Lysis module with closed-loop control mechanism

Abstract

A system may include a sonotrode to contact a first portion of a lysing chamber to provide ultrasonic energy to the lysing chamber, a heat spreader to contact a second portion of a lysing chamber to provide thermal energy to the lysing chamber, an infrared sensor to measure a temperature of the lysing chamber, and a controller to compare the temperature of the lysing chamber to a temperature profile and control the sonotrode based on the comparison of the temperature of the lysing chamber to the temperature profile.

Description

LYSIS MODULE WITH CLOSED-LOOP CONTROL MECHANISMBACKGROUND

[0001] Lysis may be performed as part of pathogen analysis to break apart cell structures. Lysis of pathogens may be performed using heat, filtering, pressure, enzymes, and / or detergents to cause cell membranes of the pathogens to rupture, allowing for extraction or amplification of genetic material. Amplification of genetic material, as in polymerase chain reaction (PCR), allows for analysis and identification of pathogens.BRIEF DESCRIPTION OF THE DRAWINGS

[0002] FIG. 1 illustrates an example system for controlling a temperature of a lysing chamber.

[0003] FIG. 2 is a flow chart of an example method for controlling a temperature of a lysing chamber.

[0004] FIG. 3 A illustrates a first example heat spreader including a first opening with straight walls.

[0005] FIG. 3B illustrates a second example heat spreader including a second opening with sloped walls.

[0006] FIG. 4 is an example graph including a temperature profile, a first temperature measurement, and a second temperature measurement.

[0007] FIG. 5 is an example graph showing a difference between a lysing chamber temperature and an infrared (IR) sensor measurement.

[0008] The foregoing and other features of the present disclosure will become apparent from the following description and appended claims, taken in conjunction with the accompanying drawings. Understanding that these drawings depict only several examples in accordance with the disclosure and are therefore, not to be considered limiting of its scope, the disclosure will be described with additional specificity and detail through use of the accompanying drawings.DETAILED DESCRIPTION

[0009] Nucleic acid-based molecular testing, such as polymerase chain reaction (PCR) amplification can be used to detect, identify, and analyze genetic material of cells, such as pathogens. PCR works by causing genetic material (e.g., DNA) to iteratively denature and anneal / elongate to create copies of the genetic material (i.e., amplify the amount of genetic material) to obtain a sufficient amount of genetic material for analysis. This amplification reaction requires an initial amount of genetic material extracted from a pathogen. However, it is difficult to extract the initial amount of genetic material for the amplification reaction from pathogen cells without destroying the genetic material. To extract the initial amount of genetic material for the amplification reaction, the pathogen cells must be destroyed (e.g., lysed) to release the genetic material without harming the genetic material.

[0010] Some example lysing procedures use various combinations of heat, physical force, and chemicals, to achieve cell / spore / tissue disruption. These lysing techniques often require a number of manual steps such as transferring samples between containers at different temperatures and adding chemical reagents to the samples. Some automatic lysing equipment allows for programming a lysing protocol with predefined steps that are automatically executed. However, these lysing protocols have poor lysing efficiency, meaning that they do not lyse effectively in short periods of time (e.g., under ten minutes). A length of a lysing process impacts a speed of an overall nucleic acid testing process. In an example, a longer lysing process for a pathogen increases a wait time for lab results, requiring medical personnel and a patient to wait longer for a diagnosis, Additionally, these automated lysing protocols are not sensitive to variable conditions, such as ambient temperature, sample temperature, and sample volume, which may cause the temperature of the lysing chamber to differ from a target temperature, or from a target temperature profile.

[0011] The present disclosure addresses these shortcomings, providing systems and methods for precisely controlling the temperatures of a lysing chamber for quick and efficient lysing of pathogens and other cells. By controlling a sonotrode using a closed control loop including an infrared sensor, the temperature of a lysing chamber can be controlled within 1° C despite variations in ambient temperature, variations in coupling between the sonotrode and the lysing chamber, variations in sample volume, and variations in sample temperature. This precise control of the temperature of the lysing chamber allows for lysing pathogens in approximately one minute.

[0012] Various examples discussed herein are directed to a device for controlling the temperature of a lysing chamber using an infrared sensor and a sonotrode in a closed control loop. The device includes the infrared sensor, the sonotrode, and a heat spreader. The heat spreader generally maintains a target temperature while the sonotrode is controlled to cause the temperature of the lysing chamber (as measured by the infrared sensor) to match a predetermined temperature profile. The device can receive a cartridge that includes the lysing chamber such that the sonotrode and the heat spreader contact opposite sides of the lysing chamber. Different cartridges can include different biological samples in their respective lysing chambers. The cartridges can be removably inserted in the device for lysing and removed once the lysing / analysis process is completed. The device mechanically interfaces with an inserted cartridge to lyse the biological sample in the lysing chamber of the cartridge. The sonotrode and heat spreader contact the lysing chamber to provide heat and ultrasonic energy to lyse the biological sample in the lysing chamber. In this way, the device, including the infrared sensor, the sonotrode, and the heat spreader, can receive multiple different cartridges to lyse the biological samples in cartridges when the cartridges are inserted. The cartridges can be removed from the device for further processing and analysis. The infrared sensor can measure the temperature of the lysing chamber through an opening in the heatspreader, which opening can be tapered to prevent heat from the heat spreader from interfering with the infrared sensor’s measurements. The closed-loop thermal control, coupled with mixing of the lysate medium provided by the sonotrode, allows the device to accurately and precisely control the temperature of the lysing chamber to match an arbitrary temperature profile. In this way, the device can provide precise and repeatable lysing conditions for a variety of pathogens, or other biological samples. While various embodiments and examples are discussed in the context of lysing pathogens, the same discussion applies to lysing other cells or biological materials, such as plant, animal, and human cells.

[0013] FIG. 1 illustrates an example system 100 for controlling a temperature of a lysing chamber 105. The system 100 controls the temperature of the lysing chamber 105 to cause heat to and cavitation to break down cell membranes of a pathogen in the lysing chamber 105 to extract genetic material of the pathogen for analysis (e.g., using PCR). The temperature of the lysing chamber 105 may follow a temperature profile to fully lyse the pathogen while avoiding damaging the pathogen. The system 100 controls the temperature of the lysing chamber 105 to follow the temperature profile in order to lyse the pathogen, as discussed herein.

[0014] The system 100 includes a sonotrode 110, otherwise referred to as an ultrasonic horn or ultrasonic transducer. The sonotrode 110 generates ultrasonic vibrations. In an example, the sonotrode 110 includes a stack of piezoelectric transducers that, when supplied with an alternating current at an ultrasonic frequency, expand and contract to provide ultrasonic energy to the lysing chamber 105. The sonotrode 110 may generate ultrasonic energy or ultrasonic vibrations based on an input signal to the sonotrode 110. An intensity of the ultrasonic vibrations or an amount of the ultrasonic energy provided by the sonotrode 110 may be based on an amount of power supplied in the input signal to the sonotrode 110. Thesonotrode 110 contacts the lysing chamber 105 to provide the ultrasonic energy or ultrasonic vibrations to the lysing chamber 105. The sonotrode 110 may contact a portion of the lysing chamber 105 that is thicker than the thin film window. The sonotrode 110 contacts an exterior of the lysing chamber 105 such that the sonotrode 110 does not contact or contaminate the contents of the lysing chamber 105. Additionally, the sonotrode 110, contacting the exterior of the lysing chamber 105, is not contaminated by the contents of the lysing chamber 105. In this way, the sonotrode 110 does not require cleaning or decontamination between lysing operations (e.g., between lysing contents of a first lysing chamber in a first cartridge and lysing contents of a second lysing chamber in a second cartridge). The ultrasonic vibrations provided by the sonotrode 110 travel through a wall of the lysing chamber 105 to mix and heat the contents of the lysing chamber 105.

[0015] The system 100 includes a heat spreader 120. In an example, the heat spreader 120 includes a copper mass that is heated using resistive heating. The heat spreader 120 may provide heating and / or cooling for the lysing chamber 105. In an example, the heat spreader 120 maintains a constant temperature, providing heating for the lysing chamber 105 when the lysing chamber 105 is below the constant temperature, and providing cooling for the lysing chamber 105 when the lysing chamber 105 is above the constant temperature. The heat spreader 120 may include sufficient thermal mass to maintain a constant temperature. The constant temperature of the heat spreader 120 may allow for precise control of a temperature of the lysing chamber 105. The heat spreader 120 may contact a portion of the lysing chamber 105. In an example, the heat spreader 120 contacts an entire surface of the thin film window except a portion left uncovered for temperature measurements.

[0016] The heat spreader 120 may stabilize the temperature of the lysing chamber 105, allowing for fine adjustments of the temperature of the lysing chamber 105 by the sonotrode 110. The heat spreader 120 may increase the temperature of the lysing chamber 105 abovethe ambient temperature to the temperature of the heat spreader 120, such that the sonotrode 110 can adjust the temperature of the lysing chamber 105 from the temperature of the heat spreader 120. In this way, the temperature of the lysing chamber 105 can be controlled using fine adjustments of the energy provided by the sonotrode 110, as the sonotrode 110 does not have to heat the lysing chamber 105 from the ambient temperature. In an example, a bacteria needs to be lysed at 80° C for a set amount of time, and the heat spreader 120 maintains a temperature of 60° C such that the sonotrode 110 can adjust the temperature of the lysing chamber 105 (and provide mixing of the contents of the lysing chamber 105) up from 60° C to 80° C for the set amount of time. In an example, a virus needs to be lysed at 90° C for a set amount of time, and the heat spreader 120 maintains a temperature of 80° C such that the sonotrode 110 can adjust the temperature of the lysing chamber 105 (and provide mixing of the contents of the lysing chamber 105) up from 80° C to 90° C for the set amount of time.

[0017] The system 100 includes an infrared (IR) sensor 130. The IR sensor 130 is used to measure a temperature of the lysing chamber 105. In an example, the IR sensor 130 generates a voltage based on an amount of IR radiation entering the IR sensor 130. In some implementations, the IR sensor 130 determines a temperature of the lysing chamber 105 based on the amount of IR radiation entering the IR sensor 130. In some implementations, the IR sensor 130 generates a signal (e.g., voltage, current) based on the amount of IR radiation entering the IR sensor 130. The IR sensor 130 is positioned adjacent the lysing chamber 105 to detect IR radiation from the lysing chamber 105. In some implementations, the lysing chamber 105 includes a thin film window to facilitate measurements of the contents of the lysing chamber 105 using the IR sensor 130, as discussed in conjunction with FIG. 3A and FIG. 3B. In an example, the lysing chamber 105 has a polypropylene (PP) wall including a portion (i.e., thin film window) that is approximately 300 pm thick to facilitate temperature measurements of the contents of the lysing chamber 105 using the IR sensor 130. The thinfilm window may be transparent to IR to facilitate temperature measurements of the contents of the lysing chamber 105. The thin film window may be thermally conductive such that the temperature of the thin film window is the same as the temperature of the contents of the lysing chamber 105. The thin film window may have a small thermal mass and a high thermal diffusivity such that the thin film window exhibits a small thermal time constant. The thin film window may have a thickness less than one millimeter. In an example, a thin polymer layer of about three hundred micrometers has a thermal time constant of about two seconds when exposed to the contents the lysing chamber 105. In an example, a thin polymer layer of about one hundred micrometers has a thermal time constant of about one second when exposed to the contents of the lysing chamber 105. In some implementations, the thin film window includes a polymer and / or a metal. In an example, the thin film window includes polypropylene (PP). In an example, the thin film window includes stainless steel having a low emissivity coating. An implementation of the thin film window including a metal may be thinner than an implementation of the thin film window including a polymer, to account for the higher specific thermal mass of the metal. In an example, the thin film window includes a layer of stainless steel that is less than one hundred micrometers thick. The thicker the thin film window of a given material, the higher the thermal time constant. The thickness of the thin film window may have a power relationship with the thermal time constant such that the time constant is proportional to a power of the thickness of the thin film window. Thus, the thickness of the thin film window may be determined based on a material of the thin film window.

[0018] In some implementations, the IR sensor 130 includes a covering to isolate the IR sensor 130 from rapid changes in ambient temperature. The covering may have a thermal mass to reduce rapid changes in temperature at the IR sensor 130. In an example, the IR sensor 130 includes a metal sheath to absorb heat and slow down changes in a temperature of the IRsensor 130. In some implementations, the IR sensor 130 includes a thermometer to measure the ambient temperature to adjust an output of the IR sensor 130. In an example, the IR sensor 130 includes a thermistor that measures the ambient temperature to adjust the signal generated by the IR sensor 130 to account for the ambient temperature.

[0019] In some implementations, the heat spreader 120 includes an opening to allow IR radiation from the lysing chamber 105 to reach the IR sensor 130, or to allow measurements of the temperature of the lysing chamber 105 using the IR sensor 130 through the opening. The opening in the heat spreader 120 may allow the IR sensor 130 to detect the IR radiation from the lysing chamber 105 for measuring the temperature of the lysing chamber 105. In an example, the heat spreader 120 includes a circular opening for the IR sensor 130 to measure the temperature of the lysing chamber 105. In some implementations, the opening is tapered, as discussed in conjunction with FIG. 3A and FIG. 3B.

[0020] The system 100 includes a controller 140. The controller 140 receives signals from the IR sensor 130 and transmits signals to the sonotrode 110. The controller 140 may receive a signal from the IR sensor 130 indicating the temperature of the lysing chamber 105. As discussed above, the signal may include a voltage or current corresponding to an amount of IR radiation detected by the IR sensor 130 and / or the signal may indicate the temperature of the lysing chamber 105 as measured by the IR sensor 130. The controller 140 transmits signals to the sonotrode 110 to control an amount of ultrasonic energy emitted by the sonotrode 110. The ultrasonic energy emitted by the sonotrode 110 affects the temperature of the lysing chamber 105. The IR sensor 130, the controller 140, and the sonotrode 110 form a closed control loop for controlling the temperature of the lysing chamber 105. In an example, the controller 140 determines the temperature of the lysing chamber 105 based on a signal from the IR sensor 130 and generates, based on the temperature of the lysing chamber 105, a signalfor the sonotrode 110 to control an amount of energy (ultrasonic energy) provided by the sonotrode 110 to the lysing chamber 105.

[0021] The controller 140 may compare the temperature of the lysing chamber 105 to a temperature profile. The temperature profile may define target temperatures within a time period. The controller 140 may control the sonotrode 110 based on the comparison of the temperature of the lysing chamber 105 to the temperature profile. In an example, the controller 140 compares a current temperature of the lysing chamber 105 to a current target temperature defined in the temperature profile to determine an amount of energy to provide to the lysing chamber 105 using the sonotrode 110. By measuring the temperature of the lysing chamber 105 using the IR sensor 130 and providing energy to the lysing chamber 105 using the sonotrode 110, the controller 140 can precisely control the temperature of the lysing chamber 105 (e.g., to match the temperature profile). The controller 140, the IR sensor 130, and the sonotrode 110 form a closed control loop where the controller 140 measures the temperature of the lysing chamber 105 using the IR sensor 130 and changes the temperature of the lysing chamber 105 using the sonotrode 110. In this way, the controller 140 can use the sonotrode 110 to precisely control the temperature of the lysing chamber 105, as informed by the temperature measurements taken using the IR sensor 130.

[0022] In some implementations, the controller 140 compares a rate of change of the temperature of the lysing chamber 105 to the temperature profile, or a rate of change in the temperature profile. In some implementations, the controller 140 compares the temperature of the lysing chamber 105 to the temperature profile to determine one or more of a difference between the temperature of the lysing chamber 105 and the temperature profile, an integral of past differences between the temperature of the lysing chamber 105 and the temperature profile, and a rate of change of the difference between the temperature of the lysing chamber 105 and the temperature profile. In an example, the controller 140 is a proportional-integral-derivative (PID) controller. The controller 140 reduces an error between the temperature of the lysing chamber 105 and the temperature profile. Reducing the error between the temperature of the lysing chamber 105 and the temperature profile can include reducing a difference between the temperature of the lysing chamber 105 and the temperature profile, reducing an error between the rate of change of the temperature of the lysing chamber 105 and the temperature profile, and reducing an integral of differences between the temperature of the lysing chamber 105 and the temperature profile.

[0023] In some implementations, the controller 140 controls a temperature of the heat spreader 120. The controller 140 may control the temperature of the heat spreader 120 and the ultrasonic energy provided by the sonotrode 110 to control the temperature of the lysing chamber 105. In an example, the controller 140 increases the temperature of the heat spreader 120 and an amount of energy provided by the sonotrode 110 to increase the temperature of the lysing chamber 105. In an example, the controller 140 maintains the temperature of the heat spreader 120 at a constant temperature and changes the amount of energy provided by the sonotrode 110 to control the temperature of the lysing chamber 105. In some implementations, the controller 140 includes a separate heat spreader controller, or the system 100 includes a separate heat spreader controller to control the temperature of the heat spreader 120. In an example, the separate heat spreader controller provides power to the heat spreader 120 to maintain the heat spreader 120 at a target heat spreader temperature by comparing the temperature of the heat spreader 120 (e.g., measured using a thermistor coupled to the heat spreader 120) to the target heat spreader temperature. The target heat spreader temperature may be a temperature profile including target temperatures for a period of time similar to the temperature profile for the lysing chamber 105. In an example, a temperature profile for the heat spreader 120 includes a constant target heat spreader temperature for a duration of a lysing cycle. The controller 140 (or heat spreader controller), and the heat spreader thermistorform a closed control loop where the controller 140 measures the temperature of the heat spreader 120 using the heat spreader thermistor and provides power to the heat spreader 120 to control the temperature of the heat spreader 120. In this way, the system 100 can include two control loops: a first control loop for controlling the temperature of the lysing chamber 105 using the IR sensor 130, the sonotrode 110, and the controller 140, and a second control loop for controlling the temperature of the heat spreader 120 using the heat spreader thermistor and the controller 140.

[0024] In some implementations, the lysing chamber 105 can be introduced to the system 100 for the system 100 to control the temperature of the lysing chamber 105. The temperature of the lysing chamber 105 can be controlled by the system 100 according to a temperature profile to lyse a pathogen in the lysing chamber 105. Heat and cavitation energy provided to the lysing chamber 105 as the system 100 follows the temperature profile may be sufficient to lyse the pathogen without use of lysates or bead (e.g., magnetic or glass beads). In this way, a solution containing the pathogen can be dispensed into the lysing chamber 105 to lyse the pathogen and dispensed from the lysing chamber 105 for immediate hybridization and amplification as part of a PCR process.

[0025] In an example, the lysing chamber 105 is part of a cartridge that is inserted in the system 100 and is not part of the system 100 itself. The lysing chamber 105 may be disposed (i.e., the system 100 includes a space for the lysing chamber 105) between the sonotrode 110 and the heat spreader 120. In some implementations, the sonotrode 110 and the heat spreader 120 contact substantially opposite sides (e.g., sides separated by 180° ± 10%) of the lysing chamber 105. In an example, the sonotrode 110 and the heat spreader 120 are on opposite sides of a cartridge including the lysing chamber 105 and contact different surfaces of the lysing chamber 105 exposed on opposite surfaces of the cartridge). In some implementations, the sonotrode 110 and the heat spreader 120 are orthogonal to each other. In an example, thesonotrode 110 contacts a side of the lysing chamber 105 and the heat spreader 120 contacts a bottom of the lysing chamber 105. In an example, the heat spreader 120 contacts one or more sides of the lysing chamber 105 and the sonotrode 110 contacts a bottom of the lysing chamber 105. In an example, the sonotrode 110 contacts a same side of the lysing chamber 105 as the heat spreader 120. In an example, the sonotrode 110 contacts the lysing chamber 105 through a second opening in the heat spreader 120. The lysing chamber 105 may be pressurized to improve contact between the lysing chamber 105 and the sonotrode 110 and the heat spreader 120, which is especially effective in the areas in which the thin film serves as the only “wall” for the lysing chamber 105, as the pressure moves the thin film towards the components of the device. In an example, the thin film, when the lysing chamber 105 is not pressurized, does not form a uniform surface and so does not have full contact the heat spreader 120. In this example, pressurizing the lysing chamber 105 causes the thin wall to move towards the heat spreader 120 to have full contact with the heat spreader 120.

[0026] The sonotrode 110 provides ultrasonic energy to the lysing chamber 105 that can increase the temperature of the lysing chamber 105 and mix the contents of the lysing chamber 105. In an example, the sonotrode 110 causes cavitation in the contents of the lysing chamber 105, causing mixing of the contents of the lysing chamber 105 and potentially aiding in lysing of the contents of the lysing chamber 105. In this way, energy transfer between the heat spreader 120 and the contents of the lysing chamber 105 can be improved. Additionally, the mixing can improve temperature measurements taken using the IR sensor 130 by causing the temperature of the contents of the lysing chamber 105 to be uniform. Mixing the contents of the lysing chamber 105 by the sonotrode 110 reduces temperature inequalities within the lysing chamber 105 such that temperature measurements at a portion of the lysing chamber 105 represent an overall temperature of the lysing chamber 105. In an example, the mixing provided by the sonotrode 110 causes a surface of the contents of the lysing chamber 105 incontact with the thin film window to have a same temperature as a center of the contents of the lysing chamber 105 such that temperature measurements of the thin film window taken using the IR sensor 130 accurately represent the temperature of the contents of the lysing chamber 105.

[0027] In some implementations, the sonotrode 110 provides ultrasonic energy to the lysing chamber 105 prior to temperature measurements taken using the IR sensor 130 to ensure mixing of the contents of the lysing chamber 105 prior to the temperature measurements. This pre-mixing of the contents of the lysing chamber 105 facilitates accurate initial temperature readings, preventing errors in controlling the sonotrode 110. By mixing the contents of the lysing chamber 105 before taking temperature measurements and following the temperature profile, control signals based on inaccurate temperature measurements can be avoided. In an example, a surface of the contents of the lysing chamber 105 in contact with the thin film window may have a temperature that is higher than a temperature of a center of the contents of the lysing chamber 105, which could cause a temperature measurement taken using the IR sensor 130 to be erroneously high, causing the controller 140 to reduce an amount of energy provided by the sonotrode 110. However, by pre-mixing the contents of the lysing chamber 105 by providing ultrasonic vibrations using the sonotrode 110, the temperature of the contents of the lysing chamber 105 can be uniform (i.e., the contents of the lysing chamber 105 in contact with the thin film window have the same temperature as the center of the contents of the lysing chamber 105), allowing for accurate temperature measurements using the IR sensor 130.

[0028] The controller 140 may control the sonotrode 110 based on a ratio of cavitation intensity to heating to prevent damage to the contents of the lysing chamber 105 due to cavitation. The ratio of cavitation intensity to heating may be a ratio of an amount of energy provided to the lysing chamber 105 from the sonotrode 110 and an amount of energy providedto the lysing chamber 105 from the heat spreader 120. In an example, the controller 140 maintains the ratio of cavitation intensity to heating below a predetermined threshold. In an example, the controller 140 maintains the cavitation intensity below a predetermined threshold. In this way, the controller 140 can prevent damage to the contents of the lysing chamber 105. For example, if the temperature of the lysing chamber 105 is below a target temperature, the controller 140 could attempt to increase the temperature of the lysing chamber 105 by providing an amount of cavitation energy (e.g., shearing forces) that can damage genetic material. However, by limiting the amount of cavitation energy (i.e., cavitation intensity), or controlling the ratio of cavitation intensity to heating, the controller 140 can increase the temperature of the lysing chamber 105 without damaging the genetic material. The controller 140 may determine the ratio of cavitation intensity to heating based on a target temperature of the heat spreader 120 (heating) and control signals from the controller 140 to the sonotrode 110 (cavitation energy). The controller 140 may adjust the control signals to the sonotrode 110 to maintain the ratio below a predetermined threshold. In this way, a rate of change of the temperature of the lysing chamber 105 may be restricted, by restricting the energy delivered to the lysing chamber 105 by the sonotrode 110, in order to avoid damaging the genetic material.

[0029] In some implementations, the controller 140 restricts a rate of change of the temperature of the lysing chamber 105 and the ratio of cavitation energy to heating. In this way, the controller 140 can limit the shear forces on the genetic material to avoid damaging the genetic material. By maintaining the ratio of cavitation energy to heating within a predetermined range, the controller 140 can facilitate lysing of pathogens (e.g., breaking cell membranes) without damaging the genetic material. The controller 140 can change the output of the sonotrode 110 (frequency, intensity, etc.) to adjust an amount of heat and an amount of cavitation power provided by the sonotrode 110 to the lysing chamber 105.

[0030] FIG. 2 is a flow chart of an example method 200 for controlling a temperature of a lysing chamber. The method 200 may include more, fewer, or different operations than shown. The operations may be performed in the order shown, a different order, or concurrently. The method 200 may be performed by the controller 140 of FIG. 1. The method 200 may be performed as part of sample preparation for nucleic acid testing (e.g., PCR analysis). The method 200 may be performed to control a temperature of a lysing chamber in order to lyse a pathogen to extract genetic material of the pathogen. The pathogen is introduced into the lysing chamber along with a transport medium and, in some examples, glass or magnetic beads. The temperature of the lysing chamber is controlled according to operations of the method 200 to break down cell membranes of the pathogen and release the genetic material of the pathogen (i.e., lyse the pathogen), and the contents of the lysing chamber are dispensed into an amplification chamber for hybridization and amplification of the genetic material of the pathogen. Once the genetic material of the pathogen is amplified, the genetic material can be analyzed to identify the pathogen.

[0031] At operation 210, a controller measures, using an IR sensor, a temperature of a lysing chamber. In some implementations, the method 200 includes heating the lysing chamber using a heat spreader in contact with the lysing chamber. In some embodiments, a second controller heats the lysing chamber using the heat spreader in contact with the lysing chamber. In some embodiments, the controller heats the lysing chamber using the heat spreader in contact with the lysing chamber. The heat spreader may include an opening, with the IR sensor directed through the opening towards the lysing chamber, as discussed in conjunction with FIG. 1. The IR sensor may be aligned (through the opening) with a thin film window of the lysing chamber in contact with the contents of the lysing chamber to measure the temperature of the lysing chamber (i.e., temperature of the contents of the lysing chamber), as discussed in conjunction with FIG. 3 A and FIG. 3B. The IR sensor may be directed towardthe thin film window of the lysing chamber to receive IR from the thin film window (i.e., from the contents of the lysing chamber).

[0032] In some implementations, the controller, using the sonotrode, applies ultrasonic energy to the lysing chamber to mix the contents of the lysing chamber prior to comparing the temperature of the lysing chamber to the temperature profile. In an example, the controller applies ultrasonic energy to the lysing chamber to mix the contents of the lysing chamber prior to measuring, using the IR sensor, the temperature of the lysing chamber. In this way, the contents of the lysing chamber are “pre-mixed,” increasing an accuracy of an initial temperature measurement using the IR sensor. In an example, the pre-mixing is performed for approximately one second.

[0033] At operation 220, the controller compares the temperature of the lysing chamber to a temperature profile. An example of a temperature profile is shown in FIG. 4. In some implementations, the controller selects the temperature profile from a set of temperature profiles. The set of temperature profiles can include temperature profiles for lysing different pathogens, or types of pathogens (e.g., different viruses and bacteria). The temperature profile can be selected to lyse a target pathogen possibly included in the contents of the lysing chamber. The temperature profile can be selected to lyse a target pathogen based on the contents of the lysing chamber, including the target pathogen, enzymes, a solution, glass beads, and / or magnetic beads. In an example, the target pathogen is a bacteria, such that a temperature profile for lysing bacteria is used. In an example, the target pathogen is a virus, such that a temperature profile for lysing viruses is used. In an example, the target pathogen is E. Coli and the lysing chamber includes E. Coli and glass beads, such that a temperature profile for lysing E. Coli in the presence of glass beads is used. In an example, the target pathogen is Bacillus thuringiensis and the lysing chamber includes Bacillus thuringiensis, but no beads, such that a temperature profile for lysing Bacillus thuringiensis without beads isused. As discussed herein, the system does not require the use of beads (magnetic or glass), as the temperature and cavitation are sufficient to lyse target pathogens. In this way, lysing can be performed without providing beads in the lysing chamber.

[0034] At operation 230, the controller generates a signal to control an output of a sonotrode based on the comparison of the temperature of the lysing chamber to the temperature profile. The controller may generate the signal based on the comparison as well as a temperature of the heat spreader and / or an ambient temperature. The controller may generate the signal based on various aspects of the comparison of the temperature of the lysing chamber to the temperature profile, such as proportion and rate of change, as discussed in conjunction with FIG. 1. In an example, the controller generates the signal to reduce an error between the temperature of the lysing chamber and the temperature profile.

[0035] At operation 240, the controller transmits the generated signal to the sonotrode to provide ultrasonic energy to the lysing chamber. The generated signal may define a power level of the sonotrode, or an amount of energy delivered by the sonotrode to the lysing chamber. In an example, the generated signal is a control command to the sonotrode to cause the sonotrode to draw an amount of power corresponding to the control command. In an example, the generated signal includes electrical power that causes the sonotrode to operate at the target power level. In an example, the power level of the sonotrode corresponds to an amount of energy to be provided to the lysing chamber to increase the temperature of the lysing chamber to a target temperature defined by a temperature profile. In an example, the power level of the sonotrode is proportional to a difference between the temperature of the lysing chamber and a target temperature defined by a temperature profile. In an example, the power level of the sonotrode corresponds to a ratio of cavitation energy to heating.

[0036] The lysing of the contents of the lysing chamber may be performed as part of a nucleic acid testing process for analyzing and / or identifying a pathogen. In some implementations,the method 200 includes selecting the temperature profile from a set of temperature profiles based on a target pathogen, where the temperature profile is configured to lyse the target pathogen, as discussed herein. The method 200 may include providing the lysing chamber adjacent the infrared sensor and in contact with the sonotrode. In an example, the lysing chamber is part of a cartridge that is placed between the infrared sensor and the sonotrode, as discussed in conjunction with FIG. 1. The method 200 may include, in response to the temperature of the lysing chamber being within a predetermined threshold of the temperature profile throughout the temperature profile, dispensing the contents of the lysing chamber for analysis of the target pathogen. In an example, the temperature of the lysing chamber is within the predetermined threshold of the temperature profile throughout the temperature profile based on each temperature measurement of the temperature of the lysing chamber being within the predetermined threshold. In an example, the temperature of the lysing chamber is within the predetermined threshold of the temperature profile throughout the temperature profile based on an average temperature of the lysing chamber being within the predetermined threshold. In an example, the temperature of the lysing chamber is within the predetermined threshold of the temperature profile throughout the temperature profile based on an aggregate difference (e.g., integral) between the temperature of the lysing chamber and the temperature profile being within the predetermined threshold. The contents of the lysing chamber may be dispensed into an amplification chamber. The method 200 may include selecting reagents for the nucleic acid testing based on the target pathogen and performing the nucleic acid testing (within the amplification chamber) using the dispensed contents of the lysing chamber and the selected reagents. In an example, the selected reagents include a polymerase, primers, and nucleotides. Based on the results of the nucleic acid testing, the target pathogen can be analyzed and / or identified.

[0037] In some implementations, the nucleic acid testing is performed within the lysing chamber. Thus, instead of dispensing the contents of the lysing chamber, an additional temperature profile (e.g., PCR temperature profile) can be used to perform the nucleic acid testing within the lysing chamber. The additional temperature profile may be a hybridization or annealing temperature profile configured to facilitate annealing of the primers to genetic material of the target pathogen. The additional temperature profile may have a lower average temperature than the temperature profile used for lysing the target pathogen. Additional reagents may be added to the lysing chamber to perform the nucleic acid testing, such as the polymerase, primers, and nucleotides.

[0038] FIG. 3A illustrates a first heat spreader 320a including a first opening 322a with straight walls. FIG. 3B illustrates a second heat spreader 320b including a second opening 322b with sloped walls. The first heat spreader 320a is in contact with a lysing chamber 305, with the first opening 322a allowing for measurements of a temperature of the lysing chamber 305 using an IR sensor 330, similar to FIG. 1. The lysing chamber 305 includes a thin film 307 (window) to facilitate measurements of the lysing chamber 305 (i.e. contents of the lysing chamber 305). In some implementations, the lysing chamber 305 is molded polypropylene (PP) and the thin film 307 is a thinner layer of PP than the rest of the lysing chamber 305. In an example, the lysing chamber 305 (without the thin film 307) is formed by molding PP, and the thin film 307 is formed over an opening in the molded lysing chamber 305. As discussed herein, the lysing chamber 305 may be pressurized to facilitate contact between the contents of the lysing chamber 305 and the thin film 307. In an example, the thin film 307 is transparent, or partially transparent, to facilitate temperature measurements through the thin film 307. In an example, the thin film 307 is transparent, or partially transparent to infrared radiation, to facilitate temperature measurements through the thin film 307.

[0039] The thin film 307 may have a small thermal mass and a high thermal diffusivity such that the thin film 307 has a small thermal time constant (i.e., time for its temperature to match the temperature of the contents of the lysing chamber 305). The thin film 307 may include a polymer and / or a metal. In an example, the thin film 307 is PP. In an example, the thin film 307 is stainless steel. The thickness of the thin film 307 may be less than one millimeter. In an example, the thin film 307 is about three hundred micrometers thick. In an example, a lag between a temperature of an interior surface of the thin film 307 and a temperature of an exterior surface of the thin film 307 is less than one second. The IR sensor 330 is aligned with (e.g., pointed at) the thin film 307 to facilitate temperature measurements of the contents of the lysing chamber 305 through the thin film 307 using the IR sensor 330. In an example, the IR sensor 330 is directed toward the thin film 307 and is at a distance from the thin film 307 such that IR from the thin film 307 (i.e., from the contents of the lysing chamber 305) is captured by the IR sensor 330.

[0040] The second heat spreader 320b is illustrated as being in contact with the lysing chamber 305, with the IR sensor 330 positioned for measuring the temperature of the lysing chamber 305 through the second opening 322b. The second heat spreader 320b may be similar to the first heat spreader 320a (e.g., same material, same mass), with the exception that the second opening 322b in the second heat spreader 320b has sloped walls, or is tapered such that a first portion of the second opening 322b nearer the IR sensor 330 is wider than a second portion of the second opening 322b farther from the IR sensor 330. In an example, the second opening 322b is a circular passage defining a first, larger circle on a first surface of the second heat spreader 320b adjacent the IR sensor 330 and a second, smaller circle on a second surface of the second heat spreader 320b adjacent the lysing chamber 305. The tapered, or sloped second opening 322b reduces an amount of IR radiation from the second heat spreader 320b that reaches the IR sensor 330 relative to the first opening 322a. IR radiation from the firstheat spreader 320a may impact the thin film 307 and be reflected into the IR sensor 330, reducing an accuracy of measurements of the temperature of the lysing chamber 305. However, less IR radiation from the second heat spreader 320b is reflected into the IR sensor 330 due to the tapered second opening 322b.

[0041] In some implementations, the thin film 307 includes a high emissivity (anti-reflective) coating to reduce an amount of IR radiation from the first heat spreader 320a or the second heat spreader 320b that is reflected into the IR sensor 330.EXAMPLES

[0042] As discussed herein, the device may use a closed-loop control to accurately control the temperature of a lysing chamber by controlling a sonotrode based on temperature measurements from an IR sensor. FIG. 4 illustrates examples of controlling lysing chamber temperatures according to a temperature profile, and FIG. 5 illustrates an accuracy of IR sensor temperature readings of a temperature of a lysing chamber.

[0043] FIG. 4 is an example graph 400 including a temperature profile 401, a first temperature measurement 410, and a second temperature measurement 420. The temperature profile 401 may be a target temperature profile including target temperatures within a time period. The first temperature measurement 410 and the second temperature measurement 420 may include temperature measurements throughout the time period as measured using an IR sensor. A controller measured the temperature of a lysing chamber, compared the temperature of the lysing chamber to the temperature profile 401, and controlled a sonotrode to adjust the temperature of the lysing chamber to follow the temperature profile 401, as discussed in conjunction with FIG. 1. The first temperature measurement 410 was measured during a first lysing cycle when the heat spreader maintained a constant temperature of eighty degrees Celsius and the second temperature measurement 420 was measured during a second lysingcycle when the heat spreader maintained a constant temperature of sixty degrees Celsius. The controller was able to follow the temperature profile 401 in both cases by controlling the sonotrode. In the case where the heat spreader maintained the constant temperature of sixty degrees Celsius, the heat spreader provided heat to the lysing chamber while the temperature of the lysing chamber was below sixty degrees Celsius and the heat spreader drew heat from the lysing chamber (i.e., provided cooling) while the temperature of the lysing chamber was above sixty degrees Celsius.

[0044] The temperature profile 401 includes a filling period 403 and a lysing period 405. The lysing chamber may be filled (e.g., pathogens, medium, beads, etc. dispensed into the lysing chamber) during the filling period 403. Once the lysing chamber is filled, the pathogen is lysed during the lysing period 405. The lysing period 405 has a higher average temperature than the filling period 403 to facilitate lysing the pathogen. The filling period 403 and the lysing period 405 may have similar durations. In an example, the filling period 403 is about thirty seconds long and the lysing period 405 is about thirty-five seconds long. The filling period 403 and the lysing period 405 may have different durations and / or temperature values for different temperature profiles, such as different temperature profiles for lysing different target pathogens. While various embodiments and examples described herein discuss target pathogens, other organisms or sources of genetic material can be lysed according to the systems and methods described herein to extract their genetic material for analysis.

[0045] In an example, the first temperature measurement 410 is a temperature measurement of the lysing chamber 105 of FIG. 1 captured using the IR sensor 130 during a lysing cycle with the heat spreader 120 maintaining a constant temperature of 80° C. During the filling period 403 of the temperature profile 401, the lysing chamber 105 is filled with 800 pl of solution containing a hybridization buffer, a universal transfer medium, and a bacterial lysing target, such that the lysing chamber 105 (having a volume of 1.6 ml in this example) is halffull. The lysing chamber 105 is pressurized to facilitate thermal contact between a wall of the lysing chamber and the heat spreader 120. The solution is at ambient temperature before being dispensed into the lysing chamber 105, and the temperature of the solution increases due to the heat spreader 120. At the end of the filling period 403, the entirety of the solution is within the lysing chamber 105 and the sonotrode 110 begins to provide ultrasonic energy to the lysing chamber 105, mixing the solution, causing cavitation within the solution, and increasing the temperature of the solution. During the lysing period 405, controller 140 controls the sonotrode 110 to maintain the temperature of the solution on the temperature profile 401 using feedback from the IR sensor 130 in the form of the first temperature measurement 410. The sonotrode 110 accelerates the heating of the solution by providing mixing of the solution (facilitating heat transfer between the heat spreader 120 and the solution) and by injecting thermal energy into the solution via cavitation. The controller adjusts the output of the sonotrode 110 based on a comparison of the first temperature measurement 410 to the temperature profile 401 to cause the temperature of the solution and the first temperature measurement 410 to follow the temperature profile 401. At the end of the lysing period 405, the solution is dispensed into a hybridization chamber and the first temperature measurement 410 (corresponding to signals from the IR sensor 130 directed towards the lysing chamber 105) ceases to accurately reflect the temperature of the solution once the solution flows out of the lysing chamber 105.

[0046] In an example, the second temperature measurement 420 is a temperature measurement of the lysing chamber 105 of FIG. 1 captured using the IR sensor 130 during a lysing cycle with the heat spreader 120 maintaining a constant temperature of 60° C. During the filling period 403 of the temperature profile 401, the lysing chamber 105 is filled with 800 pl of solution containing a hybridization buffer, a universal transfer medium, and a bacterial lysing target, such that the lysing chamber 105 (having a volume of 1.6 ml in thisexample) is half full. The lysing chamber 105 is pressurized to facilitate thermal contact between a wall of the lysing chamber and the heat spreader 120. The solution is at ambient temperature before being dispensed into the lysing chamber 105, and the temperature of the solution increases due to the heat spreader 120. At the end of the filling period 403, the entirety of the solution is within the lysing chamber 105 and the sonotrode 110 begins to provide ultrasonic energy to the lysing chamber 105, mixing the solution, causing cavitation within the solution, and increasing the temperature of the solution. During the lysing period 405, controller 140 controls the sonotrode 110 to maintain the temperature of the solution on the temperature profile 401 using feedback from the IR sensor 130 in the form of the second temperature measurement 420. The heat spreader 120, once the temperature of the solution rises above the temperature of the heat spreader 120 (60° C), ceases to provide heat to the solution and begins to remove heat from the solution. The sonotrode 110 provides mixing of the solution (facilitating heat transfer between the heat spreader 120 and the solution) and controls the temperature of the solution by injecting thermal energy into the solution via cavitation. The controller adjusts the output of the sonotrode 110 based on a comparison of the second temperature measurement 420 to the temperature profile 401 to cause the temperature of the solution and the second temperature measurement 420 to follow the temperature profile 401. At the end of the lysing period 405, the solution is dispensed into a hybridization chamber and the second temperature measurement 420 (corresponding to signals from the IR sensor 130 directed towards the lysing chamber 105) ceases to accurately reflect the temperature of the solution once the solution flows out of the lysing chamber 105.

[0047] The first temperature measurement 410 and the second temperature measurement 420 demonstrate how the system (e.g., the system 100 of FIG. 1) uses a closed control loop to control the sonotrode to cause the temperature of the lysing solution to follow the temperature profile 401 despite differences in the temperature of the heat spreader between the firsttemperature measurement 410 and the second temperature measurement 420. Similarly, the system is able to follow the temperature profile 401 despite changes in ambient temperature, solution volume, and solution composition. Thus, the system is able to follow an arbitrary temperature profile, or more specifically, to follow various different temperature profiles for lysing different pathogens. Additionally, the system does not require any chemical lysing, as the temperature and cavitation are sufficient to lyse target pathogens. This allows for hybridization and amplification of the genetic material of the target pathogens without chemical treatment (i.e., neutralizing chemical lysates).

[0048] FIG. 5 is an example graph 500 showing a difference 510 between a lysing chamber temperature and an IR sensor measurement. In an example, the graph 500 shows the difference 510 between the temperature of the lysing chamber 105 and temperature measurements taken using the IR sensor 130 in the system 100 of FIG. 1. The lysing chamber temperature may be measured using a thermometer inside of the lysing chamber. In an example, the lysing chamber temperature is measured using a thermistor submerged within the contents of the lysing chamber, which is performed purely for experimental purpose as it should be understood that using the IR sensor avoids the need for an additional sensor inside the vessel. The IR sensor measurement may be measured using an IR sensor adjacent the lysing chamber, such as the IR sensor 130 of FIG. 1. The difference 510 may show a level of accuracy of the IR sensor measurement. The graph 500 include a sonotrode activity region 512 indicating when a sonotrode applied ultrasonic energy to the lysing chamber. As discussed herein, the ultrasonic energy causes cavitation within the contents of the lysing chamber to mix the contents of the lysing chamber. As shown in the graph 500, the difference 510 is lower within the sonotrode activity region 512, indicating that an accuracy of the temperature measurements taken using the IR sensor is greater when the sonotrode is mixing the contents of the lysing chamber. This accuracy allows for precise, repeatable control of thetemperature of the lysing chamber using the closed control loop of the IR sensor, the controller, and the sonotrode.

[0049] In the preceding detailed description, reference is made to the accompanying drawings, which form a part hereof. In the drawings, similar symbols typically identify similar components, unless context dictates otherwise. The illustrative examples described in the detailed description, drawings, and claims are not meant to be limiting. Other implementations may be utilized, and other changes may be made, without departing from the scope of the subject matter presented here. It will be readily understood that the aspects of the present disclosure, as generally described herein, and illustrated in the figures, can be arranged, substituted, combined, and designed in a wide variety of different configurations, all of which are explicitly contemplated and made part of this disclosure.

[0050] The herein described subject matter sometimes illustrates different components contained within, or connected with, different other components. It is to be understood that such depicted architectures are merely exemplary, and that in fact many other architectures can be implemented which achieve the same functionality. In a conceptual sense, any arrangement of components to achieve the same functionality is effectively "associated" such that the desired functionality is achieved. Hence, any two components herein combined to achieve a particular functionality can be seen as "associated with" each other such that the desired functionality is achieved, irrespective of architectures or intermedial components. Likewise, any two components so associated can also be viewed as being "operably connected," or "operably coupled," to each other to achieve the desired functionality, and any two components capable of being so associated can also be viewed as being "operably couplable," to each other to achieve the desired functionality. Specific examples of operably couplable include but are not limited to physically mateable and / or physically interactingcomponents and / or wirelessly interactable and / or wirelessly interacting components and / or logically interacting and / or logically interactable components.

[0051] With respect to the use of substantially any plural and / or singular terms herein, those having skill in the art can translate from the plural to the singular and / or from the singular to the plural as is appropriate to the context and / or application. The various singular / plural permutations may be expressly set forth herein for sake of clarity. For example, recitations of plural elements can be understood to include of the element discussed.

[0052] It will be understood by those within the art that, in general, terms used herein, and especially in the appended claims (e.g., bodies of the appended claims) are generally intended as "open" terms (e.g., the term "including" should be interpreted as "including but not limited to," the term "having" should be interpreted as "having at least," the term "includes" should be interpreted as "includes but is not limited to," etc.). It will be further understood by those within the art that if a specific number of an introduced claim recitation is intended, such an intent will be explicitly recited in the claim, and in the absence of such recitation no such intent is present. For example, as an aid to understanding, the following appended claims may contain usage of the introductory phrases "at least one" and "one or more" to introduce claim recitations. However, the use of such phrases should not be construed to imply that the introduction of a claim recitation by the indefinite articles "a" or "an" limits any particular claim containing such introduced claim recitation to inventions containing only one such recitation, even when the same claim includes the introductory phrases "one or more" or "at least one" and indefinite articles such as "a" or "an" (e.g., "a" and / or "an" should typically be interpreted to mean "at least one" or "one or more"); the same holds true for the use of definite articles used to introduce claim recitations. In addition, even if a specific number of an introduced claim recitation is explicitly recited, those skilled in the art will recognize that such recitation should typically be interpreted to mean at least the recited number (e.g., thebare recitation of "two recitations," without other modifiers, typically means at least two recitations, or two or more recitations). Furthermore, in those instances where a convention analogous to "at least one of A, B, and C, etc." is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (e.g., "a system having at least one of A, B, and C" would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and / or A, B, and C together, etc.). In those instances where a convention analogous to "at least one of A, B, or C, etc." is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (e.g., "a system having at least one of A, B, or C" would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and / or A, B, and C together, etc.). It will be further understood by those within the art that virtually any disjunctive word and / or phrase presenting two or more alternative terms, whether in the description, claims, or drawings, should be understood to contemplate the possibilities of including one of the terms, either of the terms, or both terms. For example, the phrase "A or B" will be understood to include the possibilities of "A" or "B" or "A and B." Further, unless otherwise noted, the use of the words “approximate,” “about,” “around,” “substantially,” etc., mean plus or minus ten percent.

[0053] The foregoing description of illustrative examples has been presented for purposes of illustration and of description. It is not intended to be exhaustive or limiting with respect to the precise form disclosed, and modifications and variations are possible in light of the above teachings or may be acquired from practice of the disclosed examples. It is intended that the scope of the invention be defined by the claims appended hereto and their equivalents.

Claims

WHAT IS CLAIMED IS:

1. A system, comprising: a sonotrode to contact a first portion of a lysing chamber to provide ultrasonic energy to the lysing chamber; a heat spreader to contact a second portion of a lysing chamber to provide thermal energy to the lysing chamber; an infrared sensor to measure a temperature of the lysing chamber; and a controller to: compare the temperature of the lysing chamber to a temperature profile; and control the sonotrode based on the comparison of the temperature of the lysing chamber to the temperature profile.

2. The system of claim 1, wherein the heat spreader includes an opening through which the infrared sensor measures the temperature of the lysing chamber.

3. The system of claim 2, wherein the opening is tapered such that a first portion of the opening nearer the infrared sensor is wider than a second portion of the opening farther from the infrared sensor.

4. The system of claim 1, wherein the controller is to control the sonotrode based on a ratio of cavitation intensity to heating.

5. The system of claim 1, the controller to compare the temperature of the lysing chamber to the temperature profile by reducing an error between the temperature of the lysing chamber and the temperature profile.

6. The system of claim 1, further comprising a heat spreader controller to control the heat spreader based on a comparison of a temperature of the heat spreader to a target heat spreader temperature.

7. The system of claim 1, further comprising a covering on the infrared sensor to isolate the infrared sensor from rapid changes in ambient temperature.

8. The system of claim 1, wherein the first portion of the lysing chamber and the second portion of the lysing chamber are on substantially opposite sides of the lysing chamber.

9. A method comprising: measuring, by a controller, using an infrared sensor, a temperature of a lysing chamber; comparing, by the controller, the temperature of the lysing chamber to a temperature profile; generating, by the controller, a signal to control an output of a sonotrode based on the comparison of the temperature of the lysing chamber to the temperature profile; and transmitting, by the controller, the generated signal to the sonotrode to provide ultrasonic energy to the lysing chamber.

10. The method of claim 9, further comprising: heating, by a second controller, the lysing chamber using a heat spreader in contact with the lysing chamber, wherein the heat spreader includes an opening, and wherein the infrared sensor is directed through the opening towards the lysing chamber.

11. The method of claim 10, wherein the generated signal defines a power level of the sonotrode.

12. The method of claim 10, wherein the infrared sensor is aligned with a thin film window of the lysing chamber to measure the temperature of the lysing chamber, the thin film window in contact with a contents of the lysing chamber.

13. The method of claim 10, further comprising: selecting the temperature profile from a set of temperature profiles based on a target pathogen, the temperature profile configured to lyse the target pathogen; providing the lysing chamber adjacent the infrared sensor and in contact with the sonotrode;in response to the temperature of the lysing chamber being within a predetermined threshold of the temperature profile throughout the temperature profile, dispensing the contents of the lysing chamber for analysis of the target pathogen; selecting reagents for a polymerase chain reaction (PCR) based on the target pathogen; and performing the PCR using the dispensed contents of the lysing chamber and the selected reagents.

14. The method of claim 9, further comprising applying, by the controller, using the sonotrode, ultrasonic energy to the lysing chamber to mix a contents of the lysing chamber prior to comparing, by the controller, the temperature of the lysing chamber to the temperature profile.

15. The method of claim 9, further comprising selecting, by the controller, the temperature profile from a set of temperature profiles.

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