Micro-cavity laser multi-tumor marker sensor based on air cladding fiber

Abstract

The invention discloses a micro-cavity laser multi-tumor marker sensor based on an air cladding optical fiber, and relates to the technical field of optical fiber laser sensors, the micro-cavity laser multi-tumor marker sensor comprises an optical module, a micro-cavity regulation and control and sample detection module and a signal processing module; the microcavity regulation and control and sample detection module comprises an air cladding optical fiber, a polytetrafluoroethylene capillary hose and a micro sample injection pump; a circle of closely-arranged micro-channels are arranged around the periphery of a pure quartz fiber core of the air cladding optical fiber and are optical fiber air cladding layers, gain liquid with the refractive index higher than that of quartz is filled in the optical fiber air cladding layers, total internal reflection is formed on an optical fiber section liquid-quartz interface, an optical fiber micro-cavity is formed, and the interaction between light and matter is enhanced; pump light emitted by the optical module vertically enters the surface of the air cladding optical fiber, and a generated laser signal enters the signal processing module. According to the micro-cavity laser multi-tumor marker sensor based on the air cladding optical fiber, the problems that in the prior art, the sensing sensitivity is low, and high-sensitivity marker detection of multiple markers is difficult to achieve are solved.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of optical fiber laser sensor, and in particular to a microcavity laser multi-tumor marker sensor based on air-clad optical fiber. BACKGROUND

[0002] Chemiluminescence immunoassay is one of the most sensitive immune detection methods widely used in clinical, which uses the high specificity of antigen-antibody combination to identify target molecules, uses enzymes (such as horseradish peroxidase, etc.) to mark the detection antibody, and uses enzyme catalysis to produce chemiluminescent substances, so that one enzyme molecule can catalyze the generation of tens of thousands of photon signals to realize the amplification of detection signals. However, the chemical luminescence method has problems such as wide emission spectrum and limited luminescent materials, resulting in poor wavelength multiplexing capability and difficulty in realizing multi-marker detection.

[0003] In the application scene of high-sensitivity tumor marker screening, high-sensitivity detection is required, and standardized detection of multiple markers of different abundances is required, and the existing immune detection method is difficult to realize multi-marker detection on the same platform in different detection ranges. SUMMARY

[0004] The purpose of the present application is to provide a microcavity laser multi-tumor marker sensor based on air-clad optical fiber, which solves the problems of low sensing sensitivity and difficulty in realizing high-sensitivity multi-marker detection in the prior art.

[0005] To achieve the above purpose, the present application provides a microcavity laser multi-tumor marker sensor based on air-clad optical fiber, which comprises an optical module, a microcavity control and sample detection module, and a signal processing module. The microcavity control and sample detection module comprises an air-clad optical fiber, a polytetrafluoroethylene capillary hose and a micro-injection pump; the air-clad optical fiber is connected to the micro-injection pump through the polytetrafluoroethylene capillary hose; the air-clad optical fiber comprises a pure quartz core, an air cladding and a quartz protective layer from inside to outside; the air cladding is a ring of closely arranged air microchannels surrounding the pure quartz core; the air cladding is filled with gain liquid with a higher refractive index than quartz; the liquid and quartz interface of the pure quartz optical fiber cross section forms total internal reflection, forming a fiber microcavity to enhance the interaction between light and matter; the Q value and output laser wavelength of the fiber microcavity are adjusted by adjusting the refractive index of the filled gain liquid; The pump laser emitted by the optical module is vertically incident on the surface of the air-clad optical fiber, supporting laser resonance similar to the echo wall mode, and the output laser signal is input into the signal processing module after passing through the optical module; When the sensor is used for marker concentration detection, the refractive index of the filled liquid is adjusted to make the sensor work in the dynamic range required for the marker, and the integral processing of the generated laser spectrum signal is performed; When the sensor is used for marking, the longitudinal mode wavelength and intensity information in the generated laser spectrum are encoded into a binary string to form a two-dimensional code containing the dynamic range information of the sensor.

[0006] The air-clad optical fiber microcavity enhances light and matter interaction, realizes high-sensitivity tumor marker detection, and adjusts the effective refractive index of the filling liquid by using liquid crystal to control the wavelength and microcavity Q value of the outgoing laser, thereby realizing wavelength marking and multi-dynamic range detection of various tumor markers.

[0007] Preferably, the optical module comprises a laser pulser, a beam splitter, an energy meter, a dichroic mirror and a microscope objective; the pulsed laser outputs pump laser, which is split into two vertical pump lasers after passing through the beam splitter, one of which is incident into the energy meter to monitor the beam energy in real time, and the other of which is incident into the microcavity control and sample detection module after passing through the dichroic mirror reflection and the microscope objective convergence in turn.

[0008] Preferably, the signal processing module comprises a collection element, a transmission optical fiber, a spectrum analyzer and a computer; the collection element is connected to the spectrum analyzer through the transmission optical fiber, the spectrum analyzer transmits the spectrum results to the computer, and the computer processes the data according to the required function.

[0009] Preferably, the laser signal generated by the microcavity control and sample detection module is separated from the pump laser direction by passing through the dichroic mirror and converging through the microscope objective, and the laser signal is collected by the collection element and coupled into the transmission optical fiber.

[0010] Preferably, when detecting the concentration of the marker, the refractive index of the filling liquid in the air cladding is adjusted to detect markers of different abundances, and the generated spectrum results are integrated.

[0011] Preferably, the refractive index of the filling liquid is adjusted, and under the condition of the optimal refractive index, the Q value of the fiber microcavity is optimal for detecting low-abundance markers; the refractive index of the filling liquid is reduced, the Q value of the fiber microcavity is reduced, the output wavelength is blue-shifted, and the sensing dynamic range is translated to high concentration, which is used for detecting high-abundance markers. When adjusting the refractive index of the filling liquid, the method for obtaining the optimal refractive index is as follows: the liquid crystal and the gain liquid are mixed in different volume ratios, the integral intensity of the output spectrum is measured under the same pumping condition, and the volume ratio at which the integral intensity of the spectrum is the strongest is the optimal volume ratio, and the refractive index at this time is the optimal refractive index.

[0012] Preferably, the process for detecting the concentration of the marker is as follows: S11, using a magnetic microparticle chemiluminescence method, diluting the standard in a 10-fold concentration gradient, mixing equal amounts of each concentration of the marker to be tested with a suspension of magnetic beads coated with the capture antibody of the marker to be tested, incubating at room temperature for 30 minutes, and then washing away the unbound marker to be tested; the standard is a known concentration of the marker to be tested; S12, mixing the magnetic bead suspension with horseradish peroxidase-labeled detection antibody, incubating at room temperature for 30 minutes, and then washing away the unbound detection antibody; S13, adding chemiluminescence substrate, reacting for 20 minutes, and then adding stop solution; S14, using magnetic separation technology to obtain the supernatant without magnetic beads, mixing the supernatant with liquid crystals according to the optimized volume ratio, and filling into the air cladding through a micro-sampling pump; S15, calculating the spectral integral intensity of each concentration of the marker to be tested, and obtaining the curve of the spectral integral intensity changing with the concentration of the marker to be tested; S16, repeating steps S11-S15 for different markers, and adjusting the filling liquid refractive index to obtain the curve of the spectral integral intensity of the marker sample with different abundances changing with the concentration of the marker; S17, after pretreatment of the marker liquid to be tested, injecting it into the air cladding through a micro-sampling pump, starting the pulsed laser, and calculating the spectral integral intensity by integrating the received spectrum with a computer. The spectral integral intensity is substituted into the curve of the corresponding marker to obtain the concentration of the marker to be tested.

[0013] Preferably, when marking a certain sensing dynamic range, the wavelength and intensity information of the longitudinal mode in the spectrum is encoded into a binary string to form a two-dimensional code representing the sensing dynamic range information; The process of converting the spectral signal into a barcode label is as follows: S21, selecting the amplitude with the highest intensity of the laser longitudinal mode in the spectrum, setting 50% of the amplitude as the threshold, and selecting all wavelength positions in the spectrum with a laser longitudinal mode intensity not lower than the threshold; S22, dividing the wavelengths into 50 wavelength intervals with the longitudinal mode free spectral range as the interval, and respectively corresponding to 50 binary characters, wherein the first 49 intervals are left-closed and right-open intervals, and the last interval is a closed interval; S23, the rule for obtaining a binary barcode label with an encoding capacity of 50 is: if the wavelength position obtained in S1 is in a certain wavelength interval, the bit corresponding to the interval is the number "1", otherwise it is the number "0".

[0014] Preferably, the pulsed laser outputs a wavelength of 532 nm, and the output laser energy is continuously adjustable within the range of 0-5 .

[0015] Preferably, the obtained binary bar code label corresponds to the tumor marker species to be detected and its detection dynamic range one by one.

[0016] When a high refractive index liquid is filled in the air-clad optical fiber, total internal reflection is formed at the peripheral quartz interface of the liquid, which constitutes a light feedback similar to the whispering gallery mode, supports laser resonance; the resonant light is bound in the filled liquid, increases the interaction between light and the measured substance, and improves the sensing sensitivity. The refractive index of the filled liquid can be regulated by a microflow control system composed of a polytetrafluoroethylene capillary tube and a microsyringe pump, thereby regulating the wavelength of the output laser and the Q value of the fiber microcavity, and using the wavelength to form a binary bar code label to mark the dynamic range and the marker of the corresponding fiber microcavity sensor.

[0017] Therefore, the microcavity laser multi-tumor marker sensor based on the air-clad optical fiber has the following beneficial effects: (1) The microcavity structure of the air-clad optical fiber enhances the interaction between light and matter, improves the sensing sensitivity, can regulate the sensing dynamic range, and can be marked by wavelength coding, which can solve the high sensitivity detection of markers and the detection requirement of multi-marker marking with different abundance in the application scene of tumor marker screening; (2) The micro-hole ring structure in the cross-section air-clad of the air-clad optical fiber can support a whispering gallery mode, enhance the interaction between light and matter, and improve the sensing sensitivity; (3) The refractive index of the filled liquid can be adjusted to regulate the output laser wavelength and the Q value of the fiber microcavity, realize the regulation of the sensing dynamic range, and realize the marker detection by wavelength.

[0018] The technical solutions of the present application will be further described in detail below with reference to the drawings and examples. BRIEF DESCRIPTION OF DRAWINGS

[0019] Fig. 1 Fig. 1 is a structural schematic diagram of the microcavity laser multi-tumor marker sensor based on the air-clad optical fiber of the present application; Fig. 2 Fig. 2 is a schematic diagram of the fiber microcavity resonance of the embodiment of the present application.

[0020] REFERENCE NUMERALS 1, pulse laser; 2, beam splitter; 3, energy meter; 4, dichroic mirror; 5, microscope objective; 6, air-clad optical fiber; 61, pure quartz core; 62, air-clad; 63, quartz protective layer; 7, polytetrafluoroethylene capillary tube; 8, microsyringe pump; 9, collection element; 10, transmission optical fiber; 11, spectrum analyzer; 12, computer. DETAILED DESCRIPTION

[0021] The following detailed description of embodiments of the application provided in the accompanying drawings is not intended to limit the scope of the application as claimed, but merely represents selected embodiments of the application. Based upon the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without creative work are within the scope of protection of the present application.

[0022] Referring to Figs. 1-2 , the microcavity laser multi-tumor marker sensor based on air-clad optical fiber comprises an optical module, a microcavity control and sample detection module, and a signal processing module. The optical module comprises a laser pulser 1, a beam splitter 2, an energy meter 3, a dichroic mirror 4, and a microscope objective 5. The pulsed laser 1 outputs pump laser, which is split into two vertical pump lasers after passing through the beam splitter 2. One of the pump lasers is incident into the energy meter 3 to monitor the beam energy in real time, and the other pump laser is sequentially reflected by the dichroic mirror 4 and converged by the microscope objective 5 before being vertically incident into the microcavity control and sample detection module. The pulsed laser 1 outputs a wavelength of 532 nm, and the output laser energy is continuously adjustable within the range of 0-5 .

[0023] The microcavity control and sample detection module comprises an air-clad optical fiber 6, a polytetrafluoroethylene capillary tube 7, and a micro-injection pump 8. The air-clad optical fiber 6 is connected to the micro-injection pump 8 through the polytetrafluoroethylene capillary tube 7. The air-clad optical fiber 6 comprises a pure quartz core 61, an air cladding 62 arranged on the periphery of the pure quartz core 61, and a quartz protective layer 63 arranged on the periphery of the air cladding 62. The air cladding 62 is a ring structure of closely arranged micro-holes on the periphery of the pure quartz core 61, forming an air micro-channel. The air cladding 62 is filled with a gain liquid with a higher refractive index than quartz, and the liquid interface between the pure quartz core 61 and the quartz forms total internal reflection, forming a fiber microcavity to enhance the interaction between light and matter. By adjusting the refractive index of the filled gain liquid, the Q value of the fiber microcavity and the output laser wavelength are controlled. The output light of the optical module is vertically incident onto the surface of the air-clad optical fiber 6 to generate laser signal output. The laser signal enters the signal processing module after passing through the optical module.

[0024] The signal processing module comprises a collection element 9, a transmission optical fiber 10, a spectral analyzer 11, and a computer 12. The collection element 9 is connected to the spectral analyzer 11 through the transmission optical fiber 10. The spectral analyzer 11 transmits the spectral results to the computer 12, and the computer 12 processes the data according to the required functions.

[0025] The laser signal generated by the microcavity control and sample detection module is separated from the laser direction by converging through the microscope objective 5 and passing through the dichroic mirror 4. The laser signal is collected by the collection element 9 and coupled into the transmission optical fiber 10.

[0026] When detecting the concentration of the marker, the refractive index of the filling liquid in the air cladding 62 is adjusted to detect markers with different abundances, and the generated spectral results are integrated.

[0027] The refractive index of the filling liquid is adjusted, and under the condition of the optimal refractive index, the Q value of the fiber microcavity reaches the upper limit of the threshold, which is used to detect low-abundance markers; the refractive index of the filling liquid is reduced, the Q value of the fiber microcavity is reduced, the output wavelength is blue-shifted, and the sensing dynamic range is translated to high concentration, which is used to detect high-abundance markers. The method for obtaining the optimal refractive index is as follows: mix the liquid crystal with the gain liquid according to different volume ratios, measure the integral intensity of the output spectrum under the same pumping condition, and the volume ratio when the spectral integral intensity is the strongest is the optimal volume ratio, and the refractive index at this time is the optimal refractive index.

[0028] The process of detecting the concentration of the marker is as follows: S11, using the magnetic microparticle chemiluminescence method, diluting the standard in a 10-fold concentration gradient, mixing equal amounts of each concentration of the marker to be detected with a magnetic bead suspension coated with the capture antibody of the marker to be detected, incubating at room temperature for 30 minutes, and then washing away the unbound marker to be detected; the standard is a known concentration of the marker to be detected; S12, mixing the magnetic bead suspension with horseradish peroxidase-labeled detection antibody, incubating at room temperature for 30 minutes, and then washing away the unbound detection antibody; S13, adding chemiluminescence substrate, reacting for 20 minutes, and then adding termination liquid; S14, using magnetic separation technology to obtain supernatant without magnetic beads, mixing the supernatant with liquid crystal according to the optimized volume ratio, and filling it into the air cladding 62 through the micro-sampling pump 8; S15, calculating the spectral integral intensity of each concentration of the marker to be detected, and obtaining the curve of the spectral integral intensity changing with the concentration of the marker to be detected; S16, for different markers, repeating steps S11-S15, and adjusting the refractive index of the filling liquid according to the required detection dynamic range, to obtain the curve of the spectral integral intensity of the marker sample with different abundances changing with the concentration of the marker; S17, after pretreating the marker liquid to be detected, injecting it into the air cladding 62 through the micro-sampling pump 8, starting the pulsed laser 1, and the computer 12 integrating the received spectrum to obtain the spectral integral intensity, and substituting the spectral integral intensity into the curve of the corresponding marker, the concentration of the marker to be detected can be obtained.

[0029] When labeling, the longitudinal mode wavelength and intensity information in the spectrum are encoded into a binary string to form a two-dimensional code representing the sensing dynamic range information. The process of converting the spectral signal into a bar code label is as follows: S21, screen out the amplitude with the highest laser longitudinal mode intensity in the spectrum, set 50% of the amplitude as a threshold, and screen out all wavelength positions with laser longitudinal mode intensity not lower than the threshold in the spectrum; S22, divide the wavelength into 50 wavelength intervals with the longitudinal mode free spectral range as the interval, and correspond to 50 binary characters respectively, wherein the first 49 intervals are left-closed right-open intervals, and the last interval is a closed interval; S23, the rule for obtaining a binary barcode label with a coding capacity of 50 is that if the wavelength position obtained in S1 is in a certain wavelength interval, the bit corresponding to the interval is the number '1', otherwise, it is the number '0'.

[0030] The obtained binary barcode label corresponds to the tumor marker species and its detection dynamic range one by one.

[0031] When the high refractive index liquid is filled in the air-clad optical fiber 6, the liquid forms total internal reflection at the interface of the peripheral quartz protective layer 63, constitutes light feedback similar to the whispering gallery mode, and supports laser resonance; the resonant light is bound in the filled liquid, increases the interaction between light and the measured substance, and improves the sensing sensitivity. The refractive index of the filled liquid can be regulated by the microflow control system composed of the polytetrafluoroethylene capillary tube 7 and the micro sample pump 8, thereby the wavelength of the output laser and the Q value of the fiber microcavity can be regulated, and the wavelength is used to form a binary barcode label to mark the dynamic range and the marker of the corresponding fiber microcavity sensor.

[0032] Therefore, the microcavity laser multi-tumor marker sensor based on the air-clad optical fiber in the application can enhance the interaction between light and substance by using the microcavity structure of the air-clad optical fiber, improve the sensing sensitivity, regulate the sensing dynamic range, and mark the detection by using the wavelength coding, so as to solve the high sensitivity detection of the marker and the detection requirement of multi-marker marking with different abundance in the application scene of tumor marker screening; the air-clad optical fiber is used as a sensing unit, the micro-hole ring structure in the cross-section air-clad of the air-clad optical fiber can support the whispering gallery mode, enhance the interaction between light and substance, and improve the sensing sensitivity; the refractive index of the filled liquid can be regulated to regulate the output laser wavelength and the Q value of the fiber microcavity, realize the regulation of the sensing dynamic range, and realize the marking detection by using the wavelength.

[0033] Finally, it should be noted that: the above examples are only used to illustrate the technical solutions of the application rather than limit them, although the application has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the application can still be modified or replaced by equivalents, and these modifications or equivalent replacements cannot make the modified technical solutions deviate from the spirit and scope of the technical solutions of the application.

Claims

1. A microcavity laser multi-tumor marker sensor based on an air-clad optical fiber, characterized by, The application relates to a sensor for detecting a marker concentration, and belongs to the technical field of sensors. The sensor comprises an optical module, a microcavity regulation and sample detection module and a signal processing module. The microcavity regulation and sample detection module comprises an air-clad optical fiber, a polytetrafluoroethylene capillary hose and a micro-injection pump. The air-clad optical fiber is connected with the micro-injection pump through the polytetrafluoroethylene capillary hose. The air-clad optical fiber comprises a pure quartz core, an air cladding and a quartz protective layer from inside to outside. The air cladding is a ring of closely arranged air microchannels surrounding the pure quartz core. The air cladding is filled with a gain liquid with a higher refractive index than quartz.

2. The air-clad optical fiber-based microcavity laser multi-tumor marker sensor of claim 1, wherein: The liquid-quartz interface of the cross section of the optical fiber forms total internal reflection, thereby forming a fiber microcavity to enhance the interaction between light and matter.

3. The air-clad optical fiber-based microcavity laser multi-tumor marker sensor of claim 2, wherein: The Q value and the output laser wavelength of the fiber microcavity are regulated by adjusting the refractive index of the filled gain liquid.

4. The air-clad optical fiber-based microcavity laser multi-tumor marker sensor of claim 3, wherein: The pump laser emitted by the optical module is vertically incident on the surface of the air-clad optical fiber, and the generated laser signal output enters the signal processing module after passing through the optical module.

5. The air-clad optical fiber-based microcavity laser multi-tumor marker sensor of claim 4, wherein: When the sensor is used for detecting the concentration of a marker, the refractive index of the filled liquid is adjusted so that the sensor works in the dynamic range required by the marker.

6. The air-clad optical fiber-based microcavity laser multi-tumor marker sensor of claim 5, wherein: The longitudinal mode wavelength and intensity information in the generated laser spectrum are encoded into a binary string to form a two-dimensional code containing the dynamic range information of the sensor. The optical module comprises a laser pulser, a beam splitter, an energy meter, a dichroic mirror and a microscope objective.

7. The air-clad optical fiber-based microcavity laser multi-tumor marker sensor of claim 6, wherein, The pulsed laser outputs pump laser, which is divided into two vertical pump lasers after passing through the beam splitter. One of the pump lasers enters the energy meter, and the other pump laser is reflected by the dichroic mirror and then converges through the microscope objective to be vertically incident on the microcavity regulation and sample detection module. The signal processing module comprises a collection element, a transmission optical fiber, a spectrum analyzer and a computer. The collection element is connected with the spectrum analyzer through the transmission optical fiber. The spectrum analyzer transmits the spectrum result to the computer, and the computer processes data according to the required function. The laser signal generated by the microcavity regulation and sample detection module is separated from the pump laser in the direction through the microscope objective and the dichroic mirror. When the concentration of a marker is detected, the refractive index of the liquid filled in the air cladding is adjusted to detect markers with different abundances, and the generated spectrum result is integrated. The optimal Q value of the fiber microcavity is obtained under the optimal refractive index condition, and is used for detecting a marker with low abundance. The Q value of the fiber microcavity is reduced, the output wavelength is blue-shifted, the sensing dynamic range is translated to high concentration, and the marker with high abundance is detected. The optimal refractive index is obtained by mixing liquid crystal and gain liquid in different volume ratios. The process for detecting the concentration of a marker is as follows: S11, standard samples are diluted according to a 10-fold concentration gradient, and equal amounts of each concentration of the marker to be detected are mixed with a magnetic bead suspension coated with a capture antibody of the marker to be detected. After incubation at room temperature for 30 minutes, the unbound marker to be detected is washed away. The standard sample is a marker to be detected with a known concentration. S12, mix the magnetic bead suspension with the horseradish peroxidase-labeled detection antibody, incubate at room temperature for 30 minutes, and then wash away the unbound detection antibody; S13, add chemiluminescent substrate, react for 20 minutes, and then add stop solution; S14, obtain the supernatant without magnetic beads by using magnetic separation technology, mix the supernatant with liquid crystals according to the optimized volume ratio, and fill into the air cladding by using a micro-sampling pump; S15, calculate the spectral integral intensity of each concentration of the marker to be detected, and obtain the curve of the spectral integral intensity changing with the concentration of the marker to be detected; S16, repeat steps S11-S15 for different markers, and adjust the refractive index of the filling liquid according to the required detection dynamic range to obtain the curve of the spectral integral intensity of the marker sample with different abundance changing with the concentration of the marker; S17, after pretreatment of the marker liquid to be detected, inject the marker liquid into the air cladding by using a micro-sampling pump, start the pulsed laser, and calculate the spectral integral intensity by integral processing of the received spectrum by using a computer, and then substitute the spectral integral intensity into the curve of the corresponding marker to obtain the concentration of the marker to be detected.

8. The air-clad optical fiber-based microcavity laser multi-tumor marker sensor of claim 7, wherein: When marking a certain sensing dynamic range, the longitudinal mode wavelength and intensity information in the spectrum are encoded into a binary string to form a two-dimensional code containing the sensing dynamic range information. The process of converting the spectral signal into a barcode label is as follows: S21, select the amplitude with the highest laser longitudinal mode intensity in the spectrum, set 50% of the amplitude as a threshold, and select the wavelength position with laser longitudinal mode intensity not lower than the threshold in the spectrum; S22, divide the wavelength into 50 wavelength intervals with the longitudinal mode free spectral range as the interval, and respectively correspond to 50 binary characters, wherein the first 49 intervals are left-closed and right-open intervals, and the last interval is a closed interval; S23, the rule for obtaining a binary barcode label with an encoding capacity of 50 is that if the wavelength position obtained in S1 is in a certain wavelength interval, the bit corresponding to the interval is the number "1", otherwise it is the number "0".

9. The air-clad optical fiber-based microcavity laser multi-tumor marker sensor of claim 8, wherein: The output wavelength of the pulse laser is 532 nm, and the output laser energy is continuously adjustable in the range of 0-5 W.

10. The air-clad optical fiber-based microcavity laser multi-tumor marker sensor of claim 9, wherein: The obtained binary barcode label corresponds to the tumor marker species and its detection dynamic range one by one.

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