Highly sensitive chemiluminescence detection system and method - Patents.com

Abstract

A luminescence detection system for use in an immunoassay test, the luminescence detection system including a sample holder configured to hold a test sample containing a labeled component, the labeled component in the test sample undergoing a chemiluminescence reaction to emit luminescence radiation in a first wavelength range, a photodetector having a light entrance window configured to receive the emitted light and having a maximum detection efficiency wavelength range, and a conversion member disposed adjacent the light entrance window and operative to convert the luminescence radiation in the first wavelength range to incoming radiation in a second wavelength range, the incident peak of the incoming radiation falling within the maximum detection efficiency wavelength range for which the quantum efficiency of the photodetector is 10% or greater. As in another aspect, a luminescence detection method is provided.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application No. 63 / 145,396, filed February 3, 2021, entitled "HIGH-SENSITIVITY CHEMILUMINESCENCE DETECTION SYSTEMS AND METHODS," the disclosure of which is incorporated by reference in its entirety for all purposes.

[0002] The present disclosure relates to optical detection in immunoassays, and more particularly to chemiluminescence detection systems and methods configured to perform measurements of luminescence emissions emanating from a reaction vessel. [Background technology]

[0003] Chemiluminescence (CL) is defined as the emission of electromagnetic radiation caused by a chemical reaction to produce light. Chemiluminescence immunoassay (CLIA) is an assay that combines chemiluminescence technology with immunochemical reactions. For example, ATELLICA® IM1300, IMMULITE® 1000, and ADVIA® Centaur, available from the present assignee, are instruments based on chemiluminescence immunoassay.

[0004] Similar to other labeling immunoassays (e.g., RIA, FIA, ELISA), CLIA systems utilize chemical probes capable of producing luminescence emission through a chemical reaction to quantify an analyte (a target component). In some automated immunoassay systems, a sample container (e.g., a cuvette) containing an extracted component (e.g., a DNA probe) extracted from a specimen (e.g., a biological specimen such as serum or plasma or urine) that has been labeled to form a labeled component can be placed at a desired position in the system. A reaction can then be performed to obtain a numerical value of the luminescence intensity of the luminescence emission emitted from the labeled component.

[0005] For example, in some embodiments, acridinium ester labels are used to label components such as antibodies, proteins, and some peptides. Exposure of the acridinium ester label to an alkaline solution breaks the ester bond, releasing an unstable compound that decomposes and induces a flash of luminescent light emitted at a distinct wavelength peak (hereinafter emission peak). Luminescence, as defined herein, is the emission of light from a substance as it returns from an excited state to its ground state. Summary of the Invention [Problem to be solved by the invention]

[0006] However, existing luminescence detection systems may be deficient in some respects insofar as the luminescence intensity they produce may be insufficient. Therefore, improved systems and methods for luminescence detection, such as in immunoassay systems, are desirable. [Means for solving the problem]

[0007] In some embodiments, a luminescence detection system is provided that includes a sample holder configured to hold a test sample in solution that includes a labeled component, where the labeled component in the test sample undergoes a chemiluminescence reaction to emit luminescence radiation in a first wavelength range; a photodetector having a light entrance window configured to receive the emitted light and having a maximum detection efficiency wavelength range; and a conversion member disposed adjacent the light entrance window of the photodetector and operative to convert the luminescence radiation in the first wavelength range to incoming radiation in a second wavelength range, the incoming peak of the incoming radiation falling within the maximum detection efficiency wavelength range, the maximum detection efficiency wavelength range being a wavelength range in which the quantum efficiency of the photodetector is 10% or greater.

[0008] In some embodiments, a luminescence detection system is provided that includes a sample holder configured to hold a labeled component in solution, where the labeled component undergoes a chemiluminescence reaction, where luminescence radiation is produced having an emission peak within a first wavelength range of 550 nm to 800 nm, a photodetector having a light receiving area configured to receive the luminescence radiation, the photodetector having a wavelength range of maximum detection efficiency, and having a quantum efficiency of 10% or greater for all wavelengths within the wavelength range of maximum detection efficiency, and a conversion coating applied to the light receiving area and operative to convert the emitted radiation to an incoming radiation having an incoming peak that falls within the wavelength range of maximum detection efficiency.

[0009] In some embodiments, a luminescence detection method is provided that includes providing a luminescence detection system that includes a sample holder that holds a labeled component in solution, a photodetector having a light receiving area and a wavelength range of maximum detection efficiency, a conversion coating disposed adjacent the light receiving area that causes a chemiluminescence reaction with the labeled component to produce luminescence radiation in a first wavelength range, and a conversion coating that receives and converts the luminescence radiation to a second wavelength range having an incident peak within the wavelength range of maximum detection efficiency with a quantum efficiency of at least 10%.

[0010] Numerous other aspects are provided in accordance with these and other aspects of the present disclosure. Other features and aspects of the present disclosure will become more fully apparent from the following detailed description, the claims, and the accompanying drawings. [Brief description of the drawings]

[0011] [Figure 1A] FIG. 1 is a schematic diagram of a chemiluminescence detection system according to an embodiment of the present disclosure. [Figure 1B] 1B is an enlarged cross-sectional schematic diagram of a portion of the chemiluminescence detection system of FIG. 1A according to an embodiment of the present disclosure. [Figure 1C] FIG. 2 is an enlarged cross-sectional schematic diagram of a portion of an alternative chemiluminescence detection system including a slide-in substrate including a conversion coating thereon, according to an embodiment of the present disclosure. [Figure 2A] FIG. 1 is a spectral plot of luminescence emission (e.g., red emission) from a processed specimen contained in a holder and including a red dye label tagged to a component according to an embodiment of the present disclosure. [Figure 2B] FIG. 2 is a spectral plot of quantum efficiency (%) versus wavelength (nm) of a photomultiplier tube (PMT) in a luminescence detection system according to an embodiment of the present disclosure. [Figure 2C] FIG. 2 is a spectral plot of luminescence radiation downconverted to a second wavelength range by operation of a conversion coating adjacent to the light entrance window in accordance with an embodiment of the present disclosure. [Diagram 3] FIG. 13 is a spectral plot of both quantum efficiency (%) and downconverted luminescence emission versus wavelength (nm) showing incident peaks of converted luminescence that fall within the maximum detection efficiency wavelength range according to an embodiment of the present disclosure. [Figure 4] FIG. 2 is a flow chart illustrating an exemplary luminescence detection method according to an embodiment of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] In view of the above problems and concerns, a system and method are provided that have relatively improved sensitivity.The chemiluminescence technology in immunoassays relies on the chemiluminescence tag with the chemiluminescence label having high quantum yield at the emission wavelength specific to the tag and conjugate.Current photomultiplier tube (PMT) detectors used to read chemiluminescence emission have maximum sensitivity (maximum quantum efficiency%) at a specific wavelength.Unfortunately, as the inventors recognize, this maximum quantum efficiency may not be at the same wavelength as the highest quantum yield of chemiluminescence emission.Therefore, the detection sensitivity of existing chemiluminescence detection systems may be insufficient.

[0013] In particular, previous systems have used blue dye labels (e.g., with a nominal emission wavelength of about 398 nm to 420 nm) because this best matches the wavelength of the detector's maximum quantum efficiency (%), which is a wavelength of about 375 nm. However, the inventors further recognize that light intensity or energy flux is proportional to the photon flux, i.e., the number of photons per unit time per unit surface, and not to the individual photon energy. Thus, the number of photons at low frequencies (high wavelengths) will be greater than the number of photons at high frequencies (low wavelengths). Thus, the photon flux from the use of blue dye labels can be improved by using dye labels with a higher luminescence emission wavelength range, such as red dye labels. However, the quantum efficiency of conventional sensors is reduced when red dye labels are used because the luminescence emission wavelength moves away from the maximum quantum efficiency. In fact, switching to red dye labels can reduce quantum sensitivity by more than a factor of 100.

[0014] Therefore, in order to improve detection sensitivity, according to the first aspect of the present disclosure, the chemiluminescence emission must be matched to the maximum sensitivity wavelength of the detector. However, this is a challenge in existing systems, since the blue label detector has a relatively low photon flux as described above. Therefore, in existing luminescence detection systems, sensitivity is reduced due to a mismatch between the incident luminescence spectrum and the spectral absorption characteristics of the detector. Since the intensities of various assays are read out using a single detector, regardless of the maximum quantum yield, the intensity is reduced at least at some wavelengths, affecting sensitivity. As a result, the reduced sensitivity is simply tolerated in existing systems.

[0015] Thus, according to one aspect, a luminescence detection system is provided that can measure luminescence radiation with high sensitivity. In some embodiments, the luminescence detection system can be implemented in an existing analyzer as a hardware retrofit upgrade. For example, the luminescence detection system can replace an existing luminescence detection system utilized in the analyzer. In accordance with one or more features of the present disclosure, the improved luminescence detection system passes photons that are already in the maximum detection efficiency wavelength range (maximum detection window). However, photons outside the maximum detection efficiency wavelength range (maximum detection window) are converted (e.g., down-converted) to fall within the maximum detection efficiency wavelength range (maximum detection window). Thus, using the conversion (e.g., down-conversion), intensity reduction can be minimized.

[0016] Thus, according to the embodiments of the present disclosure, a higher total value of the photoluminescence immunoassay can be achieved, resulting in higher sensitivity. Furthermore, the embodiments of the present disclosure allow the option of using higher quantum yield labels (e.g., red dye labels) that are currently out of range with conventional instruments. In addition, the embodiments of the present disclosure allow the conversion of "waste photons" to detected photons by using a light conversion layer (conversion layer) added to or used with the photodetector. Thus, a wider range of immunoassays, potentially with higher sensitivity, can be used with the luminescence detection system of the present disclosure.

[0017] Thus, in accordance with embodiments of the present disclosure, a luminescence detection system is provided that may be implemented within an immunoassay instrument to provide improved intensity of luminescence radiation as well as improved luminescence radiation detection sensitivity. Additionally, a luminescence detection method is provided that is adapted to provide improved detection of luminescence emitted from a chemiluminescence reaction.

[0018] It should therefore be appreciated that the methods and systems described herein can not only increase the intensity of luminescence emissions, but can simultaneously increase the overall detection sensitivity, thus dramatically improving the overall signal strength of a luminescence detection system.

[0019] Further details and examples of the apparatus, systems and methods of the present disclosure are provided with reference to FIGS. 1A-4.

[0020] 1A-1B show an exemplary embodiment of a luminescence detection system 100 configured and operable to perform a method of measuring the intensity of luminescent light (e.g., luminescent emission) emanating from a chemiluminescent reaction of a labeled component 114 provided in a test sample solution 112 contained in a sample holder 110 disposed at a sample position 111 in the luminescence detection system 100. The test sample solution 112 includes a solution containing the labeled component 114 plus a solution added to cause a chemiluminescent reaction with the labeled component. Thus, the sample holder 110 is configured to hold the test sample containing the labeled component 114 in the solution 112, which is derived from a processed biological specimen. The biological specimen can be any biological fluid, such as serum, plasma, urine, cerebrospinal fluid, etc. The sample holder 110 can be an optically transparent or translucent cuvette or other vessel, such as plastic or glass. The walls of the sample holder 110 can be flat or curved, or a combination thereof. The sample holder 110 is placed in the sample position 111 by entry through a door or lid 113 or other suitable entry method.

[0021] The dye label may be any suitable dye label that undergoes a chemiluminescence reaction and thus emits luminescence radiation 116 in a first wavelength range. For example, the dye label may emit luminescence radiation 116 in a wavelength range 222 of 550 nm to 800 nm, for example as shown in FIG. 2A. Furthermore, the luminescence radiation 116 may have a spectral response having a luminescence peak 236 and a spectral distribution of luminescence intensity 237 centered about the luminescence peak 236, as shown. This particular dye label has a luminescence peak 236 at about 605 nm to about 650 nm. The spectral distribution of the luminescence intensity 237 may be a non-normal distribution as shown, with more than 50% of the normalized intensity located above the luminescence peak 236.

[0022] Thus, the labeling component 114 undergoes a chemiluminescence reaction upon addition of an appropriate agent to emit luminescence radiation 116 in a first wavelength range 222. The labeling component can be any labeled analyte of interest, such as a labeled antibody, a labeled autoantibody, a labeled antigen, a labeled protein, a labeled DNA probe, a labeled marker, etc. Nucleic acid probes and haptens can also be labeled. Labeling can be achieved indirectly by binding a conjugate or directly by direct enzyme conjugation. For example, acridinium esters are direct chemiluminescence labels for antibodies and DNA probes. Acridinium esters used as direct labels are attached to the probes by hybridization reactions. Acridinium esters can be reacted with alkaline peroxides (e.g., hydrogen peroxide) under basic conditions to obtain an excited state, which emits light at a defined wavelength. Derivatives such as acridinium sulfonamide ester labels can also be used. Other types of luminophores and enzyme labels may also be used. The method can be used as a biochemical technique used in immunology to identify and detect the concentrations of various components (e.g., serum concentrations of antibodies, autoantibodies for the diagnosis of autoimmune diseases, hormones, polypeptides, drugs, vitamins, tumor markers, infectious disease markers, inflammation markers, myocardial damage markers, etc.).

[0023] 1A and 1B, the luminescence detection system 100 further comprises a photodetector 118, such as a photomultiplier tube (PMT), having a light entrance window 120 configured to receive at least a portion of the luminescence radiation 116 (photons) emitted from the chemiluminescence reaction. The light entrance window 120 may have, for example, a circular shape in plan view and a sufficiently large light receiving area. Other shapes are possible. As shown in FIG. 2B, the photodetector 118 has a maximum detection efficiency wavelength range 224. The maximum detection efficiency wavelength range 224 is, for example, a range in which the quantum efficiency is 10% or more, as shown. However, in some parts of the maximum detection efficiency wavelength range 224, the quantum efficiency may be 15% or more, 20% or more, or 22% or more.

[0024] As can be seen from FIG. 2B, the maximum detection efficiency wavelength range 224 of the photodetector 118 is quite efficient for receiving blue luminescence emission having a wavelength range of about 398 nm to 420 nm. However, the blue dye label emits a relatively low photon emission intensity and therefore cannot provide a high detection level. However, the red dye label has a much higher photon emission intensity, but as can be seen from FIG. 2A, the red light emitting at about 550 nm to 800 nm has a too low quantum efficiency, e.g., less than about 1%. Therefore, the detection sensitivity is very low when the red dye label is used in a blue-dominated detector.

[0025] However, according to various embodiments herein, as shown in Figure 1A and enlarged Figure 1B, a conversion coating 122 is provided adjacent the light entrance window 120. For example, in a first embodiment, the conversion coating 122 can be applied directly to a substrate including the photocathode 118C within the light entrance window 120 of the photodetector 118.

[0026] The conversion coating 122 functions to convert at least a portion of the luminescent radiation 116 into incoming radiation 126 that is shifted to a wavelength that falls within a second wavelength range 228 as shown in FIG. 2C. The second wavelength range 228 can be 300 nm to 550 nm, or even 325 nm to 525 nm in some embodiments. As shown, the incoming radiation 126 (photons) that contacts the photocathode 118C of the photodetector 118 can have an incident peak 230 (FIG. 2C). The photocathode 118C converts the incoming photons into electrons.

[0027] The conversion coating 122 is designed such that the incident peak 230 falls within the maximum detection efficiency wavelength range 224 of the photodetector 118, as best shown in FIG. 3. Thus, in this embodiment, the red-dominated light is, in effect, converted or shifted to blue-dominated light. Thus, a dual benefit is achieved: increased sensitivity by downshifting the incident peak 230 to fall within the maximum detection efficiency wavelength range 224, along with the higher photon emission resulting from the use of red-dominated light. The maximum detection efficiency wavelength range 224 may be, for example, 300 nm to 530 nm. In some embodiments, it is desired that the incident peak 230 substantially coincides with the position of the quantum efficiency peak 232 within the maximum detection efficiency wavelength range 224. By "substantially coincident," it is meant that the positions of the two peaks 230, 232 do not differ by more than 50 nm, thereby achieving maximum or near maximum detection sensitivity. Detection using the photodetector 118 may be performed at one or more suitable time increments after introduction of the agent that causes the chemiluminescent reaction.

[0028] Referring again to FIG. 1A, the luminescence detection system 100 further comprises and is controlled by a suitable controller 134. The controller 134 may comprise a suitable processor and memory for storing the signal obtained from the output detection circuit 136. The output of the output detection circuit 136 is provided from an anode 138 at the end of a series of dynode stages 140. As a result of the photoelectric effect, electrons are emitted from the surface of the photocathode 118C. The absorbed energy causes the electron emission. These electrons are directed by a focusing electrode 118F to an electron multiplier including the dynode stages 140, where the electrons are multiplied by a process of secondary emission. Such an arrangement of the dynode stages 140 can amplify the small current emitted by the photocathode 118C, typically by a factor of one million or more. The output detection circuit 136 can then measure the resulting current at the anode 138, thereby estimating the amount of spectral luminescence emission. Any suitable conventional output detection circuit and high voltage power supply 139 can be used.

[0029] The photodetector 118, which includes a photomultiplier tube (PMT), is comprised of an evacuated glass housing that encloses a series of dynode stages 140. The conversion coating 122 is designed such that the luminescence peak 236 is shifted through the luminescence radiation 116 passing through the conversion coating 122 to the incoming radiation 126 impinging on the photocathode 118C. In particular, the wavelength shift may be sufficient to bring the shifted incoming peak 230 within the maximum detection efficiency wavelength range 224. In some embodiments, the shift may be, for example, 100 nm or more, 120 nm or more, or even 150 nm or more.

[0030] The conversion coating 122 is provided, for example, in the form of a transparent support matrix with suspended dye molecules or quantum dots. Coating of the conversion coating 122 is accomplished by directly coating the light entrance window 120 with the conversion coating 122. Optionally, in an alternative embodiment, a transparent substrate 123 (e.g., a window pane-like element) can include the conversion coating 122 applied thereon and is placed in front of the photocathode 118C, for example, by receiving the transparent substrate 123 in a slot 127. Each of these embodiments may be retrofittable to existing PMT detectors.

[0031] The conversion coating 122 may be a thin transparent layer of 10 nm to 100 nm with included conversion elements (suspended dye molecules or quantum dots). A reflective member 124, such as a reflective coating (e.g., a narrow band reflective coating), is applied over the conversion coating 122. The reflective member 124 may have a narrow band centered around the quantum efficiency peak 232 (FIG. 2B) of the photocathode 118C. In some embodiments, the reflective member 124 may include a long pass dichroic mirror that passes the luminescence radiation 116 in the first wavelength range 222 and rejects at least some light outside the first wavelength range 222. This may help to avoid absorption in other parts of the spectrum. In further embodiments, the reflective member 124 includes a universal detector that passes all emitted radiation but reflects and back reflects the incoming radiation 126 in the second wavelength range 228 towards the photodetector 118.

[0032] As will be appreciated, an example of down-conversion is described, however, the present disclosure is equally applicable to up-conversion. Thus, whatever dye and photodetector is selected for the luminescence detection system, the luminescence emission is shifted in wavelength to substantially match the maximum quantum efficiency range 224 of the photodetector 118. Any suitable up-conversion coating may be used.

[0033] 4 shows a flow chart illustrating a luminescence detection method 400 for use in, for example, an immunoassay test. The method 400 includes, in block 402, providing a luminescence detection system (e.g., luminescence detection system 100) including a sample holder (e.g., sample holder 110) that holds a labeled component (e.g., labeled component 114) from a biological sample in a solution (e.g., solution 112) and a photodetector (e.g., photodetector 118) having a light receiving area (e.g., light entrance window 120) and a maximum detection efficiency wavelength range (e.g., maximum detection efficiency wavelength range 224), with a conversion coating (e.g., conversion coating 122) applied adjacent to the light receiving area (e.g., light entrance window 120). The conversion coating 122 is applied directly to a face of the cathode 118C. Optionally, the conversion coating 122 can be applied as a coating on a transparent substrate 123 disposed in front of the cathode 118C, such as a sliding transparent glass panel coated with the conversion coating 122 shown in FIG. 1C.

[0034] The method 400 further includes initiating a chemiluminescent reaction with the label component to produce luminescent radiation (e.g., luminescent radiation 116) in a first wavelength range, which can be, for example, 550 nm to 800 nm, although other suitable ranges are possible, provided the dye label luminesces in that range.

[0035] The method 400 further includes, at block 406, receiving and converting the luminescent radiation (e.g., luminescent radiation 116) using a conversion coating (e.g., conversion coating 122) to a second wavelength range (second wavelength range 228) having an incident peak (e.g., incident peak 230) within a maximum detection efficiency wavelength range (e.g., maximum detection efficiency wavelength range 224) having a quantum efficiency (%) of at least 10% of the maximum detection efficiency wavelength range. In some embodiments, the maximum detection efficiency wavelength range is between 300 nm and 530 nm.

[0036] Although the embodiments are described herein with reference to specific examples, the scope of the disclosure is not intended to be limited to the details and specific examples described herein. Rather, various modifications of the embodiments and details may be made within the scope of the claims and equivalents.

Claims

1. 1. A luminescence detection system comprising: a sample holder configured to hold in solution a test sample including a labeled component, the labeled component in the test sample undergoing a chemiluminescence reaction and emitting luminescent radiation in a first wavelength range, where the first wavelength range is 550 nm to 800 nm; a photodetector having a light entrance window configured to receive the emitted light and having a wavelength range of maximum detection efficiency; a conversion member disposed adjacent a light entrance window of the photodetector and operative to convert luminescence radiation of a first wavelength range to incident radiation of a second wavelength range having an incident peak within a maximum detection efficiency wavelength range, the maximum detection efficiency wavelength range being a wavelength range for which the quantum efficiency of the photodetector is 10% or greater; The luminescence detection system comprising:

2. The luminescence detection system of claim 1 , wherein the conversion member comprises a conversion coating applied directly to the light entrance window.

3. 10. The luminescence detection system of claim 1, wherein the conversion member comprises a conversion coating applied to a transparent substrate positioned in front of the light entrance window.

4. The luminescence detection system of claim 1 , wherein the conversion is an upconversion.

5. The luminescence detection system of claim 1 , wherein the conversion is a down-conversion.

6. 10. The luminescence detection system of claim 1, wherein the quantum efficiency is 15% or greater.

7. The luminescence detection system of claim 6 , wherein the quantum efficiency is 20% or greater.

8. 7. The luminescence detection system of claim 6, wherein the quantum efficiency is 22% or greater.

9. 2. The luminescence detection system of claim 1, wherein the first wavelength range has a luminescence peak between 605 nm and 650 nm.

10. The luminescence detection system of claim 1 , wherein the second wavelength range is from 300 nm to 550 nm.

11. The luminescence detection system of claim 10, wherein the second wavelength range is from 325 nm to 525 nm.

12. 2. The luminescence detection system of claim 1, wherein the wavelength range of maximum detection efficiency is from 300 nm to 530 nm.

13. 10. The luminescence detection system of claim 1, wherein the light detector comprises a photomultiplier tube.

14. 10. The luminescence detection system of claim 1, further comprising a reflecting member disposed in front of the conversion member.

15. 15. The luminescence detection system of claim 14, wherein the reflective member comprises a longpass dichroic mirror that passes luminescence radiation in the first wavelength range and rejects at least some light outside the first wavelength range.

16. 15. The luminescence detection system of claim 14, wherein the reflective member comprises a universal detector that passes all luminescence radiation but reflects incoming radiation in the second wavelength range back towards the photodetector.

17. 1. A luminescence detection system comprising: a sample holder configured to hold a labeled component in solution, the labeled component undergoing a chemiluminescence reaction and luminescence radiation occurring having an emission peak within a first wavelength range, where the first wavelength range is from 550 nm to 800 nm; a photodetector having a light receiving area configured to receive luminescence radiation, the photodetector having a wavelength range of maximum detection efficiency, the photodetector having a quantum efficiency of 10% or greater for all wavelengths within the wavelength range of maximum detection efficiency; a conversion coating applied to the light receiving area and operative to convert the luminescent radiation into an incoming radiation having an incoming peak that falls within a wavelength range of maximum detection efficiency; The luminescence detection system comprising:

18. 18. The luminescence detection system of claim 17, wherein the wavelength range of maximum detection efficiency is from 300 nm to 530 nm.

19. 1. A luminescence detection method comprising: providing a luminescence detection system including a sample holder holding a labeled component in solution and a photodetector having a light receiving area and a wavelength range of maximum detection efficiency, the conversion coating being applied adjacent to the light receiving area; causing a chemiluminescent reaction with the label component to produce luminescent radiation in a first wavelength range, where the first wavelength range is from 550 nm to 800 nm; receiving and converting the luminescent radiation by a conversion coating to a second wavelength range having an incident peak within a maximum detection efficiency wavelength range with a quantum efficiency of at least 10% of the maximum detection efficiency wavelength range; The luminescence detection method comprising:

20. 20. The luminescence detector of claim 19, wherein the second wavelength range is from 300 nm to 550 nm. How to get out.

21. The luminescence detection method according to claim 19, wherein the wavelength range of maximum detection efficiency is from 300 nm to 530 nm.

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