SYSTEM AND METHOD FOR DETECTING FLUORESCENCE RADIATION

Abstract

System for detecting fluorescent radiation, comprising: a light source for emitting excitation light; a sample unit with a sample arranged therein; a first optical fiber for connecting the light source to the sample unit; an avalanche photodiode array detector for receiving fluorescence radiation generated by the sample when the sample is irradiated with the excitation light; and a second optical fiber for connecting the sample to the avalanche photodiode array detector, wherein the second optical waveguide has a numerical aperture equal to or greater than 0.15 and the second optical waveguide is arranged such that a longitudinal axis of the second optical waveguide is perpendicular to a longitudinal axis of the first optical waveguide, and wherein the fluorescence radiation detection limit of the system for detecting fluorescence radiation is equal to or greater than one fluorescent particle per microliter for fluorescent particles having a mean diameter of approximately two micrometers.

Description

BACKGROUND OF THE INVENTIONThe present invention relates to detecting fluorescent radiation, and more particularly to systems and methods for detecting fluorescent radiation.Fluorescent labels are used to label a particular molecule, such as a protein of interest, an antibody, or an amino acid. Fluorescence detectors are used to quantitatively measure the fluorescence radiation generated by a sample to be evaluated. Thus, when the fluorescence detector detects fluorescent radiation, the fluorescent label and therefore the molecule of interest is present in the sample to be evaluated. Fluorescence detectors may use numerous components in complex configurations, consume much power, and / or take the size of a laboratory table, for example. Fluorescence detectors can also have sample volumes and / or detection limits below which a fluorescence radiation of samples cannot be detected.Documents have already been published in this context: the document US 2009 / 0 312 188 A1 describes a system and method for sequencing nucleic acids by a phase-based synthesis. In this case, a matrix of optical waveguides is also used. The document US 2012 / 0 220 022 A1 relates in principle to the technical field of "high-content screening" and in particular in a cytometric flow system. This involves acquiring line scan images of, for example, a plurality of different samples of cells simultaneously. Document US 2001 / 0 034 025 A1 relates to methods and apparatuses for detecting polynucleotide hybridization. At least one polynucleotide has a luminescent capacity. The corresponding radiation is detected from a sample assay. Furthermore, the document US 2003 / 0 152 308 A1 describes a fluorescence sensor which is based on a capillary waveguide. An optical / fluid connection is connected to one end of the capillary. Finally, document CN 103 245 641A describes a measurement head for a photoelectric measurement instrument, in particular a spectrometer, which is used to determine optical brightness properties of a printed color measurement strip during color printing.Therefore, there is a need for a system for detecting fluorescent radiation by means of which one or more of the above disadvantages can be eliminated.SUMMARYThis object is achieved by the subject matters of the independent claims. Further embodiments are specified by the respective dependent claims.According to an embodiment of the present invention, a system for detecting fluorescent radiation includes: a light source for emitting excitation light; a sample unit having a sample disposed therein; a first optical fiber for connecting the light source to the sample unit; an avalanche photodiode array detector for receiving the fluorescent radiation generated by the sample when the sample is irradiated with the excitation light; and a second optical fiber for connecting the sample unit to the avalanche photodiode array detector, wherein the second optical fiber has a numerical aperture equal to or greater than 0.15, and the second optical fiber is disposed such that a longitudinal axis of the second optical fiber is perpendicular to a longitudinal axis of the first optical fiber.According to another embodiment of the present invention, a method for detecting fluorescent radiation includes: emitting excitation light from a light source through a first optical fiber onto a sample in a sample unit; and receiving the fluorescent radiation generated from the sample through an avalanche photodiode array detector through a second optical fiber when the sample is irradiated with the excitation light; wherein the second optical fiber has a numerical aperture of equal to or greater than 0.15 and is arranged such that a longitudinal axis of the second optical fiber is perpendicular to a longitudinal axis of the first optical fiber.According to another embodiment of the present invention, a computer-assisted method for detecting fluorescent radiation comprises: emitting excitation light by a processor of a computer system from a light source through a first optical fiber onto a sample in a sample unit; receiving the fluorescent radiation generated by the sample by an avalanche photodiode array detector through a second optical fiber when the sample is irradiated with the excitation light, wherein the second optical fiber has a numerical aperture equal to or greater than about 0.15 and is arranged such that a longitudinal axis of the second optical fiber is perpendicular to a longitudinal axis of the first optical fiber; receiving sample information from the avalanche photodiode array detector by the processor of the computer system; and storing the sample data by the processor of the computer system in a memory.BRIEF DESCRIPTION OF THE DRAWINGSThe accompanying figures, wherein reference numerals designate identical or functionally similar elements throughout the several views, and together with the following detailed representation, are incorporated in and form a part of the specification, serve to illustrate various embodiments and explain various principles and advantages of the present invention, wherein: FIG. 1A is a functional diagram of an embodiment of the system for detecting fluorescent radiation; FIG. 1B is a functional diagram of the sample volume in the embodiment of the fluorescence radiation detection system in FIG. 1A ; FIG. 2 is a photograph of an embodiment of the system for detecting fluorescent radiation; FIG. 3A is a schematic diagram of an embodiment of the system for detecting fluorescent radiation using a microfluidic chip; FIG. 3B is a functional diagram of a portion of the microfluidic chip in FIG. 5 ; FIG. 4 is a block diagram illustrating an embodiment of a data processing system; FIG. 5 is a graph of signal intensity as a function of concentration and dilution using fluorescent spherical particles having an average diameter of 2 micrometers; FIG. 6 is a graph of signal intensity as a function of volume and concentration of a sample using fluorescent spherical particles having an average diameter of 50 nanometers; FIG. 7 is a diagram showing the system for detecting fluorescent radiation in a linear mode; and FIG. 8 is a diagram showing the system for detecting fluorescent radiation in a photon counting mode.DETAILED DESCRIPTIONReferring now to FIG. 1A, a functional diagram of an embodiment of the system for detecting fluorescent radiation is shown. The system for detecting fluorescent radiation 100 includes a light source 110 for emitting excitation light. A first optical waveguide 120 serves to connect the light source 110 to a sample unit 130, on which a sample (not shown) is arranged. An avalanche photodiode array detector 140 serves to receive the fluorescent radiation generated by the sample when the sample is irradiated with the excitation light. A second optical fiber 150 serves to connect the sample unit 130 to the avalanche photodiode array detector 140 ("APD"). The second optical waveguide 150 is arranged such that a longitudinal axis of the second optical waveguide 150 is perpendicular to a longitudinal axis of the first optical waveguide 120.One or more optical filters 160 may be used in the fluorescence radiation detection system 100. Any filter suitable for use in a system for detecting fluorescent radiation may be used. According to an embodiment, the one or more filters 160 comprise a dielectric filter, an absorption filter, an optical fiber grating filter, or a combination comprising at least one of the foregoing filters. According to an embodiment, a filter 160 is arranged between the light source 110 and the first optical waveguide 120. According to another embodiment, a filter 160 is arranged between the second optical waveguide 150 and the APD matrix detector 140.According to an embodiment, the fluorescence radiation detection system 100 further comprises a computer system 170 having a memory (not shown) and a processor (not shown) coupled to exchange data with the memory, the light source 110, and the APD matrix detector 140. The processor is configured to activate the light source 110 to emit excitation light; receive sample information from the APD matrix detector 140; and store the sample information in the memory.According to an embodiment, the processor of computer system 170 is further configured to select an operating mode for APD matrix detector 140. According to an aspect of the embodiment, the processor is configured to select a photon counting mode for detecting photons for the APD matrix detector 140. According to another aspect of the embodiment, the processor is configured to select a linear photomultiplier mode for detecting photons for the APD matrix detector 140.According to an embodiment, the second optical fiber 150 has a numerical aperture equal to or greater than about 0.15. According to another embodiment, the second optical fiber 150 has a numerical aperture equal to or greater than 0.20. According to yet another embodiment, the second optical fiber 150 has a numerical aperture equal to or greater than 0.25. According to yet another embodiment, the second optical fiber 150 has a numerical aperture equal to or greater than 0.30.The sample unit 130 may be of any shape and / or material suitable for holding a sample in a position for detection by the APD matrix detector 140. According to one embodiment, the sample unit 130 is a static sample unit, e.g. a cuvette. According to another embodiment, the sample unit 130 is a dynamic sample unit, e.g. a microfluidic channel.The sample unit 130 can receive samples of different volumes, including relatively small volumes. According to one embodiment, the sample unit 130 has a holding volume of less than or equal to about one cubic centimeter. According to an embodiment, a volume of a sample in the sample unit 130 is equal to or less than about 100 nanoliters. According to another embodiment, a volume of a sample in the sample unit 130 is equal to or less than 50 nanoliters. According to another embodiment, a volume of a sample in the sample unit 130 is equal to or less than about 40 nanoliters. According to yet another embodiment, a volume of a sample in the sample unit 130 is from about 30 nanoliters to about 100 nanoliters, in particular from about 32 nanoliters to about 50 nanoliters, more particularly from about 35 nanoliters to about 40 nanoliters, and most particularly from about 38 nanoliters.The APD matrix detector 140 receives and detects the fluorescent radiation generated by the sample in the sample unit 130. Avalanche photodiodes are photodiodes that can generate a relatively strong electrical signal in response to receiving a relatively weak optical signal. The APD matrix detector 140 thus has high sensitivity. According to one embodiment, the APD matrix detector 140 is configured to selectively transition between a relatively low concentration photon counting mode and a relatively high concentration linear photomultiplier mode.The configuration of the fluorescence radiation detection system 100 is also very compact compared to table systems for detecting fluorescence radiation. According to an embodiment, the system for detecting fluorescent radiation 100 is portable. According to one embodiment, the system for detecting fluorescent radiation 100 is operated with rechargeable batteries. The fluorescence radiation detection system 100 uses fewer system elements than other fluorescence radiation detection systems. According to one embodiment, the system for detecting fluorescent radiation 100 does not have any filters. According to another embodiment, the system for detecting fluorescent radiation 100 does not have lenses.By the orthogonal arrangement of the first optical waveguide 120 and the second optical waveguide 150, the relatively large numerical aperture of the second optical waveguide 150 and the APD matrix detector 140, relatively small volumes and / or concentrations of fluorescent markers can be detected by the system for detecting fluorescent radiation 100. FIG. 1B shows a functional diagram of the sample volume according to the embodiment of the system for detecting fluorescent radiation in FIG. 1A. The volume of a sample 180 in the sample unit (not shown) that is irradiated with the excitation light from the light source 110 and detected by the APD matrix detector 140 is represented as the volume in which the excitation light cone 190 and the fluorescence emission cone 200 overlap. The orthogonal arrangement of the first optical waveguide 120 and the second optical waveguide 150 reduces a capture of scattered excitation light and / or scattered light and thereby the background signal in the APD matrix detector 140, such that a fluorescence radiation can be detected in a relatively small volume of the sample 180. According to an embodiment, the excitation light cone 190 or its volume, the fluorescence emission cone 200 or its volume and / or the amount of light emitted by the light source are adjusted as desired by varying the optical waveguides used as the first optical waveguide 120 and / or as the second optical waveguide 150.The system for detecting fluorescent radiation 100 has a higher sensitivity than other systems for detecting fluorescent radiation. According to an embodiment, the system for detecting fluorescent radiation 100 has a fluorescence detection limit equal to or greater than one fluorescent particle per microliter for fluorescent particles having an average diameter of about two micrometers. According to another embodiment, the fluorescence radiation detection system 100 has a fluorescence detection limit equal to or greater than about 100 fluorescence particles per microliter for fluorescence particles having an average diameter of about 50 nanometers.FIG. 2 shows a photograph of an embodiment of the system for detecting fluorescent radiation 200. The elements of the system for detecting fluorescent radiation 200 are the same as described above for the system for detecting fluorescent radiation 100 shown in FIG. 1. From the photograph of the system for detecting fluorescent radiation 100, it can be seen that the first optical waveguide, which connects the light source to the sample unit, is located at one end close to the light source and at the other end close to the sample unit. The end of the first optical waveguide close to the sample unit forms a coupling point (interface) 210 between the first optical waveguide and the sample unit. It can also be seen from the photograph of the system for detecting fluorescent radiation 200 that the second optical waveguide, which connects the sample unit to the APD matrix detector, is located at one end close to the sample unit and at the other end close to the APD matrix detector. The end of the second optical waveguide near the APD matrix detector forms a coupling point (interface) 220 between the first optical waveguide and the sample unit.According to one embodiment, one or both ends of the first optical waveguide are not conical. According to another embodiment, one or both ends of the second optical waveguide are not conical. According to yet another embodiment, one or both ends of the first optical fiber are not tapered and one or both ends of the second optical fiber are not tapered.FIG. 3A shows a schematic diagram of an embodiment of the system for detecting fluorescent radiation integrated into a microfluidic chip 300. Microfluidic chip 300 includes a microfluidic channel 310 through which a sample fluid flows. The first optical waveguide (or "waveguide") 320 is disposed at a location perpendicular to the second optical waveguide (or "waveguide") 330. The remaining features of the system for detecting fluorescent radiation 200 are the same as described with reference to FIG. 1.FIG. 3B shows a functional diagram of a portion of the microfluidic chip 300 of FIG. 3A. The first optical fiber 320 transmits excitation light from a light source (not shown) to a sample in the microfluidic channel 310. The second optical waveguide 330 emits fluorescent radiation generated by the sample onto an APD matrix detector (not shown).According to an embodiment, a method for detecting fluorescent radiation includes: emitting excitation light from a light source through a first optical fiber onto a sample in a sample unit; and receiving the fluorescent radiation generated from the sample through an avalanche photodiode array detector through a second optical fiber when the sample is irradiated with the excitation light; wherein the second optical fiber has a numerical aperture equal to or greater than about 0.15 and is arranged such that a longitudinal axis of the second optical fiber is perpendicular to a longitudinal axis of the first optical fiber.According to another embodiment, a computer-assisted method for detecting fluorescent radiation comprises: emitting, by a processor of a computer system, excitation light from a light source onto a sample in a sample unit through a first optical fiber; receiving, by an avalanche photodiode array detector through a second optical fiber when the sample is irradiated with the excitation light, fluorescent radiation generated by the sample, wherein the second optical fiber has a numerical aperture equal to or greater than 0.15 and is arranged such that a longitudinal axis of the second optical fiber is perpendicular to a longitudinal axis of the first optical fiber; receiving, by the processor of the computer system, sample information from the avalanche photodiode array detector; and storing, by the processor of the computer system, the sample information in a memory.FIG. 4 shows a block diagram illustrating a data processing system. The data processing system 400 is based on a suitably configured processing system configured to implement the one or more embodiments described herein. Any suitably configured processing system may be used for the data processing system 400 in the embodiments described herein. Components of the data processing system 400 may include, but are not limited to, one or more processors or processing units 410, a system memory 420, and a bus 430 that couples various system components together, including system memory 420 to the processor 410.Bus 430 represents one or more of various arbitrary types of bus structures, including a memory bus or memory controller, a peripheral bus, an accelerated graphics port, and a local or processor bus using any of a variety of bus architectures. For example, without limitation, architectures such as the industry standard architecture bus, the micro channel architecture bus, the enhanced ISA bus, the video electronics standards local association bus, and the peripheral component interconnects bus may be considered.System memory 420 may also include computer readable media in the form of volatile memory such as random access memory ("RAM") 435 and / or cache memory 440. Other removable / non-removable, volatile / non-volatile computer system storage media may be used as the data processing system 400. For example only, a storage system 450 may be provided for reading from or writing to a non-removable or removable non-volatile medium, such as one or more hard drives and / or magnetic media (commonly referred to as a "hard drive"). A magnetic disk drive for reading from and writing to a removable, non-volatile magnetic disk (e.g., a "floppy disk"), and an optical disk drive for reading from or writing to a removable, non-volatile optical disk such as a CD-ROM, DVD-ROM, or other optical medium may be provided. In such cases, each medium may be connected to bus 430 through one or more data medium interfaces. The memory 420 may include at least one program product having a series of program modules configured to perform the functions of the embodiment described herein.For example, a program / utility 460 having a series of program modules 470, as well as an operating system, one or more application programs, other program modules, and program data may be stored in memory 420, without limitation. Any operating system, one or more application programs, other program modules and / or program data, and certain combinations thereof, may include an implementation of a network environment. The program modules 470 may generally perform the functions and / or procedures of the embodiments described herein.The computing system 400 may also communicate with one or more external devices 480, such as a keyboard, a pointing device, a display 490, etc.; one or more devices that enable a user to act on the computing system 400; and / or any devices, e.g., a network card, a modem, etc., that enable the computing system / server 400 to communicate with one or more other computing devices. Such a data exchange can take place via I / O interfaces 500. Further, the data processing system 400 may communicate with one or more networks, such as a local area network, a wide area network, and / or a public network, e.g., the Internet, via a network adapter 510. The network adapter 510 shown exchanges data with the other components of the data processing system 400 via bus 430. Other hardware and / or software components may also be used in conjunction with data processing system 400. Examples include, but are not limited to: microcode, device drivers, redundant processing devices, external disk drive arrays, RAID systems, tape drives, and data archive storage systems.According to some aspects of the embodiment described herein, it may be a system, method, or computer program product. Accordingly, the embodiments described herein may take the form of a complete hardware embodiment, a complete software embodiment (including firmware, resident software, microcode, etc.), or an embodiment that incorporates software and hardware aspects, all of which may generally be referred to herein as a "circuit", "module", or "system.". Moreover, embodiments described herein may take the form of a computer program product embodied in one or more computer readable media having computer readable program code stored thereon.A combination of one or more computer readable media may be used. The computer readable medium may be a computer readable signal medium or a computer readable storage medium. A computer readable storage medium may be, for example, but is not limited to, an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, device, or device, or any suitable combination thereof. More specific examples (a non-exhaustive enumeration) of the computer readable storage medium may include the following: an electrical connection having one or more wires, a portable computer diskette, a hard disk, a random access memory, a read-only memory, an erasable read-only memory, an optical fiber, a portable compact disc read-only memory, an optical storage unit, a magnetic storage unit, or any suitable combination thereof. In connection with this document, a computer readable storage medium may be any tangible medium that can contain or store a program for use by or in connection with a system, apparatus, or device.A computer readable signal medium may include a propagating data signal having computer readable program code embodied therein, for example, in baseband or as part of a carrier wave. Such a propagating signal may take any of a variety of forms including, but not limited to, electromagnetic, optical, or any suitable combination thereof. A computer readable signal medium may be any computer readable medium that is not a computer readable storage medium and that can transmit, forward, or transport a program for use by or in connection with at least one system, apparatus, or device for executing instructions.Program code stored on a computer readable medium may be transmitted using any suitable medium, including, but not limited to, wireless, wireline, optical fiber, RF, etc., or any suitable combination thereof.Computer program code for carrying out operations for the embodiments described herein may be written in any component of one or more programming languages, including an object oriented programming language such as Java, Smalltalk, C++ or the like, and conventional programming languages such as the "C" programming language or similar programming languages. The program code may execute entirely on a user's computer, partly on the user's computer, as a stand-alone software package, partly on the user's computer and partly on a remote computer or entirely on the remote computer or server. In the latter case, the remote computer may be connected to the user's computer by any type of network, including a local area network (LAN) or a wide area network (WAN), or the connection may be made to an external computer (for example, via the Internet using an Internet Service Provider).Above, aspects of the present invention have been discussed with reference to flowchart diagrams and / or block diagrams of methods, apparatus (systems) and computer program products according to various embodiments of the invention. It will be appreciated that each block of the flowchart and / or block diagrams, and combinations of blocks in the flowchart and / or block diagrams, may be implemented by instructions of a computer program. These computer program instructions may be provided to a processor of a general purpose computer, special purpose computer, or other programmable data processing apparatus to produce a machine such that the instructions executed by the processor of the computer or other programmable data processing apparatus produce a means for implementing the functions / acts specified in the flowchart and / or block diagram block or blocks.The computer program instructions may also be loaded onto a computer, other programmable data processing apparatus, or other devices to cause a series of operations to be performed on the computer, other programmable apparatus, or other devices to produce a computer-assisted process such that the instructions executed on the computer or other programmable apparatus provide processes for implementing the functions / acts specified in the flowchart and / or block diagram block or blocks.The following examples were set forth to demonstrate the high sensitivity of the system for detecting fluorescent radiation. FIG. 5 is a graph showing signal intensity in arbitrary units as a function of a concentration of the number of fluorescent particles N per microliter (N / μl) and the dilution of a sample using fluorescent spherical particles having an average diameter of two micrometers. From the diagram in FIG. 5, it can be seen that a fluorescence radiation down to a concentration of 2.6 N / μl and even down to approximately 1.0 N / μl was detected.FIG. 6 is a graph showing signal intensity as a function of volume and concentration of a sample using fluorescent beads having an average diameter of 50 nanometers. In this experiment, the same conditions and parameters as described with reference to FIG. 5 were observed, using fluorescent spherical particles having an average diameter of 50 nanometers only instead of the fluorescent spherical particles having an average diameter of 2 micrometers. It can be seen from the diagram in FIG. 5 that a fluorescence radiation of the significantly smaller fluorescent spherical particles was detected down to a concentration of 200 N / μl and even down to concentrations of 200 N / μl.FIG. 7 is a diagram showing the APD matrix detector in the system for detecting fluorescent radiation in a linear mode. It can be seen from FIG. 7 that in linear mode an integrated multiphoton signal is used to detect fluorescent radiation in a sample having a relatively high concentration of 5×10 6 / milliliters (500:1).FIG. 8 is a diagram showing the system for detecting fluorescent radiation in a photon counting mode. It can be seen from FIG. 8 that in the photon counting mode, a single photon signal is used to detect fluorescent radiation in a sample having a relatively low fluorescent spherical particle concentration of 1×10 5 / milliliters (20,000:1).The flowchart and block diagrams in the figures illustrate the architecture, functionality, and operation of possible implementations of systems, methods, and computer program products according to various embodiments of the present invention. Accordingly, each block in the flowchart or block diagram may represent a module, segment, or portion of instructions, including one or more executable instructions for implementing the one or more specified logical functions. According to some alternative implementations, the functions specified in the block may occur in a different order from the figures. For example, two blocks shown in succession may, in fact, be executed substantially simultaneously depending on the functionality provided, or the blocks may sometimes be executed in the reverse order. It is also noted that each block in the block diagrams and / or flowchart, and combinations of blocks in the block diagrams and / or flowchart, may be implemented by special purpose hardware systems that perform the specified functions or acts, or combinations thereof, or by special purpose hardware and computer instructions.The descriptions of the various embodiments of the present invention have been presented for purposes of illustration and do not claim completeness or limitation to the disclosed embodiments. Those skilled in the art will readily appreciate modifications and variations without departing from the scope and spirit of the described embodiments. The terms used herein were chosen to best explain the principles of the embodiments and the practical application or technical improvement over commercially available technologies, or to enable others skilled in the art to understand the embodiments disclosed herein.These computer program instructions may be stored in a computer readable medium that can cause a computer, other programmable data processing apparatus, or other devices to function in a particular manner such that the instructions stored in the computer readable medium produce an article of manufacture including instructions for implementing the functions / acts specified in the flowchart and / or block diagram block or blocks.

Claims

A system for detecting fluorescent radiation, comprising: a light source for emitting excitation light; a sample unit having a sample disposed therein; a first optical fiber for connecting the light source to the sample unit; an avalanche photodiode array detector for receiving fluorescent radiation generated by the sample when the sample is irradiated with the excitation light; and a second optical fiber for connecting the sample to the avalanche photodiode array detector, wherein the second optical fiber has a numerical aperture equal to or greater than 0.15 and the second optical fiber is arranged such that a longitudinal axis of the second optical fiber is perpendicular to a longitudinal axis of the first optical fiber, and wherein the fluorescence radiation detection limit of the fluorescence radiation detection system is equal to or greater than one fluorescent particle per microliter for fluorescent particles having an average diameter of about two micrometers.The fluorescent radiation detection system of claim 1, further comprising: a memory; a processor of a computer system coupled to communicate with the memory, the light source, and the avalanche photodiode array detector, the processor configured to: activate the light source to emit excitation light; receive sample information from the avalanche photodiode array detector; and store the sample information in the memory.The system for detecting fluorescent radiation of claim 2, wherein the processor is further configured to select an operating mode for the avalanche photodiode array detector.The system for detecting fluorescent radiation of claim 3, wherein the processor is configured to select a photon counting mode for the avalanche photodiode array detector in photon detection, or wherein the processor is configured to select a linear photomultiplier mode for the avalanche photodiode array detector in photon detection.The system for detecting fluorescent radiation according to claim 1, wherein a volume of a sample in the sample unit is equal to or less than about 100 nanoliters.The system for detecting fluorescent radiation according to claim 1, wherein a volume of a sample in the sample unit is equal to or less than 50 nanoliters.The fluorescent radiation detection system of claim 1, wherein the fluorescence radiation detection limit of the fluorescent radiation detection system is equal to or greater than about 100 fluorescent particles per microliter for fluorescent particles having an average diameter of about 50 nanometers.The system for detecting fluorescent radiation of claim 1, wherein the second optical fiber has a numerical aperture equal to or greater than about 0.20, or wherein the second optical fiber has a numerical aperture equal to or greater than 0.25.The system for detecting fluorescent radiation according to claim 1, wherein a sample unit uptake volume is less than or equal to about one cubic centimeter.The system for detecting fluorescent radiation according to claim 1, wherein the sample unit is a static sample unit or a dynamic sample unit.The fluorescence radiation detection system of claim 1, wherein the fluorescence radiation detection system further comprises a filter disposed between the light source and the first optical fiber.The fluorescence radiation detection system of claim 1, wherein the fluorescence radiation detection system further comprises a filter disposed between the second optical fiber and the avalanche photodiode array detector.The fluorescent radiation detection system of claim 1, wherein the fluorescent radiation detection system does not include a lens.A method for detecting fluorescent radiation, comprising: emitting excitation light from a light source through a first optical fiber to a sample in a sample unit; and receiving the fluorescent radiation generated from the sample through an avalanche photodiode array detector through a second optical fiber when the sample is irradiated with the excitation light; wherein the second optical fiber has a numerical aperture equal to or greater than about 0.15 and is arranged such that a longitudinal axis of the second optical fiber is perpendicular to a longitudinal axis of the first optical fiber, and wherein a fluorescence radiation detection limit of a mature system for detecting fluorescent radiation is equal to or greater than one fluorescent particle per microliter for fluorescent particles having an average diameter of about two micrometers.A computer-assisted method for detecting fluorescent radiation, the method comprising: emitting, by a processor of a computer system, excitation light from a light source onto a sample in a sample unit via a first optical fiber; receiving, from an avalanche photodiode array detector via a second optical fiber, fluorescent radiation generated by the sample when the sample is irradiated with the excitation light, wherein the second optical fiber has a numerical aperture equal to or greater than 0.15 and is arranged such that a longitudinal axis of the second optical fiber is perpendicular to a longitudinal axis of the first optical fiber, wherein a fluorescence detection limit of a system used for detecting fluorescent radiation is equal to or greater than one fluorescent particle per microliter for fluorescent particles having an average diameter of about two micrometers; receiving sample information by the processor of the computer system from the avalanche photodiode array detector; and storing the sample information by the processor of the computer system in a memory.

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