Waveguide structure with aperture array

Abstract

The waveguide structure (100) includes one or more fluid channels (118) intersected by waveguides (114). The aperture layer (470) of the waveguide structure includes an aperture array (472) adjacent to one or more fluid channels, which allows emission signals from analytes in the fluid channels to be detected through the aperture layer. The aperture layer can be etched using a first etching step, while voids in the substrate of the waveguide structure can be etched using a second etching step, the first etching step being more precise than the second etching step. The aperture array can have one or more one-dimensional aperture signature patterns associated with specific fluid channels of the device, such that signals can be demultiplexed and correlated to one of the multiple channels using the signature patterns.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application No. 63 / 013,168, filed April 21, 2020, the entire contents of which are incorporated herein by reference.

[0002] The present disclosure relates generally to waveguides and their fabrication, and more particularly to waveguide structures such as optofluidic chips having fluid core channels and / or aperture arrays disposed adjacent to the fluid core waveguide. [Background technology]

[0003] Waveguide structures, such as optical and optofluidic chips, are of great importance in modern biomedical research. These waveguide structures may comprise solid-core waveguides, fluidic channels, and / or fluidic-core waveguides, which may be coplanar with one another and may intersect one another in various configurations.

[0004] Known techniques for collecting signals from waveguide structures include in-plane signal collection using one or more photodetectors positioned coplanar with the analyte-containing waveguide (e.g., coplanar with the fluid core waveguide), for example, by using one or more in-plane waveguides to direct light to one or more photodetectors. Known techniques for collecting signals from waveguide structures also include out-of-plane signal collection using one or more photodetectors positioned above or below the plane of the analyte-containing waveguide. Summary of the Invention

[0005] As discussed above, known techniques for collecting signals from waveguide structures include using one or more in-plane or out-of-plane waveguides. However, known techniques for collecting signals do not provide sufficient capability for precise control of out-of-plane signal detection in complex applications, such as demultiplexing signals generated from multiple different fluid channels and / or multiple different excitation spot patterns. Therefore, there is a need for improved systems and methods for collecting signals from waveguide structures.

[0006] Disclosed herein are improved waveguide structures, methods for fabricating the improved waveguide structures, and methods for using the improved waveguide structures. The improved waveguide structures disclosed herein may include one or more hollow-core analyte channels, such as multiple hollow-core analyte channels running parallel to one another, whereby each of the one or more hollow-core analyte channels may be filled with a liquid containing a respective analyte. When excited by an excitation light source, the analytes in the one or more hollow-core analyte channels may emit output optical signals, such as by fluorescence, which may be collected by one or more photodetectors. As described herein, out-of-plane collection of the output optical signals may be facilitated by using an aperture layer of the waveguide structure, the aperture layer comprising an aperture array (e.g., a one-dimensional or two-dimensional array) disposed beneath the one or more hollow-core analyte channels, thereby allowing output / emitted light to exit the one or more hollow-core analyte channels and pass through the aperture layer in a spatial pattern defined by the aperture array.

[0007] In some embodiments, an aperture array may be used to define one or more patterns for directing emitted light to one or more spatially distributed optical elements and / or photodetectors. In some embodiments, a two-dimensional aperture array may be used to enable demultiplexing of signals collected from different hollow-core analyte channels. For example, a system may be configured such that different hollow-core analyte channels contain different types of analyte, and the system may be configured to automatically identify an output signal as being attributable to a particular one of the hollow-core analyte channels with a known pattern of apertures in an aperture layer disposed below the channel based on the spatial, spectral, and / or temporal pattern of the output signal. For example, in an embodiment in which an analyte flows through an analyte channel and passes through multiple apertures disposed below the analyte channel, the detected output optical signal passing through the multiple apertures may form a series of temporally distributed intensity spikes. In some embodiments, the system may be configured to automatically recognize and count the number of detected spikes and identify which of the multiple analyte channels the output optical signal is attributable to by matching the number of counted spikes with the number of apertures disposed below the analyte channel.

[0008] In some embodiments, the waveguide structure may include multiple aperture layers. For example, an aperture layer disposed above the waveguide layer may comprise an aperture array configured to partially block and partially transmit excitation light incident on the waveguide structure. Thus, instead of or in addition to using an aperture layer to form a two-dimensional pattern of emitted light from the multiple fluidic channels, the aperture layer may also be used to form a pattern of excitation light incident on the multiple fluidic channels.

[0009] In some embodiments, a first waveguide structure is provided, the first structure comprising: a waveguide layer including one or more fluid channels; at least one waveguide intersecting a plurality of the fluid channels; a first aperture layer including a first array of apertures, each of the one or more fluid channels adjacent to at least one of the apertures in the first array of apertures; and a cover layer attached to the waveguide layer to close the one or more fluid channels.

[0010] In some embodiments of the first waveguide structure, the aperture array has one or more respective one-dimensional aperture patterns, each of the one or more one-dimensional aperture patterns positioned adjacent to a respective one or more fluid channels.

[0011] In some embodiments of the first waveguide structure, each of the plurality of respective one-dimensional aperture patterns has a different number of apertures.

[0012] In some embodiments of the first waveguide structure, each of the plurality of respective one-dimensional aperture patterns has a different aperture spacing.

[0013] In some embodiments of the first waveguide structure, each of the plurality of respective one-dimensional aperture patterns has a different aperture size.

[0014] In some embodiments of the first waveguide structure, the first aperture layer comprises chromium, nickel, another metal, and / or one or more ARROW layers.

[0015] In some embodiments of the first waveguide structure, the first aperture layer is micro-fabricated using one or more of sputtering, e-beam evaporation, spin coating, and coating.

[0016] In some embodiments of the first waveguide structure, the at least one waveguide that intersects the one or more fluid channels includes one or more of a solid core waveguide, an MMI waveguide, and a tunable fluid core MMI waveguide.

[0017] In some embodiments of the first waveguide structure, at least one waveguide that intersects the one or more fluid channels includes a solid core waveguide formed in the waveguide layer, the solid core waveguide being formed by one or more of: (i) etching a plurality of voids in the waveguide layer to define the solid core waveguide therebetween; and (ii) doping the waveguide layer to define the solid core waveguide with one or more doped regions in the waveguide layer.

[0018] In some embodiments, the first waveguide structure comprises a substrate layer coupled to the waveguide layer and a substrate void formed in the substrate layer adjacent to one or more of the one or more fluid channels, such that light leaking from the one or more fluid channels adjacent the void through one or more of the apertures in the first aperture array propagates into the substrate void.

[0019] In some embodiments of the first waveguide structure, the substrate cavity has a larger diameter than one or more of the apertures in the first aperture layer.

[0020] In some embodiments, the first waveguide structure comprises a second aperture layer disposed on a side of the waveguide layer opposite the first aperture layer, the second aperture layer including a second aperture array, and each of the one or more fluid channels adjacent to at least one of the apertures in the second aperture array.

[0021] In some embodiments of the first waveguide structure, the second aperture layer is disposed on or in the cover layer.

[0022] In some embodiments of the first waveguide structure, the aperture array is a two-dimensional aperture array forming a plurality of one-dimensional aperture patterns, and the one or more fluid channels include a plurality of fluid channels, each of the plurality of fluid channels adjacent to at least one of the apertures of the two-dimensional aperture array.

[0023] In some embodiments, a first method for fabricating a waveguide structure is provided, the first method including etching an aperture array in an aperture layer of the waveguide structure, the aperture array having one or more respective one-dimensional aperture patterns, each of the one or more one-dimensional aperture patterns configured to allow light to be emitted from a respective fluid channel of a set of one or more fluid channels of the waveguide structure.

[0024] In some embodiments, the first method includes etching one or more fluid channels in a waveguide layer of a waveguide structure and attaching a cover layer to the waveguide layer to close the one or more fluid channels.

[0025] In some embodiments, the first method includes etching a substrate layer of the waveguide structure to create a substrate cavity, such that light leaking from one or more fluid channels through one or more of the apertures in the first aperture layer propagates into the substrate cavity.

[0026] In some embodiments of the first method, etching into the substrate layer comprises a wet etching process step.

[0027] In some embodiments of the first method, etching into the aperture layer includes a first etching step having a first spatial accuracy, and etching into the substrate layer includes a second etching step having a second spatial accuracy, the first spatial accuracy being finer than the second spatial accuracy.

[0028] In some embodiments of the first method, etching into the aperture layer is performed before etching into the substrate layer.

[0029] In some embodiments of the first method, the substrate cavity has a larger diameter than one or more of the apertures in the first aperture layer.

[0030] In some embodiments, the first method includes etching a first waveguide void and a second waveguide void in a waveguide layer, wherein etching the first void and the second void creates a solid core waveguide in the waveguide layer between the first void and the second void, the solid core waveguide intersecting the one or more fluid channels.

[0031] In some embodiments of the first method, etching into the aperture layer includes performing a metal etching step.

[0032] In some embodiments, a second method for fabricating a waveguide structure is provided, the second method including etching one or more fluid channels in a waveguide layer of the waveguide structure, each of the one or more fluid channels being aligned with one or more apertures disposed in an aperture layer of the waveguide structure, and attaching a cover layer to the waveguide layer to close the one or more fluid channels.

[0033] In some embodiments, a system for analyte detection is provided, the system comprising: an aperture layer including a plurality of apertures forming a first analyte channel, a second analyte channel, a first pattern of apertures aligned with the first analyte channel, and a second pattern of apertures aligned with the second analyte channel; a detector configured to detect light emitted through the apertures of the first pattern and light emitted through the apertures of the second pattern; and one or more processors configured to receive a signal from the detector representing the light emitted through one of the apertures of the first pattern and the apertures of the second pattern; and determine, based on the received signal, whether the signal corresponds to the first channel or the second channel.

[0034] In some embodiments of the system, determining whether the signal corresponds to the first channel or the second channel is based on determining whether the number of bursts in the signal corresponds to the number of apertures in the first pattern or the number of apertures in the second pattern.

[0035] In some embodiments of the system, determining whether the signal corresponds to the first channel or the second channel is based on determining whether the duration of the light burst represented by the signal corresponds to the diameter of the apertures of the first pattern or the diameter of the apertures of the second pattern.

[0036] In some embodiments of the system, determining whether the signal corresponds to a first channel or a second channel is based on determining whether the time spacing of two or more bursts represented in the signal corresponds to the physical spacing of two or more apertures in the first pattern or the physical spacing of two or more apertures in the second pattern.

[0037] In some embodiments of the system, determining whether the signal corresponds to the first channel or the second channel is based on determining whether the wavelengths of one or more bursts represented in the signal correspond to spectral characteristics of one or more apertures of the first pattern or to spectral characteristics of one or more apertures of the second pattern.

[0038] In some embodiments, a second waveguide structure is provided, the structure comprising: a waveguide layer including a plurality of fluid channels; at least one waveguide intersecting the plurality of fluid channels; a first aperture layer including a first two-dimensional aperture array, each of the plurality of fluid channels adjacent to at least one of the apertures of the first two-dimensional aperture array; and a cover layer attached to the waveguide layer to close the plurality of fluid channels.

[0039] In some embodiments of the second waveguide structure, the two-dimensional aperture array has a plurality of respective one-dimensional aperture patterns, each of the plurality of one-dimensional aperture patterns being positioned adjacent to a respective one of the fluid channels.

[0040] In some embodiments of the second waveguide structure, each of the plurality of respective one-dimensional aperture patterns has a different number of apertures.

[0041] In some embodiments of the second waveguide structure, each of the plurality of respective one-dimensional aperture patterns has a different aperture spacing.

[0042] In some embodiments of the second waveguide structure, each of the plurality of respective one-dimensional aperture patterns has a different aperture size.

[0043] In some embodiments of the second waveguide structure, the first aperture layer comprises chromium, nickel, another metal, and / or one or more ARROW layers.

[0044] In some embodiments of the second waveguide structure, the first aperture layer is micro-fabricated using one or more of sputtering, e-beam evaporation, spin coating, and coating.

[0045] In some embodiments of the second waveguide structure, the at least one waveguide intersecting the plurality of fluid channels includes one or more of a solid core waveguide, an MMI waveguide, and a tunable fluid core MMI waveguide.

[0046] In some embodiments of the second waveguide structure, at least one waveguide that intersects the plurality of fluid channels includes a solid core waveguide formed in the waveguide layer, the solid core waveguide being formed by one or more of: (i) etching a plurality of voids in the waveguide layer to define the solid core waveguide therebetween; and (ii) doping the waveguide layer to define the solid core waveguide with one or more doped regions in the waveguide layer.

[0047] In some embodiments of the second waveguide structure, the structure comprises a substrate layer coupled to the waveguide layer and a substrate void formed in the substrate layer adjacent to one or more of the fluid channels, such that light leaking from one or more of the fluid channels through one or more of the apertures of the first two-dimensional aperture array propagates into the substrate void.

[0048] In some embodiments of the second waveguide structure, the substrate cavity has a larger diameter than one or more of the apertures in the first aperture layer.

[0049] In some embodiments of the second waveguide structure, the structure comprises a second aperture layer disposed on a side of the waveguide layer opposite the first aperture layer, the second aperture layer including a second two-dimensional aperture array, and each of the plurality of fluid channels adjacent to at least one of the apertures in the second two-dimensional aperture array.

[0050] In some embodiments of the second waveguide structure, the second aperture layer is disposed on or in the cover layer.

[0051] In some embodiments, a third method for fabricating a waveguide structure is provided, the first method including etching a two-dimensional aperture array in an aperture layer of the waveguide structure, the two-dimensional aperture array having a plurality of respective one-dimensional aperture patterns, each of the plurality of one-dimensional aperture patterns configured to allow light to be emitted from a respective fluid channel of the waveguide structure.

[0052] In some embodiments of the third method, the first method includes etching a plurality of fluid channels in a waveguide layer of a waveguide structure and attaching a cover layer to the waveguide layer to close the plurality of fluid channels.

[0053] In some embodiments of the third method, the first method includes etching a substrate layer of the waveguide structure to create a substrate cavity, such that light leaking from one or more fluid channels through one or more of the openings in the first opening layer propagates into the substrate cavity.

[0054] In some embodiments of the third method, etching into the substrate layer comprises a wet etching process step.

[0055] In some embodiments of the third method, etching into the aperture layer includes a first etching step having a first spatial accuracy, and etching into the substrate layer includes a second etching step having a second spatial accuracy, the first spatial accuracy being finer than the second spatial accuracy.

[0056] In some embodiments of the third method, etching into the aperture layer is performed before etching into the substrate layer.

[0057] In some embodiments of the third method, the substrate cavity has a larger diameter than one or more of the apertures in the first aperture layer.

[0058] In some embodiments of the third method, the first method includes etching a first waveguide void and a second waveguide void in a waveguide layer, wherein etching the first void and the second void creates a solid core waveguide in the waveguide layer between the first void and the second void, and the solid core waveguide intersects the plurality of fluid channels.

[0059] In some embodiments of the third method, etching into the aperture layer includes performing a metal etching step.

[0060] In some embodiments, a fourth method for fabricating a waveguide structure is provided, the second method including etching a plurality of fluid channels in a waveguide layer of the waveguide structure, each of the plurality of fluid channels being aligned with one or more openings disposed in an opening layer of the waveguide structure, and attaching a cover layer to the waveguide layer to close the plurality of fluid channels.

[0061] In some embodiments, any one or more of the features or aspects of any one or more of the embodiments described above may be combined with each other and / or with other features or aspects of any method, system, technique, or device disclosed herein. [Brief explanation of the drawings]

[0062] [Figure 1] 1A and 1B show two schematic diagrams of a waveguide structure according to some embodiments. [Figure 2] 1A and 1B show two schematic diagrams of a waveguide structure having an air gap formed in a substrate layer, according to some embodiments. [Figure 3] 1A and 1B show two schematic diagrams of a waveguide structure with an air gap formed in a substrate layer and a focusing lens, according to some embodiments. [Figure 4] 1A and 1B show two schematic diagrams of a waveguide structure with an aperture layer, a focusing lens, and an air gap formed in a substrate layer, according to some embodiments. [Figure 5A] 1 shows a schematic diagram of a waveguide structure with a plurality of fluid channels arranged alongside each other and with an aperture layer containing a two-dimensional aperture array. [Figure 5B] 1 shows a schematic diagram of a waveguide structure with a plurality of fluid channels arranged alongside each other and with an aperture layer containing a two-dimensional aperture array. [Figure 5C] 5B shows three example time-varying light intensity signals resulting from light emitted from the three fluidic channels shown in FIG. 5A. [Figure 6]1 illustrates a system for analyte detection, according to some embodiments. [Figure 7] 1 illustrates a computer according to some embodiments. [Figure 8] 1 illustrates a method for fabricating a waveguide structure according to some embodiments. [Figure 9] 1 illustrates a method for fabricating a waveguide structure according to some embodiments. [Figure 10] 1 illustrates a method for analyzing a signal representative of light emitted through an aperture layer of a waveguide structure, according to some embodiments. DETAILED DESCRIPTION OF THE INVENTION

[0063] Disclosed herein are waveguide structures and fabrication techniques thereof. In some embodiments, as described herein, a waveguide structure may include one or more fluidic channels (e.g., multiple fluidic channels running parallel to one another) in a waveguide layer of the structure. One or more aperture layers may be disposed above and / or below the waveguide layer, and the one or more aperture layers may be configured to partially block and / or transmit light through a plurality of apertures disposed in each aperture layer, the plurality of apertures being arranged in an array adjacent to one or more of the multiple fluidic channels. The aperture array(s) may partially block and partially transmit light entering and / or exiting a fluidic channel, thereby forming predetermined zones within the fluidic channel through which excitation light may enter and / or emission light may escape. By forming predetermined excitation / emission zones, the signals emitted from various channels may be controlled by the aperture layer(s), which may be used to improve the signal-to-noise ratio and / or for spatial / temporal demultiplexing of various signals received from different fluidic channels.

[0064] Although the present disclosure illustrates and describes, by way of example, some embodiments in which multiple fluid channels (e.g., two or more fluid channels flowing parallel to one another) are used with one or more two-dimensional aperture arrays, those skilled in the art will understand in light of this disclosure that one or more of the systems, methods, and / or techniques described herein may be applicable in the same or similar manner to embodiments in which a single fluid channel and one or more one-dimensional aperture arrays are provided. In some embodiments, the one-dimensional aperture array may have a pattern of apertures adjacent to a single fluid channel within a waveguide structure, and the one-dimensional aperture array may improve the accuracy of excitation and / or signal collection, e.g., by improving the signal-to-noise ratio. In some embodiments, the one-dimensional aperture array may be used in a manner similar to the manner in which the two-dimensional aperture arrays described herein may be used, e.g., to collect light emitted through the aperture array and analyze the collected signals for one or more analyte detection, flow rate determination, channel / analyte / device identification, and / or demultiplexing. In some embodiments, the identification of aperture patterns, associated channels, associated devices, and / or associated analytes may be determined using a one-dimensional aperture array in the same or similar manner as described herein for determining which of multiple analyte channels is associated with each pattern in a two-dimensional aperture array.

[0065] In some embodiments, as described herein, one or more of the waveguide structures disclosed herein can be formed using a single lithography / etching process followed by a bonding process. This fabrication approach can replace the inconvenient and extensive series of steps required by conventional fabrication techniques. For example, a waveguide structure (e.g., a two-dimensional waveguide structure) can be formed from a chip including a substrate layer and a waveguide layer over the substrate layer. In some embodiments, the substrate layer can be formed from silicon or other suitable material, and the waveguide layer can be formed from one or more oxides, such as low-temperature oxide, phosphorus-doped oxide, silicon oxynitride, or other suitable material. The waveguide layer, in some embodiments, can have a thickness of 1 μm, 5 μm, 10 μm, or 20 μm or more. The waveguide layer, in some embodiments, can have a thickness of 1 μm, 5 μm, 10 μm, or 20 μm or less. The material(s) used for the waveguide layer may be selected so that the material effectively transmits light and may form both the solid core of the solid core waveguide and the walls of the fluid channels and / or the walls of the fluid core waveguide.

[0066] After the waveguide layer is disposed (e.g., placed or deposited) on the substrate layer, one or more etching steps may be performed to form one or more of a solid core waveguide and one or more fluid channels (which may also be fluid core waveguides in some embodiments). To form the fluid channels, the hollow cores of the channels may be etched from the waveguide layer.

[0067] In some embodiments, the dimensions of the fluid channel can be varied to affect the flow rate of the fluid through the fluid channel. In some embodiments, fluid flow through the fluid channel can be induced by one or more of vacuum, positive pressure, electroosmosis, and / or electrophoresis. In some embodiments, the geometry of the fluid channel can be configured to induce flow focusing via sheath flow. In some embodiments, the height and / or width of the fluid channel can be 0.25 μm, 0.5 μm, 1 μm, 5 μm, 10 μm, 25 μm, 50 μm, 100 μm, 250 μm, 500 μm, or 1000 μm or less. In some embodiments, the height and / or width of the fluid channel can be 0.25 μm, 0.5 μm, 1 μm, 5 μm, 10 μm, 25 μm, 50 μm, 100 μm, 250 μm, 500 μm, or 1000 μm or more. In some embodiments, the flow rate through the fluidic channels can be less than or equal to 0.005 μL / min, 0.01 μL / min, 0.1 μL / min, 1 μL / min, 10 μL / min, 100 μL / min, or 500 μL / min. In some embodiments, the flow rate through the fluidic channels can be greater than or equal to 0.005 μL / min, 0.01 μL / min, 0.1 μL / min, 1 μL / min, 10 μL / min, 100 μL / min, or 500 μL / min.

[0068] To form the solid core waveguide, air gaps may be etched from the waveguide layer on either side of the solid core waveguide, thereby forming the solid core waveguide from the remaining material of the waveguide layer left in the air gap. In some embodiments, the etching step may include a dry etch, such as reactive ion etching, deep reactive ion etching, and / or neutral discharge etching, and in some embodiments, the etching step may include a wet etch, such as etching with buffered hydrofluoric acid. In some embodiments, in addition to etching the air gaps to define regions on either side of the solid core waveguide, the etching process may also include etching regions at the ends of the solid core waveguide, thereby forming ends of the optical waveguide (e.g., optical facets) into which light may be coupled.

[0069] After etching the waveguide layer to form the solid core waveguide(s) and fluid channel(s), a cover layer may be applied on top of the waveguide layer to close the open tops of the fluid channels and / or close one or more of the voids. In some embodiments, the cover layer may comprise bonding glass, an ARROW layer, a totally reflective coated material (e.g., a low refractive index material such as TEFLON® AF), or a metal coated material. In some embodiments, the cover layer may have a thickness of 1 μm, 5 μm, 10 μm, 50 μm, 100 μm, 150 μm, or 200 μm, 300 μm, or 500 μm or less. In some embodiments, the cover layer may be 1 μm, 5 μm, or 10 μm, 50 μm, 100 μm, 150 μm, or 200 μm, 300 μm, or 500 μm or more. In some embodiments, the cover layer may be attached to the waveguide layer (or to another layer of the waveguide structure, as further described below) by permanent or non-permanent bonding, adhesive, or other suitable means.

[0070] After etching and attachment of the cover layer is complete, the fluid channel can be filled with a fluid (e.g., gas and / or liquid), e.g., the gas or liquid contains an analyte that is excited by excitation light, which propagates along the solid core waveguide and enters the fluid channel. In some embodiments, radiation from the analyte in the fluid channel can be collected out-of-plane (e.g., by a photodetector above or below) or in-plane (e.g., when the fluid channel is a fluid core waveguide, the fluid channel directs the radiation to an in-plane photodetector, or a solid core waveguide structure that does not use a fluid core waveguide captures the radiation).

[0071] In some embodiments, as described further below, the performance of a fluid channel as a fluid core waveguide (e.g., for in-plane detection of emitted light) can be improved by reducing the wall thickness, reducing the average refractive index of the cladding material, or etching away portions of the substrate layer below the channel.

[0072] 1A and 1B show two schematic views of a waveguide structure 100 according to some embodiments. Fig. 1A shows cross-sectional views of the waveguide structure 100 from two angles, divided into two perspectives by a dotted line indicating a 90° angle 102. Fig. 1B shows an overhead view of the waveguide structure 100.

[0073] 1A, the waveguide layer 104 may be formed from one or more oxide layers. In some embodiments, a low-index oxide layer 106 may be disposed on a substrate (e.g., silicon) layer 108, and a high-index oxide layer 110 may be disposed on the low-index oxide layer 106. The two oxide layers may together form the waveguide layer 104. As light 112 propagates through the high-index oxide layer 110, it may be internally reflected along the solid core waveguide 114 by air gaps 116 and / or the low-index oxide layer 106. In some embodiments, both the low-index oxide layer 106 and the substrate layer 108 may be replaced with a low-index substrate layer.

[0074] As shown in FIG. 1A , the etching step forming the voids 116 and fluid channels 118 can be performed by simultaneously etching into and / or through the high-index oxide layer 110 and the low-index oxide layer 106. That is, rather than etching the oxide layers separately and then aligning the voids / channels etched in the oxide layers, etching can be performed after the layers are already bonded together, thereby achieving automatic alignment. As shown in the example of FIG. 1 , the channels 118 and / or voids 116 can be formed in some embodiments by etching completely through the high-index oxide layer 110 from above and partially into the low-index oxide layer 106 from above. In some embodiments, the waveguide structure 100 can include a cover layer 120, which can be applied on top of the waveguide layer 104 to close the open top of the fluid channels 118 and / or close one or more voids 116.

[0075] In some embodiments of any of the waveguide structures disclosed herein, one or more of the waveguide layers may be disposed or deposited on top of another of the layers, hi some embodiments, one or more of the layers may be deposited by sputtering, spin-on, plasma-enhanced chemical vapor deposition (PECVD), low-pressure chemical vapor deposition (LPCVD), electron beam evaporation, and / or any other deposition method.

[0076] Because there is only one lithography step, it can be very straightforward to use this method to create more complex waveguide structures to expose individual dies (e.g., electron beam defined features) in this process. Furthermore, this workflow does not require mask alignment between fabrication steps.

[0077] In some embodiments of waveguide structure 100 and / or other waveguide structures discussed herein, the refractive index of the high refractive index oxide (e.g., layer 110) may be less than or equal to 1, 2, 3, or 4. In some embodiments of FIG. 1 and / or other waveguide structures discussed herein, the refractive index of the high refractive index oxide (e.g., layer 110) may be greater than or equal to 1, 2, 3, or 4.

[0078] In some embodiments of waveguide structure 100 and / or other waveguide structures discussed herein, the refractive index of the low refractive index oxide (e.g., layer 106) may be less than or equal to 1, 2, 3, or 4. In some embodiments of FIG. 1 and / or other waveguide structures discussed herein, the refractive index of the low refractive index oxide (e.g., layer 106) may be greater than or equal to 1, 2, 3, or 4.

[0079] In some embodiments of waveguide structure 100 and / or other waveguide structures, the refractive index of the doped oxide may be less than or equal to 1, 2, 3, or 4. In some embodiments of FIG. 1 and / or other waveguide structures discussed herein, the refractive index of the doped oxide may be greater than or equal to 1, 2, 3, or 4.

[0080] In some embodiments, the thickness of the oxide layer adjacent to the substrate layer (e.g., low refractive index oxide layer 106) can be 0.05 μm, 0.1 μm, 0.5 μm, 1 μm, 5 μm, 10 μm, or 50 μm or less. In some embodiments, the thickness of the oxide layer adjacent to the substrate layer (e.g., low refractive index oxide layer 106) can be 0.05 μm, 0.1 μm, 0.5 μm, 1 μm, 5 μm, 10 μm, or 50 μm or more. In some embodiments, a thicker oxide layer adjacent to the substrate layer (e.g., low refractive index oxide layer 106) can improve waveguide conductivity and / or reduce background photoluminescence from adjacent silicon / substrate materials.

[0081] In some embodiments, the thickness of the core oxide layer (e.g., high refractive index oxide layer 110) can be 0.5 μm, 1 μm, 2.5 μm, 5 μm, 7.5 μm, 10 μm, or 15 μm or less. In some embodiments, the thickness of the core oxide layer (e.g., high refractive index oxide layer 110) can be 0.5 μm, 1 μm, 2.5 μm, 5 μm, 7.5 μm, 10 μm, or 15 μm or more.

[0082] Additionally or alternatively, in some embodiments, a transparent or translucent material may be used for a substrate, such as substrate layer 108. In some embodiments, using a transparent or translucent substrate may serve as an alternative to etching the substrate layer, as it may be possible to detect optofluidic signals through the transparent or translucent substrate material without having to machine the wafer substrate, which may provide advantages in some embodiments such as increased stability and reduced cost.

[0083] 2A and 2B show two schematic views of a waveguide structure 200 having an air gap 236 formed in a substrate layer 208, according to some embodiments. Figure 2A shows cross-sectional views of the waveguide structure 200 from two angles, divided into two perspectives by a dotted line indicating a 90° angle 202. Figure 2B shows an overhead view of the waveguide structure 200.

[0084] The waveguide structure 200 shown in FIG. 2 may share any one or more features in common with the waveguide structure 100 shown in FIG. 1, and may differ from the structure 100 shown in FIG. 1 in that, in addition to the top-down etching performed to create the fluid channels 218 and solid core waveguides 214 in the waveguide layer 204, a bottom-up etching may also be performed to remove portions of the substrate layer 208 and expose the underside of the waveguide layer 204 to one or more voids 236 below the fluid channels 218 and / or solid core waveguides 214. By creating one or more voids 236 below the fluidic channels 218 and / or solid core waveguides 214, the need for an ARROW layer or low refractive index oxide layer may be eliminated, as the voids 236 cut out of the substrate layer 208 may themselves prevent light 212 within the solid core waveguides 214 and / or fluidic channels 218 (which may function as fluidic core waveguides) from leaking downwardly out of the waveguides 214 / channels 218.

[0085] In some embodiments, etching into the substrate layer 208, such as by etching into the side of the substrate layer 208 opposite the waveguide layer 204, as shown in FIG. 2, may additionally or alternatively be used to form one or more fluid channels and / or other fluid pathway structures through the substrate layer 208.

[0086] In some embodiments, etching into the substrate layer 208, such as by etching into the side of the substrate layer 208 opposite the waveguide layer 204 as shown in FIG. 2, may additionally or alternatively be used to form structures on the waveguide structure 200 for use in physically positioning the waveguide structure 200. In some embodiments, micromachining of the substrate 208 may be used to form one or more kinematic structures. In some embodiments, one or more structures formed by etching into the substrate layer 208 may be used to attach and / or physically interact with a physical positioning and / or alignment system. In some embodiments, one or more structures formed by etching into the substrate layer 208 may be filled with, receive, and / or otherwise attach to a magnetic material and / or one or more magnetic components for use in a kinematic application.

[0087] 3A and 3B show two schematic views of a waveguide structure 300 having an air gap 336 formed in a substrate layer 308 and including a focusing lens 338, according to some embodiments. FIG. 3A shows cross-sectional views of the waveguide structure 300 from two angles, divided into two perspectives by a dotted line indicating a 90° angle 302. FIG. 3B shows an overhead view of the waveguide structure 300.

[0088] The waveguide structure 300 shown in FIG. 3 may share any one or more features in common with the waveguide structure 200 shown in FIG. 2 and may differ from the structure 200 shown in FIG. 2 in that the structure 300 may further comprise one or more lenses, for example, for use in out-of-plane excitation light collection. As shown, one or more lenses, such as lens 338, may be included in or attached to the cover layer 320, for example, by adhesive bonding, permanent or non-permanent bonding, or by fabrication within the cover layer 320 itself, to collect the excitation light 312 from the fluidic channel 318 at the top. Alternatively or additionally, one or more lenses, such as lens 340, may be attached below the fluidic channel 318 after etching the lower cavity 336 from the substrate 308 to collect the excitation light 312 from the fluidic channel 318 at the bottom. In some embodiments, the one or more lenses 338, 340 may be formed from a polymeric material, a dielectric material, glass, or any other suitable material.

[0089] Figure 4 shows two schematic views of a waveguide structure 400 having an air gap 416 formed in a substrate layer 408, with focusing lenses 438, 440, and with an aperture layer 470, according to some embodiments. Figure 4A shows cross-sectional views of the waveguide structure 400 from two angles, divided into two perspectives by a dotted line indicating a 90° angle 402. Figure 4B shows an overhead view of the waveguide structure.

[0090] 4 may share any one or more features in common with the waveguide structure 300 shown in FIG. 3 and may differ from the waveguide structure 300 discussed with respect to FIG. 3 in that the structure 400 may further include an aperture layer 470 configured to allow light from a signal to pass through apertures 472 for collection while blocking other light. In some embodiments, one or more apertures formed in the aperture layer 470 may be positioned near the fluidic channels 418 and near the lenses 440 embedded in the substrate layer 408, which may allow signal light to pass from the fluidic channels 418 through the aperture layer 470 into the lenses 440 in the substrate 408 for collection, while background light that does not pass through the apertures 472 may instead be blocked by opaque portions of the aperture layer 470.

[0091] In some embodiments, aperture layer 470 may include one or more adjacent apertures, apertures of different shapes, multiple apertures forming one or more patterns, and / or spectrally dependent apertures (e.g., aperture layer 470 may, in some embodiments, include a stack of ARROW layers). In some embodiments, one or more apertures in aperture layer 470 may be used to spatially filter the excitation light, such that, for example, only an excitation light beam incident on waveguide structure 400 may be allowed to pass through one or more apertures in aperture layer 470.

[0092] 4, aperture layer 470 may be disposed above substrate layer 408 (e.g., a silicon layer) and lens 440 embedded in substrate layer 408, and may be disposed below and adjacent to fluidic channel 418. In some embodiments, aperture layer 470 may be embedded in a portion of waveguide layer 404, such as by being sandwiched between two different low-index oxide layers, as shown in the example of FIG. 4. In some embodiments, a three-layer sandwich, with two low-index oxide layers surrounding aperture layer 470, may itself be sandwiched between a substrate layer and a high-index oxide layer, as shown in FIG.

[0093] 4 and 3, the waveguide layer 404 in FIG. 4 has both a low-index oxide layer (e.g., layer 406) and a high-index oxide layer (e.g., layer 410). In some embodiments, placing the aperture layer 470 between two low-index oxide layers (and / or keeping the aperture layer in the middle of the single low-index oxide layer 406) may optically isolate the aperture layer 470 from the waveguides in the waveguide layer 404, thereby preventing the aperture layer 470 from absorbing light from the waveguides. Furthermore, placing aperture layer 470 between two low-index oxide layers (and / or maintaining the aperture layer in the center of a single low-index oxide layer 406) may physically separate aperture layer 470 from substrate layer 408 and / or from the upper portion of the waveguide layer (e.g., layer 410), thereby allowing etching and other post-processing steps to be performed on substrate layer 408 and / or the upper portion of the waveguide layer (e.g., layer 410) without destroying or damaging aperture layer 470.

[0094] In some embodiments, aperture layer 470 may include chromium, nickel, another metal, one or more ARROW layers (e.g., patterned ARROW layers), and / or another opaque material configured to block background light. In some embodiments, aperture layer 470 may be micro-fabricated using micro-fabrication (including, for example, sputtering, e-beam evaporation, spin coating, and / or one or more coating techniques) so that one or more features of the aperture itself may be formed. In some embodiments, substrate layer 408 (e.g., a silicon substrate layer) may be coated with a thick layer (e.g., about 2 μm or thicker) of optically transparent material, which forms bottom low-index oxide layer 406 (which in some embodiments may have the same or similar dimensions as other bottom low-index oxide layers discussed herein). Micro-fabrication may then be used to create one or more features (e.g., one or more holes) in a thin layer (e.g., about 0.1 μm or thicker) of patterned absorbing material to form aperture layer 470 (which in some embodiments may have the same or similar dimensions as other aperture layers discussed herein). Next, a thick layer of optically transparent low-index material (e.g., about 1 μm, 5 μm, or 10 μm or more) may be deposited on the aperture layer, and another low-index oxide layer separating the aperture layers may be formed (the low-index oxide layer separating the aperture layers may, in some embodiments, have the same or similar dimensions as other bottom or substrate-adjacent low-index oxide layers discussed herein). Next, a high-index material may be deposited on the low-index oxide layer, and high-index regions of the waveguide layer may be formed (the high-index regions may have the same or similar thicknesses as other high-index oxide layers discussed herein). Next, the fluid core waveguide 418 and the solid core waveguide 414 may be simultaneously defined in the waveguide layer 404 using a single lithography process that may be aligned to the features of the absorbing layer (e.g., aligned to form fluid channels over the openings in the aperture layer 470).

[0095] In some embodiments, the substrate 408 of the waveguide structure 400 of Figure 4 may include a low refractive index material, such as a low refractive index oxide. In some embodiments, an aperture layer 470 sharing one or more features in common with those described with respect to Figure 4 may be incorporated into any one or more of the other non-axial detection waveguide structures described herein.

[0096] Figure 5 shows two schematic diagrams of a waveguide structure 500 with three analyte channels and an aperture layer, according to some embodiments. Figure 5A shows an overhead view of the waveguide structure 500. Figure 5B shows a partial cross-sectional view of the waveguide structure. Figure 5C shows time-varying intensity signals from light emitted from the three analyte channels of the waveguide structure 500.

[0097] 5 may share any one or more features in common with the waveguide structure 400 shown in FIG. 4 and may differ from the waveguide structure 400 discussed with respect to FIG. 3 in that, as discussed further below, structure 500 may include multiple fluid channels (e.g., analyte channels) running alongside one another rather than a single fluid channel. Waveguide structure 500 may further differ from waveguide structure 400 in that it may include one or more two-dimensional aperture arrays formed in one or more of the aperture layers of waveguide structure 500, as discussed further below. Waveguide structure 500 may further differ from waveguide structure 400 in that, instead of or in addition to a substrate layer positioned below the fluid channel(s) (e.g., positioned on the same side of the fluid channel(s) as the substrate layer, as shown by aperture layer 470 in FIG. 4), waveguide structure 500 may include a second aperture layer positioned above the fluid channel(s) (e.g., positioned on the opposite side of the fluid channel(s) from the substrate), as discussed further below.

[0098] In some embodiments, the waveguide structure 500 may include multiple fluid channels 518 running alongside (e.g., parallel to) one another. The fluid channels 518 may be formed in the waveguide layer 514, may share any one or more features in common with the fluid channels 418 of the structure 400, and may be formed according to any one or more of the same techniques, such as by etching into the waveguide layer 514. In some embodiments, multiple fluid channels running alongside one another in the waveguide structure 500 may allow for improved throughput / parallelization and / or allow different protocols / procedures to be performed simultaneously, such as by different fluid channels having different fluids and / or different analytes.

[0099] 5A , one or more of the fluidic channels 518 may be configured to intersect with and be illuminated by one or more waveguides 514. In some embodiments, the waveguide(s) 514 may share any one or more features in common with the waveguides 414 of structure 400 and may be formed according to any one or more of the same techniques, for example, by etching voids in the waveguide layer 504. In some embodiments, the waveguide(s) 514 may include a solid core waveguide, multiple waveguides connected by one or more y-splitters, one or more MMI waveguides, one or more hollow core waveguides, and / or one or more tunable fluid core MMI waveguides. In some embodiments, any one or more of the waveguide(s) 514 may intersect with one or more of the fluidic channels 518, including by passing through one or more of the fluidic channels 518 in succession and then intersecting by being inserted into another of the fluidic channels 518. In the example shown in FIG. 5A , the waveguide(s) 514 include multiple solid-core waveguides connected via a y-splitter, sending a four-spot pattern of excitation light to each of the three fluidic channels 518. In some embodiments, similar spot patterns of illumination light may be generated by one or more MMI waveguides and / or by using one or more aperture layers, as discussed in more detail below.

[0100] In some embodiments, the waveguide structure 500 may include one or more aperture layers, such as the aperture layer 570 shown in Figures 5A and 5B. As described herein, the one or more aperture layers included in the structure 500 may include a plurality of apertures arranged in a two-dimensional array or other two-dimensional pattern, such that the apertures allow some, but not all, light to pass through the aperture layer in a spatial pattern defined by the distribution of the apertures. The aperture layer may be used to control the passage of excitation light entering one or more fluidic channels, and additionally or alternatively, the aperture layer may be used to control the passage of emission / output light propagating outward from one or more fluidic channels.

[0101] In some embodiments, aperture layer 570 may be disposed below fluidic channels 518 (e.g., between fluidic channels 518 and the substrate layer of structure 500) and configured to partially block emitted / output light emitted from one or more of fluidic channels 518 and propagating downward toward the substrate layer. In some embodiments, aperture layer 570 may share any one or more features in common with aperture layer 470 described above with reference to FIG. 4. Positioning each aperture in aperture layer 570 below each of fluidic channels 518 may allow emitted / output light to exit each fluidic channel at a predetermined space, thereby defining a “zone” (e.g., an excitation zone and / or an emission zone) adjacent the aperture within the fluidic channel where a signal from the channel may be collected by a sensor disposed on the side of the aperture layer opposite the channel. In this manner, a signal from an analyte in a channel may only be detected when the analyte is present in the zone adjacent the aperture, even if the analyte emits emitted / output light when present elsewhere.

[0102] In some embodiments, in addition to or instead of the aperture layer 570, the waveguide structure 500 may include a second aperture layer (not shown in FIGS. 5A or 5B ) disposed over the fluidic channels 518 (e.g., on the side of the fluidic channels 518 opposite the substrate layer of the structure 500). In some embodiments, the second aperture layer may be configured to partially block excitation / input light from entering one or more of the fluidic channels 518. In some embodiments, the second aperture layer may share any one or more features in common with the aperture layer 470 described above with reference to FIG. 4 and / or the aperture layer 570 described immediately above, except that the second aperture layer may be disposed on the out-of-plane excitation side of the fluidic channels rather than the out-of-plane emission side of the fluidic channels. In some embodiments, the second aperture layer may be configured to partially block output light from exiting one or more of the fluidic channels 518. In some embodiments, the use of two aperture layers disposed on different sides of one or more fluidic channels may enable spatial and / or spectral filtering of input and / or output light on one or both sides of one or more fluidic channels. For example, aperture layer 570 may be disposed in or on an oxide layer that underlies the waveguide layer and overlies the substrate layer, while a second aperture layer may alternatively be disposed in or on an oxide layer that is disposed over the waveguide layer.

[0103] Additionally or alternatively, the second aperture layer may be disposed in or on a cover layer disposed above the waveguide layer (or on one or more layers disposed above the waveguide layer), such as a cover layer sharing any one or more features in common with cover layer 120 described above with respect to FIG. 1 . In some embodiments, one or more apertures may be defined in cover layers of various compositions. For example, a base cover layer may be formed using a transparent / semi-transparent material, such as a soft material (e.g., a plastic foil) or a hard material (e.g., a glass wafer). An opaque material may then be uniformly coated (e.g., by spin coating, spraying, evaporation, vapor deposition, etc.) on top of the transparent / semi-transparent base cover layer. One or more holes may then be formed in the opaque layer using one or more methods, such as embossing, laser ablation, or lithography, to form an optically functional aperture layer in the substrate that allows light to pass through the holes, yet still retains fluid within one or more fluid channels bounded by the cover layer.

[0104] In some embodiments, one or more of a variety of bonding techniques may be used to form a hermetic seal between the aperture-patterned cover layer and the components of the waveguide structure to which it is bonded. In some embodiments, different bonding techniques may be used based on the composition / geometry of the base layer and / or the optically opaque aperture layer. Bonding methods may include heat, fusion, frit, eutectic, etc. One advantage of incorporating apertures in the cover layer is that their fabrication can then be performed separately from one or more other components of the waveguide structure (e.g., before securing the cover layer to the waveguide structure), thereby reducing various tolerance stackups, increasing flexibility in the manufacturing workflow, and / or enabling the incorporation of various (e.g., non-CMOS) materials.

[0105] Respective apertures in the second aperture layer may be positioned over respective fluidic channels 518 to allow excitation / input light to enter the respective fluidic channels at predetermined intervals, thereby defining “zones” (e.g., excitation and / or emission zones) adjacent the apertures within the fluidic channels where excitation light from an out-of-plane excitation light source positioned on the opposite side of the aperture layer from the channel may enter the channel. In this manner, even if the excitation light is broadly incident on the analyte (e.g., by flood excitation), such that the analyte emits emitted / output light when the analyte is present elsewhere, the excitation light may only enter the channel and impinge on the analyte when the analyte is present in the zone adjacent the aperture. In some embodiments in which the second aperture layer is positioned in or on a cover layer of structure 500, one or more optical features (e.g., lenses such as lens 438 described above with respect to FIG. 4 ) may be positioned within the cover layer such that they align with one or more apertures to promote light passing through the apertures into the fluidic channels.

[0106] In some embodiments in which the waveguide structure 500 includes both an aperture layer 570 and a second aperture layer disposed on the opposite side of the fluid channel from the aperture layer 570, the two aperture layers may include one or more corresponding aperture pairs that are aligned and configured to allow light to enter and exit at the same corresponding zones within the fluid channel.

[0107] In some embodiments, the waveguide structure 500 can be configured to generate spatial and / or temporal patterns of emitted / output light using one or more aperture layers of the structure. In some embodiments, the aperture layer 570 can be used to define a spatial pattern of emission / output signals from one or more fluidic channels, such as to route signals from different fluidic channels to different sensors. In some embodiments, the aperture layer 570 can be used to define a spatial and / or temporal pattern of emission / output signals from multiple fluidic channels of the structure 500 to facilitate demultiplexing of signals collected from various channels. For example, the aperture layer 570 can define a two-dimensional aperture array, such as shown in FIG. 5A , whereby each of the fluidic channels 518 is disposed over a different linear pattern of apertures. As a result, the output / emission signals from each of the channels can be collected (e.g., by a single sensor) and demultiplexed by using the different linear patterns of apertures (e.g., different temporal signatures read by a detector) as signatures for each channel.

[0108] For example, as shown in FIG. 5C , light emission signals emitted from three fluid channels 518 of the waveguide structure 500 can be collected by a single sensor (or by two or more sensors). As a sample flows through the top channel of the diagram and passes through the zones located above each opening adjacent to the channel, the sample can emit emitted / output light through the corresponding openings in the aperture layer 570. As shown in FIG. 2C , the flow of sample through the two openings adjacent to the top channel of the diagram can generate a characteristic excitation light pattern of two peaks. Similarly, the middle channel of the diagram can generate a characteristic excitation light pattern of three peaks, and the bottom channel of the diagram can generate a characteristic excitation light pattern of four peaks. One or more processors can be configured to automatically recognize the number of peaks and identify which channel a signal is attributed to based on the pattern of the recognized openings.

[0109] While the example shown in FIG. 5C contemplates using different numbers of apertures to define characteristic aperture patterns associated with different channels, characteristic aperture patterns may also be formed by different aperture spacing and / or different aperture lengths in some embodiments. When defining characteristic aperture patterns using aperture spacing and / or aperture lengths, particle flow rates within the associated fluidic channels may be considered as part of defining the characteristic time-varying optical signal emitted from the channel through the apertures. In some embodiments, spatially identical aperture patterns may be positioned adjacent to fluidic channels having different flow rates, such that different time-varying optical signals may be generated in these channels when particles pass through the aperture patterns at different velocities. Accordingly, one or more processors may be configured to identify to which channel a time-varying optical signal is attributed based on the number of peaks, the length of the peaks, and / or the spacing of the peaks (including taking into account different analyte flow rates in the different channels).

[0110] In some embodiments, in addition to spatial and / or temporal demultiplexing of signals received through aperture layer 570, the processor may be further configured to perform spectral demultiplexing, e.g., based on the wavelengths of different signals detected through aperture layer 570. For example, one or more identical (or similar) linear aperture patterns may generate identical or similar time-varying optical signals, and the processor may be configured to distinguish between different channels based on the different optical wavelengths associated with the different channels.

[0111] In some embodiments, the waveguide structure 500 may be configured to enable spectral demultiplexing by configuring one or more apertures to allow light of different wavelengths to pass through. For example, one aperture may be configured to allow emitted light of a first wavelength to pass through, while another aperture may be configured to allow light of a second wavelength to pass through. When output signals of different wavelengths are detected, the processor may be configured to correlate from which aperture all or part of the signal was received based on the wavelength of the signal.

[0112] While the above examples contemplate using aperture layer 570 to create distinct spatial and / or temporal patterns of excitation light resulting from different fluidic channels, it should also be noted that distinct spatial and / or temporal patterns of excitation light resulting from different fluidic channels can be created, in whole or in part, using a second aperture layer of waveguide structure 500. For example, to form a linear pattern of distinct characteristics of excitation zones within multiple fluidic channels, the second waveguide structure can be used to partially block and partially transmit excitation light, such that particles within a channel emit output / emission signals only when passing through and excited within an excitation zone. For example, FIG. 5B shows an example of four excitation zones within a fluidic channel (each of the excitation zones is located over an aperture in aperture layer 570, which may or may not be used only when excitation light is incident on a given excitation zone).

[0113] In some embodiments, a two-dimensional array or pattern of apertures formed in the second aperture layer may be used to form different characteristic patterns of excitation zones in the plurality of fluidic channels 516 of the waveguide structure 500. In some embodiments, instead of or in addition to using a second aperture to create a pattern of excitation light, one or more spot patterns of excitation light may be formed using one or more waveguides, for example, by using a solid core waveguide in a y-splitter structure as shown in FIG.

[0114] In some embodiments, an aperture formed in any aperture layer of any waveguide structure disclosed herein may be positioned adjacent to only a single fluidic channel, hi some embodiments, an aperture formed in any aperture layer of any waveguide structure disclosed herein may be positioned adjacent to multiple fluidic channels, e.g., an elongated or slit-shaped aperture may allow light to enter and / or exit the multiple fluidic channels when the aperture is positioned adjacent each of the multiple fluidic channels.

[0115] In addition to enabling the multiplexing capabilities described above, the use of one or more aperture layers having a two-dimensional aperture array that allows light to enter and / or exit multiple fluidic channels improves the signal-to-noise ratio when using waveguide structures, thereby increasing accuracy and facilitating cost minimization.

[0116] In some embodiments, a metal etching step may be used to define precisely sized and precisely aligned apertures in one or more aperture layers of the waveguide structure 500. In some embodiments, a wet etching process step (e.g., KOH) may be used to create one or more apertures in a substrate layer of the waveguide structure 500, such as a single large aperture in the substrate layer below aperture layer 570 shown in FIG. 5B. In some embodiments, the alignment and sizing of one or more apertures in the substrate layer may be less critical (e.g., not require as high a level of precision) than the alignment and sizing of the apertures in the aperture layer. In some embodiments, a waveguide structure integrated with one or more aperture layers as described herein may have pre-built alignment in the waveguide structure, while larger apertures within the volume of the substrate layer only need to be roughly aligned (e.g., on the order of a few hundred microns) with respect to the optical system to form a shape sensitive enough to detect single molecules. This relaxed alignment tolerance of the substrate layer may significantly reduce the cost and complexity of the optical system downstream of the detection volume.

[0117] Instead of, or in addition to, etching through the substrate layer, a transparent substrate layer may be used.

[0118] In some embodiments, by using one or more aperture layers as described herein, a system can be created that allows for optical pinhole functionality integrated into the waveguide structure. The optical pinhole, defined by the apertures in the aperture layer, can define the radiation spot, minimize unwanted scattered light, and enable precise definition of multi-spot patterns.

[0119] In some embodiments, if background light levels (e.g., background light emitted into the fluidic channels through openings in the substrate) are too high or if multiple peaks cannot be easily distinguished from one another, the dimensions of one or more openings in one or more opening layers may be adjusted, and / or the thickness and / or material composition of the opening layer itself may be adjusted (e.g., made thicker and / or more opaque).

[0120] While the disclosure herein has discussed the use of particular oxide materials in the waveguide layers of waveguide structures, the waveguide layers of the structures disclosed herein may, in some embodiments, be formed (in whole or in part) from one or more alternative or additional materials, including, but not limited to, materials deposited using vapor deposition (e.g., oxides such as titanium dioxide deposited by plasma-enhanced chemical vapor deposition (PECVD) or low-pressure chemical vapor deposition (LPCVD)), materials formed by thermal oxidation (e.g., silicon dioxide formed from thermal oxidation of silicon), spin-on glass, any one or more other materials that may be selected or configured for background subtraction, and / or one or more plastics (e.g., polydimethylsiloxane (PDMS), cyclic olefin copolymer (COC), cyclic olefin polymer (COP)).

[0121] In some embodiments, one or more of the waveguide structures described herein may be provided with one or more buried waveguides in addition to or instead of the described waveguides. For example, buried waveguides may be implemented in addition to or instead of groove waveguides. In some embodiments, buried waveguides may provide one or more of the following advantages: enhanced single-mode operation, improved chip / wafer-to-chip reproducibility, easier integration of cover layers during channel formation (e.g., small distances (e.g., 15 μm) between liquid channels and voids that may need to be fluid-tight may no longer exist), and the use of different cover materials (e.g., due to easier sealing / bonding, as described above).

[0122] In some embodiments, a waveguide structure having a one-dimensional aperture array may be provided. In some embodiments, the one-dimensional aperture array may be provided in, as part of, or attached to a substrate or cover layer of the structure. In some embodiments, an aperture layer may be provided between the substrate and one or more waveguide layers (e.g., a waveguide oxide stack). In some embodiments, such waveguide structures, for example, when formed with one or more embedded waveguides, may be very well defined in structure, resulting in improved reproducibility. In some embodiments, when two or more apertures are formed along a single fluidic channel (e.g., in a one-dimensional aperture array), the apertures may be used to spatially filter the excitation light of one or more waveguide arrays. For example, when using MMI waveguides and / or y-splitter waveguides, multiple waveguides may intersect with the fluidic channel, and at the intersections, refractive index perturbations may cause excessive scattering, adding unwanted background to the optofluidic signal. Using a one-dimensional aperture array, this unwanted background may be spatially filtered (e.g., by optical reflection and / or optical absorption) from the collected signal. Furthermore, precise definition of the apertures in an aperture array can help define the area of ​​signal collection, thereby enabling enhanced analyte detection, improved signal-to-noise ratio, automatic identification of known aperture arrays, associated fluid channels, and / or associated analytes using signature patterns based on the number of apertures, aperture spacing, and / or aperture size, and / or determination of flow velocity by analysis of the amount of time between signals collected through different apertures with known spacing or by analysis of the amount of time signals are collected through a single aperture of known length.

[0123] In some embodiments, following fabrication of a waveguide structure according to any one or more of the fabrication techniques disclosed herein, one or more additive processes may be performed to further modify the fabricated chip, including, but not limited to, deposition, chemical modification, alteration of surface chemistry, and / or alteration of topology. In some embodiments, these one or more additive processes may be used to modify and / or enhance one or more properties of the fabricated structure, such as its hydrophobicity, smoothness, and / or reactivity.

[0124] 6 shows a system 600 for analyte detection, according to some embodiments. System 600 may include a waveguide structure 602, a photodetector 604, and a processor 606. In some embodiments, waveguide structure 602 may be any of the waveguide structures described herein (or may share any one or more features in common with any of the waveguide structures described herein), including any of the waveguide structures including one or more aperture arrays described herein. In some embodiments, system 600 may be configured to perform any of the analyte detection and / or signal analysis techniques described herein, including, but not limited to, analyte detection, flow rate determination, channel / analyte / device identification, and / or demultiplexing techniques described herein with reference to FIG. 5C .

[0125] Light emitted from the waveguide structure 602 through one or more apertures in the aperture array of the waveguide structure 602 may be detected by a photodetector 604, which may be any suitable photodetector or other sensor for detecting the emitted light. The photodetector 604 may be located out of the plane of one or more analyte channels of the waveguide structure 602. In some embodiments, the photodetector 604 may be located separately from the waveguide structure 602. In some embodiments, the photodetector 604 may be located as part of the waveguide structure 602 and / or attached to or physically integrated with the waveguide structure 602.

[0126] The light detector 604 may be communicatively coupled to the processor 606 (e.g., via one or more wired or wireless network communication protocols). The processor 606 may be implemented as a local processor, a remote processor or server, multiple processors, a distributed computing system, and / or a cloud computing system. The processor 606 may be configured to receive data representing the light detected by the light detector 604 and analyze the data. In some embodiments, the processor 606 may be configured to perform one or more analyses based on the received data and / or make one or more determinations based on the received data. While FIG. 6 depicts a system having a single light detector 604, in some embodiments, a system for analyte detection may include multiple light detectors (e.g., multiple detectors corresponding to different apertures, different aperture arrays, and / or split signals).

[0127] For example, processor 606 may be configured to automatically recognize the aperture pattern of one or more aperture arrays, e.g., by analyzing one or more of the following: the number of bursts detected from one or more apertures in the array; the duration of one or more bursts detected from one or more apertures in the array; the time interval between one or more bursts detected from one or more apertures in the array; and / or the spectral characteristics (e.g., wavelength) of one or more signal bursts detected from one or more apertures in the array. Based on the recognition of the aperture pattern, processor 606 may automatically determine the identity of an associated aperture array, an associated fluidic channel, an associated waveguide structure, and / or an associated analyte (e.g., an analyte known to be flowing in an associated channel). In some embodiments, based on the recognition of the aperture pattern, processor 606 automatically performs demultiplexing of signals received from multiple aperture arrays, e.g., by determining whether a received signal corresponds to a first aperture pattern (corresponding to a first channel) or a second aperture pattern (corresponding to a second channel). In some embodiments, processor 606 may distinguish between signals detected from different one-dimensional aperture patterns that are part of a single two-dimensional aperture array.

[0128] Additionally or alternatively, the processor 606 may be configured to automatically determine the flow velocity of the fluid within the channel, for example, by analyzing the burst duration and / or burst time interval of bursts detected from one or more apertures of the array.

[0129] Figure 7 illustrates a computer according to some embodiments. Computer 700 may be a component of a system or device according to the systems, devices, and / or methods described above, and may form all or part of processor 606 of Figure 6. In some embodiments, computer 700 may perform all or part of analyte detection, signal analysis, flow rate determination, channel / analyte / device identification, and / or demultiplexing methods, such as any of the methods or techniques described herein (including, for example, method 1000 described with respect to Figure 10).

[0130] The computer 700 may be a host computer connected to a network. The computer 700 may be a client computer or a server. As shown in FIG. 7 , the computer 700 may be any suitable type of microprocessor-based device, such as a personal computer, a workstation, a server, or any suitable type of handheld computing device, such as a phone or tablet. The computer may include, for example, one or more of a processor 710, an input device 720, an output device 730, storage 740, and a communication device 760. The input device 720 and the output device 730 may correspond to those described above and may be connectable to or integrated into the computer.

[0131] The input device(s) 720 may be any suitable device that provides input, such as a touchscreen or monitor, a keyboard, a mouse, or a voice recognition device. The output device(s) 730 may be any suitable device that provides output, such as a touchscreen, a monitor, a printer, a disk drive, or speakers.

[0132] Storage 740 may be any suitable device providing storage, such as electrical, magnetic, or optical memory, including random access memory (RAM), a cache, a hard drive, a CD-ROM drive, a tape drive, or a removable storage disk. Communication device 760 may include any suitable device capable of sending and receiving signals over a network, such as a network interface chip or card. Computer components may be connected in any suitable manner, such as via a physical bus or wirelessly. Storage 740 may be a non-transitory computer-readable storage medium containing one or more programs that, when executed by one or more processors, such as processor 710, cause the one or more processors to perform all or a portion of one or more methods, including all or a portion of any one or more of the methods or techniques described herein.

[0133] Software 750, which may be stored in storage 740 and executed by processor 710, may include, for example, programming that embodies functionality of the present disclosure (e.g., functionality incorporated in the systems, computers, servers, and / or devices described above). In some embodiments, software 750 may include a combination of servers, such as an application server and a database server.

[0134] The software 750 may also be stored on and / or transported to any computer-readable storage medium used by or connected to an instruction execution system, apparatus, or device, such as those described above, from which the instructions associated with the software may be retrieved and executed. In the context of the present disclosure, a computer-readable storage medium may be any medium that contains or can store programming, such as storage 740, used by or connected to an instruction execution system, apparatus, or device.

[0135] The software 750 may also be propagated to any carrier medium used by or connected to an instruction execution system, instruction execution apparatus, or instruction execution device, such as those described above, from which instructions associated with the software may be retrieved and executed. In the context of this disclosure, a carrier medium may be any medium capable of communicating, propagating, or carrying programming, used by or connected to an instruction execution system, instruction execution apparatus, or instruction execution device. Carrier-readable media may include, but are not limited to, electronic, magnetic, optical, electromagnetic, or infrared wired or wireless propagation media.

[0136] The computer 700 may be networked, which may be any suitable type of interconnected communication system. The network may implement any suitable communication protocol and may be protected by any suitable security protocol. The network may include any suitable configuration of network links capable of transmitting and receiving network signals, such as a wireless network connection, a T1 or T3 line, a cable network, DSL, or a telephone line.

[0137] Computer 700 may implement any operating system suitable for operating on a network. Software 750 may be written in any suitable programming language, such as C, C++, Java, or Python. In various embodiments, application software embodying functionality of the present disclosure may be deployed in a variety of configurations, such as, for example, in a client / server configuration or via a web browser as a web-based application or web service.

[0138] 8 illustrates a method 800 for fabricating a waveguide structure, according to some embodiments. In some embodiments, method 800 may be used to fabricate one or more of the waveguide structures disclosed herein and / or may share any one or more features in common with other waveguide fabrication methods disclosed herein. Those skilled in the art will understand, in light of the disclosure herein, that method 800 may be modified from the example illustrated in FIG. 8 by adding one or more additional steps, deleting one or more illustrated steps, and / or rearranging one or more steps.

[0139] In some embodiments, the method 800 includes, at block 802, etching an aperture array in an aperture layer of the waveguide structure, the aperture array comprising one or more respective one-dimensional aperture patterns, each of the one or more one-dimensional aperture patterns configured to allow light to be emitted from a respective fluid channel of a set of one or more fluid channels of the waveguide structure.

[0140] In some embodiments, the method 800 includes, at block 804, etching one or more fluid channels in a waveguide layer of the waveguide structure.

[0141] In some embodiments, the method 800 includes, at block 806, etching a substrate layer of the waveguide structure to create a substrate cavity, such that light leaking from the one or more fluid channels through one or more of the openings in the first opening layer propagates into the substrate cavity.

[0142] In some embodiments, the method 800 includes, at block 808, etching a first waveguide void and a second waveguide void in the waveguide layer, wherein etching the first void and the second void creates a solid core waveguide in the waveguide layer between the first void and the second void, the solid core waveguide intersecting the one or more fluid channels.

[0143] In some embodiments, the method 800 includes, at block 810, attaching a cover layer to the waveguide layer to close one or more fluid channels.

[0144] 9 illustrates a method for fabricating a waveguide structure, according to some embodiments. In some embodiments, method 900 may be used to fabricate one or more of the waveguide structures disclosed herein and / or may share any one or more features in common with other waveguide fabrication methods disclosed herein. Those skilled in the art will understand, in light of the disclosure herein, that method 900 may be modified from the example illustrated in FIG. 9 by adding one or more additional steps, deleting one or more illustrated steps, and / or rearranging one or more steps.

[0145] In some embodiments, the method 900 includes, at block 902, etching one or more fluid channels in a waveguide layer of the waveguide structure, each of the one or more fluid channels aligned with one or more apertures disposed in an aperture layer of the waveguide structure.

[0146] In some embodiments, the method 900 includes, at block 904, attaching a cover layer to the waveguide layer to close one or more fluid channels.

[0147] FIG. 10 illustrates a method for analyzing a signal representative of light emitted through an aperture layer of a waveguide structure, according to some embodiments.

[0148] In some embodiments, method 1000 may be used in conjunction with a waveguide structure, such as one or more of the waveguide structures disclosed herein, and / or may be used in conjunction with a system, such as system 600 and / or computer 700. In some embodiments, method 1000 may share any one or more features in common with any other techniques for analyzing signals disclosed herein. In some embodiments, method 1000 may be performed by processor 606 of system 600 based on a signal representative of light emitted through an aperture layer of waveguide structure 602, as detected by detector 604. Those skilled in the art will understand in light of the disclosure herein that method 1000 may be modified from the example shown in FIG. 10 by adding one or more additional steps, deleting one or more illustrated steps, and / or rearranging one or more steps.

[0149] In some embodiments, the method 1000 includes, at block 1002, receiving a signal from a detector representing light emitted through one of a first pattern of apertures and a second pattern of apertures, wherein the first pattern of apertures and the second pattern of apertures are formed in the aperture layer such that the first pattern of apertures is aligned with a first sample channel and the second pattern of apertures is aligned with a second sample channel.

[0150] In some embodiments, the method 1000 includes, at block 1004, determining, based on the received signal, whether the signal corresponds to a first channel or a second channel.

[0151] The foregoing description has been described with reference to specific embodiments for purposes of explanation. However, the illustrative discussion above is not intended to be exhaustive or to limit the invention to the precise forms disclosed. Many modifications and variations are possible in light of the above teachings. The embodiments were chosen and described in order to best explain the principles of the technology and their practical application. This will enable those skilled in the art to optimally utilize the technology and various embodiments, with various modifications suited to the particular use contemplated.

[0152] Although the disclosure and examples have been fully described with reference to the accompanying drawings, it should be noted that various changes and modifications will become apparent to those skilled in the art. Such changes and modifications are to be understood as being included within the scope of the disclosure and examples as defined by the claims. Finally, the entire disclosures of all patents and publications mentioned in this specification are hereby incorporated by reference.

Claims

1. A waveguide structure, a waveguide layer including one or more fluid channels; at least one waveguide intersecting the one or more fluid channels; a first aperture layer including a first aperture array, wherein each of the one or more fluid channels is adjacent to at least one of the apertures of the first aperture array in a direction perpendicular to a direction in which the one or more fluid channels extend; a cover layer attached to the waveguide layer to cover a face of the one or more fluid channels opposite an interface between the one or more fluid channels and at least one of the openings, thereby closing the one or more fluid channels; The waveguide structure.

2. 2. The waveguide structure of claim 1, wherein the aperture array has one or more respective one-dimensional aperture patterns, each of the one or more one-dimensional aperture patterns disposed adjacent a respective one of the one or more fluid channels.

3. The waveguide structure of any one of claims 1 to 2, wherein each of the one or more respective one-dimensional aperture patterns has a different number of apertures.

4. The waveguide structure according to any one of claims 1 to 3, wherein each of the one or more one-dimensional aperture patterns has a different aperture spacing.

5. The waveguide structure of any one of claims 1 to 4, wherein each of the one or more respective one-dimensional aperture patterns has a different aperture size.

6. The waveguide structure of any one of claims 1 to 5, wherein the first aperture layer comprises chromium, nickel, another metal, and / or one or more arrow layers.

7. The waveguide structure of any one of claims 1 to 6, wherein the first aperture layer is micro-fabricated using one or more of sputtering, e-beam evaporation, spin coating, and coating.

8. 8. The waveguide structure of claim 1, wherein the at least one waveguide intersecting the one or more fluid channels comprises one or more of a solid core waveguide, an MMI waveguide, and a tunable fluid core MMI waveguide.

9. 9. The waveguide structure of claim 1, wherein the at least one waveguide intersecting the one or more fluid channels includes a solid core waveguide formed in the waveguide layer, the solid core waveguide being formed by one or more of: (i) etching a plurality of voids in the waveguide layer to define the solid core waveguide therebetween; and (ii) doping the waveguide layer to define the solid core waveguide with one or more doped regions in the waveguide layer.

10. a substrate layer coupled to the waveguide layer; a substrate void formed in the substrate layer adjacent one or more of the one or more fluid channels, whereby light leaking from the one or more fluid channels adjacent the void through one or more of the apertures in the first aperture array propagates into the substrate void; and The waveguide structure of any one of claims 1 to 9, comprising:

11. The waveguide structure of claim 10 , wherein the substrate cavity is larger in diameter than one or more of the apertures in the first aperture layer.

12. a second aperture layer disposed on a side of the waveguide layer opposite the first aperture layer, the second aperture layer including a second array of apertures, each of the one or more fluid channels adjacent to at least one of the apertures in the second array of apertures; The waveguide structure of any one of claims 1 to 11, comprising:

13. The waveguide structure of claim 12 , wherein the second aperture layer is disposed on or in the cover layer.

14. the aperture array is a two-dimensional aperture array that forms a plurality of one-dimensional aperture patterns; the one or more fluid channels include a plurality of fluid channels, each of the plurality of fluid channels adjacent to at least one of the apertures of the two-dimensional aperture array; The waveguide structure according to any one of claims 1 to 13.

15. 1. A method for producing a waveguide structure, comprising: etching an aperture array into an aperture layer of the waveguide structure, the aperture array having one or more respective one-dimensional aperture patterns, each of the one or more one-dimensional aperture patterns configured to allow light to be emitted from a respective fluid channel of a set of one or more fluid channels of the waveguide structure; Including, each of the one or more fluid channels is adjacent to at least one of the apertures of the aperture array in a direction perpendicular to the direction in which the one or more fluid channels extend; The method.

16. etching the one or more fluid channels in a waveguide layer of the waveguide structure; attaching a cover layer to the waveguide layer to close the one or more fluid channels; 16. The method of claim 15, comprising:

17. etching a substrate layer of the waveguide structure to create a substrate void, whereby light leaking from the one or more fluid channels through one or more of the apertures in the aperture layer propagates into the substrate void; 17. The method of claim 15 or 16, comprising:

18. 18. The method of any one of claims 17, wherein etching into the substrate layer comprises a wet etching process step.

19. Etching the opening layer includes a first etching step having a first spatial accuracy; etching the substrate layer includes a second etching step having a second spatial accuracy; the first spatial accuracy is finer than the second spatial accuracy; The method according to any one of claims 17 to 18.

20. The method according to any one of claims 17 to 19, wherein etching into the aperture layer is carried out before etching into the substrate layer.

21. A method according to any one of claims 17 to 20, wherein the substrate cavity is larger in diameter than one or more of the apertures in the aperture layer.

22. etching a first waveguide gap and a second waveguide gap in a waveguide layer of the waveguide structure, wherein etching the first waveguide gap and the second waveguide gap creates a solid core waveguide in the waveguide layer between the first waveguide gap and the second waveguide gap, the solid core waveguide intersecting the one or more fluid channels; The method according to any one of claims 15 to 21, comprising:

23. The method of any one of claims 15 to 22, wherein etching the aperture layer comprises performing a metal etching step.

24. 1. A method for producing a waveguide structure, comprising: etching one or more fluid channels in a waveguide layer of the waveguide structure, each of the one or more fluid channels being aligned with one or more apertures disposed in an aperture layer of the waveguide structure in a direction perpendicular to a direction in which the one or more fluid channels extend; attaching a cover layer to the waveguide layer to cover a face of the one or more fluid channels opposite an interface between the one or more fluid channels and at least one of the openings, thereby closing the one or more fluid channels; The method comprising:

25. 1. A system for analyte detection, comprising: a first analyte channel; a second analyte channel; an aperture layer including a plurality of apertures forming a first pattern of apertures aligned with the first analyte channel and a second pattern of apertures aligned with the second analyte channel; a detector configured to detect light emitted through the apertures of the first pattern and light emitted through the apertures of the second pattern; one or more processors; wherein the one or more processors: receiving a signal from the detector representative of light emitted through one of the first pattern of apertures and the second pattern of apertures; determining, based on the received signal, whether the signal corresponds to the first analyte channel or the second analyte channel; The system is configured to execute the

26. 26. The system of claim 25, wherein determining whether the signal corresponds to the first analyte channel or the second analyte channel is performed based on determining whether a number of bursts in the signal corresponds to a number of apertures in the first pattern or a number of apertures in the second pattern.

27. 27. The system of claim 25, wherein determining whether the signal corresponds to the first analyte channel or the second analyte channel is performed based on determining whether a duration of a light burst represented by the signal corresponds to a diameter of an aperture in the first pattern or a diameter of an aperture in the second pattern.

28. 28. The system of claim 25, wherein determining whether the signal corresponds to the first analyte channel or the second analyte channel is performed based on determining whether the time spacing of two or more bursts represented by the signal corresponds to the physical spacing of two or more apertures in the first pattern or the physical spacing of two or more apertures in the second pattern.

29. 29. The system of claim 25, wherein determining whether the signal corresponds to the first analyte channel or the second analyte channel is performed based on determining whether wavelengths of one or more bursts represented by the signal correspond to spectral characteristics of one or more apertures in the first pattern or correspond to spectral characteristics of one or more apertures in the second pattern.

30. The waveguide structure of claim 2, wherein the one or more one-dimensional aperture patterns include a plurality of different linear patterns.

31. A method described in any one of claims 15 to 23, wherein the one or more one-dimensional opening patterns include a plurality of different linear patterns.

32. The method described in claim 24, wherein the aperture array in the aperture layer includes a plurality of one-dimensional aperture patterns.

33. The method described in claim 32, wherein any one-dimensional opening pattern among the plurality of one-dimensional opening patterns is positioned adjacent to any one of the one or more fluid channels.

34. A method as described in claim 32 or 33, wherein the multiple one-dimensional opening patterns include multiple different linear patterns.

35. A system described in any one of claims 25 to 29, wherein the openings of the first pattern are positioned adjacent to the first sample channel and the openings of the second pattern are positioned adjacent to the second sample channel.

36. A system described in any one of claims 25 to 29, 35, wherein the first pattern of openings and the second pattern of openings include a one-dimensional opening pattern.

37. The system described in claim 35, wherein the first pattern openings and the second pattern openings include a plurality of linear patterns.

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