents (mobile phase) composition that varies over time (i.e., the gradient).

The pumping system <NUM> is in fluidic communication with the mixer <NUM> to draw a continuous flow of gradient therefrom for delivery to the sample manager <NUM>. Examples of solvent delivery systems that can be used to implement the solvent delivery system <NUM> include, but are not limited to, the ACQUITY Binary Solvent Manager and the ACQUITY Quaternary Solvent Manager, manufactured by Waters Corp. of Milford, Mass.

The sample manager <NUM> may include an injector valve <NUM> having a sample loop <NUM>. The sample manager <NUM> may operate in one of two states: a load state and an injection state. In the load state, the position of the injector valve <NUM> is such that the sample manager loads the sample <NUM> into the sample loop <NUM>. The sample <NUM> is drawn from a vial contained by a sample vial carrier or any device configured to carry a sample vial such as a well plate, sample vial carrier, or the like. In the injection state, the position of the injector valve <NUM> changes so that the sample manager <NUM> introduces the sample in the sample loop <NUM> into the continuously flowing mobile phase from the solvent delivery system. The mobile phase thus carries the sample into the column <NUM>. In other embodiments, a flow through needle (FTN) may be utilized instead of a Fixed-Loop sample manager. Using an FTN approach, the sample may be pulled into the needle and then the needle may be moved into a seal. The valve may then be switched to make the needle in-line with the solvent delivery system.

The liquid chromatography system <NUM> further includes a data system <NUM> that is in signal communication with the solvent delivery system <NUM>, the sample manager <NUM> and/or the sample organizer <NUM>. The data system <NUM> may include a processor <NUM> and a switch <NUM> (e.g. an Ethernet switch) for handling signal communication between the solvent delivery system <NUM>, the sample manager <NUM>, and the sample organizer <NUM>, and otherwise controlling these components of the liquid chromatography system <NUM>, as described herein. In other embodiments, the data system <NUM> may further control various other components of the system, such as the detector <NUM>, etc. Signal communication among the various systems and instruments can be electrical or optical, using wireless or wired transmission. A host computing system <NUM> is in communication with the data system <NUM> by which a technician can download various parameters and profiles (e.g., an intake velocity profile) to the data system <NUM>. The data system <NUM> may be a single data system or a plurality of data systems controlling the various components of the liquid chromatography system <NUM>. The data system <NUM> may be an external system to each of the various other components of the liquid chromatography system <NUM>. Alternatively, one or more data systems <NUM> may be located in one or more of each of the other components of the liquid chromatography system <NUM>. The data system <NUM> may be configured to control the temperature within the operating compartments of the sample manager <NUM> and the sample organizer <NUM>, as described herein below. Further, the data system <NUM> may be configured to predict the status of the operating compartments of the sample manager <NUM>, such as by predicting when a heatsink in the operating compartment has ice and is needing defrost, or such as by predicting when a temperature controlling engine that is maintaining the temperature of the operating compartment is likely to fail.

<FIG> shows a perspective view of the liquid chromatography system <NUM> including the sample manager <NUM>, the sample organizer <NUM>, the detector <NUM>, the chromatographic column <NUM>, the solvent delivery system <NUM>, and the solvents <NUM>. Each of the sample manager <NUM>, the sample organizer <NUM>, the detector <NUM>, the chromatographic column <NUM>, the solvent delivery system <NUM> may include a housing or body within which the various features may be housed, such as the data system <NUM>, the sample loop <NUM> and injector valve <NUM>, the pumping system <NUM>, the mixer <NUM> and the tubing <NUM>. The various components <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> may be interconnected with fluidic tubes and in signal communication to the data system <NUM> of the system. The liquid chromatography system <NUM> is shown with the solvent delivery system <NUM>, sample manager <NUM>, chromatographic column <NUM>, detector <NUM> and a tray for holding the solvents <NUM> stacked together and positioned adjacent, proximate or next to the sample organizer <NUM>. The sample manager <NUM> and the sample organizer <NUM> may be connected to each other via an opening in each of the sample manager <NUM> and an opening in the sample organizer <NUM>, so that samples can be transferred there through between the sample manager <NUM> and the sample organizer <NUM>.

The sample organizer <NUM> may include a hinged door and includes an inner storage chamber or thermal chamber which may include a plurality of sample organizer shelves disposed or movably mounted within the inner storage chamber. The plurality of shelves may be located at a front of the sample organizer <NUM> proximate the hinged door. The plurality of sample organizer shelves may be movable to selectively align the plurality of sample organizer shelves within the sample manager <NUM> and a transfer system may be provided between the sample manager <NUM> and the sample organizer <NUM> that is configured to transfer samples between the sample manager <NUM> and the sample organizer <NUM>. The sample organizer <NUM> and the sample manager <NUM> may be configured to keep inner storage chamber in a temperature regulated state, as described herein below.

<FIG> depicts a schematic view of a liquid chromatography thermal system <NUM>, such as the sample manager <NUM> or the sample organizer <NUM>, for example including the data system <NUM> of <FIG>, in accordance with one embodiment. The liquid chromatography thermal system <NUM> may be a thermoelectric cooling system, Peltier device, Peltier heat pump, or solid state refrigerator. The liquid chromatography thermal system <NUM> may include a heat sink temperature sensor <NUM> configured to sense the temperature of a heat sink <NUM>, a chamber temperature sensor <NUM> configured to sense the temperature of a thermal chamber <NUM>, an ambient temperature sensor <NUM>, and an engine controller <NUM> configured to provide an output that indicates, corresponds, monitors or otherwise provides the power-level of a thermal engine <NUM>. The sensors <NUM>, <NUM>, <NUM>, and the engine controller <NUM> are shown communicatively coupled to a computer system <NUM>. This connection may either be direct or over a network (wired or wireless).

In other embodiments, additional sensors besides the sensors <NUM>, <NUM>, <NUM> may be employed. For example, contemplated embodiments include two separate heatsink temperature sensors, described in more detail hereinbelow with respect to the method of <FIG>. These embodiments may include a first heat sink temperature sensor located on a first side of a heat sink, and a second heat sink temperature sensor located on a second side of the heat sink that is opposite the first side. The first side of the heat sink may be an intake side and the second side may be an exhaust side. The first heat sink temperature sensor may be located on a compartment side of the heat sink while the second heat sink temperature sensor may be located outside of the compartment on an exhaust side. The first and second heat sink temperatures may be configured to provide temperature information to the computer system <NUM> that allows for the computer system to analyze the received information and predict detect engine failure, as described hereinbelow and shown in <FIG>. In embodiments configured to utilize two heat sink temperature sensors to detect engine failure, there may not be a need for other temperature sensors, such as the chamber temperature sensor <NUM> and the ambient temperature sensor <NUM>. However, these additional temperature sensors <NUM>, <NUM> may be utilized in a combined system that may predict both engine failure and detect frost on the heat sink. Various embodiments are contemplated that include any combination of the temperature sensors described herein.

The engine controller <NUM> may include one or more proportional integral derivative controllers (PID controller). The PID controller may provide an output to the thermal engine <NUM> to control engine power level. The PID controller may further provide an output to the computer system <NUM> that may be utilized to calculate engine power. The PID controller may be an open loop control that is configured to calculate how the thermal engine <NUM> is driven and further provides information to the computer system <NUM> for the performance of the calculations disclosed herein. The engine controller <NUM> and/or the PID controller may further include a pulse-width modulation control to limit the thermal engine <NUM> as necessary. In still other embodiments, the engine controller <NUM> may include any form of engine power sensor that may be utilized by the liquid chromatography system <NUM> in order to provide engine power information to the computer system <NUM> necessary to perform the calculations described herein.

As described above, the computer system <NUM> may be one or more data systems that are located external to either or both of the sample manager <NUM> and sample organizer <NUM>. The computer system <NUM> may alternatively be a system that is self-contained within a thermal chamber device such as the sample manager <NUM> and sample organizer <NUM>.

The thermal chamber <NUM> may be a thermal chamber located within the sample manager <NUM> and/or the sample organizer <NUM>. In one embodiment, the thermal chamber <NUM> may be a chamber that comprises the collective chambers within both of the sample manager <NUM> and the sample organizer <NUM>. The thermal chamber <NUM> may be any chamber that is an element of a liquid chromatography system.

The engine <NUM> may be a device configured to provide the power necessary to cool the thermal chamber <NUM> with the heat sink. Hereinafter, an "engine" may refer to any cooling system, engine, Peltier cooler, thermoelectric cooler, heat pump, or other power outputting device for creating a temperature difference by transferring heat between two electrical junctions. The engine <NUM> may be configured to apply a voltage across joined conductors to create an electrical current. The engine <NUM> may be connected to the computer system <NUM> such that the computer system is configured to sense or otherwise monitor the power being output by the engine <NUM>. The engine <NUM> may be at least partially located within the thermal chamber <NUM> in one embodiment such that the cool side having the heat sink <NUM> may be located within the chamber <NUM> and the warm conductor may be exposed to the ambient environment outside the thermal chamber <NUM>.

The heatsink <NUM> may be located within the thermal chamber <NUM>. The heat sink <NUM> may be one or more passive heat exchangers that are configured to absorb heat from the thermal chamber <NUM>. The heat sink <NUM> may be a cooling plate. The heat sink <NUM> may be made from an aluminum alloy, copper, or other metallic material. The heat sink <NUM> may be a flat plate or may include fins of various arrangements, or other fin-like structure, to facilitate heat transfer.

Each of the heat sink temperature sensors <NUM>, the chamber temperature sensors <NUM> and the ambient temperature sensor <NUM> may be, for example, an electrical temperature sensing device such as a thermocouple, thermistor, resistance thermometer, or silicon bandgap temperature sensor. The temperature sensors <NUM>, <NUM>, <NUM> may each be a single temperature sensor, in one embodiment. Alternatively, the temperature sensors <NUM>, <NUM>, <NUM> may each be a plurality of temperature sensors, in other embodiments, that combine to sense the temperature of one or more given elements. For example, the heat sink temperature sensor <NUM> may comprise one or more temperature sensors configured to sense the temperature of one or more heat sinks in the thermal system <NUM>. Similarly, the chamber temperature sensor <NUM> may comprise one or more temperature sensors configured to sense the temperature of the chamber <NUM> that is being temperature controlled by the engine <NUM> and the heat sink <NUM>. The ambient temperature sensor <NUM> may comprise one or more temperature sensors configured to sense the temperature of the ambient environment located outside the thermal chamber <NUM>, the sample manager <NUM> and/or the sample organizer <NUM>.

Embodiments of the computer system <NUM> may include a module system <NUM> including a receiving module <NUM>, an analyzing module <NUM>, a determining module <NUM>, and an engine control module <NUM>. A "module" may refer to a hardware based module, software based module or a module may be a combination of hardware and software. Embodiments of hardware based modules may include self-contained components such as chipsets, specialized circuitry and one or more memory devices, while a software-based module may be part of a program code or linked to the program code containing specific programmed instructions, which may be loaded in the memory device of the computer system <NUM>. A module (whether hardware, software, or a combination thereof) may be designed to implement or execute one or more particular functions or routines.

Embodiments of the receiving module <NUM> may include one or more components of hardware and/or software program code for receiving temperature measurements which may include information, data, and/or other communications related to sensed temperatures coming from each of the heatsink temperature sensor(s) <NUM>, the chamber temperature sensor(s) <NUM> and the ambient temperature sensor(s) <NUM>. The receiving module <NUM> may further be configured to receive the power level information and/or measurements, which may include information, data and/or other communications related to or otherwise quantifying the power percentage of the engine <NUM>. For example, the power information may be an amount of power being consumed by the engine <NUM> over time. The power information may further relate to the voltage and/or current being output by the engine <NUM> into the thermoelectric cooling system and the heat sink <NUM>. The receiving module <NUM> may be configured to receive this power and temperature measurement information that is being provided constantly or continuously over time. In some embodiments, the receiving module <NUM> may be configured to receive this power and temperature measurement information at periodic intervals as the sensors <NUM>, <NUM>, <NUM> and engine controller <NUM> sense respective conditions at the periodic intervals. The information and data received by the receiving modules <NUM>, <NUM>, <NUM> and engine controller <NUM> may be stored by the receiving module <NUM> in the data repository <NUM>, in some embodiments, for use by the other modules <NUM>, <NUM>, <NUM> in the processes described herein. In other embodiments, the information received may be immediately processed by the processor <NUM> and may be stored in the memory <NUM> during such processing.

Embodiments of the analyzing module <NUM> may include one or more components of hardware and/or software program code configured to analyze the temperature measurements provided by the heatsink temperature sensor(s) <NUM>, the chamber temperature sensor(s) <NUM> and the ambient temperature sensor(s) <NUM>, along with the engine power level information or measurements provided by the engine controller <NUM>. The analyzing module <NUM> may include processing this information with one or more algorithms for analyzing the efficiency of the thermal engine <NUM> from the various temperature information received along with the power output information received. The analyzing module <NUM> may be configured to continually characterize the thermal efficiency of the engine <NUM>.

Referring still to <FIG>, embodiments of the computer system <NUM> may further include the determining module <NUM>. Embodiments of the determining module <NUM> may refer to configurations of hardware, software program code, or combinations of hardware and software programs, capable of determining the efficiency of the engine <NUM> or otherwise characterizing the engine <NUM> to determine when ice has formed on the heatsink <NUM>. The determining module <NUM> may thus utilize the analysis performed by the analyzing module <NUM> of the information received by the receiving module <NUM> from the sensors <NUM>, <NUM>, <NUM> and engine controller <NUM> to determine whether ice has formed on the heat sink <NUM>. This determining may be continuous, in some embodiments. In others, the determining may be performed at periodic intervals using measurements taken from the sensors <NUM>, <NUM>, <NUM> and engine controller <NUM> at periodic intervals. In some embodiments, the determining may be based on the information provided by the engine controller <NUM>, the heatsink temperature sensor <NUM> and the chamber temperature sensor <NUM>. In other embodiments, this information may further include the ambient temperature sensor <NUM> that is located outside the thermal chamber <NUM>.

The determining module <NUM> may further be configured to determine a start temperature of the thermal compartment <NUM> for the purposes of running a defrost algorithm. The determining module <NUM> may further be configured to determine a start temperature of the heat sink <NUM> for the purposes of running a defrost algorithm. The determining module <NUM> may further be configured to determine whether or not a change in temperature between the start temperature of the compartment <NUM> and the current temperature of the compartment <NUM> is greater than a predetermined threshold temperature change.

Embodiments of the determining module <NUM> may be configured to analyze and determine or predict a status within the thermal compartment <NUM>. For example, as described above, the determining module <NUM> may be configured to determine a frost status on a heat sink <NUM> within the thermal compartment <NUM>. In other embodiments, the determining module <NUM> may be configured to predict or otherwise determine that an engine <NUM> of the thermal system <NUM> is currently failing, or likely to fail. For example, the determining module <NUM> may be configured to receive temperature information from each of two temperature sensors located on opposite sides of a heat sink, along with power information from an engine power sensor. The determining module <NUM> may utilize this information to detect or otherwise determine that an engine is not working efficiently to maintain the temperature of the heat sink and utilize one or more algorithms that correlate this determination to the status of an engine. To determine the status of the engine, the determining module <NUM> may be configured to characterize the engine by measuring the change in temperature between the two side of the heat sink and relate it to the power level of the engine. Then over the life of the instrument, the determining module <NUM> may be configured to monitor the change in temperature and power level and correlate it to a baseline efficiency known for the system. If the change in temperature begins to deviate significantly from the instrument's characterization level, the determination module <NUM> may be configured to flag that the user the efficiency has changed. The determining module <NUM> may be configured to then provide a warning indicator of engine failure detection to a user. In some embodiments, the determining module <NUM> may be configured to provide a user interface with an engine life or engine usage scale. For example, the determining module <NUM> may be configured to provide a percentage scale from <NUM> - <NUM>% that represents the life of the engine used or remaining.

With continued reference to <FIG>, embodiments of the computer system <NUM> may include the engine control module <NUM>. Embodiments of the engine control module <NUM> may include one or more components of hardware and/or software program code for controlling the engine <NUM> of the liquid chromatography thermal system <NUM>. The engine control module <NUM> may be configured to operate a defrost process on the heat sink <NUM> when the determining module <NUM> has determined that ice has formed on the heat sink <NUM>. The engine control module <NUM> may be configured to increase a temperature setpoint of the heatsink <NUM> by a predetermined number of degrees and controlling the engine <NUM> by reducing and/or eliminating the power generated by the engine <NUM> to cool the heatsink <NUM>, in order to thereby achieve this higher temperature setpoint of the heatsink <NUM>. The analyzing, determining and engine control modules <NUM>, <NUM>, <NUM> may be configured to wait a predetermined period of time after the setpoint of the heatsink has been increased to the temperature of the compartment <NUM> before checking to see if the compartment temperature has increased. If it is determined that the temperature of the compartment <NUM> has not increased, the modules <NUM>, <NUM>, <NUM> may be configured to wait another predetermined time period before once again checking to see whether the compartment temperature has increased by the threshold amount. Once it is determined by the determining module <NUM> that the compartment temperature has increased past a threshold amount, the engine control module <NUM> may be configured to increase power to the engine <NUM> back to the normal operating mode of the engine. Referring still to <FIG>, embodiments of the computer system <NUM> may be equipped with a memory device <NUM> which may store the location information, information related to the information and datasets being processed using decision tree analysis as described herein, and a processor <NUM> for implementing the tasks associated with the liquid chromatography thermal system <NUM>.

Referring now to <FIG>, a flow chart of a method for determining a status of a thermal chamber in a liquid chromatography thermal system <NUM>, such as the liquid chromatography thermal system <NUM> of <FIG>, is shown in accordance with one embodiment. The method <NUM> may include a step <NUM> of monitoring temperature of a heat sink such as the heat sink <NUM>, a thermal chamber such as the thermal chamber <NUM> and/or an ambient temperature outside the thermal chamber, such as by temperature sensors such as the sensors <NUM>, <NUM>, <NUM>. The method may further include a step <NUM> of sending these temperature measurements by the sensors <NUM>, <NUM>, <NUM> to the computer system <NUM>, for example. The method <NUM> may include another step <NUM> of monitoring the power use of an engine, such as the engine <NUM>, by a power sensing device such as the engine controller <NUM> or other engine diagnostic means. The method <NUM> may include a step <NUM> of sending power information to the computer system. The method steps <NUM> and <NUM> may be occurring simultaneous to the method steps <NUM>, <NUM> in one embodiment.

The method <NUM> may include a step <NUM> of receiving the temperature measurements and the power information generated or taken by the sensors from the steps <NUM>, <NUM>, <NUM>, <NUM>, by the computer system, by for example the receiving module <NUM>. The method <NUM> may include a next step <NUM> of analyzing, by for example the analyzing module <NUM> of the computer system, the temperature measurements, information, data or the like that is received. The method <NUM> may include a next step <NUM> of determining a status, such as whether ice has formed on a heat sink of the system, such as the heat sink <NUM>. The step <NUM> may be conducted by a module such as the determining module <NUM>. If step <NUM> determines that ice has not formed on the heat sink, the method <NUM> may include returning to steps <NUM>, <NUM> of the method <NUM>. If step <NUM> determines that ice has formed on the heat sink, the method <NUM> may include one or more steps <NUM> of running a defrost process in order to defrost the heat sink.

<FIG> depicts an expanded form of step <NUM> of the method <NUM>, which includes the steps for a defrost method for defrosting ice from a heat sink in a liquid chromatography thermal system, such as the liquid chromatography thermal system <NUM> of <FIG>, in accordance with one embodiment. A first step in the defrost method <NUM> may include a step <NUM> of triggering a defrost cycle, which may occur if it has been determined, in method <NUM>, that ice has formed on the heat sink. Upon triggering the defrost method at step <NUM>, the method <NUM> may include a step <NUM> of measuring and providing a compartment start temperature, such as the temperature of the compartment <NUM> at the start of the defrost method <NUM>. This may be provided to a memory storage location, such as the memory <NUM> of the data repository <NUM>. The defrost method <NUM> may also include a step <NUM> of changing a setpoint of a heatsink, such as the heatsink <NUM>, to a higher temperature. The higher temperature setpoint may be a temperature that is above the freezing point of water, such as above <NUM>. In one embodiment, the temperature setpoint may be between <NUM> and <NUM>. In another embodiment, the temperature setpoint may be at or around <NUM>. The defrost method <NUM> may further include reducing the power output by the engine <NUM> by the engine control module <NUM> to increase the temperature of the heat sink <NUM> to increase to slowly increase the temperature of the heatsink <NUM> and/or remove the ice thereon.

The defrost method <NUM> may include a next step <NUM> of waiting a predetermined amount of time with the higher heatsink temperature threshold. The predetermined amount of time may be a number of minutes, for example between <NUM> - <NUM> minutes. In other embodiments, the predetermined amount of time may be <NUM> - <NUM> minutes. In other embodiments, the predetermined amount of time may be at or about <NUM> minutes. Still further embodiments, a predetermined number of seconds may be waited such as <NUM> seconds, <NUM> seconds, <NUM> seconds or the like. The predetermined amount of time may be dependent on the current compartment start temperature, in one embodiment. For example, a lower compartment start temperature may have a longer predetermined wait time. The defrost method <NUM> may include a next step <NUM> of determining the current compartment temperature, by measuring the temperature of the compartment from the chamber temperature sensor <NUM> and providing the measurement to the computer system. The defrost method <NUM> may further include determining whether the change in temperature between the compartment start temperature and the current compartment temperature is greater than a threshold temperature change. The threshold temperature change may be, for example, between. <NUM> and <NUM>. In one embodiment, the threshold temperature change may be a function of the initial heatsink setpoint temperature. For example, if the initial heatsink setpoint temperature is set to a higher setpoint, threshold temperature change may be larger.

In one embodiment, the defrost cycle begins and the temperature of the heatsink may be set to <NUM>. The threshold temperature change may be set to. The initial chamber temperature may be measured at <NUM>. After two minutes waiting from the initiation of the defrost method, the temperature in the chamber is measured again, and has risen to <NUM>. The cycle continues for another two minutes, after which point the measurement of the chamber is taken at <NUM>. Here the temperature has now increased greater than the. <NUM> defined by the threshold temperature change. Thus, the defrost cycle may end at an end step <NUM>. The end step <NUM> may end the defrost method <NUM> but revert back to the method <NUM> that includes monitoring the temperatures to determine if the heat sink becomes frozen once again. If the temperature instead had again not increased the full. <NUM>, the defrost method <NUM> may revert back to the waiting step <NUM> for waiting another two minutes.

<FIG> depicts a first exemplary graph plotting temperatures over a first time period taken by three different sensors in a liquid chromatography thermal system, such as the liquid chromatography system <NUM> of <FIG>, in accordance with one embodiment. The graph is shown including an ambient temperature plot <NUM>, a compartment temperature plot <NUM>, and a heatsink temperature plot <NUM>. The graphs shown in <FIG> may be provided on a screen of a user interface, such as that of the host computing system <NUM>, during operation of the liquid chromatography thermal system. The graphs 6A - 6C shows exemplary measurements taken from sensors <NUM>, <NUM>, <NUM> and engine controller <NUM> in an exemplary thermal system. The exemplary graph corresponds to a compartment temperature set to <NUM> with an ambient condition held at <NUM>.

Beginning at <NUM> minutes, the sensors begin to provide the temperature information to the system, or the system becomes initiated. Prior to at or about the <NUM> minute mark, the lines remain flat because the system may be off, not collecting data, or otherwise not performing the method <NUM> described hereinabove. Alternatively, the system may be very steady and at equilibrium during the time prior to the <NUM> minutes mark. At or about the <NUM> minutes mark, system may be turned on. The graph displays the ambient temperature plot <NUM> remaining relatively consistent over time at roughly <NUM> - <NUM>.

However, starting at or about the <NUM> minutes mark, the chamber temperature begins to increase consistently, from at or about <NUM> to at or about <NUM>, as shown by the chamber temperature plot <NUM>. The heat sink temperature plot <NUM> also remains relatively consistent at -<NUM> throughout the entirety of the graph.

<FIG> depicts a second exemplary graph plotting engine power percentage over the first time period in a liquid chromatography thermal system, such as the liquid chromatography thermal system <NUM> of <FIG>, in accordance with one embodiment. The graph shows an engine power percentage plot <NUM> over the same period of time as the graph of <FIG>. The engine power percentage plot <NUM> begins to decrease at or about the <NUM> minutes mark, at a similar point in time as the chamber temperature begins to increase. Here, the engine power percentage plot <NUM> continues to drop over time until at or about the <NUM> minute mark. The engine power percentage plot <NUM> is shown beginning at or about <NUM>%, but then drops to <NUM>% at or about the <NUM> minute mark.

<FIG> depicts a third exemplary graph of engine characterization over the first time period in a liquid chromatography thermal system, such as the liquid chromatography thermal system <NUM> of <FIG>, in accordance with one embodiment. The graph of <FIG> shows an engine characterization plot <NUM> over time, along with a constant characterization limit <NUM>. The characterization limit of the engine may be defined as calculated heat transfer rate between the compartment and exhaust sides of the engine during steady state operation. The equation utilized to calculate the characterization limit may be: <MAT> where HS, Amb, and Cmpt are the temperature readings from the heatsink, ambient and compartment temperature sensors <NUM>, <NUM>, <NUM>, respectively, Power is the power level the engine is running found using power information provided by the engine controller <NUM>, and A and B are coefficients that are determined by the material properties of the Peltier devices and heatsinks used. The temperature information provided by the heatsink, ambient and compartment temperature sensors <NUM>, <NUM>, <NUM> may be filtered to avoid false triggers due to noise.

The engine characterization plot <NUM> may be a characterization of the efficiency of the engine, how efficiently heat can be transferred between the compartment and exhaust heatsinks, determined by the temperature and power information provided to the system by the sensors <NUM>, <NUM>, <NUM> and engine controller <NUM>. As shown, the engine characterization plot <NUM> actually begins to drop at or about the <NUM> point. As shown, a threshold characterization limit <NUM> may exist of at or about <NUM>. The engine characterization plot <NUM> is shown dropping below this characterization limit <NUM> at or about the <NUM> minute mark. This may immediately trigger the defrost method <NUM>, as described hereinabove.

In another embodiment, <FIG> depicts a first exemplary graph plotting temperatures over a second time period taken by three different sensors in a different liquid chromatography thermal system than that shown in <FIG>, in accordance with one embodiment. The graph is shown including an ambient temperature plot <NUM>, a compartment temperature plot <NUM>, and a heatsink temperature plot <NUM>. The graphs 7A - 7C shows exemplary measurements taken from sensors <NUM>, <NUM>, <NUM> and engine controller <NUM> in an exemplary thermal system. The exemplary graph corresponds to a compartment temperature set to <NUM> with an ambient condition held at <NUM>.

Beginning at <NUM> minutes, the sensors begin to provide the temperature information to the system, or the system becomes initiated. Prior to at or about the <NUM> minutes mark, the system is shown at a steady and equilibrium state. The graph displays the ambient temperature plot <NUM> remaining relatively consistent over time at roughly <NUM>. However, starting at or about the <NUM> minute mark, the chamber temperature begins to increase consistently, from at or about <NUM> to at or about <NUM>, as shown by the chamber temperature plot <NUM>. The heat sink temperature plot <NUM> also remains relatively consistent at -<NUM> throughout the entirety of the graph.

<FIG> depicts a second exemplary graph plotting engine power percentage over the second time period in a liquid chromatography thermal system, such as the liquid chromatography thermal system <NUM> of <FIG>, in accordance with one embodiment. The graph shows an engine power percentage plot <NUM> over the same period of time as the graph of <FIG>. The engine power percentage plot <NUM> begins to spike and then immediately decrease at or about the <NUM> minute mark, at a similar point in time as the chamber temperature begins to increase. Here, the engine power percentage plot <NUM> continues to drop over time until at or about the <NUM> minute mark. The engine power percentage plot <NUM> is shown beginning at or about <NUM>%, but then drops to below <NUM>% at or about the <NUM> minute mark.

<FIG> depicts a third exemplary graph of engine characterization over the second time period in a liquid chromatography thermal system, such as the liquid chromatography thermal system <NUM> of <FIG>, in accordance with one embodiment. The graph of <FIG> shows an engine characterization plot <NUM> over time, along with a constant characterization limit <NUM>. The engine characterization plot <NUM> may be a characterization of the efficiency of the engine, determined by the temperature and power information provided to the system by the sensors <NUM>, <NUM>, <NUM> and engine controller <NUM>. As shown, the engine characterization plot <NUM> actually begins to drop at or about the <NUM> minute point. As shown, a threshold characterization limit <NUM> may exist of at or about <NUM> in this embodiment. The engine characterization plot <NUM> is shown dropping below this characterization limit <NUM> at or about the <NUM> minute mark. This may immediately trigger the defrost method <NUM>, as described hereinabove.

<FIG> depicts a flow chart of a method <NUM> of predicting failure of an engine in a liquid chromatography thermal system, such as the liquid chromatography thermal system of <FIG>, in accordance with one embodiment. The method <NUM> includes a step <NUM> of monitoring a temperature of a first side of a heat sink, the first side located in the compartment of the thermal system, along with a step <NUM> of monitoring a temperature of a second side of the heat sink, the second side being an exhaust side of the heat sink that may not be in the compartment of the thermal system. The method <NUM> further includes a step <NUM> of monitoring power usage of the engine. A step <NUM> includes sending the temperature measurements from steps <NUM> and <NUM> to a computer system, such as the computer system <NUM>. A step <NUM> includes sending the power usage of the engine information or data to the computer system as well. At a step <NUM>, the computer system receives the temperature and power measurements. At a step <NUM>, a baseline system efficiency is calculated or determined or otherwise is known at system startup. At a step <NUM>, the computer system analyzes the temperature and power measurements and compares these measurements to the known baseline system efficiency from step <NUM>. At a step <NUM>, the computer system determines whether heating and cooling effectiveness has decreased based on the analysis of the temperature and power measurements compared to the baseline system efficiency. At a step <NUM>, the computer system <NUM> is configured to alert a user or field service engineer (FSE). This alert may be provided on, for example, a user interface of the chromatography system. <FIG> depicts a block diagram of a computer system for determining a status of a thermal chamber in a liquid chromatography thermal system <NUM> of <FIG>, capable of implementing methods for determining a status of a thermal chamber in a liquid chromatography thermal system of <FIG>, <FIG> and <FIG>, in accordance with embodiments of the present invention. The computer system <NUM> may generally comprise a processor <NUM>, an input device <NUM> coupled to the processor <NUM>, an output device <NUM> coupled to the processor <NUM>, and memory devices <NUM> and <NUM> each coupled to the processor <NUM>. The input device <NUM>, output device <NUM> and memory devices <NUM>, <NUM> may each be coupled to the processor <NUM> via a bus. Processor <NUM> may perform computations and control the functions of computer <NUM>, including executing instructions included in the computer code <NUM> for the tools and programs capable of implementing a method for determining a status of a thermal chamber in a liquid chromatography thermal system, in the manner prescribed by the embodiments of <FIG>,<FIG> and <FIG>, using the system for determining a status of a thermal chamber in a liquid chromatography thermal system of <FIG>, wherein the instructions of the computer code <NUM> may be executed by processor <NUM> via memory device <NUM>. The computer code <NUM> may include software or program instructions that may implement one or more algorithms for implementing the methods for determining a status of a thermal chamber in a liquid chromatography thermal system, as described in detail above. The processor <NUM> executes the computer code <NUM>. Processor <NUM> may include a single processing unit, or may be distributed across one or more processing units in one or more locations (e.g., on a client and server).

The memory device <NUM> may include input data <NUM>. The input data <NUM> includes any inputs required by the computer code <NUM>. The output device <NUM> displays output from the computer code <NUM>. Either or both memory devices <NUM> and <NUM> may be used as a computer usable storage medium (or program storage device) having a computer readable program embodied therein and/or having other data stored therein, wherein the computer readable program comprises the computer code <NUM>. Generally, a computer program product (or, alternatively, an article of manufacture) of the computer system <NUM> may comprise said computer usable storage medium (or said program storage device).

Memory devices <NUM>, <NUM> include any known computer readable storage medium, including those described in detail below. In one embodiment, cache memory elements of memory devices <NUM>, <NUM> may provide temporary storage of at least some program code (e.g., computer code <NUM>) in order to reduce the number of times code must be retrieved from bulk storage while instructions of the computer code <NUM> are executed. Moreover, similar to processor <NUM>, memory devices <NUM>, <NUM> may reside at a single physical location, including one or more types of data storage, or be distributed across a plurality of physical systems in various forms. Further, memory devices <NUM>, <NUM> can include data distributed across, for example, a local area network (LAN) or a wide area network (WAN). Further, memory devices <NUM>, <NUM> may include an operating system (not shown) and may include other systems not shown in <FIG>. In some embodiments, the computer system <NUM> may further be coupled to an Input/output (I/O) interface and a computer data storage unit. An I/O interface may include any system for exchanging information to or from an input device <NUM> or output device <NUM>. The input device <NUM> may be, inter alia, a keyboard, a mouse, etc. The output device <NUM> may be, inter alia, a printer, a plotter, a display device (such as a computer screen), a magnetic tape, a removable hard disk, a floppy disk, etc. The memory devices <NUM> and <NUM> may be, inter alia, a hard disk, a floppy disk, a magnetic tape, an optical storage such as a compact disc (CD) or a digital video disc (DVD), a dynamic random access memory (DRAM), a read-only memory (ROM), etc. The bus may provide a communication link between each of the components in computer <NUM>, and may include any type of transmission link, including electrical, optical, wireless, etc..

An I/O interface may allow computer system <NUM> to store information (e.g., data or program instructions such as program code <NUM>) on and retrieve the information from computer data storage unit (not shown). Computer data storage unit includes a known computer-readable storage medium, which is described below. In one embodiment, computer data storage unit may be a non-volatile data storage device, such as a magnetic disk drive (i.e., hard disk drive) or an optical disc drive (e.g., a CD-ROM drive which receives a CD-ROM disk). In other embodiments, the data storage unit may include a knowledge base or data repository <NUM> as shown in <FIG>.

As will be appreciated by one skilled in the art, in a first embodiment, the present invention may be a method; in a second embodiment, the present invention may be a system; and in a third embodiment, the present invention may be a computer program product. Any of the components of the embodiments of the present invention can be deployed, managed, serviced, etc. by a service provider that offers to deploy or integrate computing infrastructure with respect to systems and methods for determining a status of a thermal chamber in a liquid chromatography thermal system. Thus, an embodiment of the present invention discloses a process for supporting computer infrastructure, where the process includes providing at least one support service for at least one of integrating, hosting, maintaining and deploying computer-readable code (e.g., program code <NUM>) in a computer system (e.g., computer <NUM>) including one or more processor(s) <NUM>, wherein the processor(s) carry out instructions contained in the computer code <NUM> causing the computer system for determining a status of a thermal chamber in a liquid chromatography thermal system. Another embodiment discloses a process for supporting computer infrastructure, where the process includes integrating computer-readable program code into a computer system including a processor.

The step of integrating includes storing the program code in a computer-readable storage device of the computer system through use of the processor. The program code, upon being executed by the processor, implements a method for determining a status of a thermal chamber in a liquid chromatography thermal system. Thus, the present invention discloses a process for supporting, deploying and/or integrating computer infrastructure, integrating, hosting, maintaining, and deploying computer-readable code into the computer system <NUM>, wherein the code in combination with the computer system <NUM> is capable of performing a method for determining a status of a thermal chamber in a liquid chromatography thermal system.

A computer program product of the present invention comprises one or more computer readable hardware storage devices having computer readable program code stored therein, said program code containing instructions executable by one or more processors of a computer system to implement the methods of the present invention.

A computer system of the present invention comprises one or more processors, one or more memories, and one or more computer readable hardware storage devices, said one or more hardware storage devices containing program code executable by the one or more processors via the one or more memories to implement the methods of the present invention.

It is to be understood that although this disclosure includes the following detailed description on cloud computing, implementation of the teachings recited herein are not limited to a cloud computing environment.

Measured service: cloud systems automatically control and optimize resource use by leveraging a metering capability at some level of abstraction appropriate to the type of service (e.g., storage, processing, bandwidth, and active user accounts). Resource usage can be monitored, controlled, and reported, providing transparency for both the provider and consumer of the utilized service.

Infrastructure as a Service (IaaS): the capability provided to the consumer is to provision processing, storage, networks, and other fundamental computing resources where the consumer is able to deploy and run arbitrary software, which can include operating systems and applications. The consumer does not manage or control the underlying cloud infrastructure but has control over operating systems, storage, deployed applications, and possibly limited control of select networking components (e.g., host firewalls).

As shown, cloud computing environment <NUM> includes one or more cloud computing nodes <NUM> with which local computing devices used by cloud consumers, such as, for example, personal digital assistant (PDA) or cellular telephone 54A, desktop computer 54B, laptop computer 54C, and/or liquid chromatography system 54N may communicate. It is understood that the types of computing devices 54A, 54B, 54C and 54N shown in <FIG> are intended to be illustrative only and that computing nodes <NUM> and cloud computing environment <NUM> can communicate with any type of computerized device over any type of network and/or network addressable connection (e.g., using a web browser).

The present invention may also be implemented, wholly or in part, in a cloud computing environment. For example, the computer system <NUM> and some or all of the various modules <NUM>, <NUM>, <NUM>, <NUM> and functionality performed thereby, along with the data repository <NUM> and processor(s) <NUM> may be located on an off-site hosted cloud based system that may be connected to by the data system <NUM> or the host computing system <NUM>. Whatever, the embodiment, thus, the cloud based processing may provide instructions to the engine <NUM> based on an off-site analysis and determining based on the information provided by the various diagnostic sensors <NUM>, <NUM>, <NUM> and engine controller113 described herein above. Thus, with further reference to <FIG>, the cellular telephone 54A, the desktop computer 54B, the laptop computer 54C may each be exemplary forms of the host computing system <NUM> that is configured to provide user inputs and monitoring capabilities for the above-described system for detecting or preventing ice in a liquid chromatography thermal system <NUM>. Alternatively, the desktop computer 54A shown may be representative of a cloud based computer system <NUM> for providing calculations and controlling, remotely, the liquid chromatography system <NUM>. As shown in <FIG>, elements of, or a computer system of, the liquid chromatography system 54N may further be connected to the cloud as well to accommodate the methods for detecting or preventing ice in a liquid chromatography thermal system described herein.

Referring now to <FIG>, a set of functional abstraction layers provided by cloud computing environment <NUM> (see <FIG>) is shown. As depicted, the following layers and corresponding functions are provided:
Hardware and software layer <NUM> includes hardware and software components.

Workloads layer <NUM> provides examples of functionality for which the cloud computing environment may be utilized. Examples of workloads and functions which may be provided from this layer include: mapping and navigation <NUM>; software development and lifecycle management <NUM>; virtual classroom education delivery <NUM>; data analytics processing <NUM>; transaction processing <NUM>; and processes for detecting and preventing ice prevention <NUM>.

While embodiments of the present invention have been described herein for purposes of illustration, many modifications and changes will become apparent to those skilled in the art. Accordingly, the appended claims are intended to encompass all such modifications and changes as fall within the scope of this invention.

Claim 1:
A method for determining a status of a thermal chamber (<NUM>) in a liquid chromatography system, the method comprising:
receiving, by a computer system (<NUM>), a first temperature measurement from a first temperature sensor (<NUM>, <NUM>, <NUM>) configured to sense the temperature of a heat sink (<NUM>) located in the thermal chamber (<NUM>);
receiving, by the computer system (<NUM>), a second temperature measurement from a second temperature sensor (<NUM>, <NUM>, <NUM>) configured to sense the temperature of the thermal chamber (<NUM>);
receiving, by the computer system (<NUM>), power information related to power utilized by a temperature control engine (<NUM>) configured to maintain the temperature of the thermal chamber (<NUM>);
analyzing, by one or more processors (<NUM>) of the computer system (<NUM>), the first and second temperature measurements and the power information; and
determining, by the one or more processors (<NUM>), the status of the thermal chamber (<NUM>) by determining the efficiency of the temperature control engine (<NUM>) or determining whether ice has formed on the heat sink (<NUM>) in the thermal chamber (<NUM>).