Biolayer interferometric sensor comprising optical fiber having faceted cross-section and device using same

Abstract

A biosensor includes an optical fiber having a proximal end portion and a distal end portion. The proximal end portion is configured to receive light from a light source and to transmit reflected light to a detector. The optical fiber has a polygonal cross-section. The distal portion is configured to bind an analyte to the distal portion such that light reflected from the distal portion is phase shifted based on a thickness of the analyte bound to the distal portion.

Description

Technical Field

[0001] The present disclosure relates to optical sensors, and more particularly, to an optical sensor for interferometry having a faceted optical fiber. Background Art

[0002] Diagnostic tests based on binding events between members of an analyte-antianalyte binding pair are widely used in medical, veterinary, agricultural and research applications. Typically, such methods are used to detect the presence or amount of an analyte in a sample, and / or the rate of binding of an analyte to an antianalyte. Typical analyte-antianalyte pairs include complementary nucleic acid strands, antigen-antibody pairs, and receptor-receptor binding agents, wherein the analyte can be either member of the pair, and the antianalyte molecule is the opposing member.

[0003] Such diagnostic methods usually use solid surfaces, which have fixed anti-analyte molecules or materials, and sample analyte molecules will be specifically and have high affinity to bind to these molecules or materials in a limited detection zone. In the determination of this type called solid phase assay, the solid surface is exposed to the sample under conditions that promote the binding of analyte to fixed anti-analyte molecules. The binding event can be directly detected, such as by the change of quality, reflectivity, thickness, color or other characteristics indicating the binding event. When, for example, chromophore, fluorescence or radioactive markers are used to mark analyte in advance, the binding event can be detected by the presence and / or amount of detectable labels at the detection zone. Alternatively, the analyte can be labeled after the analyte is combined with the detection zone, such as with auxiliary fluorescently labeled anti-analyte antibodies.

[0004] The fiber interferometer measurement device can be designed to detect an analyte bound to an end surface of an optical fiber of the fiber interferometer measurement device. Analyte detection is based on a change in thickness at the end surface of the optical fiber, the change in thickness being caused by the binding of analyte molecules to said surface, the greater the amount of analyte, the greater the thickness-related change in the interference signal. The change in the interference signal is due to a phase shift between light reflected from the inner and outer surfaces of an optical resonator layer at the end of the optical fiber, wherein the outer interface comprises a binding layer.

[0005] The interferometer measurement device will produce readily observable changes in the location of peaks and valleys (extremes) of the optical spectrum, so that relatively small changes in optical thickness at the end surface of the optical fiber can be detected as significant changes in the spectral location of the peaks and valleys of the interference wavelength.

[0006] The interferometric device may include a biolayer interferometer (BLI) sensor including an optical fiber having an optical resonator layer at an end of the optical fiber, the optical resonator layer having an end surface to which an analyte may bind to form a biolayer. The signal-to-noise ratio of light reflected from an inner surface of the optical resonator and an outer surface of the optical resonator containing the biolayer may affect the ability of the interferometric device to detect small optical thickness changes in the biolayer. Summary of the invention

[0007] The present disclosure generally relates to an interferometer measurement device with an improved signal-to-noise ratio. In particular, the present disclosure relates to a BLI sensor of the interferometer measurement device, which is designed to improve the signal-to-noise ratio of light reflected from the surface of an optical resonator of the BLI sensor. The BLI sensor disclosed herein includes a faceted optical fiber, which can improve the spatial distribution of photons at the optical resonator surface of the fiber interferometer, so that the signal-to-noise ratio of light reflected from the end surface of the optical fiber is improved relative to a non-faceted optical fiber.

[0008] In one aspect of the present disclosure, a biosensor includes a faceted optical fiber having a proximal portion and a distal portion. The proximal portion is configured to receive light from a light source and transmit reflected light to a detector. The faceted optical fiber has a polygonal cross-section. The distal portion is configured to allow an analyte to bind to the distal portion such that light reflected from the distal portion is phase shifted based on the thickness of the analyte bound to the distal portion.

[0009] In another aspect of the present disclosure, a biosensor includes an optical fiber having a proximal portion and a distal portion. The proximal portion is configured to receive light from a light source and is configured to transmit reflected light to a detector. The optical fiber has a polygonal cross-section. The distal portion is configured to allow an analyte to bind to the distal portion so that light reflected from the distal portion is phase shifted based on the thickness of the analyte bound to the distal portion.

[0010] In various aspects, the optical fiber has a triangular, square, pentagonal, hexagonal, octagonal or decagonal cross section. The optical fiber can be configured to scatter light so that the light is evenly distributed in the distal portion of the optical fiber. The optical fiber can be configured to receive a light beam at a proximal portion and evenly distribute light from the received light beam at its distal portion. The optical fiber can have an improved signal-to-noise ratio compared to an optical fiber with a circular cross section. The optical fiber can have an increased sensitivity compared to an optical fiber with a circular cross section.

[0011] In some aspects, the biosensor includes an optical resonator at a distal portion. The optical resonator may include a first reflective surface and a second reflective surface. The first reflective surface may be configured to reflect light having a first phase, and the second reflective surface may be configured to reflect light having a second phase that is phase-shifted based on a thickness of an analyte bound to the optical resonator.

[0012] In certain aspects, the biosensor includes a cladding disposed around an optical fiber, the cladding being capable of forming an optical fiber assembly with the optical fiber such that the optical fiber assembly has an optical fiber having a polygonal cross-section disposed within the cladding, the cladding having a circular or oval cross-section at its outer diameter. The optical fiber can be disposed within a channel defined by the cladding.

[0013] In another aspect of the present disclosure, a biosensor includes an optical fiber having a proximal portion and a distal portion. The proximal portion is configured to receive light from a light source and is configured to transmit reflected light to a detector. The distal portion is configured to allow an analyte to bind to the distal portion so that light reflected from the distal portion is phase shifted based on the thickness of the analyte bound to the distal portion. The optical fiber has a faceted core disposed within a first cladding. The faceted core has a core cross section.

[0014] In some aspects, the first cladding defines an outer cross-section of the optical fiber. The outer cross-section can be circular or oval. The core cross-section can be triangular, square, pentagonal, hexagonal, octagonal or decagonal.

[0015] In some aspects, the optical fiber includes a second cladding disposed around the first cladding. The second cladding can define an outer cross-section having a shape different from the shape of the core cross-section. The outer cross-section can be circular or oval. The optical fiber can include a coating on the second cladding. The coating can define an outer surface of the optical fiber.

[0016] In some aspects, the first cladding is formed of glass or quartz. The second cladding can be formed of glass or quartz. The coating can be formed of polyamide or polytetrafluoroethylene. The first cladding and the second cladding can be formed of the same material, or of different materials. The faceted core and the first cladding in combination with each other can provide a desired numerical aperture of the optical fiber.

[0017] In another aspect of the present disclosure, the biosensor includes a faceted optical fiber having a proximal portion and a distal portion. The proximal portion is configured to receive light from a light source. The faceted optical fiber is configured to scatter the received light so that the light distribution at the distal portion of the faceted optical fiber is uniformly distributed. The faceted optical fiber can have an increased signal-to-noise ratio relative to a non-faceted optical fiber. The faceted optical fiber can include a faceted core arranged within the cladding. The cladding can define an outer surface having a circular or oval cross-section.

[0018] In various aspects, the biosensors detailed herein can include an optical fiber or optical fiber assembly, with the optical fiber or optical fiber assembly extending distally from the hub, and a hub attached to an optical coupler 36. The hub can separate the proximal end of the optical fiber or optical fiber assembly from a fiber bundle that provides light from a light source and returns light to a detector.

[0019] In another aspect of the present disclosure, an interferometer device includes: a first optical waveguide configured to receive light from a light source; a second optical waveguide configured to transmit reflected light to a detector; an optical coupler spatially separating a distal portion of the first optical waveguide from a distal portion of the second optical waveguide; and a biosensor attached to the optical coupler. The biosensor includes an optical fiber as described in detail herein.

[0020] In various aspects, the interferometer device includes a light source in optical communication with the first optical waveguide and configured to provide light to the first optical waveguide.The light source may be a broad spectrum light source.

[0021] In some aspects, the interferometer device includes a detector configured to receive light from the second optical waveguide. The first optical waveguide and the second optical waveguide can both be arranged in a single optical fiber bundle. The optical fiber bundle can be arranged such that the optical fiber of the first optical waveguide is arranged around a single optical fiber of the second optical waveguide.

[0022] In some aspects, the biosensor is attached to the optical coupler such that a gap is defined between the distal end of the fiber bundle and the proximal end of the optical fiber. The gap may be in the range of 25 μm to 600 μm.

[0023] In certain aspects, the biosensor can include an optical resonator located at a distal portion of an optical fiber. The optical resonator can include a first reflective surface and a second reflective surface. The first reflective surface can be configured to reflect light having a first phase, and the second reflective surface can be configured to reflect light having a second phase that is phase-shifted based on a thickness of an analyte bound to the optical resonator.

[0024] Furthermore, any embodiment or aspect described herein may be used in combination with any or all other embodiments or aspects described herein, unless inconsistent. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Various aspects of the present disclosure will be described below with reference to the accompanying drawings, which are incorporated into and constitute a part of this specification, in which:

[0026] Figure 1 is a schematic diagram of an interferometer assay device according to the present disclosure, the interferometer assay device being inserted into a well plate having an analyte;

[0027] Figure 2 yes Figure 1 an end perspective view of an optical coupler of an interferometer measurement device showing the optical fiber bundle of the device;

[0028] Figure 3 yes Figure 1 A partial perspective view of a device in which the BLI sensor is separated from the optical coupler;

[0029] Figure 4 yes Figure 3 A partial longitudinal cross-sectional view of an optical coupler and a BLI sensor, wherein the BLI sensor is attached to the optical coupler;

[0030] Figure 5 yes Figure 4 A magnified view of a portion of an optical coupler and a BLI sensor;

[0031] Figure 6 yes Figure 1 A schematic diagram of an interface between an optical fiber bundle and an optical fiber of a device;

[0032] Figure 7 yes Figure 2 a beam profile of a first optical waveguide of the optical fiber bundle;

[0033] Figure 8 yes Figure 2 A beam profile at a distal portion of a BLI sensor;

[0034] Fig. 9 yes Figure 8 A graphical representation of the beam profile at the distal portion of the BLI sensor;

[0035] Fig.10 is a perspective view of a faceted BLI sensor provided according to the present disclosure;

[0036] Fig.11 yes Fig. 9 A beam profile at a distal portion of a faceted BLI sensor;

[0037] Fig.12 yes Fig.11 A graphical representation of the beam profile at the distal portion of the BLI sensor;

[0038] Fig.13 is a beam profile at a distal portion of another faceted BLI sensor provided according to an embodiment of the present disclosure;

[0039] Fig.14 yes Fig.13 A graphical representation of the beam profile at the distal portion of the BLI sensor;

[0040] Fig.15 is a perspective view of a BLI sensor provided according to an embodiment of the present invention, which includes an optical fiber having a triangular cross-section;

[0041] Fig.16 is a perspective view of a BLI sensor provided according to an embodiment of the present invention, which includes an optical fiber having a square cross-section;

[0042] Fig.17 is a perspective view of a BLI sensor provided according to an embodiment of the present invention, which includes an optical fiber having a pentagonal cross-section;

[0043] Fig.18 is a perspective view of a BLI sensor provided according to an embodiment of the present invention, comprising an optical fiber having an octagonal cross-section;

[0044] Fig.19 is a perspective view of a BLI sensor according to an embodiment of the present invention, comprising an optical fiber having a decagonal cross-section.

[0045] Fig. 20 is a perspective view of a BLI sensor according to an embodiment of the present invention, comprising an optical fiber having a circular cross-section and having an internal hexagonal optical fiber;

[0046] Fig.21 yes Fig. 20 A magnified view of the tip of the BLI sensor;

[0047] Fig. 22 is a view of an end of an internally faceted optical fiber of another BLI sensor provided in accordance with an embodiment of the present invention, the internally faceted optical fiber having a circular cross-section and an internal hexagonal core; and

[0048] Fig.23 is a view of the tip of an internally faceted optical fiber of a BLI sensor provided in accordance with an embodiment of the present invention, the internally faceted optical fiber having an oval cross-section and having an internal octagonal core. DETAILED DESCRIPTION

[0049] The present disclosure will now be described more fully below with reference to the accompanying drawings with reference to example embodiments of the present disclosure, wherein the same reference numerals represent the same or corresponding elements in each of the several drawings. These example embodiments are described to make the present disclosure comprehensive and complete and to fully convey the scope of the present disclosure to those skilled in the art. Features from one embodiment or aspect may be combined with features from any other embodiment or aspect in any appropriate combination. For example, any individual or collective feature of the method aspect or embodiment may be applied to the device, product or component aspect or embodiment, and vice versa. The present disclosure may be embodied in a variety of different forms and should not be construed as limited to the embodiments described herein; on the contrary, these embodiments are provided to enable the present disclosure to meet applicable legal requirements. As used in the specification and the appended claims, the singular forms "a", "an", "the", etc. include plural references unless the context clearly dictates otherwise. In addition, although quantitative measurements, values, geometric relationships, etc. may be referenced herein, unless otherwise stated, one or more of these (if not all) may be absolute or approximate to take into account acceptable changes that may occur, such as those caused by manufacturing or engineering tolerances, etc.

[0050] As used herein, the term "proximal" refers to the portion of a device or a component thereof that is closer to a user or machine using the device, and the term "distal" refers to the portion of a device or a component thereof that is farther from a user or machine using the device.

[0051] An "analyte binding" molecule or material refers to any molecule or material that is capable of participating in a specific binding reaction with an analyte molecule. Examples include, but are not limited to, antibody-antigen binding reactions and nucleic acid hybridization reactions.

[0052] "Specific binding reaction" refers to a saturable, usually reversible binding reaction that can be accomplished by an excess of one of the reactants. Specific binding reactions are characterized by complementarity in shape, charge, and other binding determinants between the participants in the specific binding reaction.

[0053] "Antibody" refers to an immunoglobulin molecule having two heavy chains and two light chains prepared by any method known in the art or later developed, and includes polyclonal antibodies, such as those produced by inoculating a mammal (such as a goat, mouse, rabbit, etc.) with an immunogen, and includes monoclonal antibodies produced using the well-known Kohler Milstein hybridoma fusion technique. The term includes antibodies produced using genetic engineering methods, such as those using SCID mice reconstructed with human immunoglobulin genes, and humanized antibodies using surface remodeling techniques known in the art.

[0054] "Antibody fragments" refer to fragments of antibody molecules produced by chemical cleavage or genetic engineering techniques, as well as single-chain variable fragments (SCFvs), such as those produced using combinatorial gene libraries and phage display technology. The antibody fragments used according to the present invention generally retain the ability to bind to their cognate antigens and therefore include variable sequences and antigen binding sites.

[0055] "Biolayer" refers to analyte-binding molecules or materials with or without bound analyte.

[0056] Reference now Figure 1 According to the present disclosure, an interferometer assay device 20 is provided. The device 20 includes a light source 22, an optical assembly 26, and a detector unit 28. The bio-layer interferometer (BLI) sensor or optical assembly 26 is used as a sensing element or detector tip to detect an analyte attached to its end, as described in more detail below. The detector unit 28 detects an interference signal generated by interfering light waves reflected from the optical assembly 26.

[0057] The light source 22 directs light into the optical assembly 26, which is reflected through an optical coupling assembly (indicated by dashed lines at 30) back to the detector unit 28. The coupling assembly 30 includes a first optical waveguide or fiber 32 extending from the light source 22 to the optical assembly 26, a second optical waveguide or fiber 34 that transmits the reflected light from the optical assembly 26 to the detector 28, and an optical coupler 36 that optically couples the first optical waveguide 32 and the second optical waveguide 34. In some embodiments, the coupling assembly 36 includes a lens system that is configured to focus a light beam onto an upper surface of the optical assembly 26 and direct the reflected interference light from the optical assembly 26 to the detector 28.

[0058] The light source 22 may be a white light source, such as a light emitting diode (LED), which generates light in a wide spectral range, such as a spectral range of 400 nm or less to 700 nm or greater, typically within a spectral range of at least 100 nm. In some embodiments, the light source 22 may be a plurality of light sources, each with a different characteristic wavelength, such as an LED designed to emit light at a different selected wavelength in the visible light range. The same function may be achieved by a single light source (e.g., a white light source) having a suitable filter for directing light having different selected wavelengths to the optical assembly 26.

[0059] Detector 28 may be a spectrometer, such as a charge coupled device (CCD), capable of recording a spectrum of the reflected interference light from optical assembly 26. In some embodiments, when light source 22 operates to direct different selected wavelengths to optical assembly 26, detector 28 may be a simple photodetector for recording the light intensity of each different illumination wavelength. In some embodiments, detector 28 may include one or more filters that allow detection of light intensity at each of a plurality of selected wavelengths of the interference reflected waves, such as light intensity from a white light source.

[0060] Additional references Figure 2 , the first optical waveguide 32 and / or the second optical waveguide 34 may be in the form of a fiber optic bundle (FOB) 31. As shown, the first optical waveguide 32 includes a plurality of fiber optic elements surrounding a single fiber optic element of the second optical waveguide 34. This arrangement separates the transmission of light from the light source 22 from the transmission of reflected light from the optical assembly 26 to the detector 28. It will be appreciated that other arrangements of the first optical waveguide 32 and the second optical waveguide 34 may allow for spatial separation of light from the light source 22 and reflected light from the optical assembly 26. The separation of light from the light source 22 and reflected light from the optical assembly 26 may improve the signal-to-noise ratio (SNR) of the device 20. In some embodiments, the first optical waveguide 32 is a single optical fiber, while the second optical waveguide 34 is formed of a plurality of optical fibers.

[0061] Figure 3-Figure 5 A portion of the device 20 is shown, showing the interface between the fiber optic bundle 31 and the optical fiber 27 of the optical assembly or BLI sensor 26. As shown, when the BLI sensor 26 is attached to the optical coupler 36, the distal tip 33 of the fiber optic bundle 31 is aligned with the proximal portion 21 of the optical fiber 27. The BLI sensor 26 can be fixedly attached to the optical coupler 36 to align and maintain the position of the proximal portion 21 relative to the tip 33. The BLI sensor 26 includes a hub that attaches the BLI sensor to the optical coupler 36 and secures to the proximal portion of the optical fiber 27.

[0062] The BLI sensor 26 includes an optical fiber 27 having a proximal end and a distal end. The proximal end and / or the distal end of the optical fiber 27 may be a polished end. The distal end of the BLI sensor 26 has an optical resonator having a first reflective surface 40 and a second reflective surface 42 located on the distal side of the first reflective surface. The optical fiber 27 is transparent between its proximal end and distal end. The optical resonator may be transparent between the first reflective surface 40 and the second reflective surface 42. The distance between the first reflective surface 40 and the second reflective surface 42 defines a thickness "d" of the optical resonator. The thickness "d" may be in the range of 50 nm to 5,000 nm, for example, between 400 nm and 1,000 nm.

[0063] The second reflective surface 42 is formed by a layer of analyte binding molecules or materials that can effectively bind to analyte molecules specifically and with high affinity. That is, the analyte and anti-analyte molecules or materials are opposite members of a binding pair, which may include but is not limited to antigen-antibody pairs, complementary nucleic acids, and receptor binding agent pairs.

[0064] The refractive index of the optical resonator can be similar to the refractive index of the biological layer between the distal surface and the second reflective surface 42, so that light reflected from the second reflective surface 42 is mainly emitted from the interface between the biological layer and the fluid in which it is immersed, rather than from the interface between the optical fiber 27 and the analyte binding molecule (e.g., the first reflective surface 40). Similarly, when the analyte molecule binds to the distal portion of the optical component 26, the light reflected from the distal portion of the component mainly comes from the layer formed by the analyte binding molecule and the bound analyte, rather than from the interface region. By making the refractive index of the optical resonator similar to the refractive index of the biological layer, the signal-to-noise ratio can be improved.

[0065] First reflective surface 40 of optical component 26 may be formed as a layer of transparent material having a refractive index significantly different from that of optical fiber 27 such that the layer serves to reflect a portion of the light directed onto optical component 26 .

[0066] The thickness of the analyte binding layer provided in the distal portion of the optical element 26 can be designed to optimize overall sensitivity based on specific hardware and optical components. Conventional immobilization chemistry is used to chemically (e.g., covalently) attach the analyte binding molecule layer to the lower surface of the optical element. For example, a variety of bifunctional reagents can be used, which contain siloxane groups for chemical attachment to SiO2, and hydroxyl, amine, carboxyl or other reactive groups for attaching biomolecules (such as proteins (e.g., antigens, antibodies) or nucleic acids). It is well known that glass or glass surfaces can be etched or otherwise treated to increase the density of hydroxyl groups through which analyte binding molecules can bind. When the optical resonator at the distal end of the optical fiber 27 is formed by a polymer (such as, polystyrene), a variety of methods can be used to expose available chemically active surface groups, such as amine, hydroxyl and carboxyl groups.

[0067] The analyte binding layer is preferably formed under conditions in which the distal surface of the optical fiber 27 is densely coated so that binding of analyte molecules to the layer forces the thickness of the layer to change rather than filling the layer. The analyte binding layer may be a single layer or a multilayer matrix.

[0068] The presence, concentration and / or binding rate of an analyte on an optical component can be measured by interference of light beams reflected from two reflective surfaces in the optical component. Specifically, as analyte molecules come into contact with or separate from the surface, the average thickness of the biological layer changes accordingly. Since the thickness of all other layers remains constant, the interference waves formed by the light waves reflected from the two surfaces are phase-shifted according to this thickness change.

[0069] Assume that there are two reflected beams: a first beam reflected from the first reflective surface 40 and a second beam reflected from the analyte binding molecules and bound analyte and the surrounding medium at the second reflective surface 42. The conversion of phase shift to thickness change of bound analyte is well known in the art, as discussed at least in U.S. Pat. No. 8,305,585, and will not be discussed further for the sake of brevity.

[0070] refer to Figure 6, when the fiber bundle 31 is fixed relative to the optical fiber 27 as described above, a gap "g" is formed between the fiber bundle 31 and the proximal end of the optical fiber 27. The size of the gap "g" can reduce optical crosstalk between the light source 22 and the detector 28. For example, light transmitted from the first optical waveguide 32 can be reflected from the proximal end of the optical fiber 27 and enter the second optical waveguide 34, which transmits the reflected light to the detector 28. The reflected light can only be reflected when the angle of light from the first optical waveguide 32 hits the optical fiber 27 at an angle greater than the maximum acceptance angle of the optical fiber 27. It may be beneficial to reduce the amount of reflected light at the gap "g" to reduce background noise at the detector 28. The gap "g" can be in the range of 25µm to 600µm, for example, 50µm, 100µm, 200µm, 300µm, 400µm or 500µm. The gap "g" can be adjusted according to the materials used for the first optical waveguide 32, the second optical waveguide 34 and / or the optical fiber 27. Arranging the optical fibers of the first optical waveguide 32 around the optical fibers of the second optical waveguide 34 can reduce or minimize reflected light from the proximal end of the biosensor, thereby improving the signal-to-noise ratio (SNR) of the device 20 compared to other arrangements of the optical fibers of the first optical waveguide 32 and the second optical waveguide 34.

[0071] Reference now Figure 7-Figure 9 , a beam profile 132 of the first optical waveguide 32 and a beam profile 127 of the optical fiber 27 at its second reflective surface 40 are shown. It is noted that the optical fiber 27 has a circular profile. As shown, the beam profile 132 from the first optical waveguide 32 is provided as a ring of light having a circular profile, which is provided by each optical fiber of the first optical waveguide 32 to substantially form a ring of light around the second optical waveguide 34 (not shown, but located within the light void within the beam profile 132). When light from the first optical waveguide 32 is received and transmitted from the proximal portion 21 to the distal portion through the optical fiber 27, the beam profile 132 is substantially the same as the beam profile shown in the beam profile 127, so that the illumination profile is substantially unchanged. That is, while the light tends to fill the space between the optical fibers to form a ring of light in the beam profile 127, the light from the beam is rarely scattered to fill the area of ​​the optical fiber 27 outside the ring. Specifically, as shown in the beam profile 127, the center and the periphery of the optical fiber 27 have low light intensity. Areas of low light intensity may result in a low signal-to-noise ratio and / or allow for additive noise when light is reflected back to detector 28 .

[0072] Reference now Fig.10According to one embodiment of the present disclosure, a BLI sensor 226 having a faceted optical fiber 227 is provided. BLI sensor 226 is similar to BLI sensor 26, but uses a faceted optical fiber 227 instead of a round optical fiber 27. Faceted optical fiber 227 has a substantially constant cross-section along the length of optical fiber 227 (e.g., from its proximal portion to its distal portion). The cross-section of faceted optical fiber 227 can have a variety of shapes, including but not limited to a triangular ( Fig.15 ),square( Fig.16 ), pentagon ( Fig.17 ),hexagon( Fig.10 ), Octagon ( Fig.18 ) or a decagon ( Fig.19 ). The cost of faceted optical fibers is substantially similar to that of round optical fibers, so that such modifications can be made at little or no additional cost. As used herein, the term "faceted optical fiber" refers to an optical fiber having a polygonal cross-section. It is understood that a round optical fiber has a circular cross-section and, therefore, does not have a polygonal cross-section.

[0073] Additional references Fig.11 and Fig.12 According to an embodiment of the present disclosure, it is shown that when the optical fiber bundle 31 ( Figure 2 ) after receiving light at the first optical waveguide 32 of the faceted optical fiber 227. As shown, the beam profile 342 at the second reflective surface 242 of the faceted optical fiber 227 is uniformly distributed. Compared to a circular or ring-shaped optical fiber 27, the facets of the faceted optical fiber 227 can disturb the light within the faceted optical fiber 227 to more evenly distribute the light. Such uniform light distribution at the second reflective surface 242 can increase the signal-to-noise ratio (SNR) of the BLI sensor 226 having the faceted optical fiber 227 compared to a BLI sensor having a circular or non-faceted optical fiber. The increased SNR can increase the sensitivity of the BLI sensor 226 having the faceted optical fiber 227 compared to a BLI sensor having a circular or non-faceted optical fiber.

[0074] Reference now Fig.13 and Fig.14 , according to an embodiment of the present disclosure, a beam profile 442 at a second reflective surface of a faceted optical fiber having a square cross-section is shown. As shown, the beam profile 442 shows a uniform light distribution at its second reflective surface similar to the beam profile 342 of the faceted optical fiber 227. Such a uniform light distribution at the second reflective surface of the square cross-section faceted optical fiber can increase the signal-to-noise ratio (SNR) of the BLI sensor compared to a BLI sensor 20 having a round or non-faceted optical fiber 27. The increased SNR can increase the sensitivity of the BLI sensor having the faceted optical fiber compared to a BLI sensor having a round or non-faceted optical fiber.

[0075] refer to Figure 15-19 , shows a BLI sensor with a faceted optical fiber according to an embodiment of the present disclosure. Specifically, Fig.15 A BLI sensor 710 is shown including a faceted optical fiber 712 having a triangular cross-section, Fig.16 A BLI sensor 720 is shown having a faceted optical fiber 722 with a square cross-section, Fig.17 A BLI sensor 730 is shown having a faceted optical fiber 732 with a pentagonal cross section, Fig.18 A BLI sensor 740 is shown having a faceted optical fiber 742 with an octagonal cross section, and Fig.19 A BLI sensor 750 is shown having a faceted optical fiber 752 with a decagonal cross-section.

[0076] Reference now Fig. 20 and Fig.21 , another BLI sensor 810 is provided according to the present disclosure. BLI sensor 810 is similar to BLI sensor 26, but replaces circular optical fiber 27 with an internally faceted optical fiber 827. Internally faceted optical fiber 827 has a substantially constant cross-section along the length of optical fiber 827 (e.g., from its proximal portion to its distal portion). Optical fiber 827 has a circular or cylindrical outer surface and an internally faceted cross-section. With particular reference to Fig.21 , the optical fiber 827 has an internal faceted core 842 and a cladding 832 that forms an outer surface 834 having a circular cross-section. In some embodiments, the outer surface 834 has an elliptical cross-section. As shown, the internal faceted core 842 has a hexagonal cross-section; however, in some embodiments, the internal faceted core 842 can have a triangular, square, pentagonal, octagonal, decagonal or other faceted cross-section. The cladding 832 is disposed around the internal faceted core 842 and fixed to the internal faceted core 842. For example, the cladding 832 can be bonded or adhered to the core 842. In some embodiments, the cladding 832 is a unitary structure whose channel is sized and dimensioned to receive the core 842 in the channel. In certain embodiments, the cladding 832 and the core 842 are formed by a single or double extrusion process, in which the cladding 832 is extruded onto the core 842.

[0077] The optical fiber 827 functions in a similar manner to the faceted optical fibers (e.g., optical fibers 227, 712, 722, 732, 742). For example, the optical fiber 827 receives a light beam in the form of a light ring from the first optical waveguide and perturbs the light beam within the faceted core 842 so that at the end of the optical fiber 827, the core 842 has a uniform light distribution at the end 840 of the optical fiber 827. In some embodiments, the core 842 has a uniform light distribution and there is no or almost no light distribution in the cladding 832 at the end 840 of the optical fiber 827.

[0078] Reference now Fig. 22 According to the present disclosure, an end of another internal faceted optical fiber 847 of a BLI sensor is provided. The internal faceted optical fiber 847 can be used instead of the optical fiber of the BLI sensor described in detail herein. The internal faceted optical fiber 847 has a substantially constant cross-section along the length of the optical fiber 847 (e.g., from its proximal end portion to the distal end portion). The optical fiber 847 has a circular or cylindrical outer surface and an internal faceted cross-section. The optical fiber 847 has an internal faceted core 862, a first cladding 864, and a second cladding 852. The internal faceted core 862 can have a hexagonal cross-section as shown, or can have a triangular, square, pentagonal, octagonal, decagonal or other faceted cross-section. The first cladding 864 is disposed around the internal faceted core 862. The first cladding 864 can be a thin coating that is combined with the material of the internal faceted core 862 to provide a desired numerical aperture (NA). The first cladding 864 can be formed of a glass material, a quartz material, or other similar materials. The second cladding 852 forms the shape of the outer surface 854 of the optical fiber 847. The shape of the outer surface 854 can have a circular or elliptical cross-section. The second cladding 852 is disposed around the first cladding 864 and fixed to the first cladding 864. For example, the second cladding 852 can be bonded or adhered to the first cladding 864. In some embodiments, the second cladding 852 is a unitary structure whose channel is sized and dimensioned to receive the internal faceted core 862 and the first cladding 864 in the channel. The second cladding 852 can be formed of the same or different material as the first cladding 864. The second cladding 852 can provide additional support and / or protection for the first cladding 864. The second cladding 852 can be coated with a protective coating 856 that forms the outer surface 854 of the optical fiber 847. In some embodiments, the thickness of the protective coating is in the range of 5-10 μm. In some embodiments, the protective coating 856 is formed of polyamide, polytetrafluoroethylene (PTFE), or a similar material. In some embodiments, the optical fiber 847 does not have the second cladding 852 and / or the protective coating 856.

[0079] The overall diameter of the optical fiber 847 can be in the range of 720-730 µm. In some embodiments, the diameter of the optical fiber 847 can be less than 720 µm or greater than 730 µm. For example, the diameter of the optical fiber 847 can be in the range of 1000 µm to 1200 µm, such as 1190 µm. The overall diameter of the optical fiber 847 can be sized to be assembled with the hub to form a BLI sensor. The size of the internal faceted core 862 can be maximized relative to the overall diameter of the optical fiber 847. In some embodiments, the internal faceted core 862, the first cladding 864, and the second cladding 852 are formed by a single, double, or triple extrusion process, wherein the first cladding 864 is extruded on the core 862 and the second cladding 852 is extruded on the first cladding 864.

[0080] Reference now Fig.23 According to the present disclosure, an end of another internal faceted optical fiber 877 of a BLI sensor is provided. The internal faceted optical fiber 877 can be used to replace the optical fiber of the BLI sensor described in detail herein. The internal faceted optical fiber 877 has a substantially constant cross-section along the length of the optical fiber 877 (e.g., from its proximal end portion to the distal end portion). The optical fiber 877 has an oval outer surface and an internal faceted cross-section. The optical fiber 877 has an internal faceted core 892, a first cladding 894, and a second cladding 882. The internal faceted core 892 has an octagonal cross-section. The first cladding 894 is disposed around the internal faceted core 892. The first cladding 894 can be a thin coating that combines with the material of the internal faceted core 892 to provide a desired numerical aperture (NA). The first cladding 894 can be formed of a glass material, a quartz material, or other similar material. The second cladding 882 forms the shape of an outer surface 884 of the optical fiber 877. The shape of the outer surface 884 can have a circular or elliptical cross-section. The second cladding 882 is disposed around the first cladding 894 and fixed to the first cladding 894. For example, the second cladding 882 can be bonded or adhered to the first cladding 894. In some embodiments, the second cladding 882 is a unitary structure whose channel is sized and dimensioned to receive the internal faceted core 892 and the first cladding 894 in the channel. The second cladding 882 can be formed of the same or different material as the first cladding 894. The second cladding 882 can provide additional support and / or protection for the first cladding 894. The second cladding 882 can be coated with a protective coating 886, which forms the outer surface 884 of the optical fiber 877. In some embodiments, the thickness of the protective coating is in the range of 5-10μm. In some embodiments, the protective coating 886 is formed of polyamide, polytetrafluoroethylene (PTFE), or a similar material. In some embodiments, the optical fiber 877 does not have a second cladding 882 and / or a protective coating 886.

[0081] The overall diameter of the optical fiber 877 can be in the range of 720-730µm. In some embodiments, the diameter of the optical fiber 877 can be less than 720µm or greater than 730µm. For example, the diameter of the optical fiber 877 can be in the range of 1000µm to 1200µm, such as 1190µm. The overall diameter of the optical fiber 877 can be sized to be assembled with the hub to form a BLI sensor. The size of the internal faceted core 892 can be maximized relative to the overall diameter of the optical fiber 847. In some embodiments, the internal faceted core 862, the first cladding 894, and the second cladding 882 are formed by a single, double, or triple extrusion process, wherein the first cladding 894 is extruded on the core 892 and the second cladding 882 is extruded on the first cladding 894.

[0082] Although several embodiments of the present disclosure are shown in the accompanying drawings, the present disclosure is not intended to be limited thereto, as it is intended that the scope of the present disclosure should be as broad as the technology allows, and the specification should be understood as such. Any combination of the above embodiments is also contemplated and is within the scope of the appended claims. Therefore, the above description should not be interpreted as limiting, but only as an example of a specific embodiment. Those skilled in the art will envision other modifications within the scope of the appended claims.

Claims

1. A biosensor comprising: An optical fiber having a proximal portion and a distal portion, the proximal portion being configured to receive light from a light source and being configured to transmit reflected light to a detector, the optical fiber having a polygonal cross-section, the distal portion being configured to allow an analyte to bind to the distal portion such that light reflected from the distal portion is phase shifted based on the thickness of the analyte bound to the distal portion.

2. The biosensor according to claim 1, wherein The optical fiber has a triangular, square, pentagonal, hexagonal, octagonal or decagonal cross section.

3. The biosensor according to claim 1, wherein The optical fiber is configured to scatter light so that light is evenly distributed in the distal portion of the optical fiber.

4. The biosensor according to claim 1, wherein The optical fiber is configured to receive a light beam proximal to the end portion and to uniformly distribute light from the received light beam at the distal end portion of the optical fiber.

5. The biosensor according to claim 1, further comprising an optical resonator located at the distal portion of the optical fiber, the optical resonator comprising a first reflective surface and a second reflective surface, the first reflective surface being configured to reflect light having a first phase, and the second reflective surface being configured to reflect light having a second phase, the second phase being phase-shifted based on a thickness of an analyte bound to the optical resonator.

6. An interferometer device comprising: a first optical waveguide configured to receive light from a light source; a second optical waveguide configured to transmit the reflected light to a detector; an optical coupler that spatially separates a distal portion of the first optical waveguide from a distal portion of the second optical waveguide; as well as A biosensor is attached to the optical coupler, the biosensor comprising the optical fiber according to claim 1.

7. A biosensor comprising: An optical fiber having a proximal portion configured to receive light from a light source and configured to transmit reflected light to a detector, and a distal portion configured to allow an analyte to bind to the distal portion such that light reflected from the distal portion is phase shifted based on a thickness of the analyte bound to the distal portion, the optical fiber having a faceted core disposed within a first cladding, the faceted core having a core cross section.

8. The biosensor according to claim 7, wherein The first cladding defines an outer cross-section of the optical fiber.

9. The biosensor according to claim 8, wherein The outer cross-section is circular or oval.

10. The biosensor according to claim 7, wherein The core cross section is triangular, square, pentagonal, hexagonal, octagonal or decagonal.

11. The biosensor according to claim 7, wherein: The optical fiber includes a second cladding disposed around the first cladding, the second cladding defining an outer cross-section having a shape different from a shape of the core cross-section.

12. The biosensor according to claim 11, wherein The outer cross-section is circular or oval.

13. The biosensor according to claim 11, wherein: The optical fiber includes a coating on the second cladding, the coating defining an outer surface of the optical fiber.

14. The biosensor according to claim 13, wherein: The first cladding is formed of glass or quartz, the second cladding is formed of glass or quartz, and the coating is formed of polyamide or polytetrafluoroethylene.

15. The biosensor according to claim 11, wherein The first cladding layer and the second cladding layer are formed of the same material.

16. The biosensor according to claim 7, wherein: The faceted core and the first cladding combine with each other to provide a desired numerical aperture of the optical fiber.

17. An interferometer device comprising: a first optical waveguide configured to receive light from a light source; a second optical waveguide configured to transmit the reflected light to a detector; an optical coupler that spatially separates a distal portion of the first optical waveguide from a distal portion of the second optical waveguide; as well as A biosensor is attached to the optical coupler, the biosensor comprising the optical fiber according to claim 7.

18. A biosensor comprising: A faceted optical fiber has a proximal portion and a distal portion, the proximal portion being configured to receive light from a light source, the faceted optical fiber being configured to scatter the received light so that the light distribution at the distal portion of the faceted optical fiber is uniform.

19. The biosensor according to claim 18, wherein: The faceted optical fiber has an increased signal-to-noise ratio relative to a non-faceted optical fiber.

20. The biosensor according to claim 18, wherein The faceted optical fiber includes a faceted core disposed within a cladding defining an outer surface having a circular or oval cross-section.

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