WO2018188655A1 - Photothermal reaction analyzer - Google Patents

Photothermal reaction analyzer Download PDF

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Publication number
WO2018188655A1
WO2018188655A1 PCT/CN2018/083024 CN2018083024W WO2018188655A1 WO 2018188655 A1 WO2018188655 A1 WO 2018188655A1 CN 2018083024 W CN2018083024 W CN 2018083024W WO 2018188655 A1 WO2018188655 A1 WO 2018188655A1
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WO
WIPO (PCT)
Prior art keywords
container assembly
photothermal
photothermal reaction
analyzer
detector
Prior art date
Application number
PCT/CN2018/083024
Other languages
French (fr)
Inventor
Chenmin CHANG
Tsungju LI
Original Assignee
Riche Biotech Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Riche Biotech Inc. filed Critical Riche Biotech Inc.
Publication of WO2018188655A1 publication Critical patent/WO2018188655A1/en

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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03Cuvette constructions
    • G01N21/0332Cuvette constructions with temperature control
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01JMEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J3/00Spectrometry; Spectrophotometry; Monochromators; Measuring colours
    • G01J3/28Investigating the spectrum
    • G01J3/30Measuring the intensity of spectral lines directly on the spectrum itself
    • G01J3/36Investigating two or more bands of a spectrum by separate detectors
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01JMEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J3/00Spectrometry; Spectrophotometry; Monochromators; Measuring colours
    • G01J3/28Investigating the spectrum
    • G01J3/44Raman spectrometry; Scattering spectrometry ; Fluorescence spectrometry
    • G01J3/4406Fluorescence spectrometry
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64Fluorescence; Phosphorescence
    • G01N21/645Specially adapted constructive features of fluorimeters
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64Fluorescence; Phosphorescence
    • G01N2021/6417Spectrofluorimetric devices
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00Features of devices classified in G01N21/00
    • G01N2201/02Mechanical
    • G01N2201/023Controlling conditions in casing
    • G01N2201/0231Thermostating

Definitions

  • the present disclosure relates to in vitro diagnostic devices, and more particularly to a photothermal reaction analyzer and a method for performing an immunofluorescence reaction, an isothermal polymerase reaction, a reverse-transcriptase polymerase chain reaction, a multiplex polymerase chain reaction, a digital polymerase chain reaction, a conventional polymerase chain reaction, or a real-time polymerase chain reaction by using the photothermal reaction analyzer.
  • a polymerase chain reaction amplifies one or more fragments of DNA from single or multiple target templates.
  • the PCR typically take place in a confined space where the temperature is controlled.
  • a specific temperature program may be set by the user for the PCR.
  • Commercially available PCR analyzers are mostly thermal cyclers that control the temperature of the PCR.
  • the C-1000 TM Touch Thermal Cycler is a conventional PCR analyzer that allows the user to execute two sets of temperature programs simultaneously.
  • Commercially available PCR analyzers often provide a plurality of housing spaces, slots or wells for many sample containers.
  • the SimpliAmp TM Thermal Cycler is a conventional PCR analyzer that provides multiple slots for a plurality of samples and a remote control function.
  • Conventional PCR analyzers are also unable to perform other reactions commonly used in diagnostic applications, such as direct or indirect immunofluorescence reactions.
  • a variant of the PCR is real-time PCR or reverse-transcription PCR.
  • the results of real-time PCR can be observed optically inside the space where the reaction was taken place, because fluorescent molecules are often used in the reaction.
  • the fluorescent molecules can be excited by lasers of specific wavelengths and emit fluorescent signals that are indicative of the reaction.
  • Most of the PCR analyzers are equipped with optical components for the detection of fluorescence in the real-time PCR.
  • the optical components usually comprise a detector and an excitation source.
  • the fluorescent molecules in the sample container may be excited by the excitation light from the excitation source, and the detector detects the fluorescent signals from the excited fluorescent molecules. Therefore, the optical components need to be aligned with the slot to receive fluorescence signals in the sample container.
  • the optical components are required to move along the X-Y plane from one slot to another, in order to align themselves with the sample containers housed in the slot.
  • the CFX96 TM Real-Time PCR Detection System has an “optics shuttle” that travel across the 96-well plate when detecting fluorescence signals, and the green LED fires directly over a well.
  • the movement of the optical components in conventional real-time PCR analyzers require precise alignment between the optical components and the sample containers, slots, or wells. This alignment is the key for providing reliable and successful real-time PCR results.
  • conventional PCR analyzers or real-time PCR analyzers uses a single heating block as a thermal conductor to change the temperature of the sample containers.
  • the heating block elevates the temperature of the sample containers by having direct contacts with the sample containers.
  • the heating block may also have some direct contacts with the surrounding environment, or be housed in a thin shell.
  • the sample containers in the single thermal conductor would also be easily affected by temperatures in the surrounding environment. If it is extremely cold or hot in the surrounding environment, the temperature of the sample containers in the PCR analyzer would be affected. Reactions performed under inaccurate temperature may be inefficient and unreliable.
  • conventional PCR analyzers using the single thermal conductor design are not suitable to be used in the outdoor or at extreme environments.
  • the present disclosure provides a portable photothermal reaction analyzer with fixed optical components and multiple thermal conductors.
  • An embodiment of the present disclosure provides a photothermal reaction analyzer.
  • the photothermal reaction analyzer comprises a plurality of photothermal reaction units.
  • Each of the photothermal reaction units includes a container assembly having a slot, a sample container is fitted in the slot and for containing reagents for performing a photothermal reaction, a temperature control module coupled to the container assembly for controlling a first temperature program for the container assembly and a second temperature program for the sample container, and an optics module coupled to the container assembly and for emitting and detecting light.
  • the optics module is stationary relative to the container assembly.
  • the container assembly further comprises at least one opening connected to the slot, and one of the optics modules is coupled to the container assembly via the opening.
  • the container assembly further comprises at least two openings connected to the slot, and each of the optics modules comprises at least one excitation source for emitting an excitation light and at least one detector for detecting a visible light or a fluorescence signal.
  • the excitation source and the detector are coupled to the container assembly via the openings, respectively.
  • the optics module is configured to emit a blue excitation light, a green excitation light, an orange excitation light, a red excitation light, or any combination thereof.
  • the optics module is configured to detect a green fluorescence, a cyan fluorescence, an orange fluorescence, a red fluorescence, or any combination thereof.
  • the optics module is further configured to filter the fluorescence into a range of wavelength.
  • the temperature control module comprises a heating element coupled to one of the container assemblies via the opening (s) for heating the sample container, a container assembly temperature sensor, a sample temperature sensor, and a cooling component.
  • the heating element can be an electromagnetic wave generator.
  • the excitation source comprises a blue light excitation source, a green light excitation source, an orange excitation light source, or a red excitation light source.
  • the detector comprises a light emitting diode (LED) , a semiconductor laser diode (LD) , or any combination thereof.
  • LED light emitting diode
  • LD semiconductor laser diode
  • the detector comprises a green fluorescence detector, a cyan fluorescence detector, an orange flurescence detector, or a red fluorescence detector.
  • the detector comprises a photodiode (PD) , an avalanche photodiode (APD) , a photomultiplier tube (PMT) , a silicon photomultiplier (SIPM) , or any combination thereof.
  • PD photodiode
  • APD avalanche photodiode
  • PMT photomultiplier tube
  • SIPM silicon photomultiplier
  • the optics module further comprises a filter disposed between the excitation source and the detector and for filtering the fluorescence into a range of wavelength.
  • the detector comprises one or more imaging components for capturing at least one image of an inner side of the container assembly.
  • the photothermal reaction analyzer comprises a plurality of container assemblies, a container assembly receiving device, a plurality of temperature control modules, and a plurality of optics modules.
  • the container assembly receiving device comprises a plurality of cavities, and each of the cavities houses one of the container assemblies.
  • Each of the sample containers is fitted in one of the slots and for containing reagents for performing a photothermal reaction.
  • the temperature control module is coupled to the container assembly receiving device for controlling a third temperature program of the container assembly receiving device and the second temperature program for the sample containers.
  • Each of the optics modules is coupled to one of the container assemblies and for emitting and detecting light.
  • the optics modules are stationary relative to the container assemblies.
  • the photothermal analyzer comprises a container assembly block comprising a plurality of slots, a plurality of sample containers, a temperature control module, and a plurality of optics modules. Each of the sample containers fitted in one of the slots and for containing reagents for performing a photothermal reaction.
  • the temperature control module is coupled to the container assembly block for controlling a fourth temperature program of the container assembly block and the second temperature program for the sample containers.
  • Each of the optics modules is coupled to one of the slots of the container assembly block. The optics modules are stationary relative to the container assembly block.
  • the container assembly block further comprises a plurality of openings, and each of the openings is connected to one of the slots.
  • One of the optics modules is coupled to the slot via the opening.
  • the container assembly block further comprises a plurality of openings, at least two of the openings are connected to one of the slots, each of the optics modules comprises at least one excitation source for emitting an excitation light and at least one detector for detecting a visible light or a fluorescence signal.
  • the excitation source and the detector are coupled to one of the slots in the container assembly block via the openings, respectively.
  • the temperature control module comprises a plurality of heating elements for heating the sample containers, a container assembly block temperature sensor, a sample temperature sensor, and a cooling component.
  • Each of the heating element is coupled to one of the slots in the container assembly block via the opening (s) .
  • the heating element is an electromagnetic wave generator.
  • the photothermal reaction performed by the photothermal reaction analyzer or photothermal reaction unit is an immunofluorescence reaction, an isothermal polymerase reaction, a reverse-transcriptase polymerase chain reaction, a multiplex polymerase chain reaction, a digital polymerase chain reaction, a conventional polymerase chain reaction, or a real-time polymerase chain reaction.
  • the photothermal reaction analyzer unit further comprising a control module for controlling the temperature control module and the optics module.
  • FIG. 1 is an exploded view of the structure of a photothermal reaction analyzer in accordance with an embodiment of the present disclosure.
  • FIG. 2 is a schematic illustration of the optical configuration among an excitation source, a sample container and a fluorescence detector in accordance with an embodiment of the present disclosure.
  • FIG. 3 is a perspective view of a container assembly receiving device of the photothermal reaction analyzer as depicted in FIG. 1 in accordance with an embodiment of the present disclosure.
  • FIG. 4 is an exploded view of a photothermal reaction analyzer in accordance with an embodiment of the present disclosure.
  • FIG. 5 is a block diagram showing the functional relationship of the photothermal reaction analyzer as depicted in FIG. 1 in accordance with an embodiment of the present disclosure.
  • FIG. 6 is a schematic illustration of a housing for the photothermal reaction analyzer in accordance with an embodiment of the present disclosure.
  • FIG. 7 is a flowchart showing a method for performing an immunofluorescence reaction using the photothermal reaction analyzer in accordance with an embodiment of the present disclosure.
  • FIG. 8 is results of the immunofluorescence reaction as depicted in FIG. 7 in accordance with an embodiment of the present disclosure.
  • FIG. 9 is a flowchart showing a method for performing a polymerase chain reaction using the photothermal reaction analyzer in accordance with an embodiment of the present disclosure.
  • a photothermal reaction unit 10 is provided in accordance with an embodiment of the present disclosure.
  • the photothermal reaction analyzer comprises a plurality of photothermal reaction units 10.
  • Each of the photothermal reaction units 10 includes a container assembly 140 having a slot 141, a sample container 110 is fitted in the slot 141 and for containing reagents for performing a photothermal reaction, a temperature control module 120 coupled to the container assembly for controlling a first temperature program for the container assembly 140 and a second temperature program for the sample container 110, and an optics module 130 coupled to the container assembly 140 and for emitting and detecting light.
  • the optics module 130 is stationary relative to the container assembly 140.
  • the sample container 110 is a transparent container having a closed space for containing the reagents.
  • the sample container 110 may be an eppendorf tube, a capillary tube, a microfluidic chip, a tip, or other containers with transparent wall and closed space.
  • the reagents may include one or more heat-generating reactants.
  • the heat-generating reactant can generate heat by irradiation with electromagnetic waves.
  • the reactant may be a transition metal material, and the transition metal material can be a transition metal oxide, a transition metal hydroxide, a Group III metal compound doped with the transition metal, a silicon dioxide doped with the transition metal oxide, or a silicon dioxide doped with the transition metal hydroxide.
  • the temperature of the reactant is elevated when irradiated by infrared irradiation.
  • the reagents may also include reagents for immunofluorescence reactions, or reagents for polymerase chain or real-time polymerase chain reactions.
  • the reagents for the immunofluorescence reaction may include analytes, fluorescent dyes, markers, and any other reagents necessary for an immunofluorescence reaction.
  • the reagents for the polymerase chain or real-time PCR may include analytes, polymerases, dNTPs, primers, probes, fluorescent dyes, template sequences, and any other reagents necessary for a PCR or real-time PCR.
  • the temperature control module 120 comprises a heating element 121 coupled to the container assembly 140 via the opening (not shown) for heating the sample container 110, a container assembly temperature sensor 124, a sample temperature sensor 122, and a cooling component 123.
  • the temperature control module 120 controls a first temperature program for the container assembly 140 and a second temperature program for the sample container 110.
  • the first temperature program regulates the temperature of the container assembly 140.
  • the first temperature program is designed for the container assembly to be in a consistent temperature, independent of the temperature of the surrounding environment.
  • the temperature of the container assembly 140 may be elevated or lowered slightly according to the first temperature program. Therefore, the photothermal reactions in the sample container 110 can be started in a stable condition, with little or no interference from the temperature of the surrounding environment.
  • the second temperature program is a predetermined program for the sample container 110 to be in one or more designated temperatures.
  • the second temperature program may include one or more designated temperatures, one or more time frames for the sample container 110 to be in a designated temperature, and one or more time frames for temperature ramping from one temperature to another.
  • the second temperature program may direct the sample container 110 to be in 65°C for 10 minutes, 95°C for 5 minutes, and ramping from 65°C to 95°C to be within 60 seconds.
  • the second temperature program can be designed by the user to specifically meet the temperature requirements of an immunofluorescence reaction, an isothermal polymerase reaction, a reverse-transcriptase polymerase chain reaction, a multiplex polymerase chain reaction, a digital polymerase chain reaction, a conventional polymerase reaction, or a real-time polymerase chain reaction.
  • the photothermal analyzer of the present disclosure is capable to perform an immunofluorescence reaction, an isothermal polymerase reaction, a reverse-transcriptase polymerase chain reaction, a multiplex polymerase chain reaction, a digital polymerase chain reaction, a conventional polymerase chain reaction, a real-time polymerase chain reaction, or any other in-vitro reactions with temperature restrictions.
  • the conventional polymerase chain reaction may require designated temperatures for denaturation, annealing, and elongation. However, the isothermal polymerase chain reaction or the immunofluorescence reaction may only require one or several designated temperatures.
  • the temperature control module 120 includes a heating element 121.
  • the heating element 121 is controlled by the second temperature program for heating the temperature of the sample container 110.
  • the heating element 121 is placed at the bottom of the sample container 110.
  • the heating element 121 may be an electromagnetic wave generator emitting one or more electromagnetic wave.
  • the electromagnetic waves emitted by the heating element 121 have a frequency range of 200 kHz to 500 THz.
  • the electromagnetic wave is in the spectrum of infrared.
  • the heating element 121 is an infrared laser diode.
  • the heating element 121 may emit electromagnetic waves to cause the heat-generating reactant raising the temperature of the reagents in the sample container 110.
  • the electromagnetic waves with specific wavelengths may induce elevated temperatures of the reactants in the reagent.
  • the temperature control module 120 may further include a sample temperature sensor 122.
  • the sample temperature sensor 122 is in direct contact with the sample container 110 for sensing the temperature of the sample container 110.
  • the sample temperature sensor 122 is a thermocouple.
  • sample temperature sensor 122 may also be integrated with the heating element 121 on the same component to reduce the volume and the power consumption of the sample temperature sensor 122 and the heating element 121.
  • the temperature control module 120 may further include a cooling element 123 for cooling the container assembly 140.
  • the cooling element 123 does not directly contact the sample container 110.
  • the cooling element 123 is controlled by the first temperature program.
  • the cooling element 123 can be an air cooling element, a fluid cooling element, an air-fluid hybrid cooling element, a semiconductor cooler.
  • the air cooling element may be a fan or components generating air flow to cool down the surrounding environment.
  • the fluid cooling element may be a cryocooler or components using fluids to cool down the surrounding environment.
  • the semiconductor cooler may be a semiconductor cooling plate or chip, such as a TE cooler (thermoelectric cooler) .
  • the sample container 110 is heated by the heating element 121, and is cooled by the container assembly 140, whereby the container assembly 140 can be cooled by the cooling element 123.
  • the temperature of the sample container 110 is detected by a sample temperature sensor 122.
  • the heating element 121, the sample temperature sensor 122 and the cooling element 123 are communicatively coupled to control and detect the temperature of the reagents in the sample container 110.
  • the optics module 130 can be configured to emit a blue excitation light, a green excitation light, an orange excitation light, a red excitation light, or any combination thereof.
  • the optics module 130 can also be configured to detect a green fluorescence, a cyan fluorescence, an orange fluorescence, a red fluorescence, or any combination thereof.
  • the optic module 130 can also be configured to filter the fluorescence into a range of wavelength.
  • the optics module 130 includes one or more excitation sources and one or more detectors.
  • the optics module 130 can also be configured to have different excitation sources emitting different wavelengths of excitation lights, or to have different detectors detect different wavelengths of fluorescence.
  • the excitation source 131a and 131b, the detector 132a and 132b are shown as an exemplary design in FIG. 1.
  • the excitation source 131a and 131b may emit an excitation light to the reagents in the sample container 110.
  • the fluorescent dyes in the reagents emit fluorescence when excited by the excitation light from the excitation source 131a and 131b.
  • the excitation source 131a and 131b may be one or more light sources.
  • the excitation source 131a and 131b may selectively emit different wavelengths of excitation lights, therefore the fluorescence from different fluorescent dyes can be emitted.
  • the detector 132a and 132b may selectively detect the fluorescence emitted by the different fluorescent dyes.
  • the optics module 130 includes at least two excitation sources 131a and 131b.
  • the excitation source 131a can be a blue fluorescence excitation source and the excitation source 131b can be a green fluorescence excitation source. Other excitation light source, such as cyan fluorescence source, orange fluorescence source, or red fluorescence source are also applicable.
  • the excitation source 131a emits electromagnetic radiation having a wavelength ranged from about 450 nm to 495 nm, and the excitation source 131b emits electromagnetic radiation having a wavelength ranged from about 495 nm to 570 nm.
  • the excitation source 131a or 131b is a light emitting diode (LED) or a semiconductor laser diode (LD) , such as a blue LED, a blue LD, a green LED, or a green LD.
  • the excitation source is selected according to the fluorescent dye of the reagents. For example, if the fluorescent dye is SYBR, the excitation source 131a can be activated automatically or manually. If the fluorescent dye is ROX, the excitation source 131b can be activated automatically or manually. More excitation sources may also be provided according to the experimental requirements.
  • the fluorescence detector 132a and 132b may detect one or more wavelength of light.
  • One detector 132a may be configured to detect different wavelength of fluorescence excited by multiple excitation source 131a and 131b.
  • different wavelength of fluorescence excited by multiple excitation source 131a and 131b may be detected by multiple detector 132a and 132b.
  • the detector 132a is a green fluorescence detector and the detector 132b is a red fluorescence detector.
  • Other fluorescence detectors can also be applied, such as cyan fluorescence or orange fluorescence.
  • the selection of fluorescence detectors is based on the fluorescent dye being used.
  • the detector 132a detects green fluorescence, and the detector 132b detects red fluorescence having a wavelength ranged from about 620 nm to 750 nm.
  • the detector 132a is a photodiode (PD) , avalanche photodiode (APD) , photomultiplier tube (PMT) , silicon photomultipliers (SIPM) and any other photomultiplier or photodiode components.
  • the detector 132a and 132b may be selected and activated according to the fluorescence excited by the reagents.
  • the detector 132a and 132b may be manually selected or automatically activated.
  • the fluorescent dye can be excited by the excitation light from the excitation source 131a if the fluorescent dye is SYBR, and the detector 132a can be activated manually or automatically.
  • the excitation source 131a, the sample container 110 and the detector 132a are aligned in an optical arrangement for the detector 132a to receive fluorescence from the sample container 110.
  • the fluorescent dye can be excited by the excitation light from the excitation source 132a if the fluorescent dye is ROX, and the detector 132b can be activated manually or automatically.
  • the excitation source 131b, the sample container 110 and the detector 132b are aligned in an optical arrangement for the detector to receive fluorescence or to capture image from the sample container 110.
  • the optics module 130 may include detectors of other wavelength according to experiment requirements.
  • the optics module 130 may further include one or more filters and one or more imaging components.
  • the filter filters the fluorescence into desired wavelengths.
  • the imaging component captures one or more images inside the container assembly 140. Specifically, the imaging component captures one or more images of the reagents in the sample container 110.
  • the imaging components may be positioned to receive the fluorescence filtered by the filter, therefore the imaging components only captures one or more images in a range of particular wavelengths.
  • the imaging component, the filter, the detector 132, the sample container 110 and the excitation source 131a and 131b are in an optical arrangement so the imaging component may obtain images of the sample container 110.
  • the detector 132a may be integrated with the excitation source 131a on the same component, and the detector 132b may also be integrated with the excitation source 131b on the same component, in order to reduce the volume and the power consumption of the detectors and the excitation sources.
  • the photothermal reaction unit 10 may optionally include one or more container assembly 140 for fitting the sample container 110.
  • the heating element 121 and the sample temperature sensor 122 are coupled to the container assembly 140, and positioned in the bottom portion of the container assembly 140 and below the sample container 110.
  • the optics module 130 is coupled to the container assembly 140 and positioned on a side wall of the container assembly 140.
  • the optics module 130 optically focuses on the transparent portion of the sample container 110.
  • the cooling element 123 is positioned outer surface of the container assembly 140.
  • the container assembly 140 is made of one or more high thermal conductivity materials.
  • the high thermal conductivity material may include metallic or non-metallic materials.
  • the container assembly 140 further comprises at least one opening connected to the slot 141, and the optic module 130 comprises excitation sources 131a, 131b for emitting excitation light and detectors 132a, 132b for detecting visible light or a fluorescence signal.
  • the container assembly 140 comprises a slot 141 for fitting the sample container 110 and a plurality of openings for coupling the detector 132a, the detector 132b, the excitation source 131a, the excitation source 131b, and the heating element 121 to the container assembly 140.
  • FIG. 1 only the openings 142a and 142b for coupling the detector 132b and the excitation source 131b to the container assembly 140 are marked for illustrative purposes.
  • the container assembly 140 may have one or more openings for coupling multiple excitation sources or detectors to the container assembly 140. If the excitation source 131a, 131b and the detectors 132a, 132b are integrated on the same component, then only one opening on the container assembly 140 is needed for the coupling of the excitation to the container assembly 140.
  • the optics module 130 is fixed to the container assembly 140. During the photothermal reaction, the optics module 130 is stationary relative to the container assembly 140, therefore the distance between the optics module 130 and the sample container 110 would not change. This stationary configuration between the optics module 130 and the container assembly 140 made it possible for the photothermal reaction unit 10 to be operated outside the laboratory or to be portable. Because re-calibration of the optics module 130 is not required after moving the photothermal reaction unit 10 from one location to another location.
  • the temperature control module 120 may also include a container assembly temperature sensor 124.
  • the container assembly temperature sensor 124 is in direct contact with the container assembly 140, and is placed beside the container assembly 140 for detecting the temperature of the container assembly 140.
  • the container assembly temperature sensor 124 submits temperature information to the first temperature program.
  • the container assembly temperature sensor 124 is a thermocouple.
  • the container assembly temperature sensor 124 can detect the temperature of the container assembly 140 in a contactless manner.
  • the container assembly temperature sensor 124 is an infrared light temperature sensor.
  • the container assembly temperature sensor 124 may also be integrated with the cooling element 123 on the same component to reduce the volume and the power consumption of the container assembly temperature sensor 124 and the cooling element 123.
  • the optical arrangement between the excitation source, the detector, and the sample container in the photothermal reaction analyzer or the photothermal reaction unit are provided in accordance with an embodiment of the present disclosure.
  • the optical arrangement between the excitation source 131, sample container 110 and detector 132 are configured to optimize the signal detection.
  • the angle ⁇ between the excitation source 131, the sample container 110 and the detector 132 is minimized so that the images of the reagents in the sample container 110 can be captured by the detector 132 without distortion.
  • the angle ⁇ can be 0 to 60 degree.
  • the angle ⁇ should be as close to 0 degree as possible.
  • the photothermal reaction analyzer 20 comprises a plurality of container assemblies 140, a container assembly receiving device 150, a plurality of temperature control modules (not shown) , and a plurality of optic modules 130.
  • the container assembly receiving device 150 comprises a plurality of cavities 151, and each of the cavities 151 houses one of the container assemblies 140.
  • Each of the sample containers 110 is fitted in one of the slots 141 and for containing reagents for performing a photothermal reaction.
  • the temperature control module (not shown) is coupled to the container assembly receiving device 150 for controlling a third temperature program of the container assembly receiving device 150 and the second temperature program for the sample containers 110.
  • Each of the optics modules 130 is coupled to one of the container assemblies 140 and for emitting and detecting light. In each of the photothermal reaction analyzers 20, the optics modules 130 are stationary relative to the container assemblies 140.
  • a plurality of container assembly temperature sensors or cooling elements can be positioned on each of the container assembly 140 with similar configuration as illustrated in FIG. 1, whereas the container assembly temperature sensor and the cooling elements and in contact with the container assembly receiving device 150 (not shown) .
  • the cooling elements 123 can also being replaced by a single cooling element, wherein the single cooling element is coupled on the container assembly receiving device 150.
  • the temperature of the surrounding environment is stabilized by the container temperature sensor 124 and the cooling element 123 according to a third temperature program.
  • the third temperature program regulates the temperature of the container assembly receiving device 150.
  • the third temperature program is designed for the container assembly receiving device 150 to be in a consistent temperature, independent of the temperature of the surrounding environment.
  • each of the container assembly 140 is coupled with a heating element 121 (not shown) , and the temperature of the reaction in the sample container 110 is regulated by the heating element 121 according to the second temperature program.
  • Each of the sample containers 110 in FIG. 3 may be regulated to be in a different temperature in the same time by the second temperature program.
  • the optics module 130 is fixed to the container assembly 140. During the photothermal reaction, the optics module 130 is stationary relative to the container assembly 140, therefore the distance between the optics module 130 and the sample container 110 would not change. This stationary configuration between the optics module 130 and the container assembly 140 made it possible for the photothermal reaction analyzer 20 to be operated outside the laboratory or to be portable. Because re-calibration of the optics module 130 is not required after moving the photothermal reaction analyzer 20 from one location to another location.
  • the photothermal reaction analyzer 30 comprises a container assembly block 250 comprising a plurality of slots 251, a plurality of sample containers 110, a temperature control module 120, and a plurality of optics modules 130.
  • a container assembly block 250 comprising a plurality of slots 251, a plurality of sample containers 110, a temperature control module 120, and a plurality of optics modules 130.
  • Each of the sample containers 110 fitted in one of the slots 251 and for containing reagents for performing a photothermal reaction.
  • the temperature control module 120 is coupled to the container assembly block 250 for controlling a fourth temperature program of the container assembly block 250 and the second temperature program for the sample containers 110.
  • Each of the optics modules 130 is coupled to one of the slots 251 of the container block.
  • the optics modules 130 are stationary relative to the container assembly block 250.
  • the container assembly block 250 may be integrated with the sample container 110, and the optics module 130 of FIG. 1.
  • the container assembly block 250 comprises a plurality of slots, and each slot houses a sample container 110.
  • the container assembly block 250 further comprises a plurality of openings, wherein the opening 252a may house an excitation source and another opening 252b may house a detector.
  • a temperature control module 120 may be coupled to the container assembly block 250.
  • the temperature control module 120 in combination with the container assembly block 250 comprises a cooling element (not shown) , a container assembly block temperature sensor (not shown) , a plurality of sample temperature sensor 122, and a plurality of heating elements 121.
  • a heating element 121 and a sample temperature sensor 122 are provided for regulating temperature of the sample container 110.
  • the heating element 121 and the sample temperature sensor 122 are used to regulate the temperature of the sample container 110 according to the second temperature program.
  • the cooling element and the container assembly block temperature sensor are coupled to the container assembly block 250 (not shown) .
  • a fourth temperature program regulates the temperature of the container assembly block 250.
  • the fourth temperature program is designed for the container assembly block 250 to be in a consistent temperature, independent of the temperature of the surrounding environment. Therefore, the photothermal reactions in the sample container 110 can be started in a stable condition, with little or no interference from the temperature of the surrounding environment.
  • the container assembly block 250 is coupled with a heating element 121, and the temperature of the reaction in the sample container 110 is regulated by the heating element 121 according to the second temperature program.
  • Each of the sample containers 110 in FIG. 4 may be regulated to be in a different temperature in the same time by the second temperature program.
  • the container assembly block 250 has a better thermal conductivity by reducing elements, and therefore enables the temperature control module 120 to effectively regulates the temperature of the container assembly block 250 according to the fourth temperature program.
  • the optics module 130 is fixed to the container assembly block 250. During the photothermal reaction, the optics module 130 is stationary relative to the container assembly block 250, therefore the distance between the optics module 130 and the sample container 110 would not change. This stationary configuration between the optics module 130 and the container assembly block 250 made it possible for the photothermal reaction analyzer 30 to be operated outside the laboratory or to be portable. Because re-calibration of the optics module 130 is not required after moving the photothermal reaction analyzer 30 from one location to another location.
  • the control module of the photothermal reaction analyzer is provided in accordance with an embodiment of the present disclosure.
  • One or more of the photothermal reaction units 10, the photothermal reaction analyzers 20, and the photothermal reaction analyzers 30 may include a control module 160.
  • the control module 160 controls the operations of the temperature control module 120 and the optics module 130.
  • the control module 160 includes an input unit 161, a microprocessor 162, and an output unit 163.
  • the input unit 161 is in communication with the microprocessor 162, the detector 132, the sample temperature sensor 122 and the container assembly temperature sensor 124.
  • the input unit 161 can input one or more instruction by a user, and obtain information from the detector 132, the sample temperature sensor 122 and the container assembly temperature sensor 124.
  • the input unit 161 may include an input interface and an analog-to-digital signal conversion element.
  • the instructions may be input by the user to the input interface of the input unit 161.
  • the analog-to-digital signal conversion element converts and transmits the instructions.
  • the input interface may be a button, an array of buttons, a keyboard, a touch screen or the like.
  • the instructions may be a start command, a stop command, a pause command or any other instructions for facilitating the reactions in the photothermal reaction unit 10.
  • the microprocessor 162 is in communication with the input unit 161 and the output unit 163.
  • the microprocessor 162 obtains the instruction from the input unit 161, and sends out one or more operation instruction to the output unit 163.
  • the microprocessor 162 receives temperature information from the container assembly temperature sensor 124 and sends instructions to the cooling element 123 according to the first temperature program to regulate the temperature of the container assembly 140, the third temperature program to regulate the temperature of the container assembly receiving device 150, or the fourth temperature program to regulate the temperature of the container assembly block 250.
  • the microprocessor 162 receives temperature information from the sample temperature sensor 122 and sends instructions to the heating element 121 according to the second temperature program.
  • the microprocessor 162 can analyze the information from the detector 132 to obtain the result of experiment, and sends out the result of experiment to the output unit 163.
  • the microprocessor 162 may be a Microprocessor Unit (MPU) , a Microcontroller Unit (MCU) , a Central Processing Unit (CPU) or any other data processing components.
  • MPU Microprocessor Unit
  • MCU Microcontroller Unit
  • CPU Central Processing Unit
  • the output unit 163 is in communication with the microprocessor 162, the heating element 121, the excitation source 131a and 131b and the cooling element 123.
  • the output unit 163 can output the operation instruction to the heating element 121, the excitation source 131a and 131b and the cooling element 123. Further, the output unit 163 can output the result of experiment from the microprocessor 162.
  • the output unit 163 may include a display interface and a digital-to-analog signal conversion element.
  • the display interface displays the result of experiment from the microprocessor 162.
  • the digital-to-analog signal conversion unit converts and transmits the result of experiment.
  • the display interface may be a display, a printer, or the like.
  • control module 160 may include a communication unit 164 and a memory 165.
  • the communication unit 164 is in communication with the memory 165.
  • the communication unit 164 is in communication with the microprocessor 162 and an external device.
  • the communication unit 164 is used for transmitting information between the photothermal reaction unit 10 and the external device.
  • the communication unit 164 may include one or more of wireless communication components, such as Bluetooth components, WIFI components, or the like.
  • the external device may be a computing device, such as a computer, a tablet, a smartphones, a laptop, or the like. Further, users can input one or more instruction from the communication unit 164 or from one or more computing devices in communication with the communication unit 164, and obtain the result of experiment from the microprocessor 162.
  • the memory 165 is in communication with the microprocessor 162.
  • the memory 165 is used for storing the operation flow and the result of experiments from the microprocessor 162.
  • the memory 165 may be a Random Access Memory (RAM) , a memory card, or any other memory storage components.
  • RAM Random Access Memory
  • the temperature control module 120, the 2, the sample temperature sensor 122, the cooling element 123, the container assembly temperature sensor 124, the optics module 130, the container assembly 140, and the sample container 110 correspond to those elements that are designated by the same reference numerals in FIG. 1, respectively.
  • the excitation source 131 is a collection of the excitation source 131a and 131b
  • the detector 132 is a collection of the detector 132a and 132b.
  • the photothermal reaction unit 10 in FIG. 1 may further include a housing 170 for housing the container assembly receiving device 150 and the control module 160.
  • FIG. 7 a procedure of performing an immunofluorescence reaction using the above photothermal reaction analyzer is provided in accordance with an embodiment of the present disclosure.
  • the procedures in FIG. 7 may be automatically instructed by the photothermal reaction analyzer or manually instructed by the user.
  • 211 involves determining whether the reagent in the sample container needs to be heated. If it is necessary for the reagent to be heated, the microprocessor would instruct the photothermal reaction analyzer to proceed to 212. If it is not necessary for the reagent to be heated, the microprocessor would instruct the photothermal reaction analyzer to proceed to 213.
  • the reagent may include one or more analytes, fluorescent dyes, markers, antibodies and other required reagents for the immunofluorescence reaction or the PCR.
  • the marker and the fluorescent dye are used to signify the reaction results.
  • the marker may be specifically bind to the analyte.
  • the marker may be chemically bind to an antibody or the analyte in the immunofluorescence reaction.
  • the fluorescent dye can be bind to an antibody or the analyte in the immunofluorescence reaction.
  • the analyte may be one or more protein, peptide, or nucleic acids from one or more materials of biological origin.
  • the biological origin comprises one or more of biological tissue, cells. body fluids, or body fluid derivatives.
  • the biological origin may be blood, serum, plasma, slides mounted with biological tissue, slides mounted with cells, or any other biological tissue derivatives.
  • the reagent may include one or more heat-generating reactants.
  • the heat-generating reactant can generate heat by irradiation with electromagnetic waves, such as a transition metal heated by infrared irradiation.
  • the reactant may be a transition metal material, and the transition metal material can be a transition metal oxide, a transition metal hydroxide, a Group III metal compound doped with the transition metal, a silicon dioxide doped with the transition metal oxide, or a silicon dioxide doped with the transition metal hydroxide.
  • the temperature of the reactant is elevated when irradiated by infrared irradiation.
  • the temperature control module may include a heating element, a cooling element, a sample temperature sensor and a container assembly temperature sensor.
  • the designated temperature in 212 is directed to the temperature required for the immunofluorescence reaction.
  • electromagnetic waves is needed in 212 to raise the temperature of the reagents to the designated temperature.
  • the electromagnetic waves have a frequency range of 200 kHz to 500 THz.
  • the electromagnetic wave is in the spectrum of infrared light.
  • the temperature of the reagents is detected by the photothermal reaction analyzer, the reagent stays in a designated temperature for a predetermined time frame.
  • the predetermined time frame is set according to the reaction time required for the immunofluorescence reaction.
  • the 213 involves exciting the fluorescence of the reagent with an excitation light by the excitation source.
  • Different excitation lights may be emitted according to the fluorescent dye in the reagent.
  • the fluorescent dye in the reagent is SYBR, a blue light with a wavelength of 450 nm to 495 nm can be emitted.
  • the fluorescent dye in the reagent is ROX, a green fluorescence with a wavelength of 495 nm to 570 nm can be emitted.
  • the 214 involves detecting the fluorescence of the reagent by the detector. Different fluorescents may be detected according to the fluorescent dye in the reagents. For example, if the fluorescent dye in the reagent is SYBR, the green fluorescence can be detected. If the fluorescent dye in the reagent is ROX, the red fluorescence can be detected.
  • FIG. 8 is the image and fluorescent signal of the sample container when conducting the immunofluorescence reaction, in accordance with an embodiment of the present disclosure.
  • the fluorescent signal can be captured by the detector and accumulated in the reaction.
  • the column B of the FIG. 8 is the fluorescent signals from the sample container measured by the photodiode (PD) of the detector;
  • the column A of FIG. 8 is the images from the sample container taken by the imaging component of the detector.
  • SYBR is not presented in the reagent in the sample container, therefore the image taken by the imaging component of the detector is without the green fluorescence emitted by SYBR, as shown by the upper half of column A of FIG. 8.
  • the upper half of column B of FIG. 8 shows when none of the green fluorescence is detected in the sample container, the reaction time required by the immunofluorescence reaction would be longer.
  • SYBR is presented in the reagent in the sample container, therefore the image taken by the imaging component of the detector is with the green fluorescence emitted by SYBR, as shown by the lower half of column A of FIG. 8.
  • the lower half of column B of FIG. 8 shows when the green fluorescence is detected in the sample container, the reaction time would be shorter than the reaction without SYBR.
  • 211 further comprising: loading the reagents into the sample container and placing the sample container into the container assembly of the photothermal reaction analyzer.
  • 211 further comprises the following steps of 2111-2113:
  • 2111 involves inputting one or more instruction by the user.
  • the instruction may be a start command.
  • 2111 may include the user input one or more instruction to the photothermal reaction analyzer.
  • the instruction may be computer-implemented methods containing operation flow.
  • the memory unit of the microprocessor may store the computer-implemented methods.
  • the microprocessor may send out one or more instructions to the temperature control module and the optics module. If it is not necessary, the microprocessor may send out one or more instructions to the temperature control module and the optics module.
  • the optics module may include one or more detectors and excitation sources.
  • the computer-implemented methods may be loaded from the memory by the microprocessor to determining whether the reagent needs to be heated.
  • the microprocessor sends out one or more instructions to the temperature control module and the optics module via an output unit.
  • 214 further comprises the following steps of 2141-2143:
  • 2141 involves obtaining one or more fluorescence information of the reagent from the detector by the microprocessor.
  • 2142 involves analyzing of the fluorescence information and obtaining the result of experiment by the microprocessor.
  • Step 2143 involves determining whether the reaction is completed. If it is completed, the microprocessor may send out a stop command to the temperature control module and the optics module. Preferably, Step 2143 may further involves storing the result of experiment to the memory. Further, the result of experiments may be transmitted to an external device.
  • a method of performing a PCR using the above photothermal reaction analyzer comprising:
  • 221 involves heating the reagent in the sample container to a designated temperature by the temperature control module according to the second temperature program.
  • the reagent may include one or more polymerases, dNTPs, primers, template sequences, and other required reagents for the PCR.
  • the reagent may include one or more heat-generating reactants.
  • the heat-generating reactant can generate heat by irradiation with electromagnetic waves, such as a transition metal heated by infrared irradiation.
  • the reactant may be a transition metal material, and the transition metal material can be a transition metal oxide, a transition metal hydroxide, a Group III metal compound doped with the transition metal, a silicon dioxide doped with the transition metal oxide, or a silicon dioxide doped with the transition metal hydroxide.
  • the temperature of the reactant is elevated when irradiated by infrared light.
  • the second temperature program then instructs the control module for the heating element to emitt electromagnetic waves to raise the temperature of the reagent to one or more designated temperatures.
  • the electromagnetic waves have a frequency range of 200 kHz to 500 THz.
  • the electromagnetic wave is in the spectrum of infrared light.
  • the designated temperature is according to the second temperature program and are the temperatures required for each stage of the PCR.
  • sensing the temperature of the reagents and keeping the reagent in a designated temperature for the predetermined time frame is according to the time needed in the protocol of the PCR and is.
  • 221 further comprising: loading the reagents into the sample container and placing the sample container into the container assembly of the photothermal reaction analyzer.
  • 221 further comprises the following steps of 2211-2213:
  • 2211 involves inputting one or more instruction by the user.
  • the instruction may be a start command.
  • 2211 may include the user input one or more instruction to the photothermal reaction analyzer.
  • the instruction may be computer-implemented methods containing operation flow.
  • the memory unit of the microprocessor may store the computer-implemented methods.
  • the 2212 involves sending out a heating instruction to the temperature control module by the microprocessor.
  • the computer-implemented methods may be loaded from the memory by the microprocessor to determining whether the reagent needs to be heated.
  • the microprocessor sends out one or more instructions to the temperature control module and the optics module via an output unit.
  • 221 further comprises the following steps of 222-223:
  • 222 involves determining whether the reaction is completed according to the reaction time. If it is completed, the microprocessor would send out a stop command to the temperature control module. Preferably, 222 may further involves displaying the completion signal or transmitting the result of experiments to an external device.
  • a method of performing a real-time PCR using the above photothermal reaction analyzers or photothermal reaction units are provided in accordance with one or more embodiments of the present disclosure.
  • the method comprising:
  • the 231 involves heating the reagent in the sample container to a designated temperature by the temperature control module.
  • the reagent may include one or more analytes, polymerases, dNTPs, primers, probe sequences, template sequences, fluorescent dyes, and others requiring for the real-time PCR.
  • the fluorescent dye can be bind to the probe sequences.
  • the reagent may include one or more heat-generating reactants.
  • the heat-generating reactant can generate heat by irradiation with electromagnetic waves, such as a transition metal heated by infrared irradiation.
  • the reactant may be a transition metal material, and the transition metal material can be a transition metal oxide, a transition metal hydroxide, a Group III metal compound doped with the transition metal, a silicon dioxide doped with the transition metal oxide, or a silicon dioxide doped with the transition metal hydroxide.
  • the temperature of the reactant is elevated when irradiated by infrared irradiation.
  • electromagnetic waves are needed to raising the temperature of the reagents to the designated temperature.
  • the electromagnetic waves have a frequency range of 200 kHz to 500 THz.
  • the electromagnetic wave is in the spectrum of infrared.
  • the designated temperature is set according to the temperature required for each stage of the real-time PCR.
  • sensing the temperature of the reagents and keeping the reagent in a designated temperature for a predetermined time frame is according to the time required for each stage of the real-time PCR.
  • the 232 involves exciting the fluorescence of the reagent with an excitation light by the excitation source.
  • Different excitation lights may be emitted according to the fluorescent dye in the reagent.
  • the fluorescent dye in the reagent is SYBR, a blue light with a wavelength of 450 nm to 495 nm can be emitted.
  • the fluorescent dye in the reagent is ROX, a green fluorescence with a wavelength of 495 nm to 570 nm can be emitted.
  • the 233 involves detecting the fluorescence of the reagent by the detector.
  • Different fluorescents may be detected according to the fluorescent dye in the reagents. For example, if the fluorescent dye in the reagent is SYBR, the green fluorescence can be detected by the detector. If the fluorescent dye in the reagent is ROX, the red fluorescence can be detected by the detector.
  • 231 further comprising: loading the reagent into a sample container and putting the sample container into a container assembly of the photothermal reaction analyzer.
  • 231 further comprises the following steps of 2311-2313.
  • 2311 involves inputting one or more instruction by users.
  • the instruction may be a start command.
  • 2311 may include the user input one or more instruction to the photothermal reaction analyzer.
  • the instruction may be computer-implemented methods containing operation flow.
  • the memory unit of the microprocessor may store the computer-implemented methods.
  • the microprocessor sends out one or more instructions to the temperature control module and the optics module.
  • the computer-implemented methods containing the operation flow may be loaded from the memory by the microprocessor.
  • the microprocessor determines whether the reagent needs to be heated by the microprocessor.
  • the microprocessor sends out one or more instructions to the temperature control module and the optics module via an output unit.
  • 233 further comprises the following steps of 2331-2333:
  • 2331 involves obtaining one or more fluorescence information of the reagent from the detector by the microprocessor.
  • 2333 involves determining whether the reaction is completed. If it is completed, the microprocessor will send out a stop command to the temperature control module and the optics module.
  • the result of experiment is then stored in the memory unit. Further, an external device may display the result of experiments or transmit the result of experiments.

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Abstract

A photo-thermal reaction analyzer (20, 30) is disclosed. The photo-thermal reaction analyzer (20, 30) comprises a plurality of photo-thermal reaction units (10). Each of the photo-thermal reaction units (10) includes a container assembly (140) having a slot (141, 251), a sample container (110) fitted in the slot (141, 251) and for containing reagents for performing a photo-thermal reaction, a temperature control module (120) coupled to the container assembly (140) for controlling a first temperature program for the container assembly (140) and a second temperature program for the sample container (110), and an optics module (130) coupled to the container assembly (140) and for emitting and detecting light. In each of the photo-thermal reaction units (10), the optics module (130) is stationary relative to the container assembly (140).

Description

PHOTOTHERMAL REACTION ANALYZER
CROSS-REFERENCE TO RELATED APPLICATION
This application claims priority to U.S. Provisional Application No. 62/484,944, filed on April 13, 2017, which is hereby incorporated by reference in its entirety.
FIELD OF THE INVENTION
The present disclosure relates to in vitro diagnostic devices, and more particularly to a photothermal reaction analyzer and a method for performing an immunofluorescence reaction, an isothermal polymerase reaction, a reverse-transcriptase polymerase chain reaction, a multiplex polymerase chain reaction, a digital polymerase chain reaction, a conventional polymerase chain reaction, or a real-time polymerase chain reaction by using the photothermal reaction analyzer.
BACKGROUND OF THE INVENTION
A polymerase chain reaction (PCR) amplifies one or more fragments of DNA from single or multiple target templates. The PCR typically take place in a confined space where the temperature is controlled. A specific temperature program may be set by the user for the PCR. Commercially available PCR analyzers are mostly thermal cyclers that control the temperature of the PCR. The C-1000 TM Touch Thermal Cycler is a conventional PCR analyzer that allows the user to execute two sets of temperature programs simultaneously. Commercially available PCR analyzers often provide a plurality of housing spaces, slots or wells for many sample containers. The SimpliAmp TM Thermal Cycler is a conventional PCR analyzer that provides multiple slots for a plurality of samples and a remote control function. Conventional PCR analyzers are also unable to perform other reactions commonly used in diagnostic applications, such as direct or indirect immunofluorescence reactions.
A variant of the PCR is real-time PCR or reverse-transcription PCR. The results of  real-time PCR can be observed optically inside the space where the reaction was taken place, because fluorescent molecules are often used in the reaction. The fluorescent molecules can be excited by lasers of specific wavelengths and emit fluorescent signals that are indicative of the reaction. Most of the PCR analyzers are equipped with optical components for the detection of fluorescence in the real-time PCR. The optical components usually comprise a detector and an excitation source. The fluorescent molecules in the sample container may be excited by the excitation light from the excitation source, and the detector detects the fluorescent signals from the excited fluorescent molecules. Therefore, the optical components need to be aligned with the slot to receive fluorescence signals in the sample container. When multiple reactions are presented in the sample containers in the real-time PCR analyzers, the optical components are required to move along the X-Y plane from one slot to another, in order to align themselves with the sample containers housed in the slot. The CFX96 TM Real-Time PCR Detection System has an “optics shuttle” that travel across the 96-well plate when detecting fluorescence signals, and the green LED fires directly over a well. In other words, the movement of the optical components in conventional real-time PCR analyzers require precise alignment between the optical components and the sample containers, slots, or wells. This alignment is the key for providing reliable and successful real-time PCR results.
Due to the precise alignment needed between the optical components and the sample containers, conventional real-time PCR analyzers are often stationary and sold as non-portable devices. Any movement or tilt to the conventional real-time PCR analyzers may results in displacement of the optical components. Calibrating the optical components is needed after moving a stationary conventional real-time PCR analyzer. The need for calibration of the optical components limits the application of conventional real-time PCR analyzers. To perform real-time PCR outside the laboratory is therefore not applicable.
Furthermore, conventional PCR analyzers or real-time PCR analyzers uses a single heating block as a thermal conductor to change the temperature of the sample containers. The heating block elevates the temperature of the sample containers by having direct contacts with the sample containers. The heating block may also have some direct contacts with the  surrounding environment, or be housed in a thin shell. However, the sample containers in the single thermal conductor would also be easily affected by temperatures in the surrounding environment. If it is extremely cold or hot in the surrounding environment, the temperature of the sample containers in the PCR analyzer would be affected. Reactions performed under inaccurate temperature may be inefficient and unreliable. Thus, conventional PCR analyzers using the single thermal conductor design are not suitable to be used in the outdoor or at extreme environments.
Therefore, it is desirable to provide a photothermal reaction analyzer with multiple thermal conductor design so that the temperatures in the surrounding environment would have minimum or no effect to the temperature of the sample containers.
Therefore, it is desirable to provide a portable and agile photothermal reaction analyzer with fixed optical components so that the optical components are not needed to be re-calibrate after being moved.
It is also desirable to provide a photothermal reaction analyzer capable of performing thermal cycling applications and immunofluorescence reactions.
It is also desirable to provide a photothermal reaction analyzer equipped with laser, infrared light, optical detection and temperature detection to carry out the PCR and other reactions associated with excitation light.
It is also desirable to provide a photothermal reaction analyzer with that detects PCR and other reactions by taking images of the reagents in the sample container.
SUMMARY OF THE INVENTION
The present disclosure provides a portable photothermal reaction analyzer with fixed optical components and multiple thermal conductors.
An embodiment of the present disclosure provides a photothermal reaction analyzer. The photothermal reaction analyzer comprises a plurality of photothermal reaction units. Each of the photothermal reaction units includes a container assembly having a slot, a  sample container is fitted in the slot and for containing reagents for performing a photothermal reaction, a temperature control module coupled to the container assembly for controlling a first temperature program for the container assembly and a second temperature program for the sample container, and an optics module coupled to the container assembly and for emitting and detecting light. In each of the photothermal reaction units, the optics module is stationary relative to the container assembly.
In a preferred embodiment, the container assembly further comprises at least one opening connected to the slot, and one of the optics modules is coupled to the container assembly via the opening.
In a preferred embodiment, the container assembly further comprises at least two openings connected to the slot, and each of the optics modules comprises at least one excitation source for emitting an excitation light and at least one detector for detecting a visible light or a fluorescence signal. The excitation source and the detector are coupled to the container assembly via the openings, respectively.
In a preferred embodiment, the optics module is configured to emit a blue excitation light, a green excitation light, an orange excitation light, a red excitation light, or any combination thereof.
In a preferred embodiment, the optics module is configured to detect a green fluorescence, a cyan fluorescence, an orange fluorescence, a red fluorescence, or any combination thereof.
In a preferred embodiment, the optics module is further configured to filter the fluorescence into a range of wavelength.
In a preferred embodiment, the temperature control module comprises a heating element coupled to one of the container assemblies via the opening (s) for heating the sample container, a container assembly temperature sensor, a sample temperature sensor, and a cooling component. The heating element can be an electromagnetic wave generator.
In a preferred embodiment, the excitation source comprises a blue light excitation source, a green light excitation source, an orange excitation light source, or a red excitation  light source.
In a preferred embodiment, the detector comprises a light emitting diode (LED) , a semiconductor laser diode (LD) , or any combination thereof.
In a preferred embodiment, the detector comprises a green fluorescence detector, a cyan fluorescence detector, an orange flurescence detector, or a red fluorescence detector.
In a preferred embodiment, the detector comprises a photodiode (PD) , an avalanche photodiode (APD) , a photomultiplier tube (PMT) , a silicon photomultiplier (SIPM) , or any combination thereof.
In a preferred embodiment, the optics module further comprises a filter disposed between the excitation source and the detector and for filtering the fluorescence into a range of wavelength.
In a preferred embodiement, the detector comprises one or more imaging components for capturing at least one image of an inner side of the container assembly.
Another embodiment of the present disclosure provides a photothermal reaction analyzer. The photothermal reaction analyzer comprises a plurality of container assemblies, a container assembly receiving device, a plurality of temperature control modules, and a plurality of optics modules. The container assembly receiving device comprises a plurality of cavities, and each of the cavities houses one of the container assemblies. Each of the sample containers is fitted in one of the slots and for containing reagents for performing a photothermal reaction. The temperature control module is coupled to the container assembly receiving device for controlling a third temperature program of the container assembly receiving device and the second temperature program for the sample containers. Each of the optics modules is coupled to one of the container assemblies and for emitting and detecting light. The optics modules are stationary relative to the container assemblies.
Another embodiment of the present disclosure provides a photothermal reaction analyzer. The photothermal analyzer comprises a container assembly block comprising a plurality of slots, a plurality of sample containers, a temperature control module, and a plurality of optics modules. Each of the sample containers fitted in one of the slots and for  containing reagents for performing a photothermal reaction. The temperature control module is coupled to the container assembly block for controlling a fourth temperature program of the container assembly block and the second temperature program for the sample containers. Each of the optics modules is coupled to one of the slots of the container assembly block. The optics modules are stationary relative to the container assembly block.
In a preferred embodiment, the container assembly block further comprises a plurality of openings, and each of the openings is connected to one of the slots. One of the optics modules is coupled to the slot via the opening.
In a preferred embodiment, the container assembly block further comprises a plurality of openings, at least two of the openings are connected to one of the slots, each of the optics modules comprises at least one excitation source for emitting an excitation light and at least one detector for detecting a visible light or a fluorescence signal. The excitation source and the detector are coupled to one of the slots in the container assembly block via the openings, respectively.
In a preferred embodiment, the temperature control module comprises a plurality of heating elements for heating the sample containers, a container assembly block temperature sensor, a sample temperature sensor, and a cooling component. Each of the heating element is coupled to one of the slots in the container assembly block via the opening (s) . The heating element is an electromagnetic wave generator.
In a preferred embodiment, the photothermal reaction performed by the photothermal reaction analyzer or photothermal reaction unit is an immunofluorescence reaction, an isothermal polymerase reaction, a reverse-transcriptase polymerase chain reaction, a multiplex polymerase chain reaction, a digital polymerase chain reaction, a conventional polymerase chain reaction, or a real-time polymerase chain reaction.
In a preferred embodiment, the photothermal reaction analyzer unit further comprising a control module for controlling the temperature control module and the optics module.
BRIEF DESCRIPTION OF THE DRAWINGS
Many aspects of the present exemplary embodiments can be better understood with reference to the following drawings. The components in the drawings are not necessarily drawn to scale, the emphasis instead being placed upon clearly illustrating the principles of the present exemplary embodiments. Moreover, in the drawings, like reference numerals designate corresponding parts throughout the several views.
FIG. 1 is an exploded view of the structure of a photothermal reaction analyzer in accordance with an embodiment of the present disclosure.
FIG. 2 is a schematic illustration of the optical configuration among an excitation source, a sample container and a fluorescence detector in accordance with an embodiment of the present disclosure.
FIG. 3 is a perspective view of a container assembly receiving device of the photothermal reaction analyzer as depicted in FIG. 1 in accordance with an embodiment of the present disclosure.
FIG. 4 is an exploded view of a photothermal reaction analyzer in accordance with an embodiment of the present disclosure.
FIG. 5 is a block diagram showing the functional relationship of the photothermal reaction analyzer as depicted in FIG. 1 in accordance with an embodiment of the present disclosure.
FIG. 6 is a schematic illustration of a housing for the photothermal reaction analyzer in accordance with an embodiment of the present disclosure.
FIG. 7 is a flowchart showing a method for performing an immunofluorescence reaction using the photothermal reaction analyzer in accordance with an embodiment of the present disclosure.
FIG. 8 is results of the immunofluorescence reaction as depicted in FIG. 7 in accordance with an embodiment of the present disclosure.
FIG. 9 is a flowchart showing a method for performing a polymerase chain  reaction using the photothermal reaction analyzer in accordance with an embodiment of the present disclosure.
DETAILSED DESCRIPTION OF THE PREFERRED EMBODIMENTS
In order to enhance an understanding of the principles of the present disclosure, several exemplary embodiments of the present disclosure will now be described in detail below and with reference to the drawings. It is to be noted that no limitation of the scope of the present disclosure is intended. Alterations and modifications in the illustrated device, and further applications of the principles of the present disclosure as illustrated therein, as would normally occur to a person having ordinary skill in the art to which the present disclosure relates, are contemplated, and desired to be protected.
Referring to FIG. 1, a photothermal reaction unit 10 is provided in accordance with an embodiment of the present disclosure. The photothermal reaction analyzer comprises a plurality of photothermal reaction units 10. Each of the photothermal reaction units 10 includes a container assembly 140 having a slot 141, a sample container 110 is fitted in the slot 141 and for containing reagents for performing a photothermal reaction, a temperature control module 120 coupled to the container assembly for controlling a first temperature program for the container assembly 140 and a second temperature program for the sample container 110, and an optics module 130 coupled to the container assembly 140 and for emitting and detecting light. In each of the photothermal reaction units 10, the optics module 130 is stationary relative to the container assembly 140.
The sample container 110 is a transparent container having a closed space for containing the reagents. The sample container 110 may be an eppendorf tube, a capillary tube, a microfluidic chip, a tip, or other containers with transparent wall and closed space. The reagents may include one or more heat-generating reactants. The heat-generating reactant can generate heat by irradiation with electromagnetic waves. The reactant may be a transition metal material, and the transition metal material can be a transition metal oxide, a transition metal hydroxide, a Group III metal compound doped with the transition metal, a silicon dioxide doped with the transition metal oxide, or a silicon dioxide doped with the transition metal hydroxide. The temperature of the reactant is elevated when irradiated by infrared irradiation.
Further, the reagents may also include reagents for immunofluorescence reactions, or reagents for polymerase chain or real-time polymerase chain reactions. The reagents for the immunofluorescence reaction may include analytes, fluorescent dyes, markers, and any other reagents necessary for an immunofluorescence reaction. The reagents for the polymerase chain or real-time PCR may include analytes, polymerases, dNTPs, primers, probes, fluorescent dyes, template sequences, and any other reagents necessary for a PCR or real-time PCR.
The temperature control module 120 comprises a heating element 121 coupled to the container assembly 140 via the opening (not shown) for heating the sample container 110, a container assembly temperature sensor 124, a sample temperature sensor 122, and a cooling component 123. The temperature control module 120 controls a first temperature program for the container assembly 140 and a second temperature program for the sample container 110. The first temperature program regulates the temperature of the container assembly 140. Preferably, the first temperature program is designed for the container assembly to be in a consistent temperature, independent of the temperature of the surrounding environment. The temperature of the container assembly 140 may be elevated or lowered slightly according to the first temperature program. Therefore, the photothermal reactions in the sample container 110 can be started in a stable condition, with little or no interference from the temperature of the surrounding environment. The second temperature program is a predetermined program for the sample container 110 to be in one or more designated temperatures. The second temperature program may include one or more designated temperatures, one or more time frames for the sample container 110 to be in a designated temperature, and one or more time frames for temperature ramping from one temperature to another. For example, the second temperature program may direct the sample container 110 to be in 65℃ for 10 minutes, 95℃ for 5 minutes, and ramping from 65℃ to 95℃ to be within 60 seconds. The second temperature program can be designed by the user to specifically meet the temperature requirements of an immunofluorescence reaction, an isothermal polymerase reaction, a reverse-transcriptase polymerase chain reaction, a multiplex polymerase chain reaction, a digital polymerase chain reaction, a conventional polymerase reaction, or a real-time polymerase chain reaction. The photothermal analyzer of the present disclosure is capable to  perform an immunofluorescence reaction, an isothermal polymerase reaction, a reverse-transcriptase polymerase chain reaction, a multiplex polymerase chain reaction, a digital polymerase chain reaction, a conventional polymerase chain reaction, a real-time polymerase chain reaction, or any other in-vitro reactions with temperature restrictions. The conventional polymerase chain reaction may require designated temperatures for denaturation, annealing, and elongation. However, the isothermal polymerase chain reaction or the immunofluorescence reaction may only require one or several designated temperatures.
The temperature control module 120 includes a heating element 121. The heating element 121 is controlled by the second temperature program for heating the temperature of the sample container 110. Preferably, the heating element 121 is placed at the bottom of the sample container 110. The heating element 121 may be an electromagnetic wave generator emitting one or more electromagnetic wave. The electromagnetic waves emitted by the heating element 121 have a frequency range of 200 kHz to 500 THz. Preferably, the electromagnetic wave is in the spectrum of infrared. Preferably, the heating element 121 is an infrared laser diode. The heating element 121 may emit electromagnetic waves to cause the heat-generating reactant raising the temperature of the reagents in the sample container 110. The electromagnetic waves with specific wavelengths may induce elevated temperatures of the reactants in the reagent.
In another exemplary embodiment, the temperature control module 120 may further include a sample temperature sensor 122. The sample temperature sensor 122 is in direct contact with the sample container 110 for sensing the temperature of the sample container 110. Preferably, the sample temperature sensor 122 is a thermocouple.
In another exemplary embodiment, the sample temperature sensor 122 may also be integrated with the heating element 121 on the same component to reduce the volume and the power consumption of the sample temperature sensor 122 and the heating element 121.
In another exemplary embodiment, the temperature control module 120 may further include a cooling element 123 for cooling the container assembly 140. The cooling element 123 does not directly contact the sample container 110. The cooling element 123 is  controlled by the first temperature program. Preferably, the cooling element 123 can be an air cooling element, a fluid cooling element, an air-fluid hybrid cooling element, a semiconductor cooler. The air cooling element may be a fan or components generating air flow to cool down the surrounding environment. The fluid cooling element may be a cryocooler or components using fluids to cool down the surrounding environment. The semiconductor cooler may be a semiconductor cooling plate or chip, such as a TE cooler (thermoelectric cooler) . The sample container 110 is heated by the heating element 121, and is cooled by the container assembly 140, whereby the container assembly 140 can be cooled by the cooling element 123. The temperature of the sample container 110 is detected by a sample temperature sensor 122. The heating element 121, the sample temperature sensor 122 and the cooling element 123 are communicatively coupled to control and detect the temperature of the reagents in the sample container 110.
The optics module 130 can be configured to emit a blue excitation light, a green excitation light, an orange excitation light, a red excitation light, or any combination thereof. The optics module 130 can also be configured to detect a green fluorescence, a cyan fluorescence, an orange fluorescence, a red fluorescence, or any combination thereof. The optic module 130 can also be configured to filter the fluorescence into a range of wavelength.
The optics module 130 includes one or more excitation sources and one or more detectors. The optics module 130 can also be configured to have different excitation sources emitting different wavelengths of excitation lights, or to have different detectors detect different wavelengths of fluorescence. The  excitation source  131a and 131b, the  detector  132a and 132b are shown as an exemplary design in FIG. 1. The  excitation source  131a and 131b may emit an excitation light to the reagents in the sample container 110. The fluorescent dyes in the reagents emit fluorescence when excited by the excitation light from the  excitation source  131a and 131b. The  excitation source  131a and 131b may be one or more light sources. The  excitation source  131a and 131b may selectively emit different wavelengths of excitation lights, therefore the fluorescence from different fluorescent dyes can be emitted. The  detector  132a and 132b may selectively detect the fluorescence emitted by the different fluorescent  dyes.
In the present exemplary embodiment, the optics module 130 includes at least two  excitation sources  131a and 131b. The excitation source 131a can be a blue fluorescence excitation source and the excitation source 131b can be a green fluorescence excitation source. Other excitation light source, such as cyan fluorescence source, orange fluorescence source, or red fluorescence source are also applicable. In the present exemplary embodiment, the excitation source 131a emits electromagnetic radiation having a wavelength ranged from about 450 nm to 495 nm, and the excitation source 131b emits electromagnetic radiation having a wavelength ranged from about 495 nm to 570 nm. Preferably, the  excitation source  131a or 131b is a light emitting diode (LED) or a semiconductor laser diode (LD) , such as a blue LED, a blue LD, a green LED, or a green LD. The excitation source is selected according to the fluorescent dye of the reagents. For example, if the fluorescent dye is SYBR, the excitation source 131a can be activated automatically or manually. If the fluorescent dye is ROX, the excitation source 131b can be activated automatically or manually. More excitation sources may also be provided according to the experimental requirements.
The  fluorescence detector  132a and 132b may detect one or more wavelength of light. One detector 132a may be configured to detect different wavelength of fluorescence excited by  multiple excitation source  131a and 131b. Alternatively, different wavelength of fluorescence excited by  multiple excitation source  131a and 131b may be detected by  multiple detector  132a and 132b.
In the present exemplary embodiment, the detector 132a is a green fluorescence detector and the detector 132b is a red fluorescence detector. Other fluorescence detectors can also be applied, such as cyan fluorescence or orange fluorescence. The selection of fluorescence detectors is based on the fluorescent dye being used. The detector 132a detects green fluorescence, and the detector 132b detects red fluorescence having a wavelength ranged from about 620 nm to 750 nm. Preferably, the detector 132a is a photodiode (PD) , avalanche photodiode (APD) , photomultiplier tube (PMT) , silicon photomultipliers (SIPM) and any other photomultiplier or photodiode components. The  detector  132a and 132b may be  selected and activated according to the fluorescence excited by the reagents. The  detector  132a and 132b may be manually selected or automatically activated. For example, the fluorescent dye can be excited by the excitation light from the excitation source 131a if the fluorescent dye is SYBR, and the detector 132a can be activated manually or automatically. The excitation source 131a, the sample container 110 and the detector 132a are aligned in an optical arrangement for the detector 132a to receive fluorescence from the sample container 110. The fluorescent dye can be excited by the excitation light from the excitation source 132a if the fluorescent dye is ROX, and the detector 132b can be activated manually or automatically. The excitation source 131b, the sample container 110 and the detector 132b are aligned in an optical arrangement for the detector to receive fluorescence or to capture image from the sample container 110. The optics module 130 may include detectors of other wavelength according to experiment requirements.
The optics module 130 may further include one or more filters and one or more imaging components. The filter filters the fluorescence into desired wavelengths. The imaging component captures one or more images inside the container assembly 140. Specifically, the imaging component captures one or more images of the reagents in the sample container 110. The imaging components may be positioned to receive the fluorescence filtered by the filter, therefore the imaging components only captures one or more images in a range of particular wavelengths. The imaging component, the filter, the detector 132, the sample container 110 and the  excitation source  131a and 131b are in an optical arrangement so the imaging component may obtain images of the sample container 110.
In another exemplary embodiment, the detector 132a may be integrated with the excitation source 131a on the same component, and the detector 132b may also be integrated with the excitation source 131b on the same component, in order to reduce the volume and the power consumption of the detectors and the excitation sources.
In the present exemplary embodiment, the photothermal reaction unit 10 may optionally include one or more container assembly 140 for fitting the sample container 110. The heating element 121 and the sample temperature sensor 122 are coupled to the container  assembly 140, and positioned in the bottom portion of the container assembly 140 and below the sample container 110. The optics module 130 is coupled to the container assembly 140 and positioned on a side wall of the container assembly 140. The optics module 130 optically focuses on the transparent portion of the sample container 110. The cooling element 123 is positioned outer surface of the container assembly 140. The container assembly 140 is made of one or more high thermal conductivity materials. The high thermal conductivity material may include metallic or non-metallic materials.
The container assembly 140 further comprises at least one opening connected to the slot 141, and the optic module 130 comprises  excitation sources  131a, 131b for emitting excitation light and  detectors  132a, 132b for detecting visible light or a fluorescence signal. The container assembly 140 comprises a slot 141 for fitting the sample container 110 and a plurality of openings for coupling the detector 132a, the detector 132b, the excitation source 131a, the excitation source 131b, and the heating element 121 to the container assembly 140. In FIG. 1, only the  openings  142a and 142b for coupling the detector 132b and the excitation source 131b to the container assembly 140 are marked for illustrative purposes. The container assembly 140 may have one or more openings for coupling multiple excitation sources or detectors to the container assembly 140. If the  excitation source  131a, 131b and the  detectors  132a, 132b are integrated on the same component, then only one opening on the container assembly 140 is needed for the coupling of the excitation to the container assembly 140.
The optics module 130 is fixed to the container assembly 140. During the photothermal reaction, the optics module 130 is stationary relative to the container assembly 140, therefore the distance between the optics module 130 and the sample container 110 would not change. This stationary configuration between the optics module 130 and the container assembly 140 made it possible for the photothermal reaction unit 10 to be operated outside the laboratory or to be portable. Because re-calibration of the optics module 130 is not required after moving the photothermal reaction unit 10 from one location to another location.
The temperature control module 120 may also include a container assembly temperature sensor 124. In the present exemplary embodiment, the container assembly  temperature sensor 124 is in direct contact with the container assembly 140, and is placed beside the container assembly 140 for detecting the temperature of the container assembly 140. The container assembly temperature sensor 124 submits temperature information to the first temperature program. Preferably, the container assembly temperature sensor 124 is a thermocouple. In other exemplary embodiments, the container assembly temperature sensor 124 can detect the temperature of the container assembly 140 in a contactless manner. Preferably, the container assembly temperature sensor 124 is an infrared light temperature sensor.
In another exemplary embodiment, the container assembly temperature sensor 124 may also be integrated with the cooling element 123 on the same component to reduce the volume and the power consumption of the container assembly temperature sensor 124 and the cooling element 123.
Referring to FIG. 2, the optical arrangement between the excitation source, the detector, and the sample container in the photothermal reaction analyzer or the photothermal reaction unit are provided in accordance with an embodiment of the present disclosure. The optical arrangement between the excitation source 131, sample container 110 and detector 132 are configured to optimize the signal detection. The angle α between the excitation source 131, the sample container 110 and the detector 132 is minimized so that the images of the reagents in the sample container 110 can be captured by the detector 132 without distortion. The angle α can be 0 to 60 degree. The smaller the angle α leads to the better image quality of the reagents in the sample container 110. Preferably, the angle α should be as close to 0 degree as possible.
Referring to FIG. 3, another photothermal reaction analyzer 20 is provided in accordance with an embodiment of the present disclosure. The photothermal reaction analyzer 20 comprises a plurality of container assemblies 140, a container assembly receiving device 150, a plurality of temperature control modules (not shown) , and a plurality of optic modules 130. The container assembly receiving device 150 comprises a plurality of cavities 151, and each of the cavities 151 houses one of the container assemblies 140. Each of the sample  containers 110 is fitted in one of the slots 141 and for containing reagents for performing a photothermal reaction. The temperature control module (not shown) is coupled to the container assembly receiving device 150 for controlling a third temperature program of the container assembly receiving device 150 and the second temperature program for the sample containers 110. Each of the optics modules 130 is coupled to one of the container assemblies 140 and for emitting and detecting light. In each of the photothermal reaction analyzers 20, the optics modules 130 are stationary relative to the container assemblies 140.
In FIG. 3, a plurality of container assembly temperature sensors or cooling elements can be positioned on each of the container assembly 140 with similar configuration as illustrated in FIG. 1, whereas the container assembly temperature sensor and the cooling elements and in contact with the container assembly receiving device 150 (not shown) . The cooling elements 123 can also being replaced by a single cooling element, wherein the single cooling element is coupled on the container assembly receiving device 150. The temperature of the surrounding environment is stabilized by the container temperature sensor 124 and the cooling element 123 according to a third temperature program. The third temperature program regulates the temperature of the container assembly receiving device 150. Preferably, the third temperature program is designed for the container assembly receiving device 150 to be in a consistent temperature, independent of the temperature of the surrounding environment. Therefore, the photothermal reactions in the sample container 110 can be started in a stable condition, with little or no interference from the temperature of the surrounding environment. Each of the container assembly 140 is coupled with a heating element 121 (not shown) , and the temperature of the reaction in the sample container 110 is regulated by the heating element 121 according to the second temperature program. Each of the sample containers 110 in FIG. 3 may be regulated to be in a different temperature in the same time by the second temperature program.
The optics module 130 is fixed to the container assembly 140. During the photothermal reaction, the optics module 130 is stationary relative to the container assembly 140, therefore the distance between the optics module 130 and the sample container 110 would  not change. This stationary configuration between the optics module 130 and the container assembly 140 made it possible for the photothermal reaction analyzer 20 to be operated outside the laboratory or to be portable. Because re-calibration of the optics module 130 is not required after moving the photothermal reaction analyzer 20 from one location to another location.
Referring to FIG. 4, another photothermal reaction analyzer 30 is provided in accordance with an embodiment of the present disclosure. The photothermal reaction analyzer 30 comprises a container assembly block 250 comprising a plurality of slots 251, a plurality of sample containers 110, a temperature control module 120, and a plurality of optics modules 130. Each of the sample containers 110 fitted in one of the slots 251 and for containing reagents for performing a photothermal reaction. The temperature control module 120 is coupled to the container assembly block 250 for controlling a fourth temperature program of the container assembly block 250 and the second temperature program for the sample containers 110. Each of the optics modules 130 is coupled to one of the slots 251 of the container block. The optics modules 130 are stationary relative to the container assembly block 250.
The container assembly block 250 may be integrated with the sample container 110, and the optics module 130 of FIG. 1. The container assembly block 250 comprises a plurality of slots, and each slot houses a sample container 110. The container assembly block 250 further comprises a plurality of openings, wherein the opening 252a may house an excitation source and another opening 252b may house a detector. A temperature control module 120 may be coupled to the container assembly block 250. The temperature control module 120 in combination with the container assembly block 250 comprises a cooling element (not shown) , a container assembly block temperature sensor (not shown) , a plurality of sample temperature sensor 122, and a plurality of heating elements 121. For each slot 251 of the container assembly block 250, a heating element 121 and a sample temperature sensor 122 are provided for regulating temperature of the sample container 110. The heating element 121 and the sample temperature sensor 122 are used to regulate the temperature of the sample  container 110 according to the second temperature program. The cooling element and the container assembly block temperature sensor are coupled to the container assembly block 250 (not shown) . A fourth temperature program regulates the temperature of the container assembly block 250. Preferably, the fourth temperature program is designed for the container assembly block 250 to be in a consistent temperature, independent of the temperature of the surrounding environment. Therefore, the photothermal reactions in the sample container 110 can be started in a stable condition, with little or no interference from the temperature of the surrounding environment. The container assembly block 250 is coupled with a heating element 121, and the temperature of the reaction in the sample container 110 is regulated by the heating element 121 according to the second temperature program. Each of the sample containers 110 in FIG. 4 may be regulated to be in a different temperature in the same time by the second temperature program.
Comparing to FIG. 3, the container assembly block 250 has a better thermal conductivity by reducing elements, and therefore enables the temperature control module 120 to effectively regulates the temperature of the container assembly block 250 according to the fourth temperature program.
The optics module 130 is fixed to the container assembly block 250. During the photothermal reaction, the optics module 130 is stationary relative to the container assembly block 250, therefore the distance between the optics module 130 and the sample container 110 would not change. This stationary configuration between the optics module 130 and the container assembly block 250 made it possible for the photothermal reaction analyzer 30 to be operated outside the laboratory or to be portable. Because re-calibration of the optics module 130 is not required after moving the photothermal reaction analyzer 30 from one location to another location.
Referring to FIG. 5, The control module of the photothermal reaction analyzer is provided in accordance with an embodiment of the present disclosure. One or more of the photothermal reaction units 10, the photothermal reaction analyzers 20, and the photothermal reaction analyzers 30 may include a control module 160. The control module 160 controls the  operations of the temperature control module 120 and the optics module 130. The control module 160 includes an input unit 161, a microprocessor 162, and an output unit 163.
The input unit 161 is in communication with the microprocessor 162, the detector 132, the sample temperature sensor 122 and the container assembly temperature sensor 124. The input unit 161 can input one or more instruction by a user, and obtain information from the detector 132, the sample temperature sensor 122 and the container assembly temperature sensor 124. The input unit 161 may include an input interface and an analog-to-digital signal conversion element. The instructions may be input by the user to the input interface of the input unit 161. The analog-to-digital signal conversion element converts and transmits the instructions. Preferably, the input interface may be a button, an array of buttons, a keyboard, a touch screen or the like. The instructions may be a start command, a stop command, a pause command or any other instructions for facilitating the reactions in the photothermal reaction unit 10.
The microprocessor 162 is in communication with the input unit 161 and the output unit 163. The microprocessor 162 obtains the instruction from the input unit 161, and sends out one or more operation instruction to the output unit 163. When adjusting the temperature of the container assembly 140, the microprocessor 162 receives temperature information from the container assembly temperature sensor 124 and sends instructions to the cooling element 123 according to the first temperature program to regulate the temperature of the container assembly 140, the third temperature program to regulate the temperature of the container assembly receiving device 150, or the fourth temperature program to regulate the temperature of the container assembly block 250. When adjusting the temperature of the sample container 110, the microprocessor 162 receives temperature information from the sample temperature sensor 122 and sends instructions to the heating element 121 according to the second temperature program. Further, the microprocessor 162 can analyze the information from the detector 132 to obtain the result of experiment, and sends out the result of experiment to the output unit 163. Preferably, the microprocessor 162 may be a Microprocessor Unit (MPU) , a Microcontroller Unit (MCU) , a Central Processing Unit (CPU) or any other data  processing components.
The output unit 163 is in communication with the microprocessor 162, the heating element 121, the  excitation source  131a and 131b and the cooling element 123. The output unit 163 can output the operation instruction to the heating element 121, the  excitation source  131a and 131b and the cooling element 123. Further, the output unit 163 can output the result of experiment from the microprocessor 162. The output unit 163 may include a display interface and a digital-to-analog signal conversion element. The display interface displays the result of experiment from the microprocessor 162. The digital-to-analog signal conversion unit converts and transmits the result of experiment. Preferably, the display interface may be a display, a printer, or the like.
Further, the control module 160 may include a communication unit 164 and a memory 165. The communication unit 164 is in communication with the memory 165.
The communication unit 164 is in communication with the microprocessor 162 and an external device. The communication unit 164 is used for transmitting information between the photothermal reaction unit 10 and the external device. Preferably, the communication unit 164 may include one or more of wireless communication components, such as Bluetooth components, WIFI components, or the like. The external device may be a computing device, such as a computer, a tablet, a smartphones, a laptop, or the like. Further, users can input one or more instruction from the communication unit 164 or from one or more computing devices in communication with the communication unit 164, and obtain the result of experiment from the microprocessor 162.
The memory 165 is in communication with the microprocessor 162. The memory 165 is used for storing the operation flow and the result of experiments from the microprocessor 162. Preferably, the memory 165 may be a Random Access Memory (RAM) , a memory card, or any other memory storage components.
It is noted that in FIG. 5, the temperature control module 120, the 2, the sample temperature sensor 122, the cooling element 123, the container assembly temperature sensor 124, the optics module 130, the container assembly 140, and the sample container 110  correspond to those elements that are designated by the same reference numerals in FIG. 1, respectively. The excitation source 131 is a collection of the  excitation source  131a and 131b, and the detector 132 is a collection of the  detector  132a and 132b.
Referring to FIG. 6, a housing of the photothermal reaction unit of the photothermal reaction analyzer is provided in accordance with an embodiment of the present disclosure. The photothermal reaction unit 10 in FIG. 1 may further include a housing 170 for housing the container assembly receiving device 150 and the control module 160.
Referring to FIG. 7, a procedure of performing an immunofluorescence reaction using the above photothermal reaction analyzer is provided in accordance with an embodiment of the present disclosure. The procedures in FIG. 7 may be automatically instructed by the photothermal reaction analyzer or manually instructed by the user.
211 involves determining whether the reagent in the sample container needs to be heated. If it is necessary for the reagent to be heated, the microprocessor would instruct the photothermal reaction analyzer to proceed to 212. If it is not necessary for the reagent to be heated, the microprocessor would instruct the photothermal reaction analyzer to proceed to 213.
The reagent may include one or more analytes, fluorescent dyes, markers, antibodies and other required reagents for the immunofluorescence reaction or the PCR. The marker and the fluorescent dye are used to signify the reaction results. The marker may be specifically bind to the analyte. Preferably, the marker may be chemically bind to an antibody or the analyte in the immunofluorescence reaction. The fluorescent dye can be bind to an antibody or the analyte in the immunofluorescence reaction. The analyte may be one or more protein, peptide, or nucleic acids from one or more materials of biological origin. The biological origin comprises one or more of biological tissue, cells. body fluids, or body fluid derivatives. The biological origin may be blood, serum, plasma, slides mounted with biological tissue, slides mounted with cells, or any other biological tissue derivatives.
If the reagent needs to be heated, the reagent may include one or more heat-generating reactants. The heat-generating reactant can generate heat by irradiation with  electromagnetic waves, such as a transition metal heated by infrared irradiation. The reactant may be a transition metal material, and the transition metal material can be a transition metal oxide, a transition metal hydroxide, a Group III metal compound doped with the transition metal, a silicon dioxide doped with the transition metal oxide, or a silicon dioxide doped with the transition metal hydroxide. The temperature of the reactant is elevated when irradiated by infrared irradiation.
212 involves heating the reagent to a designated temperature by the temperature control module according to the second temperature program. Preferably, the temperature control module may include a heating element, a cooling element, a sample temperature sensor and a container assembly temperature sensor. The designated temperature in 212 is directed to the temperature required for the immunofluorescence reaction.
Further, electromagnetic waves is needed in 212 to raise the temperature of the reagents to the designated temperature. The electromagnetic waves have a frequency range of 200 kHz to 500 THz. Preferably, the electromagnetic wave is in the spectrum of infrared light.
In another exemplary embodiment, the temperature of the reagents is detected by the photothermal reaction analyzer, the reagent stays in a designated temperature for a predetermined time frame. The predetermined time frame is set according to the reaction time required for the immunofluorescence reaction.
213 involves exciting the fluorescence of the reagent with an excitation light by the excitation source. Different excitation lights may be emitted according to the fluorescent dye in the reagent. For example, if the fluorescent dye in the reagent is SYBR, a blue light with a wavelength of 450 nm to 495 nm can be emitted. If the fluorescent dye in the reagent is ROX, a green fluorescence with a wavelength of 495 nm to 570 nm can be emitted.
214 involves detecting the fluorescence of the reagent by the detector. Different fluorescents may be detected according to the fluorescent dye in the reagents. For example, if the fluorescent dye in the reagent is SYBR, the green fluorescence can be detected. If the fluorescent dye in the reagent is ROX, the red fluorescence can be detected.
The reaction time would be longer if no fluorescent dyes is presented in the sample  container. FIG. 8 is the image and fluorescent signal of the sample container when conducting the immunofluorescence reaction, in accordance with an embodiment of the present disclosure. The fluorescent signal can be captured by the detector and accumulated in the reaction. The column B of the FIG. 8 is the fluorescent signals from the sample container measured by the photodiode (PD) of the detector; the column A of FIG. 8 is the images from the sample container taken by the imaging component of the detector. In the upper half of FIG. 8, SYBR is not presented in the reagent in the sample container, therefore the image taken by the imaging component of the detector is without the green fluorescence emitted by SYBR, as shown by the upper half of column A of FIG. 8. The upper half of column B of FIG. 8 shows when none of the green fluorescence is detected in the sample container, the reaction time required by the immunofluorescence reaction would be longer. In the lower half of FIG. 8, SYBR is presented in the reagent in the sample container, therefore the image taken by the imaging component of the detector is with the green fluorescence emitted by SYBR, as shown by the lower half of column A of FIG. 8. The lower half of column B of FIG. 8 shows when the green fluorescence is detected in the sample container, the reaction time would be shorter than the reaction without SYBR.
In another exemplary embodiment, 211 further comprising: loading the reagents into the sample container and placing the sample container into the container assembly of the photothermal reaction analyzer.
In another exemplary embodiment, 211 further comprises the following steps of 2111-2113:
2111 involves inputting one or more instruction by the user. The instruction may be a start command. Preferably, 2111 may include the user input one or more instruction to the photothermal reaction analyzer. The instruction may be computer-implemented methods containing operation flow. The memory unit of the microprocessor may store the computer-implemented methods.
2112 involves determining whether the reagent needs to be heated. If it is necessary, the microprocessor may send out one or more instructions to the temperature  control module and the optics module. If it is not necessary, the microprocessor may send out one or more instructions to the temperature control module and the optics module. Preferably, the optics module may include one or more detectors and excitation sources.
Preferably, the computer-implemented methods may be loaded from the memory by the microprocessor to determining whether the reagent needs to be heated.
Preferably, the microprocessor sends out one or more instructions to the temperature control module and the optics module via an output unit.
In another exemplary embodiment, 214 further comprises the following steps of 2141-2143:
2141 involves obtaining one or more fluorescence information of the reagent from the detector by the microprocessor.
2142 involves analyzing of the fluorescence information and obtaining the result of experiment by the microprocessor.
2143 involves determining whether the reaction is completed. If it is completed, the microprocessor may send out a stop command to the temperature control module and the optics module. Preferably, Step 2143 may further involves storing the result of experiment to the memory. Further, the result of experiments may be transmitted to an external device.
As an exemplary embodiment of the present disclosure, a method of performing a PCR using the above photothermal reaction analyzer, comprising:
221 involves heating the reagent in the sample container to a designated temperature by the temperature control module according to the second temperature program.
The reagent may include one or more polymerases, dNTPs, primers, template sequences, and other required reagents for the PCR.
The reagent may include one or more heat-generating reactants. The heat-generating reactant can generate heat by irradiation with electromagnetic waves, such as a transition metal heated by infrared irradiation. The reactant may be a transition metal material, and the transition metal material can be a transition metal oxide, a transition metal  hydroxide, a Group III metal compound doped with the transition metal, a silicon dioxide doped with the transition metal oxide, or a silicon dioxide doped with the transition metal hydroxide. The temperature of the reactant is elevated when irradiated by infrared light.
The second temperature program then instructs the control module for the heating element to emitt electromagnetic waves to raise the temperature of the reagent to one or more designated temperatures. The electromagnetic waves have a frequency range of 200 kHz to 500 THz. Preferably, the electromagnetic wave is in the spectrum of infrared light.
The designated temperature is according to the second temperature program and are the temperatures required for each stage of the PCR.
In another exemplary embodiment, sensing the temperature of the reagents and keeping the reagent in a designated temperature for the predetermined time frame. The predetermined time frame is according to the time needed in the protocol of the PCR and is.
In another exemplary embodiment, 221 further comprising: loading the reagents into the sample container and placing the sample container into the container assembly of the photothermal reaction analyzer.
In another exemplary embodiment, 221 further comprises the following steps of 2211-2213:
2211 involves inputting one or more instruction by the user. The instruction may be a start command. Preferably, 2211 may include the user input one or more instruction to the photothermal reaction analyzer. The instruction may be computer-implemented methods containing operation flow. The memory unit of the microprocessor may store the computer-implemented methods.
2212 involves sending out a heating instruction to the temperature control module by the microprocessor. The computer-implemented methods may be loaded from the memory by the microprocessor to determining whether the reagent needs to be heated. Preferably, the microprocessor sends out one or more instructions to the temperature control module and the optics module via an output unit.
In another exemplary embodiment, 221 further comprises the following steps of  222-223:
222 involves determining whether the reaction is completed according to the reaction time. If it is completed, the microprocessor would send out a stop command to the temperature control module. Preferably, 222 may further involves displaying the completion signal or transmitting the result of experiments to an external device.
Referring to FIG. 9, a method of performing a real-time PCR using the above photothermal reaction analyzers or photothermal reaction units are provided in accordance with one or more embodiments of the present disclosure. The method comprising:
231 involves heating the reagent in the sample container to a designated temperature by the temperature control module.
The reagent may include one or more analytes, polymerases, dNTPs, primers, probe sequences, template sequences, fluorescent dyes, and others requiring for the real-time PCR. The fluorescent dye can be bind to the probe sequences.
The reagent may include one or more heat-generating reactants. The heat-generating reactant can generate heat by irradiation with electromagnetic waves, such as a transition metal heated by infrared irradiation. The reactant may be a transition metal material, and the transition metal material can be a transition metal oxide, a transition metal hydroxide, a Group III metal compound doped with the transition metal, a silicon dioxide doped with the transition metal oxide, or a silicon dioxide doped with the transition metal hydroxide. The temperature of the reactant is elevated when irradiated by infrared irradiation.
Further, electromagnetic waves are needed to raising the temperature of the reagents to the designated temperature. The electromagnetic waves have a frequency range of 200 kHz to 500 THz. Preferably, the electromagnetic wave is in the spectrum of infrared. The designated temperature is set according to the temperature required for each stage of the real-time PCR.
In another exemplary embodiment, sensing the temperature of the reagents and keeping the reagent in a designated temperature for a predetermined time frame. The predetermined time frame is according to the time required for each stage of the real-time  PCR.
232 involves exciting the fluorescence of the reagent with an excitation light by the excitation source. Different excitation lights may be emitted according to the fluorescent dye in the reagent. For example, if the fluorescent dye in the reagent is SYBR, a blue light with a wavelength of 450 nm to 495 nm can be emitted. If the fluorescent dye in the reagent is ROX, a green fluorescence with a wavelength of 495 nm to 570 nm can be emitted.
233 involves detecting the fluorescence of the reagent by the detector. Different fluorescents may be detected according to the fluorescent dye in the reagents. For example, if the fluorescent dye in the reagent is SYBR, the green fluorescence can be detected by the detector. If the fluorescent dye in the reagent is ROX, the red fluorescence can be detected by the detector.
In another exemplary embodiment, 231 further comprising: loading the reagent into a sample container and putting the sample container into a container assembly of the photothermal reaction analyzer.
In another exemplary embodiment, 231 further comprises the following steps of 2311-2313.
2311 involves inputting one or more instruction by users. The instruction may be a start command. Preferably, 2311 may include the user input one or more instruction to the photothermal reaction analyzer. The instruction may be computer-implemented methods containing operation flow. The memory unit of the microprocessor may store the computer-implemented methods.
2312 involves the microprocessor sends out one or more instructions to the temperature control module and the optics module. Preferably, the computer-implemented methods containing the operation flow may be loaded from the memory by the microprocessor. The microprocessor then determines whether the reagent needs to be heated by the microprocessor.
Preferably, the microprocessor sends out one or more instructions to the temperature control module and the optics module via an output unit.
In another exemplary embodiment, 233 further comprises the following steps of 2331-2333:
2331 involves obtaining one or more fluorescence information of the reagent from the detector by the microprocessor.
2332 involves analyzing the fluorescence information and obtaining the result of experiment by the microprocessor.
2333 involves determining whether the reaction is completed. If it is completed, the microprocessor will send out a stop command to the temperature control module and the optics module.
The result of experiment is then stored in the memory unit. Further, an external device may display the result of experiments or transmit the result of experiments.
It is to be further understood that even though numerous characteristics and advantages of the present exemplary embodiments have been set forth in the foregoing description, together with details of the structures and functions of the exemplary embodiments, the disclosure is illustrative only, and changes may be made in details, especially in matters of shape, size, and arrangement of parts within the principles of the disclosure to the full extent indicated by the broad general meaning of the terms in which the appended claims are expressed.

Claims (54)

  1. A photothermal reaction analyzer, comprising:
    a plurality of photothermal reaction units, each of the photothermal reaction units comprising:
    a container assembly comprising a slot;
    a sample container fitted in the slot for containing reagents for performing a photothermal reaction;
    a temperature control module coupled to the container assembly for controlling a first temperature program for the container assembly and a second temperature program for the sample container; and
    an optics module coupled to the container assembly and for emitting and detecting light,
    wherein the optics module is stationary relative to the container assembly.
  2. The photothermal reaction analyzer of claim 1, wherein the container assembly further comprises at least one opening connected to the slot, and one of the optics modules is coupled to the container assembly via the opening.
  3. The photothermal reaction analyzer of claim 1, wherein the optics module is configured to emit a blue excitation light, a green excitation light, an orange excitation light, a red excitation light, or any combination thereof.
  4. The photothermal reaction analyzer of claim 1, wherein the optics modules is configured to detect a green fluorescence, a cyan fluorescence, an orange fluorescence, a red fluorescence, or any combination thereof.
  5. The photothermal reaction analyzer of claim 4, wherein the optics module is further  configured to filter the fluorescence into a range of wavelength.
  6. The photothermal reaction analyzer of claim 1, wherein the temperature control module comprises a heating element coupled to one of the container assemblies via the opening for heating the sample container, a container assembly temperature sensor, a sample temperature sensor, and a cooling component.
  7. The photothermal reaction analyzer of claim 6, wherein the heating element is an electromagnetic wave generator.
  8. The photothermal reaction analyzer of claim 1, wherein each of the container assemblies further comprise at least two openings connected to the slot, and each of the optics modules comprises at least one excitation source for emitting an excitation light and at least one detector for detecting a visible light or a fluorescence signal, and the excitation source and the detector are coupled to the container assembly via the openings, respectively.
  9. The photothermal reaction analyzer of claim 8, wherein the excitation source comprises a blue light excitation source, a green light excitation source, an orange excitation light source, or a red excitation light source.
  10. The photothermal reaction analyzer of claim 8, wherein the detector comprises a light emitting diode (LED) , a semiconductor laser diode (LD) , or any combination thereof.
  11. The photothermal reaction analyzer of claim 8, wherein the detector comprises a green fluorescence detector, a cyan fluorescence detector, an orange fluorescence detector, or a red fluorescence detector.
  12. The photothermal reaction analyzer of claim 8, wherein the detector comprises a photodiode (PD) , an avalanche photodiode (APD) , a photomultiplier tube (PMT) , a silicon photomultiplier (SIPM) , or any combination thereof.
  13. The photothermal reaction analyzer of claim 8, wherein the optics module further comprises a filter disposed between the excitation source and the detector and for filtering the fluorescence into a range of wavelength.
  14. The photothermal reaction analyzer of claim 8, wherein the detector comprises one or more imaging components for capturing at least one image of an inner side of the container assembly.
  15. The photothermal reaction analyzer of claim 8, wherein each of the temperature control module comprises a heating element coupled to one of the container assemblies via the openings for heating the sample containers, a container assembly temperature sensor, a sample temperature sensor, and a cooling component.
  16. The photothermal reaction analyzer of claim 15, wherein the heating element is an electromagnetic wave generator.
  17. The photothermal reaction analyzer of claim 1, wherein the photothermal reaction performed by the photothermal reaction analyzer is an immunofluorescence reaction, a isothermal polymerase reaction, a reverse-transcriptase polymerase chain reaction, a multiplex polymerase chain reaction, a digital polymerase chain reaction, a conventional polymerase chain reaction, or a real-time polymerase chain reaction.
  18. The photothermal reaction analyzer of claim 1, further comprising a control module for  controlling the temperature control modules and the optics modules.
  19. A photothermal reaction analyzer, comprising:
    a plurality of container assemblies, each of the container assemblies comprising a slot;
    a container assembly receiving device comprising a plurality of cavities, and each of the cavities houses one of the container assemblies;
    a plurality of sample containers, each of the sample containers fitted in one of the slots and for containing reagents for performing a photothermal reaction;
    a temperature control module coupled to the container assembly receiving device and for controlling a third temperature program of the container assembly receiving device and the second temperature program for the sample containers;
    a plurality of optics modules, each of the optics modules coupled to one of the container assemblies and for emitting and detecting light,
    wherein the optics modules are stationary relative to the container assemblies.
  20. The photothermal reaction analyzer of claim 19, wherein each of the container assemblies further comprises at least one opening connected to the slot, and one of the optics modules is coupled to the container assembly via the opening.
  21. The photothermal reaction analyzer of claim 19, wherein the optics modules are configured to emit a blue excitation light, a green excitation light, an orange excitation light, a red excitation light, or any combination thereof.
  22. The photothermal reaction analyzer of claim 19, wherein the optics modules are configured to detect a green fluorescence, a cyan fluorescence, an orange fluorescence, a red fluorescence, or any combination thereof.
  23. The photothermal reaction analyzer of claim 22, wherein the optics modules are further configured to filter the fluorescence into a range of wavelength.
  24. The photothermal reaction analyzer of claim 19, wherein the temperature control module comprises a plurality of heating elements for heating the sample containers, a container assembly temperature sensor, a sample temperature sensor, and a cooling component, and each of the heating elements is coupled to one of the container assemblies via the opening.
  25. The photothermal reaction analyzer of claim 24, wherein the heating element is an electromagnetic wave generator.
  26. The photothermal reaction analyzer of claim 19, wherein each of the container assemblies further comprises at least two openings connected to the slot, and each of the optics modules comprises at least one excitation source for emitting an excitation light and at least one detector for detecting a visible light or a fluorescence signal, and the excitation source and the detector are coupled to the container assembly via the openings, respectively.
  27. The photothermal reaction analyzer of claim 26, wherein the excitation source comprises a blue light excitation source, a green light excitation source, an orange excitation light source, or a red excitation light source.
  28. The photothermal reaction analyzer of claim 26, wherein the detector comprises a light emitting diode (LED) , a semiconductor laser diode (LD) , or any combination thereof.
  29. The photothermal reaction analyzer of claim 26, wherein the detector comprises a green fluorescence detector, a cyan fluorescence detector, an orange fluorescence detector, or a red fluorescence detector.
  30. The photothermal reaction analyzer of claim 26, wherein the detector comprises a photodiode (PD) , an avalanche photodiode (APD) , a photomultiplier tube (PMT) , a silicon photomultiplier (SIPM) , or any combination thereof.
  31. The photothermal reaction analyzer of claim 26, wherein the optics module further comprises a filter for filtering the fluorescence into a range of wavelength, and the filter is disposed between the excitation source and the detector.
  32. The photothermal reaction analyzer of claim 26, wherein the detector comprises one or more imaging components for capturing at least one image of an inner side of the container assembly.
  33. The photothermal reaction analyzer of claim 26, wherein the temperature control module comprises a plurality of heating elements for heating the sample containers, a container assembly temperature sensor, a plurality of sample temperature sensors, and a cooling component, and each of the heating element is coupled to one of the container assembly via the openings.
  34. The photothermal reaction analyzer of claim 33, wherein the heating element is an electromagnetic wave generator.
  35. The photothermal reaction analyzer of claim 19, wherein the photothermal reaction performed by the photothermal reaction analyzer is an immunofluorescence reaction, an isothermal polymerase reaction, a reverse-transcriptase polymerase chain reaction, a multiplex polymerase chain reaction, a digital polymerase chain reaction, a conventional polymerase chain reaction, or a real-time polymerase chain reaction.
  36. The photothermal reaction analyzer of claim 19, further comprising a control module for controlling the temperature control modules and the optics modules.
  37. A photothermal reaction analyzer, comprising:
    a container assembly block comprising a plurality of slots;
    a plurality of sample containers, each of the sample containers fitted in one of the slots and for containing reagents for performing a photothermal reaction;
    a temperature control module coupled to the container assembly block and for controlling a fourth temperature program of the container assembly block and the second temperature program for the sample containers;
    a plurality of optics modules, each of the optics modules being coupled to one of the slots of the container assembly block,
    wherein the plurality of optics modules are stationary relative to the container assembly block.
  38. The photothermal reaction analyzer of claim 37, wherein the container assembly block further comprises a plurality of openings, and each of the openings is connected to one of the slots, and one of the optics modules is coupled to the slot via the opening.
  39. The photothermal reaction analyzer of claim 37, wherein the optics modules are configured to emit a blue excitation light, a green excitation light, an orange excitation light, a red excitation light, or any combination thereof.
  40. The photothermal reaction analyzer of claim 37, wherein the optics modules are configured to detect a green fluorescence, a cyan fluorescence, an orange fluorescence, a red fluorescence, or any combination thereof.
  41. The photothermal reaction analyzer of claim 40, wherein the optics modules are further configured to filter the fluorescence into a range of wavelength.
  42. The photothermal reaction analyzer of claim 38, wherein the temperature control module comprises a plurality of heating elements for heating the sample containers, a container assembly block temperature sensor, a sample temperature sensor, and a cooling component, and each of the heating elements is coupled to one of the slots in the container assembly block via the opening.
  43. The photothermal reaction analyzer of claim 42, wherein the heating element is an electromagnetic wave generator.
  44. The photothermal reaction analyzer of claim 37, wherein the container assembly block further comprises a plurality of openings, at least two of the openings are connected to one of the slots, each of the optics modules comprises at least one excitation source for emitting an excitation light and at least one detector for detecting a visible light or a fluorescence signal, and the excitation source and the detector are coupled to one of the slots in the container assembly block via the openings, respectively.
  45. The photothermal reaction analyzer of claim 44, wherein the excitation source comprises a blue light excitation source, a green light excitation source, an orange excitation light source, or a red excitation light source.
  46. The photothermal reaction analyzer of claim 45, wherein the detector comprises a light emitting diode (LED) , a semiconductor laser diode (LD) , or any combination thereof.
  47. The photothermal reaction analyzer of claim 45, wherein the detector comprises a green fluorescence detector, a cyan fluorescence detector, an orange fluorescence detector, or a red fluorescence detector.
  48. The photothermal reaction analyzer of claim 45, wherein the detector comprises a photodiode (PD) , an avalanche photodiode (APD) , a photomultiplier tube (PMT) , a silicon photomultiplier (SIPM) , or any combination thereof.
  49. The photothermal reaction analyzer of claim 44, wherein the optics module further comprises a filter for filtering the fluorescence into a range of wavelength, and the filter is disposed between the excitation source and the detector.
  50. The photothermal reaction analyzer of claim 44, wherein the detector comprises one or more imaging components for capturing at least one image of an inner side of the slot in the container assembly block.
  51. The photothermal reaction analyzer of claim 44, wherein the temperature control module comprises a plurality of heating elements for heating the sample containers, a container assembly block temperature sensor, a sample temperature sensor, and a cooling component, and each of the heating elements is coupled to one of the slots in the container assembly block.
  52. The photothermal reaction analyzer of claim 51, wherein the heating element is an electromagnetic wave generator.
  53. The photothermal reaction analyzer of claim 37, wherein the photothermal reaction performed by the photothermal reaction analyzer is an immunofluorescence reaction, an isothermal polymerase reaction, a reverse-transcriptase polymerase chain reaction, a multiplex  polymerase chain reaction, a digital polymerase chain reaction, a conventional polymerase chain reaction, or a real-time polymerase chain reaction.
  54. The photothermal reaction analyzer of claim 37, further comprising a control module for controlling the temperature control module and the optics modules.
PCT/CN2018/083024 2017-04-13 2018-04-13 Photothermal reaction analyzer WO2018188655A1 (en)

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