DESC:TECHNICAL FIELD
[0001] The present invention generally relates to the technical field of sensor multiplexing. Particularly, aspects of the present disclosure provide a system for determination of parameters associated with a sample and a device for detection of an analyte present in a sample. The system and device of the present disclosure can find utility in myriad of applications, including usage in Polymerase Chain Reaction (PCR) device, but not limited thereto. Further aspects of the present disclosure relate to a method of operating the device.

BACKGROUND
[0002] Background description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.
[0003] Many of the application areas routinely require multi-parametric analysis i.e. one or more parameters of a sample needs to be monitored as a function of another parameter. For example, in the state-of-art, naïve solution to reading different fluorescence wavelengths is to have one sensor per sample per wavelength. Consider that 4 samples must be monitored for 3 wavelengths. This means one needs 12 fluorescence sensors. Further, if one also needs to monitor temperature of the sample, one additionally needs to employ separate temperature sensors for each sample, hence, requiring a total of 16 sensors for 4 samples. A typical thermal cycler of a PCR can process at least 18samples at a time. If one needs to measure fluorescence at 3 different wavelengths for each of the 16 samples, in accordance with the state-of-art reported solution(s), either one needs to configure a large number of sensors as part of the system/device or one would be constrained to process one sample at a time, making the overall process very time consuming.
[0004] Accordingly, there remains a long standing need in the state of art of a system for determination of parameters associated with a sample that can alleviate, at least in part, the shortcomings of the systems known in the art. Need was also felt of a device for detection of an analyte present in a sample that can alleviate, at least in part, the shortcomings of the devices known in the art.

OBJECT OF THE PRESENT DISCLOSURE
[0005] Accordingly, an object of the present disclosure is to provide for a system and device that facilitates monitoring temperature and fluorescence simultaneously by exploiting rotational symmetry of the system.
[0006] An object of the present disclosure is to provide for a system and device that facilitates accurate measure of some parameters of a multi-well plate without having to ensure positioning accuracy.
An object of the present disclosure is to provide for a system and device that minimizes sensor duplication and hence facilitates the use of a minimal number of sensors for measuring parameters associated with multiple samples.

SUMMARY
[0007] The present invention generally relates to the technical field of sensor multiplexing. Particularly, aspects of the present disclosure provide a system for determination of parameters associated with a sample and a device for detection of an analyte present in a sample. The system and device of the present disclosure can find utility in myriad of applications, including usage thereof as Polymerase Chain Reaction (PCR) device, but not limited thereto. Further aspects of the present disclosure relate to a method of operating the device.
[0008] An aspect of the present disclosure provides a system for determination of parameters associated with a sample, the system may include a platform configured to hold a plurality of samples and an array of sensors configured for determination of a plurality of parameters associated with the plurality of samples, the array of sensors may further include at least two sensors, a first sensor configured to determine a first parameter associated with a first sample, and a second sensor configured to determine a second parameter associated with a second sample. The system may further include a control unit coupled to the array of sensors, the control unit causes the system to: receive the first parameter associated with the first sample and receive a second parameter associated with the second sample, based on the determination of the second parameter associated with the second sample, a third parameter associated with the first sample, the third parameter being different from the first parameter.
[0009] In an embodiment, the first sensor may be configured to determine the first parameter without making contact with the first sample. In an embodiment, the second sensor may be configured to determine the second parameter without making contact with the second sample. In an embodiment, the first parameter may be different from the second parameter.
[0010] In an embodiment, the array of sensors may be configured such that, at an instance, the first sensor may stare at the first sample and the second sensor may stare at the second sample enabling simultaneous determination of the first parameter of the first sample and the second parameter of the second sample. The processor may cause the system to estimate, based on the determination of the second parameter of the second sample, a third parameter of the first sample.
[0011] In an embodiment, each of the first parameter, the second parameter and the third parameter may be independently selected from a group including temperature and fluorescence. In an embodiment, the first sensor may be a fluorescence sensor and the first parameter may be fluorescence. In an embodiment, the second sensor may be an IR sensor and the second parameter may be temperature.
[0012] In an embodiment, the array of sensors may be configured such that, at an instance, the fluorescence sensor may stare at the first sample and the IR sensor may stare at the second sample enabling simultaneous determination of the fluorescence of the first sample and the temperature of the second sample. The processor may cause the system to estimate, based on the determination of the temperature of the second sample, temperature of the first sample.
[0013] In an embodiment, the array of sensors may be configured on a support. In an embodiment, the support may be coupled with one or a plurality of actuators to confer any or a combination of a rotational motion and a translational motion thereto. In an embodiment, the support may be configured for allowing radial extension of the sensors.
[0014] Another aspect of the present disclosure provides a device for determination of parameters associated with a sample, the device may include a platform configured to hold a plurality of samples and an array of sensors configured for determination of a plurality of parameters associated with the plurality of samples, the array of sensors may further include at least two sensors, a first sensor configured to determine a first parameter associated with a first sample, and a second sensor configured to determine a second parameter associated with a second sample. The device may further include a control unit coupled to the array of sensors, the control unit may cause the device to: receive the first parameter associated with the first sample and receive a second parameter associated with the second sample, based on the determination of the second parameter associated with the second sample, a third parameter associated with the first sample, the third parameter being different from the first parameter.
[0015] In an embodiment, the control unit may be further configured to control temperature of few or all of the plurality of sample. In an embodiment, the control unit may be coupled with a temperature maintaining unit configured to maintain said plurality of samples at a substantially same temperature based on determination of any of the first parameter, second parameter and the third parameter.
[0016] In an embodiment, the control unit may be coupled to one or plurality of emitters configured to emit electromagnetic radiation. In an embodiment, the one or a plurality of emitters are configured to emit electromagnetic radiations in visible spectrum (wavelength ranging from 400-900 nm). In an embodiment, the emitter may include LED. In an embodiment, the first sensor may be configured to determine the first parameter without making contact with the first sample. In an embodiment, the second sensor may be configured to determine the second parameter without making contact with the second sample. In an embodiment, the first parameter may be different from the second parameter. In an embodiment, each of the first parameter, the second parameter and the third parameter may be independently selected from a group including temperature and fluorescence. In an embodiment, the array of sensors may be configured such that, at an instance, the first sensor stares at the first sample and the second sensor stares at the second sample enabling simultaneous determination of the first parameter of the first sample and the second parameter of the second sample, wherein the device may be configured to estimate, based on the determination of the second parameter of the second sample, a third parameter of the first sample. In an embodiment, the first sensor may be a fluorescence sensor and the first parameter may be fluorescence. In an embodiment, the second sensor may be an IR sensor and the second parameter may be temperature. In an embodiment, the array of sensors may be configured such that, at an instance, the fluorescence sensor may stare at the first sample and the IR sensor may stare at the second sample enabling simultaneous determination of the fluorescence of the first sample and the temperature of the second sample, wherein the device may be configured to estimate, based on the determination of the temperature of the second sample, temperature of the first sample. In an embodiment, the device may be configured to control operation of the control unit based on any of the temperature of the first sample and the temperature of the second sample. In an embodiment, the device may be configured to control output of the one or a plurality of emitters based on any of the temperature of the first sample and the temperature of the second sample. In an embodiment, the array of sensors may be configured on a support. In an embodiment, the support may be coupled with one or a plurality of actuators to confer any or a combination of a rotational motion and a translational motion thereto. In an embodiment, the support may be configured for allowing radial extension of the sensors. In an embodiment, the device may be a PCR device and the analyte may be a nucleic acid.

BRIEF DESCRIPTION OF DRAWINGS
[0017] FIG. 1 illustrates an exemplary schematic front view of the system (100) realized in accordance with an embodiment of the present disclosure.
[0018] FIG. 2 illustrates an exemplary schematic view showing an array of sensors (106) and a plurality of samples held on a platform (102) in accordance with an embodiment of the present disclosure.
[0019] FIG. 3A illustrates an exemplary schematic front view of the system realized in accordance with an embodiment of the present disclosure.
[0020] FIG. 3B-3D illustrate exemplary schematic views showing different configurations of the sensor array and samples, in accordance with embodiments of the present disclosure.
[0021] FIG. 4A illustrates an exemplary schematic front view of the device realized in accordance with embodiments of the present disclosure.
[0022] FIG. 4B an exemplary schematic front view of another variant of the device realized in accordance with embodiments of the present disclosure.
[0023] FIG. 5A and FIG. 5B illustrate exemplary views showing positioning of various components of the device, in accordance with embodiments of the present disclosure.
[0024] FIG. 6A and FIG. 6B illustrate exemplary front and back views of a reaction cassette.
[0025] FIG. 7A-7C illustrate exemplary schematic views showing various components of the device in accordance with embodiments of the present disclosure.

DETAILED DESCRIPTION
[0026] The present invention generally relates to the technical field of thermal cyclers. Particularly, the present disclosure provides a portable energy-efficient optothermal temperature cycler for small-volume chemical reactions. The temperature cycler of the present disclosure can find utility in myriad of applications, including usage thereof as Polymerase Chain Reaction (PCR) thermal cycler, but not limited thereto. Further aspects of the present disclosure provide a portable reaction cassette, and a method of operating an optothermal temperature cycler.
[0027] The following is a detailed description of embodiments of the disclosure depicted in the accompanying drawings. The embodiments are in such detail as to clearly communicate the disclosure. However, the amount of detail offered is not intended to limit the anticipated variations of embodiments; on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the present disclosure as defined by the appended claims.
[0028] Each of the appended claims defines a separate invention, which for infringement purposes is recognized as including equivalents to the various elements or limitations specified in the claims. Depending on the context, all references below to the “invention” may in some cases refer to certain specific embodiments only. In other cases it will be recognized that references to the “invention” will refer to subject matter recited in one or more, but not necessarily all, of the claims.
[0029] As used in the description herein and throughout the claims that follow, the meaning of “a,” “an,” and “the” includes plural reference unless the context clearly dictates otherwise. Also, as used in the description herein, the meaning of “in” includes “in” and “on” unless the context clearly dictates otherwise.
[0030] All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g. “such as”) provided with respect to certain embodiments herein is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention otherwise claimed. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the invention.
[0031] An aspect of the present disclosure provides a system for determination of parameters associated with a sample, the system may include: a platform configured to hold a plurality of samples; and an array of sensors configured for determination of a plurality of parameters associated with the plurality of samples, the array of sensors may include at least two sensors, a first sensor configured to determine a first parameter associated with a first sample, and a second sensor configured to determine a second parameter associated with a second sample. The system may further include a control unit coupled to the array of sensors, the control unit cause the device to: receive the first parameter associated with the first sample and receive a second parameter associated with the second sample, based on the determination of the second parameter associated with the second sample, a third parameter associated with the first sample, the third parameter being different from the first parameter.
[0032] In an embodiment, the first sensor may be configured to determine the first parameter without making contact with the first sample. In an embodiment, the second sensor may be configured to determine the second parameter without making contact with the second sample. In an embodiment, the first parameter may be different from the second parameter.
[0033] In an embodiment, the array of sensors may be configured such that, at an instance, the first sensor may stare at the first sample and the second sensor may stare at the second sample enabling simultaneous determination of the first parameter of the first sample and the second parameter of the second sample, wherein the system may be configured to estimate, based on the determination of the second parameter of the second sample, a third parameter of the first sample.
[0034] In an embodiment, the parameter to be determined may be a parameter associated with an analyte. In an exemplary embodiment, the analyte may be a nucleic acid but not limited to the like.
[0035] In an embodiment, each of the first parameter, the second parameter and the third parameter may be independently selected from a group including temperature and fluorescence. In an embodiment, the first sensor may be a fluorescence sensor and the first parameter may be fluorescence. In an embodiment, the second sensor may be an IR sensor and the second parameter may be temperature. In an embodiment, the array of sensors may be configured such that, at an instance, the fluorescence sensor stares at the first sample and the IR sensor may stare at the second sample enabling simultaneous determination of the fluorescence of the first sample and the temperature of the second sample, wherein the system may be configured to estimate, based on the determination of the temperature of the second sample, temperature of the first sample.
[0036] In an embodiment, the array of sensors may be configured on a support. In an embodiment, the support may be coupled with one or a plurality of actuators to confer any or a combination of a rotational motion and a translational motion thereto. In an embodiment, the support may be coupled with one or a plurality of actuators to confer any or a combination of a rotational motion and a translational motion to one, few or all of the one or a plurality of sensors. In an embodiment, the platform may be coupled with one or a plurality of actuators to confer any or a combination of a rotational motion and a translational motion thereto.
[0037] FIG. 1 illustrates an exemplary schematic front view of the system (100) realized in accordance with an embodiment of the present disclosure. As can be seen from FIG. 1, the system (100) includes a platform (102) configured to hold a plurality of samples (104a, 104b, collectively, 104); and an array of sensors (106a, 106b, collectively, 106) configured for determination of a plurality of parameters associated with the plurality of samples (104), the array of sensors (106) may include at least two sensors, a first sensor (106a) configured to determine a first parameter associated with a first sample (104a), and a second sensor (106b) configured to determine a second parameter associated with a second sample (104b). The system (100) may be configured to estimate, based on the determination of the second parameter associated with the second sample (104b), a third parameter associated with the first sample (104a), the third parameter being different from the first parameter.
[0038] As can also be seen from FIG. 1, the first sensor (106a) may be configured to determine the first parameter without making contact with the first sample (104a), and the second sensor (106b) may be configured to determine the second parameter without making contact with the second sample (104b). In other words, in accordance with an embodiment, each of the first sensor and the second sensor can be non-contact based sensors. However, it may be completely within the scope of the present disclosure to have any or both the first sensor and second sensor being contact based sensors.
[0039] As also illustrated in FIG. 1, the array of sensors (106) may be configured such that, at an instance, the first sensor (106a) stares at the first sample (104a) and the second sensor (106b) stares at the second sample (104b) enabling simultaneous determination of the first parameter and the second parameter.
[0040] As can also be seen from FIG. 1, the array of sensors (106) may be configured on a support (108). The support (108) can be coupled with one or a plurality of actuators (110) to confer any or a combination of a rotational motion (shown using an arrow around the rotational axis of the support) and a translational motion (shown using an arrow) to the support (108) allowing desired positioning of the first sensor (106a) and the second sensor (106b) relative to the first sample (104a) and the second sample (104b). Alternatively, the platform (102) can be coupled with one or a plurality of actuators to confer any or a combination of a rotational motion and a translational motion allowing desired positioning of the first sample (104a) and the second sample (104b) relative to the first sensor (106a) and the second sensor (106b).
[0041] In an embodiment, the system (100) may be used for determination of fluorescence and temperature of the sample as a function of time. The first sensor can be a fluorescence sensor, the first parameter can be fluorescence, the second sensor can be an IR sensor and the second parameter can be temperature. The array of sensors (106) can be positioned (e.g. by rotating the support 108) such that, at an instance, the fluorescence sensor (106a) stares at the first sample (104a) and the IR sensor (106b) stares at the second sample (104b) enabling simultaneous determination of the fluorescence of the first sample and the temperature of the second sample. In one implementation, few or all of the samples are maintained at a substantially same temperature or they are so positioned such that they are at a substantially same temperature. The term “substantially same temperature” as used herein, throughout the present disclosure, denotes the meaning that the variation in temperature between two (2) samples may be no greater than ±20 K, and preferably no greater than ±10 K (i.e. each of the sample may be maintained at a pre-determined temperature ±5 K). In case one contiguous heating block uniformly contacting each of the samples (i.e. employing contact based heating method) may be employed, the samples can easily be maintained at a substantially same temperature. In case a plurality of heating blocks may be employed, one each for the sample or one heating block spanning over (uniformly contacting) several samples, with adequate control over each of the heating blocks, the samples can be maintained at a substantially same temperature. When non-contact based heating mechanism (such as emitter) may be employed, the samples can be maintained at a substantially same temperature when the samples and/or the temperature maintenance unit (e.g. one or a plurality of emitters) exhibit symmetry, preferably, when both the samples and the temperature maintenance unit exhibit symmetry. For example, the platform can hold 4 samples arranged in a square shape (as can be seen from FIG. 2) exhibiting 4-fold radial symmetry (tetrameric). When the temperature maintenance unit may be radially symmetric (e.g. a single circular emitter or in case of plurality emitters, the emitters may be arranged in circular shape) or tetrameric (i.e. exhibit 4-fold radial symmetry, for example, by arranging emitters in a square shape), each of the samples can be maintained at a substantially same temperature. Accordingly, the temperature of each of the samples would be substantially same, provided that the quantity and nature of the samples remains same from a thermodynamic perspective [i.e., heat capacity as a function of temperature and emissivity (since an infrared temperature sensor may be employed) are similar]. In such case, fluorescence sensor (106a) can detect fluorescence of the first sample (104a) and the IR sensor (106b) can detect temperature of the second sample (104b). The system can, for example, with the use of a controller, can estimate temperature of the first sample (104a) based on the temperature of the second sample (104b), since temperature of both the first sample (104a) and the second sample (104b) remains substantially same. Accordingly, the system of the present disclosure can advantageously determine plurality of parameters associated with a sample. In alternate implementations, instead of or in conjunction to maintaining few or all of the samples at a substantially same temperature, the controller may be modeled/programmed to estimate the temperature of the first sample based on the determined temperature of the second sample. For example, the controller may be calibrated to estimate temperature of the first sample based on the determined temperature of the second sample for a source of light and other design related aspects of a particular system or device (e.g. if the array of sensors will be rotated or if the samples will be rotated or if both the array of sensors and the samples will be rotated etc.). One may even configure a controller with self-learning capability to estimate the temperature of the first sample based on the determined temperature of the second sample.
[0042] FIG. 2 illustrates an exemplary schematic view showing an array of sensors (106) and a plurality of samples held on a platform (102) in accordance with an embodiment of the present disclosure. As can be seen from FIG. 2, the array of sensors (106) may include a plurality of sensors, wherein one sensor (shown as the circular sensor with a red center) may be an IR sensor and other 3 sensors are fluorescence sensors, each of the 3 fluorescence sensors configured to measure fluorescence at different pre-determined wavelengths. The system in this case may be capable of determining fluorescence at at least three different wavelengths as a function of temperature. Since, the temperature of each of the samples may be substantially same, provision of one IR sensor suffice, which can detect temperature of one of the at least four samples while fluorescence can be detected for rest of the at least three samples. For example, temperature of each of the four samples may be maintained substantially at 70°C. At an instance, the IR sensor detects temperature of 1st sample, and each of the 3 fluorescence sensors, configured to measure fluorescence at 500nm, 600 nm and 800nm, respectively, can detect the fluorescence of each of the 2nd, 3rd and 4th sample. Once the determination may be over, the array of sensors (106) is rotated bringing the IR sensor on the 2nd sample and the 3 fluorescence sensors on the 3rd, 4th and the 1st sample. Similarly, the array of sensors (106) may be rotated 2 more times such that, for each sample, fluorescence at 3 different wavelengths as a function of temperature can be determined. Accordingly, the advantageous system of the present disclosure significantly increases throughput of the system, obviating the need of presence of multiple sets of sensors for each sample and/or obviating the constraint of having to process one sample at a time.
[0043] FIG. 3A illustrates an exemplary schematic front view of the system realized in accordance with an embodiment of the present disclosure. FIG. 3B-3D illustrate exemplary schematic views showing different configurations of the sensor array and samples, in accordance with embodiments of the present disclosure. As can be seen from the FIG. 3A-3D, in some embodiments, the sample denoted as 104c may be a blank sample (shown in FIG. 3B-3D as black solid circle) e.g. the sample may be devoid of any reagent or fluid, or the sample may just be a surface/area that may be indicative of temperature of the samples present in its vicinity (e.g. an area on the thermally conductive material, as detailed below in reference to the reaction cassette). As can also be seen from FIG. 3A, one of the sensor (e.g. an IR sensor) is configured to continuously stare at the sample denoted as 104c. One or more other sensors (e.g. fluorescence sensor, IR sensor) can be provided as part of the array of sensors.
[0044] In an embodiment, any or a combination of the support and platform are configured to make intermittent rotational motion (e.g. the rotation can be stopped momentarily to determine the parameter and once the parameter may be determined for a sample, relative position between the sensor and sample can be changed such that parameter for the next sample can be determined). Alternatively, any or a combination of the support and platform can be configured to make continuous rotational motion (i.e. it/they are continuously rotated). Continuous rotational motion may be advantageous in that – it can preclude requirement of exact alignment of the sensor(s) relative to the sample(s). In an embodiment, the support is coupled with one or a plurality of actuators to confer any or a combination of a rotational motion and a translational motion to one, few or all of the one or a plurality of sensors. In an embodiment, one, few or all of the sensors are configured with one or a plurality of actuators to confer any or a combination of a rotational motion and a translational motion thereto. In an embodiment, one, few or all of the sensors have an axis of rotation, different than that of the support or that of the platform, such that the sensor can follow a particular path, for example, spiral or helical path while determining a parameter.
[0045] Although few of the embodiments/implementations are described herein with reference to usage of IR sensor(s), it should be appreciated that any other known non-invasive or semi-invasive temperature detection mechanism(s)/sensor(s) can be employed in device of the present disclosure to serve its intended purpose. For example, in place of IR sensor, one can use IR camera, IR grid or such other non-contact based temperature sensors to detect temperature of the sample. Alternative, one can use a thermocouple or such other contact based temperature sensors that can, momentarily or continuously, touch the sample to determine temperature thereof. Alternatively, one can rely on the indirect methods of temperature detection, e.g. one can use thermochromic liquid crystals, whose optical properties depend on the temperature; one can use fluorescence dye, whose fluorescence depend on the temperature; one can use raman spectroscopy, fluorescence correlation spectroscopy or such other spectroscopic techniques where the signal depends on temperature. One can find further details on the aforesaid techniques and other techniques that can be employed for detection of temperature in the present invention in Chunsun Zhang and Da Xing “Miniaturized PCR chips for nucleic acid amplification and analysis: latest advances and future trends”, Nucleic Acids Res. 2007 Jul; 35(13): 4223–4237 (doi: 10.1093/nar/gkm389), contents whereof may be incorporated herein, in its entirety, by way of reference.
[0046] Another aspect of the present disclosure provides a device for detection of an analyte present in a sample, wherein the device may include: a platform configured to hold a plurality of samples; a control unit configured to control temperature of few or all of the plurality of samples; and an array of sensors configured for determination of a plurality of parameters associated with the plurality of samples, the array of sensors may include at least two sensors, a first sensor configured to determine a first parameter associated with a first sample, and a second sensor configured to determine a second parameter associated with a second sample, and wherein the device may be configured to estimate, based on the determination of the second parameter associated with the second sample, a third parameter associated with the first sample, the third parameter being different from the first parameter. In an embodiment, the device may be a PCR device. In an embodiment, the analyte may be nucleic acid.
[0047] In an embodiment, the control unit may be configured to maintain the plurality of samples at a substantially same temperature. In an embodiment, the device may be configured to control operation of the unit based on determination of any of the first parameter, second parameter and the third parameter.
[0048] In an embodiment, the control unit may include a temperature maintenance unit (also referred to as the heating unit hereinafter). In an embodiment, the unit may include one or a plurality of emitters configured to emit electromagnetic radiation. In an embodiment, the one or a plurality of emitters are configured to emit electromagnetic radiations in visible spectrum (wavelength ranging from 400-900 nm). In an embodiment, the emitter may include LED but not limited to it.
[0049] In an embodiment, the first sensor may be configured to determine the first parameter without making contact with the first sample. In an embodiment, the second sensor may be configured to determine the second parameter without making contact with the second sample.
[0050] In an embodiment, the first parameter may be different from the second parameter. In an embodiment, each of the first parameter, the second parameter and the third parameter are independently selected from a group including temperature and fluorescence, but not limited thereto.
[0051] In an embodiment, the array of sensors may be configured such that, at an instance, the first sensor stares at the first sample and the second sensor stares at the second sample enabling simultaneous determination of the first parameter of the first sample and the second parameter of the second sample. The device may be configured to estimate, based on the determination of the second parameter of the second sample, a third parameter of the first sample.
[0052] In an embodiment, the first sensor may be a fluorescence sensor and the first parameter may be fluorescence. In an embodiment, the second sensor may be an IR sensor and the second parameter may be temperature. In an embodiment, the array of sensors may be configured such that, at an instance, the fluorescence sensor stares at the first sample and the IR sensor stares at the second sample enabling simultaneous determination of the fluorescence of the first sample and the temperature of the second sample. The device may be configured to estimate, based on the determination of the temperature of the second sample, temperature of the first sample.
[0053] In an embodiment, the device may be configured to control operation of the temperature maintenance unit based on any of the temperature of the first sample and the temperature of the second sample. In an embodiment, the device may be configured to control output of the one or a plurality of emitters based on any of the temperature of the first sample and the temperature of the second sample.
[0054] In an embodiment, the array of sensors may be configured on a support. In an embodiment, the support may be coupled with one or a plurality of actuators to confer any or a combination of a rotational motion and a translational motion thereto. In an embodiment, the platform may be coupled with one or a plurality of actuators to confer any or a combination of a rotational motion and a translational motion thereto. In an embodiment, the support may be coupled with one or a plurality of actuators to confer any or a combination of a rotational motion and a translational motion to one, few or all of the one or a plurality of sensors. In an embodiment, one, few or all of the sensors have an axis of rotation, different than that of the support or than that of the platform, such that the sensor can follow a particular path, for example, spiral or helical path while determining a parameter. In an embodiment, the array of sensors may be capable of radial extension.
[0055] FIG. 4A illustrates an exemplary schematic front view of the device realized in accordance with embodiments of the present disclosure. As can be seen from FIG. 4A, the device (400) includes: a platform (402) configured to hold a plurality of samples (404a, 404b, collectively, 404); a control unit (405) configured to control temperature of few or all of the plurality of samples (404); and an array of sensors (406a, 406b, collectively 406) configured for determination of a plurality of parameters associated with the plurality of samples (404), the array of sensors (406) may include at least two sensors, a first sensor (406a) configured to determine a first parameter associated with a first sample (404a), and a second sensor (406b) configured to determine a second parameter associated with a second sample (404b). The device (400) may be configured to estimate, based on the determination of the second parameter associated with the second sample, a third parameter associated with the first sample, the third parameter being different from the first parameter.
[0056] As can also be seen from FIG. 4A, the first sensor (406a) may be configured to determine the first parameter without making contact with the first sample (404a) and the second sensor (406b) may be configured to determine the second parameter without making contact with the second sample (404b) i.e. both the first sensor (406a) and the second sensor (406b) are non-contact based sensors. As can also be seen from FIG. 4A and 4B, the array of sensors (406) may be configured such that, at an instance, the first sensor (406a) stares at the first sample (404a) and the second sensor (406b) stares at the second sample (404b) enabling simultaneous determination of the first parameter of the first sample (404a) and the second parameter of the second sample (404b). The device (404) may be configured to estimate, based on the determination of the second parameter of the second sample, a third parameter of the first sample. The support (408) can be coupled with one or a plurality of actuators (410) to confer any or a combination of a rotational motion (shown using an arrow around the rotational axis of support) and a translational motion (shown using an arrow) to the support (408) allowing desired positioning of the first sensor (406a) and the second sensor (406b) relative to the first sample (404a) and the second sample (404b).
[0057] FIG. 4B an exemplary schematic front view of another variant of the device realized in accordance with embodiments of the present disclosure. As can be seen from FIG. 4B, one of the sensors (e.g. an IR sensor) may be configured to continuously stare at one of the samples while one or more other sensors (e.g. fluorescence sensor, IR sensor) can be provided as part of the array of sensors to serve its intended purpose as detailed in various embodiments of the present disclosure.
[0058] In an embodiment, the device may be a PCR device. In an embodiment, the analyte may be nucleic acid (for example dsDNA but not limited to it). As would be appreciated, fluorescence readings are typically taken at specific point(s) in the PCR thermal cycle, and the temperature needs to be maintained at a constant set-point during this time (i.e. the temperature may need to be constant during detection of fluorescence), because the amplitude of the fluorescence signal depends on the temperature. Hence, the device may be configured to control operation of the control unit (405) based on the determined temperature. For example, when the control unit (405) may include one or a plurality of emitters, the device may be configured to control output of the one or a plurality of emitter based on the determined temperature of any or a combination of the first sample (404a) and the second sample (404b).
[0059] FIG. 5A and FIG. 5B illustrate exemplary views showing positioning of various components of the device, in accordance with embodiments of the present disclosure. For the sake of simplicity, the platform may be shown in FIG. 5A and 5B holding a reaction cassette having only one sample. However, it would be readily apparent that the reaction cassette having plurality of samples can be positioned on the platform in accordance with embodiments of the present disclosure. As can be seen from FIG. 5A and 5B, the device (400) includes: a platform (402) for holding the samples (404); a control unit (405) configured to control temperature of the sample(s); and an array of sensors (406) configured for determination of parameters associated with the sample(s).
[0060] FIG. 6A and FIG. 6B illustrate exemplary front and back views of a reaction cassette having one sample for the sake of simplicity. As can be seen from FIG. 6A and 6B, the reaction cassette (600) includes: a scaffold (602) made of a thermally insulating material (such as cardboard or plastic that may be resistant to higher temperature, such as about 150°C, and rapid changes in the temperature conditions), the scaffold defining at least one region (604) made of a thermally conductive material (such as Aluminium). The at least one region (604) can be configured to host a volume of one or more reagents (i.e. a sample). The at least one region defines a first surface (visible in front view, FIG. 6A) facing the one or more reagents (sample) and a second surface (visible in back view, FIG. 6B, shown as blackened surface) opposite to the first surface. In an embodiment, the first surface, in contact with the sample, may be coated with one or more materials (for example polymeric or non-polymeric materials such as PDMS, PMMA but not limited to the like.) to make the surface biocompatible. With regards the reaction cassette configured for holding a plurality of samples, which may be utilized in embodiments of the present disclosure, the scaffold (602) can define a plurality of regions made of same or different thermally conductive materials. Alternatively, the region (604) can define a plurality of depressions at its first surface (each may serve to contain a sample), as shown schematically in FIG. 4A and 4B and denoted as 404a and 404b. As also visible in FIG. 6B, the second surface of the region, intended to be directly facing the control unit (405), can have higher thermal conductivity (or higher electromagnetic radiation absorptivity in case the control unit may include one or a plurality of emitter) as compared to the first surface. For example, the second surface can be deposited with a material to increase its electromagnetic radiation absorptivity as compared to the first surface. The thermally conductive material can also define one or a plurality of area that may serve as a blank sample. For example, in case a region defines a plurality of depressions at its first surface, one of the depressions defined on the region can be intended to be a blank sample i.e. the depression being devoid of any reagent therein. In case the thermally conductive material defines a plurality of regions, each configured to hold a sample, one of the region (604) can be intended to be a blank sample i.e. the region being devoid of any reagent therein. In case the thermally conductive material defines a plurality of regions, each region defining a plurality of depressions, one of the depressions defined on each of the region can be intended to be a blank sample i.e. the depression being devoid of any reagent therein. Alternatively, the thermally conductive material may have one or a plurality of areas/parts thereon, which are not intended to hold the sample, that may serve as blank sample e.g. an area on first surface of the thermally conductive material that does not define a depression, but may be coated with a suitable material such as PVC electrical tape but not limited to it that may aid in determining temperature thereof.
[0061] With regards working, cassette (600) can be positioned on the platform (402), as shown in FIG. 5B and the control unit (405) may be switched-on, resulting in heating of the sample(s). In case the control unit includes one or a plurality of emitters (such as LED), the electromagnetic radiations emanated from the emitter fall on region (604) at its second surface, which absorbs, at least, part of the electromagnetic radiations and converts the absorbed light into heat. The emitter (such as a LED) can, for example, be configured to emit electromagnetic radiations in the visible spectrum (wavelength ranging from 400-900 nm). The thermal mass of the sample in the center may be large; this means that it will be colder than the surrounding thermally conductive material. Heat thus conducts towards the sample, increasing its temperature. All objects whose temperature may be above absolute zero emit light. This spectrum closely approximates the blackbody spectrum in many cases. We are interested in the light (electromagnetic radiations) emitted by the heated volume of one or a plurality of reagents. The surrounding thermally conductive material has a low emissivity and may be highly reflective. Thus, the signal we observe from it will not give us the temperature of the foil itself, but of some reflected object. In order to avoid this and to ensure that the signal we receive may be from the sample, an IR temperature sensor (such as, the one available commercially as “Melexis MLX90615”) can be positioned in proximity of the sample (for example, at a distance of 0-3 mm). Accordingly, the temperature of the sample can be detected accurately without actually making any thermal contact with the sample.
[0062] Once the temperature of the sample may be detected by a sensor (for example, by IR sensor), the sensor can transmit the detected temperature to the controller. The controller can then compare the detected temperature with the pre-defined temperature (which, for example, may be selected/fed by the user or may be pre-fed into the device in form of temperature cycles) and control output of the control unit (e.g. an emitter, whose brightness/output can be controlled) based on the comparison. Any conventional controller, as known to or appreciated by a person skilled in the art, may be used for controlling operation of the control unit. In an exemplary implementation, a proportional-integral-derivative (PID) controller may be used for controlling operation of the control unit based on the detected temperature. Pulse-width modulation (PWM) of ~1 kHz or higher may suffice to control the LED brightness, as the thermal mass of the system smoothens out the variation. With regards decreasing the temperature of the sample (as may be required during a PCR cycle), cooling typically occurs rapidly by contact of the region (604) holding the sample with the ambient environment. Accordingly, provision of additional heat-sink or cooling mechanism may be not necessary. Nonetheless, if need be, one can configure one or more heat-sinks or blowers (such as, a small fan) or such other cooling mechanism (such as a solenoid activated pin that touches the thermally conductive material for reducing its temperature) for rapidly decreasing the temperature of the sample. Accordingly, the device may be capable of maintaining the desired temperature of the sample based on the feedback from the sensor(s). The system and device of the present disclosure can, based on the determination of temperature of a second sample, control the control unit (such as emitter) to maintain the desired temperature of the sample (for example temperature in accordance with the thermal cycling) while effecting determination of fluorescence therefrom. The system and device of the present disclosure can, advantageously, be utilized as Real-Time Quantitative Polymerase Chain Reaction (RTPCR/QPCR) device. The system and device of the present disclosure does not necessitate usage of optical components such as focusing lenses or additional heat-sink(s) or cooling mechanism, making the overall device portable, economical, energy efficient, and easy to manufacture. The system and device of the present disclosure can be used at point-of-care settings as a diagnostic device (for example, for detection of COVID-19). The system and device of the present disclosure can also be used for performing melting curve analysis (MCA), where one measures the fluorescence as a function of temperature to find the temperature at which 50% of the amplified DNA may be dissociated. This can be done, for instance by using a dye (such as SYBR Green) whose fluorescence intensity depends on the amount of DNA that may be still not yet dissociated.
[0063] The system and device of the present disclosure are particularly suited for detection of pathogens using Polymerase Chain Reaction (PCR) as explained in greater detail in New England Biosciences, “Polymerase Chain Reaction (PCR) | NEB.” available at https://international.neb.com/applications/dna-amplification-pcr-and-qpcr/polymerase-chain-reaction-pcr, contents whereof may be incorporated herein, in its entirety, by way of reference. In PCR reaction, typically, genetic material (DNA or RNA) may be extracted from a sample such as blood, sputum, urine sample etc. of a subject, and introduced into a solution containing reagents that will specifically replicate only the DNA corresponding to the pathogen. For this reaction, first, the temperature may be raised to about 95°C for a few minutes, after which the temperature must be cycled between 3 different set-points, known as annealing temperature (typically between 48-72°C), extension temperatures (68-72°C), and denaturation temperatures (94-98°C). There are usually 25-35 such cycles, followed by a final extension step at the same temperature at the extension step. In accordance with one of the methods, an intercalating dye that specifically binds to the amplicons (which are usually a double stranded DNA or dsDNA) may be then contacted with the sample (potentially containing dsDNA copies), and upon binding, the fluorescence intensity of the dye increase. Since, the change in intensity of fluorescence may be directly proportional to the concentration of the DNA, the change in fluorescence intensity can be measured to quantify the amount of amplicon (i.e. the analyte). The other method of quantifying PCR-amplicons may be by using primers conjugated with fluorescent molecules. These probes are widely used in Real-time PCR machines and enable to multiplex the reaction by using different fluorescent dyes for different primer set. The device of the present disclosure can advantageously be used in any of abovementioned techniques.
[0064] FIG. 7A illustrates an exemplary schematic showing various components of the device in accordance with embodiments of the present disclosure. For the sake of precluding repetition, three (3) variants of the sensor array (406) are shown in FIG. 7A, wherein any of the variants of the sensor array, denoted as 406 a), 406 b) and 406 c), can be used in alternative to serve its intended purpose as laid down in embodiments of the present disclosure. As can be seen from FIG. 7A, the platform (402) holds a plurality of samples, wherein the samples exhibit rotational symmetry (i.e. samples, collectively remains “unchanged” by a rotation of 360°/n). As can also be seen from FIG. 7A, the control unit (405) includes a plurality of emitters (such as LED), wherein the control unit exhibits rotational symmetry. Hence, each of the samples may be maintained at a substantially same temperature, as explained in greater detail hereinabove. Alternatively, instead of or in conjunction to maintaining few or all of the samples at a substantially same temperature, the controller may be modeled/programmed such that the it can estimate the temperature of one sample based on the temperature of the another sample, as also explained in greater detail hereinabove. In accordance with an embodiment of the present disclosure, the array of sensors may be configured on a support (408), wherein the support may be configured for allowing radial extension of one or a plurality of sensors (as shown in FIG. 7C). Any mechanism known to or appreciated by a person skilled in the art can be used for affording radial extension of one or a plurality of sensors. Further, any or a combination of the support (408) and platform (406) can be configured with one or a plurality of actuators to confer any or a combination of a rotational motion and a translational motion to the support (408) and/or to the platform (406) allowing desired positioning of the sensors relative to the samples. Advantageously, when the device allows for radial extension of one or a plurality of sensors coupled with a rotational motion of any or a combination of the support (408) and the platform (406), a fewer number of sensor can serve a plurality of samples, significantly reducing bulk of the device. As can be seen from FIG. 7B, radial extension of one or a plurality of sensors can cater to determination of farther samples. Particularly, as shown in FIG. 7B, sensor 406a, capable of radial extension, can determine parameters associated with both sample 404a and 404aa, and the sensor 406b, capable of radial extension, can determine parameters associated with both sample 404b and 404bb. FIG. 7A illustrates an exemplary schematic showing a path (450) by sensor(s) when the sensor(s) are capable of radial extension and rotational motion may be conferred to any or a combination of the support (408) and the platform (406).
[0065] In an embodiment, any or a combination of the support (408) and platform (406) are configured to make intermittent rotational motion (e.g. the rotation may be stopped momentarily to determine the parameter and once the parameter may be determined for a sample, relative position between the sensor and sample can be changed such that parameter for the next sample can be determined). Alternatively, any or a combination of the support (408) and platform (406) are configured to make continuous rotational motion (i.e. it/they are continuously rotated). Continuous rotational motion may be advantageous in that – it can preclude requirement of exact alignment of the sensor(s) with respect to the sample(s). In an embodiment, the support may be coupled with one or a plurality of actuators to confer any or a combination of a rotational motion and a translational motion to one, few or all of the one or a plurality of sensors. In an embodiment, one, few or all of the sensors are configured with one or a plurality of actuators to confer any or a combination of a rotational motion and a translational motion thereto. In an embodiment, one, few or all of the sensors have an axis of rotation, different than that of the support or than that of the platform, such that the sensor can follow a particular path, for example, spiral or helical path while determining a parameter.
[0066] It should be understood that various other modifications and combinations of the above embodiments are contemplated and will readily appear to those skilled in the art. Thus, the present invention contemplates that any and all such subject matter may be included within the scope of the present invention. The invention in its broader aspects may be therefore not limited to the specific details, representative apparatus and methods and illustrative examples shown and described. Accordingly, departures may be made from such details without departing from the scope or spirit of Applicants' general inventive concept.

ADVANTAGES OF THE PRESENT DISCLOSURE
[0067] The present disclosure provides for a system and device that facilitates monitoring temperature and fluorescence simultaneously by exploiting rotational symmetry of the system.
[0068] The present disclosure provides for a system and device that facilitates accurate measure of some parameters of a multi-well plate without having to ensure positioning accuracy.
[0069] The present disclosure provides for a system and device that minimizes sensor duplication and hence facilitates the use of a minimal number of sensors for measuring parameters associated with multiple samples.
,CLAIMS:1. A system for determination of parameters associated with a sample, the system comprising:
a platform configured to hold a plurality of samples; and
an array of sensors configured for determination of a plurality of parameters associated with the plurality of samples, said array of sensors comprising at least two sensors, wherein a first sensor determines a first parameter associated with a first sample, and wherein a second sensor determines a second parameter associated with a second sample;
a control unit coupled to the array of sensors, said control unit causes the system to:
receive the first parameter associated with the first sample and receive a second parameter associated with the second sample;
estimate, based on the determination of the second parameter associated with the second sample, a third parameter associated with the first sample, said third parameter being different from the first parameter.
2. The system as claimed in claim 1, wherein the first sensor determines the first parameter without making contact with the first sample and wherein the second sensor determines the second parameter without making contact with the second sample, wherein, the first parameter is different from the second parameter.
3. The system as claimed in claim 1, wherein said array of sensors is configured such that, at an instance, said first sensor stares at the first sample and said second sensor stares at the second sample enabling simultaneous determination of the first parameter of the first sample and the second parameter of the second sample, wherein the processor causes the system to estimate, based on the determination of the second parameter of the second sample, a third parameter of the first sample.
4. The system as claimed in claim 1, wherein each of the first parameter, the second parameter and the third parameter are independently selected from a group including temperature and fluorescence, wherein the first sensor is a fluorescence sensor and the first parameter is fluorescence and wherein, the second sensor is an IR sensor and the second parameter is temperature.
5. The system as claimed in claim 1, wherein said array of sensors is configured such that, at an instance, said fluorescence sensor stares at the first sample and said IR sensor stares at the second sample enabling simultaneous determination of the fluorescence of the first sample and the temperature of the second sample, wherein the processor causes the system to estimate, based on the determination of the temperature of the second sample, temperature of the first sample.
6. The system as claimed in claim 1, wherein said array of sensors is configured on a support, wherein said support is coupled with one or a plurality of actuators to confer any or a combination of a rotational motion and a translational motion thereto for allowing radial extension of the sensors.
7. A device for determination of parameters associated with a sample, said device comprising:
a platform configured to hold a plurality of samples;
an array of sensors configured for determination of a plurality of parameters associated with the plurality of samples, said array of sensors comprising at least two sensors, a first sensor configured to determine a first parameter associated with a first sample, and a second sensor configured to determine a second parameter associated with a second sample; and
a control unit coupled to the array of sensors, said control unit causes the device to:
receive the first parameter associated with the first sample and receive a second parameter associated with the second sample;
estimate, based on the determination of the second parameter associated with the second sample, a third parameter associated with the first sample, said third parameter being different from the first parameter.
8. The device as claimed in claim 7, wherein the control unit is further configured to control temperature of few or all of the plurality of sample, wherein the control unit is coupled with a temperature maintaining unit configured to maintain said plurality of samples at a substantially same temperature based on determination of any of the first parameter, second parameter and the third parameter.
9. The device as claimed in claim 7, wherein said control unit is coupled to one or a plurality of emitters configured to emit electromagnetic radiation in visible spectrum.
10. The device as claimed in claim 7, wherein said array of sensors is configured on a support, wherein said support is coupled with one or a plurality of actuators to confer any or a combination of a rotational motion and a translational motion thereto for allowing radial extension of the sensors.