Portable detection system for detecting pathogens or viruses

Abstract

A portable detection system for detecting pathogens or viruses, the portable detection system comprising: at least one light source for generating an input optical signal; at least one optical sensor comprising at least one optical fiber having at least one tapered sensing region with at least one coating that reacts with a detected pathogen wherein the optical sensor is arranged to receive an input optical signal, the optical fiber having at least one tapered sensing region with at least one coating that reacts with the detected pathogen, transmitting an input optical signal through the tapered sensing region and transmitting an output optical signal from the tapered sensing region; at least one photodetector for detecting a power intensity of the output optical signal, where the photodetector is arranged to generate the output signal based on a change in power intensity of the output power at a resonant wavelength corresponding to the pathogen; and at least one microcontroller for controlling the light source, the optical sensor and the photodetector; wherein the portable detection system is arranged to cause an output to be generated based on the output signal, wherein the output is related to a detected pathogen.

Description

Technical Field

[0001] This invention generally relates to a portable detection system for detecting pathogens or viruses and its associated detachable probe. Background Technology

[0002] Systems and methods used to detect pathogens or viruses, including methods such as PCR technology and DNA sequencing, as well as systems such as automated microbial identification systems and immunodiagnostic analysis systems, require large and expensive instruments that are not typically suitable for field measurements. Summary of the Invention

[0003] The purpose of this invention is to greatly overcome or at least mitigate one or more disadvantages of existing devices.

[0004] The present invention discloses an apparatus designed to solve the above-mentioned problems by providing a portable detection system that utilizes an optical system for determining the power intensity variation of the output power at a resonant wavelength corresponding to the detection of a pathogen or virus.

[0005] According to a first aspect of this disclosure, a method is provided for a portable detection system for detecting pathogens or viruses, the portable detection system comprising: at least one light source for generating an input optical signal; at least one optical sensor including at least one optical fiber having at least one tapered sensing region having at least one coating that reacts with the pathogen to be detected, wherein the optical sensor is arranged to receive the input optical signal, transmit the input optical signal through the tapered sensing region, and transmit an output optical signal from the tapered sensing region; at least one photodetector for detecting the power intensity of the output optical signal, wherein the photodetector is arranged to generate an output signal based on a power intensity change of the output power at a resonant wavelength corresponding to the pathogen; and at least one microcontroller for controlling the light source, the optical sensor, and the photodetector; wherein the portable detection system is arranged to generate an output based on the output signal, wherein the output is correlated with the pathogen to be detected.

[0006] According to another aspect of this disclosure, an apparatus for implementing any of the above methods is provided.

[0007] Other aspects were also disclosed. Attached Figure Description

[0008] At least one embodiment of the invention will now be described with reference to the accompanying drawings and appendices, wherein: Figure 1 A tapered fiber optic sensor according to the present disclosure is shown; Figure 2An example of a phage physical adsorption system according to this disclosure is shown; Figure 3 A phage-based tapered optical fiber for detecting at least one pathogen is shown according to the present disclosure; Figure 4 A schematic diagram of a portable detection system according to this disclosure is shown; Figure 5 A schematic diagram of a portable detection system in use according to this disclosure is shown; Figure 6 An example of an optical power output signal generated by a portable detection system according to this disclosure is shown.

[0009] Figure 7 An example of a power intensity calibration curve based on pathogen concentration according to this disclosure is shown. Detailed Implementation

[0010] The examples provided in this article describe a portable detection system for detecting pathogens. It should be understood that the same principles can also be applied to the detection of viruses.

[0011] Figure 1 A tapered fiber optic sensor according to an example is shown, which has a sensing area for detecting one or more pathogens.

[0012] The optical sensor 101 is formed of an optical fiber 103 having a first non-tapered region 105 for sensing pathogens 109 (in Figure 1 The sensor comprises a conical sensing region 107 (represented by a rhombus) and a second non-conical region 111. The conical sensing region 107 has at least one coating 113 selected from a set of coatings, wherein the selected coating reacts with a pathogen to be sensed by the optical fiber 103 of the optical sensor 101. The coating 113 contains bacteriophages 115 for detecting the pathogen.

[0013] The optical sensor 101 is arranged to receive an input optical signal 117, transmit the input optical signal 117 through the conical sensing region 107, and transmit an output optical signal 119 from the conical sensing region 107.

[0014] As one example, phage-functionalized tapered optical fibers can be used as optical sensors to detect the presence of foodborne pathogens. This can be achieved by monitoring changes in the fiber's refractive index as specific bacteria are selectively captured by a corresponding phage functionalized on the sensing surface of the fiber in the sensing area of ​​the optical sensor. Phages are small viruses harmless to humans and animals, and compared to antibodies, they are less expensive, faster to produce, and have a longer shelf life. Furthermore, phages exhibit thermal stability and can be easily immobilized on optical fibers, for example, using a simple dip-coating technique.

[0015] According to one example, a standard SMF-28 optical fiber is tapered using a Vytran GPX-3000 glass processing machine. The taper profile of the optical microfiber is fixed as follows: down taper length 3 mm, up taper length 2 mm, taper length 6 mm, and taper waist diameter 7.9 μm. This is achieved through the free spectral range (i.e., the spacing between two consecutive peaks in the OM output spectrum) and the extinction ratio (i.e., 10 log...). P peak / P valley ,in P peak and P valley The reproducibility of the optical microfiber was verified by the optical power at the maximum (peak) and minimum (valley) values ​​of the output spectrum, which were consistent within 15.5 ± 1.5 nm and 10 ± 0.5 dB, respectively.

[0016] Other examples are now provided illustrating how to biochemically process the conical portion of a probe to create a sensing region. Immobilizing phage receptors onto the fiber optic sensing surface within the sensing region of an optical sensor is crucial for developing phage-based biosensors. Immobilization steps can include, for example, physical adsorption, covalent bonding, and genetic modification of the receptor.

[0017] As an example, the physical adsorption of bacteriophages on the fiber optic sensing surface in the sensing area of ​​an optical sensor can be achieved through... Figure 2 The phage physisorption system shown is formed. System 201 has a spectrometer 203 and a superluminescent diode 205, both of which are connected via optical fibers to a sensor 101 having a tapered sensing region 107. Sensor 101 is placed in a gas sensing chamber 207 having a gas inlet 209 and a gas outlet 211. Gas is collected from a gas container 213 and then injected into the gas sensing chamber 207, for example, using a gas injector 215. Yap et al., in their paper "Two Dimensional MoS2 Nanosheet-Functionalized Optical Microfiber for Room-Temperature Volatile Organic Compound Detection"... American Chemical Society Journal of Applied NanomaterialsThe method is described in more detail in ( , 2021, 4, 13440-13449), the full text of which is incorporated herein by reference. This method may result in weak binding and inconsistent phage numbers on the surface. Nevertheless, this method is still commonly used for pathogen detection, primarily because of its simple immobilization process. Other methods are also known to those skilled in the art.

[0018] According to another example, the chemical anchoring of phages to the fiber optic sensing surface in the sensing region of an optical sensor can significantly improve the coverage density on the sensing surface. For example, a cysteine-modified gold surface substrate can deposit up to 7 times more phages compared to physical adsorption on a bare gold surface, and the phage density increases to 37 times when the cysteine-modified gold surface is activated by a dual linker such as glutaraldehyde. According to this example, a two-step silica surface chemistry process based on cysteine-glutaraldehyde can be used. Succinimidyl groups are then used for chemical linking with amine groups on the phage surface. This method provides direct integration into biosensor platforms and can achieve coverage as low as 10² CFU / mL. -1 The detection limit of the target bacteria.

[0019] According to another example, bacteriophages can be genetically modified to introduce functional ligands, thereby enhancing the immobilization process on fiber optic sensing surfaces in the sensing region of optical sensors. For example, Gervais et al., in "Immobilization of biotinylated bacteriophages on biosensor surfaces"... Sensors and actuators In B 125 (2007) 615-621), biotin expressing T4 phage was immobilized on a gold surface by using a monolayer of biotin and adding streptavidin as a linker. The biotin-expressing phage can be immobilized on streptavidin-coated magnetic beads, which can be used to capture 72% to 99% of target bacteria from suspensions for analysis and detection.

[0020] The above examples can be used to functionalize tapered optical fibers to specifically sense bacteria on food.

[0021] Other examples of coatings that can be applied to fiber optic sensing surfaces in the sensing area of ​​optical sensors for other detection purposes include: (i) nanomaterials (e.g., 2D nanomaterials); (ii) copper complexes; (iii) proteins; and (iv) enzymes, which can be used for gas sensing, chemical sensing in liquids, detection of disease biomarkers, monitoring of harsh environments with toxic gases or liquids, saliva disease screening, infrastructure safety monitoring, etc. It is understood that two-dimensional (2D) nanomaterials can be single-atom-thickness materials, depending on the reactivity required to be configured in the optical sensor system. Furthermore, it is understood that multiple single-atom layers can be arranged to form the material.

[0022] Embodiments of the present invention include fabricating, characterizing, and functionalizing a cone-shaped optical sensor with a cone-shaped sensing region, and evaluating the performance of the optical sensor in terms of signal sensitivity and reproducibility, as well as its ability to quantitatively analyze bacteria on food. A portable detection system incorporating a bacteriophage-based cone-shaped fiber optic sensor can be developed to enable rapid field testing (e.g., see...). Figure 3 ).

[0023] Figure 3 A phage-based cone-shaped fiber optic sensor for detecting bacteria (e.g., Salmonella) is shown.

[0024] An optical probe 301 can be formed using an optical sensor 303 (e.g., optical sensor 101) having a biochemically treated cone-shaped sensing region 305 with a coating having active binding sites for the pathogen 307 to be detected. For example, the cone-shaped sensing region 305 can be treated with an E2 phage having active binding sites to detect pathogen 307; in this example, pathogen 307 is *Salmonella typhimurium* located on the eggshell 309 of an egg. An optical signal (shown in Figure 311, which illustrates the relationship between wavelength and input power) is generated by an optical source 313 (e.g., a laser) located within the probe 301, and a photodetector 315 within the probe 301 is used to sense power intensity changes at the resonant wavelength (shown in Figure 317). A power intensity change occurs at the resonant wavelength when pathogen binding occurs. According to this example, an optical fiber terminates at the end of the optical path with a reflector 319 for signal feedback via the optical fiber.

[0025] Figure 4 A schematic diagram of an example of the portable detection system 401 described herein is shown.

[0026] The portable detection system 401 has a housing 403 that includes at least one microcontroller 405, at least one memory 407, at least one communication module 409, at least one optical light source 411, at least one photodetector 413, at least one power supply 415, at least one sensor interface 417 for connection to an optical sensor, and an optional output device 419. In this example, the optical sensor is integrated within a connectable and detachable optical probe 421.

[0027] The optical probe 421 may be composed of an optical sensor, such as a reference sensor. Figure 1 The optical sensor 101 is described.

[0028] The optical probe 421 may have a sensor interface for connecting to the sensor interface 417 of a portable detection system. For example, this may be at least one, two, or more fiber optic connections (e.g., (421A, 421B)).

[0029] The optical probe 421 can be a disposable probe that can be discarded after one use.

[0030] Portable detection systems can be configured to generate detection results based on optical output signals associated with the pathogen being detected. For example, the detection results can be generated by the portable detection device itself, or by one or more other devices connected to the portable detection device.

[0031] In one example, the detachable optical probe may include at least one light source for generating the input optical signal.

[0032] In one example, the detachable optical probe may also have at least one photodetector for detecting the output power of the output optical signal, wherein the photodetector is arranged to detect the power intensity change of the output power at the resonant wavelength corresponding to the pathogen.

[0033] The portable detection system 401 may optionally have at least one output interface module 419 to enable the local provision of outputs for the pathogen detection process. For example, the output interface module may be arranged to generate one or more of visual, auditory, and tactile outputs based on output optical signals related to whether a pathogen has been detected.

[0034] The housing 403 can be a single piece or can be formed from multiple parts. The housing can be made of any suitable material, such as durable hard plastic.

[0035] Any suitable microcontroller or microprocessor can be used, such as an Arduino-type microcontroller, which can be used to measure optical signals from a photodetector and convert analog signals into digital signals. The same or different microcontrollers can be used for Wi-Fi communication, such as the Arduino Uno or Arduino IoT module microcontrollers.

[0036] Memory 407 can be any suitable memory used for permanently or semi-permanently storing program instructions for use by the microcontroller, as well as for semi-permanently or non-permanently storing data.

[0037] The communication module 409 may be, for example, a Wi-Fi module, for connecting to a local Wi-Fi node, thereby enabling the communication module 409 to communicate with a server on the Internet under instructions from the microcontroller 405. The communication module 409 may also be, for example, a Bluetooth module, for sharing data using the Bluetooth communication protocol. Other suitable wireless communication protocols may also be used. The communication module can be used to transmit and receive data from one or more other devices (e.g., mobile phones, tablet computers, laptops, computers, servers, and any suitable smart devices such as smartwatches, smart glasses, etc.).

[0038] The software application (“App”) can be used to access data and retrieve, acquire, transmit, store, display, share, or otherwise manipulate data and / or pathogen detection outputs traveling to and from the device. The App may provide the ability to display the results of the pathogen detection process and to display past, present, and / or historical results of the pathogen detection process.

[0039] The optical light source 411 can be a laser, a photodiode, or any other suitable light source. For example, the light source can be a fiber-coupled superluminescent diode, such as a diode that provides 15mW output at a wavelength of 780nm. The QSDM-780-15D, available from QPHOTONICS, LLC, is such an example.

[0040] The photodetector 413 can be any suitable photodetector, such as a photodiode or fiber-optic photodetector manufactured by Thorlabs, a mini or micro spectrometer manufactured by Hamamatsu Photonics KK, or a compact spectrometer manufactured by Ocean Insight.

[0041] As described above, there is a correlation between the power intensity determined by the optical output signal from the optical sensor and the concentration of the sensed pathogen (e.g., Salmonella). Therefore, a reading of the pathogen concentration can be determined based on the measured / determined power intensity. The microcontroller of the portable detection system can determine the power intensity at the resonant wavelength based on the signal generated by the photodetector. Alternatively, a separate device communicating with the portable detection system (via a communication module within the portable detection system and a separate device) can determine the power intensity at the resonant wavelength based on the signal generated by the photodetector within the portable detection system.

[0042] For example, the power source 415 can be a battery and is rechargeable. The battery is chosen to provide sufficient power to all components of the portable detection system.

[0043] The sensor interface 417 may have a first port 419A and a second port 419B, for receiving a first fiber optic connection 421A and a second fiber optic connection 421B of a connectable / detachable optical probe 421, respectively.

[0044] Output device 419 can output, for example, audio, visual, tactile, or any other suitable output signal to indicate whether a pathogen has been detected. For example, a pathogen detection can be indicated by an audio output signal (e.g., a warning beep) or a visual output signal that turns on an LED (e.g., a red LED), and a tactile output signal that uses a small motor to generate vibration to indicate the detection of a pathogen.

[0045] As described herein, the optical signals captured by the optical sensors are processed to determine the presence of pathogens. If the microcontroller has sufficient power, the data processing associated with the captured optical signals can be performed locally. Alternatively, or additionally, the data processing can be performed in any suitable device capable of communicating with the communication module (e.g., smartphone, tablet, laptop, desktop computer, server, smart device, etc.).

[0046] Alternatively, or otherwise, data processing can be performed in an app or software program capable of analyzing data that runs on any suitable electronic device (e.g., smartphone, tablet, laptop, desktop computer, etc.).

[0047] In one example, the microcontroller in the portable detection system can be configured to generate a result based on the output signal produced by a photodetector that detects the output power of the output optical signal. An output interface module can be configured to generate one or more visual, auditory, and tactile outputs based on this output.

[0048] In another example, the portable detection system (with or without an output interface module) may have a communication module arranged to transmit output-related receiving device signals to at least one receiving device. For example, the receiving device can be any suitable device capable of communicating with the communication module (e.g., smartphone, tablet, laptop, desktop computer, server, smart device, etc.).

[0049] Furthermore, in a portable detection system, the receiving device can be configured to receive a receiving device signal and, based on the receiving device signal, generate one or more visual, auditory, and tactile outputs. That is, the receiving device can have a receiving device output interface module for generating one or more visual, auditory, and tactile outputs based on that output.

[0050] In another example, the portable detection system may have an output interface module and a communication module that can communicate with a connected device (e.g., another receiving device) to enable the connected device to process the output. For example, the communication module may be arranged to transmit a receiving device signal associated with the output to the other receiving device, and subsequently receive a signal from the other receiving device, wherein the other receiving device determines whether a pathogen has been detected based on the receiving device signal. The receiving device and the other receiving device may be different devices or the same device. The output interface module may be arranged to generate one or more of visual, auditory, and tactile outputs based on the received signal.

[0051] The receiving device signal may include, for example, a set of data based on the output power detected by the photodetector, the power intensity detected by the photodetector, or any other suitable data related to the photodetector, which may be used by another receiving device to determine the presence of pathogens.

[0052] The receiving device signal may include, for example, a binary indication of the presence of a pathogen, or any other suitable data related to the determination of the presence of a pathogen, so that the portable detection system can indicate the test result.

[0053] The output can be a simple binary output, such as "yes" or "no," indicating the presence or absence of the pathogen, respectively. The output can be a color output, such as a red or green light, indicating the presence or absence of the pathogen, respectively. The output can be an audio output, such as a loud "buzzing" sound or a quiet "ding," indicating the presence or absence of the pathogen, respectively. The output can also be vibration or no vibration from a haptic device, indicating the presence or absence of the pathogen, respectively.

[0054] Figure 5 A schematic diagram of a portable detection system in use is shown.

[0055] In this example, the portable detection system 401 communicates with receiving device 501 and / or another receiving device 503 and / or server 505. The portable detection system can send data related to optical measurements to any one or all of receiving device 501, the other receiving device 503, and server 505. Any one or all of receiving device 501, the other receiving device 503, and server 505 can determine the power variation at the resonant wavelength corresponding to the pathogen. It is understood that receiving device 501 and / or the other receiving device 503 can be any suitable device, such as a mobile phone, tablet computer, laptop computer, computer, or any suitable smart device (e.g., smartwatch, smart glasses, etc.).

[0056] Figure 6 An example optical power output signal generated by a portable detection system configured to detect acetone vapor in an air sample is shown. It can be seen that the power intensity variation (y-axis) is measured at different wavelengths (x-axis), and the power intensity at the resonant wavelength is determined, i.e., based on the peak and trough values ​​of the power intensity measurements. Therefore, a microcontroller can determine the presence of a pathogen in the sample based on a provided dataset.

[0057] Figure 7 An example calibration curve of output power intensity versus pathogen concentration is shown. The figure below shows the linear relationship between the characteristic wavelength of the resonant wave and the pathogen concentration, where the wavelength increases with increasing concentration. The figure above shows that the shift in output power intensity can be measured using different characteristic wavelengths. Therefore, a portable detection system can be calibrated using the corresponding concentration.

[0058] Industrial applicability The device described in this article is suitable for the virus or pathogen sensing industry.

[0059] The above description only describes some embodiments of the present invention. Modifications and / or changes can be made to the present invention without departing from the scope and spirit of the present invention. The embodiments are for illustration only and not for limitation.

[0060] In the context of this specification, the word "comprising" means "primarily but not necessarily only includes," "has," or "contains," rather than "consisting only of." Variations of the word "comprising," such as "comprise" and "comprises," have correspondingly different meanings.

Claims

1. A portable detection system for detecting a pathogen or virus, the portable detection system comprising: at least one light source for generating an input optical signal; at least one optical sensor comprising at least one optical fiber having at least one tapered sensing region having at least one coating reactive to a detected pathogen, wherein the optical sensor is arranged to receive the input optical signal, transmit the input optical signal through the tapered sensing region, and transmit an output optical signal from the tapered sensing region; at least one photodetector for detecting a power intensity of the output optical signal, wherein the photodetector is arranged to generate an output signal based on a power intensity change of the output power at a resonant wavelength corresponding to a pathogen; and at least one microcontroller for controlling the light source, optical sensor, and photodetector; wherein the portable detection system is arranged to cause an output to be generated based on the output signal, wherein the output is related to a detected pathogen.

2. The portable detection system of claim 1, further comprising an output interface module, wherein the microcontroller is arranged to determine the power intensity change at the resonant wavelength and generate the output based on the determined power intensity change, and the output interface module is arranged to generate one or more of a visual, audible, and haptic output based on the determined power intensity change.

3. The portable detection system of claim 1 or 2, further comprising a communication module for transmitting a receiving device signal related to the output to at least one receiving device.

4. The portable detection system of claim 3, wherein, the receiving device is arranged to receive the receiving device signal, determine the power intensity change at the resonant wavelength, and generate one or more of a visual, audible, and haptic output based on the determined power intensity change.

5. The portable detection system of claim 4, wherein, the receiving device further comprises an output interface module, the output interface module is arranged to generate one or more of a visual, audible, and haptic output based on the output based on the receiving device signal.

6. The portable detection system of any one of claims 1 to 5, wherein, the coating comprises one or more of a bacteriophage, a nanomaterial, a copper complex, a protein, and an enzyme.

7. The portable detection system of any one of claims 1 to 6, wherein, the optical sensor is a connectable and detachable optical probe.

8. The portable detection system of any one of claims 1 to 7, wherein, the light source comprises a superluminescent diode.

9. The portable detection system of claim 1, further comprising a power source for providing power to one or more of the light source, optical sensor, photodetector, and microcontroller.

10. A detachable optical probe for use with the portable detection system of claim 1, the optical probe comprising a sensor interface for interfacing with the portable detection system, and an optical sensor, wherein, the optical sensor comprises an optical fiber having at least one tapered sensing region having at least one coating reactive to a detected pathogen, wherein the optical sensor is arranged to receive an input optical signal generated by at least one light source, transmit the input optical signal through the tapered sensing region, and transmit an output optical signal from the tapered sensing region.

11. The detachable optical probe of claim 10, further comprising at least one light source for generating the input optical signal.

12. The detachable optical probe of claim 10, further comprising at least one photodetector for detecting an output power of the output optical signal, wherein, The photodetector is arranged to detect a power intensity change of the output power at the resonance wavelength corresponding to the pathogen.

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