The present application relates to improving, with optical nanostructures, the performance of an instrument that analyzes samples.
In the area of instrumentation that is used for analysis of samples, microfabricated chips may be used to analyze in parallel a large number of analytes or specimens contained within one or more samples. In some cases, optical excitation radiation is delivered to multiple discrete sites on a chip at which separate analyses are performed. The excitation radiation may excite a specimen at each site, a fluorophore attached to the specimen, or a fluorophore involved in an interaction with the specimen. In response to the excitation, radiation may be emitted from a site and the emitted radiation for a site, or lack of emitted radiation, can be used to determine a characteristic of the specimen at that site.
An integrated device, comprising a substrate having a first surface; and at least one pixel formed on or in the substrate. The at least one pixel comprising a reaction chamber configured to receive a sample, and a sensor configured to detect emission light emitted from the reaction chamber and at least one optical nanostructure disposed in a plane between a waveguide and the sensor, wherein the optical nanostructure is configured to converge at least a portion of the emission light in a direction substantially perpendicular to the plane. The waveguide is configured to couple excitation light to each pixel.
An integrated device, comprising a substrate having a first surface, and at least one pixel formed on the substrate. The at least one pixel comprising a reaction chamber configured to receive a sample, a sensor configured to detect emission light emitted from the reaction chamber, a waveguide configured to couple excitation radiation to the reaction chamber, a photonic disk disposed in a plane between the waveguide and the sensor, and at least one nanostructure ring disposed in a plane between the waveguide and the sensor, the photonic disk and nanostructure ring are configured to converge at least a portion of the emission light in a direction substantially perpendicular to the plane.
A method for fabricating an integrated device, the method comprising forming, on a substrate having a first surface, a plurality of pixels such that at least some of the plurality of pixels. Forming each a pixel comprises forming a reaction chamber configured to receive a sample, and forming a sensor configured to detect emission light emitted from the reaction chamber, and fabricating the integrated device further includes forming a waveguide configured to couple excitation radiation to the reaction chamber. The method further comprising forming at least one nanostructure in a plane between the waveguide and the sensor, wherein the optical nanostructure is configured to converge at least a portion of the emission light in a direction substantially perpendicular to the plane.
The foregoing and other aspects, implementations, acts, functionalities, features, and embodiments of the present application can be more fully understood from the following description in conjunction with the accompanying drawings.
Aspects of the present application relate to photonic structures for use in integrated devices, instruments, and related systems capable of analyzing samples in parallel including identification of single molecules and nucleic acid and/or protein sequencing. In some applications, such an integrated device may benefit from the inclusion of photonic structures to couple light from a sample well to a detector. Photonic structures may increase the flux of light transmitted from the sample well to the detector and/or may concentrate the light at the detector. Increasing the flux of light transmitted to the detector and/or concentrating the light at the detector may provide larger electric fields at the detector. By providing larger electric fields at the detector, the photonic structures may increase signal-to-noise. According to some embodiments, the photonic structures may support decreased pixel sizes by concentrating emission light within a smaller area. By concentrating the emission light, a smaller detector can be used to capture the emission light.
In an integrated device, sample wells may be configured for single molecule nucleic acid and/or protein identification. To identify the single molecule nucleic acids and/or proteins contained within a sample, excitation light is transmitted to the sample wells containing the sample. Following excitation, the sample or a tag thereon may emit fluorescence. An on-chip detector may be used to detect the fluorescent light emitted from the sample, and using the detected light, information about the sample, such as the identity of the single molecule nucleic acid and/or protein, is determined. Detectors and sample wells may be grouped into pixels to provide an integrated device capable of parallel identification and/or sequencing. For example, an integrated device may have multiple pixels, where each pixel includes a detector configured to detect light, detector electronics to process the signals associated with the detector, and a sample well.
The inventors have recognized and appreciated that the pixel size, in an integrated device, may limit the number of single molecule nucleic acid and/or protein identifications that may be performed in parallel. The inventors have further appreciated that the size of the detector impacts the pixel size. Thus, smaller sensors, may provide for increases in the parallel identifying and/or sequencing capacity. However, the intensity of a single molecule emitter in a sample well may be low relative to the intensity of scattered excitation light that reaches the detector. Further, the portion of light that is detected by the detector may impact the signal to noise. When the sensor detects every photon emitted from the sample chamber, and the detector does not receive scattered excitation light, the integrated device may produce high signal-to-noise measurements.
The inventors have recognized and appreciated that photonic structures may be used to increase the transmission of light from the sample well to the detector. However, the implementing photonic structures to control the transmission of light to the detector provides challenges. For example, if portions of the emitted light are not transmitted to the detector either because the detector is too small to capture all of the emitted light, or because portions of the emitted light are emitted in directions away from the detector, then the signal-to-noise of the integrated device may be decreased.
Additionally, the sample spot (i.e., the area of the transmitted light in the detector at the sample plane) may also impact the signal-to-noise. For example, the alignment between the transmitted sample spot and the detector will impact the signal-to-noise. Light that is transmitted to the sample plane but does not illuminate the detector will not contribute to the detected signal. Additionally, light that is not absorbed by the detector may scatter around inside the device. In some applications, the electronic detection components are also sensitive to light. Thus, scattered light may induce noise in the electronic detection components, decreasing the signal-to-noise.
The inventors have recognized and appreciated that photonic structures included with the integrated device to facilitate the transmission of light from the sample well to the detector may create challenges in fabrication. For example, as features get taller (i.e., height perpendicular to the substrate surface), fabrication techniques may introduce fabrication defects and/or strain in the layers of the integrated devices. Fabrication defects and/or strain may increase the scattering of light, which may decrease the signal-to-noise of the integrated device.
The inventors having recognized the challenges described above have developed photonic structures with multiple optical components for use in an integrated device and configured to modify the transmission of light from the sample well to the detector. Some embodiments are directed to systems, methods, and techniques for providing an integrated device that include a substrate having a first surface with at least one pixel formed on the substrate. The at least one pixel including a reaction chamber configured to receive a sample, a sensor configured to detect emission light emitted from the reaction chamber, and the integrated device further including a waveguide configured to couple excitation radiation to the reaction chamber, and multiple nanostructures disposed in a plane between the waveguide and the sensor, where the optical nanostructures are configured to converge at least a portion of the emission light in a direction substantially perpendicular to the plane.
Photonic structures utilize the differences in refractive index between two or more materials to introduce amplitude and phase modulations to the transmitted light that reflect the pattern of the photonic structure. The larger the contrast in dielectric materials, the larger the amplitude and phase modulation produced by a given structure. Additionally, the thickness and the pattern of the photonic structures will impact the magnitude of the amplitude and phase shifts to the transmitted light. After the light is transmitted through the photonic structure, the amplitude and phase shift to the transmitted light varies across the photonic structure, thus as the light continues to propagate, the transmitted light interferes with itself constructively and/or destructively. In some configurations, the phase shifts may result in a focusing effect. In other configurations, the phase shifts may result in a defocusing effect. In yet other configurations, the phase shifts may result in both focusing and defocusing effects. Accordingly, while a strictly focusing effect may result in the formation of a real image and a strictly defocusing effect may result in the formation of a virtual image, mixed effects may cause the light to converge or diverge without forming an image or virtual image.
The photonic structures described herein may be configured to increase the flux transmitted to the sample plane and/or concentrate the light on the detector. In a first exemplary embodiment, a photonic structure includes multiple photonic structures that are configured in a two-dimensional pattern. The two-dimensional pattern may be centered on the z-axis in line with the sample chamber and the detector. In some embodiments, the two-dimensional pattern may be repeated for each pixel.
In some embodiments, different patterns of photonic structures may be used for different pixels of the integrated device. The pattern may be based on the center wavelength and spectral bandwidth of the light transmitted through the pixel.
In some embodiments, the pixelated pattern of photonic structures is configured to cause light transmitted through the photonic structures to converge. In some embodiments, the pixelated pattern of photonic structures is configured to cause light transmitted through the photonic structures to propagate as a collimated plane wave. In some embodiments, the pixelated pattern of photonic structures is configured to cause light transmitted through the photonic structure to diverge.
The dimensions of the photonic structures may be based on the refractive index of the material used to form the structures. In some embodiments, a refractive index between 1.7 and 4, at the target wavelength may be used to form the structures. In the illustrated embodiment of
The dimensions of the photonic structures may also be based on a desired transmission bandwidth. In some embodiments, the desired transmission bandwidth is less than 200 nm, less than 100 nm, less than 50 nm, or less than 10 nm. For example, in the illustrated embodiment of
The height and the refractive index of the photonic structure may determine the phase shift of the light that is transmitted through the respective structure. In some embodiments, the photonic structures of the pixelated pattern may have a height between 50-500 nm. In some embodiments, the photonic structures of the pixelated pattern may have a height between 200-400 nm. For example, for the embodiment represented in
The pixelated pattern may include a subwavelength spacing between adjacent photonic structures. In some embodiments, the pixelated pattern may include a spacing between adjacent photonic structures of 100-200 nm. In some embodiments, the pixelated pattern may include a spacing between adjacent photonic structures of 140-170 nm. In other embodiments, other spacings between adjacent photonic structures may be used that include subwavelength spacings that are capable of causing the transmitted light to be converged to the detector.
In some embodiments, the merged pattern of photonic structures is configured to cause light transmitted through the photonic structures to converge, propagate as a collimated plane wave, or diverge as described herein.
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In some embodiments, the enhanced microdisk photonic structures are configured to cause light transmitted through the photonic structures to converge, propagate as a collimated plane wave, or diverge as described herein.
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Photonic structures, such as those described above, may be designed by calculating the electric field of an emitter within an integrated device. In some embodiments, finite-element mode analysis may be used to simulate the optical properties of the photonic structures. An exemplary process for calculating photonic structures for use in an integrated device is described in
Process 1400 begins at block 1401 determining a target field profile of the light transmitted through the photonic structures. The target field profile includes the amplitude and the phase of the electric field directly after transmitting through the photonic structures. In some embodiments, the amplitude and phase profile can be determined based on the desired beam shape after the photonic structures. In some embodiments, the amplitude and phase profile may be determined by calculating the amplitude and phase profile that would be produced by a stack of lenses, where the stack of lenses is configured to produce a desired beam shape. For example, the desired beam shape may include converging, collimated, and/or diverging components. Additionally, or alternatively, the desired beam shape may include a beam shape or size at the detector of the integrated device.
At block 1402, a dielectric material and periodicity are selected, in accordance with some embodiments. The photonic amplitude and phase modulation of the photonic structures may be based on the contrast between the background dielectric material and the dielectric material used to form the photonic structures. In some embodiments, silicon dioxide with a dielectric constant of approximately 1.46 may be used as the background dielectric.
In some embodiments, the dielectric material of the photonic structures has a refractive index between 1.7-4. For some applications, the signal-to-noise of the integrated device may be improved by using dielectric materials that have low extinction coefficients at the target wavelength. In some embodiments, the extinction coefficient may be less than 1, less than 0.6, or less than 0.2 at the target wavelength.
Dielectric materials that provide a high refractive index (1.7-4) and low extinction coefficients include metal oxides and silicon-based materials, in accordance with some embodiments. For example, metal oxides including Titanium oxide, tantalum oxide, aluminum oxide, zirconium oxide, and hafnium oxide may be used as dielectric materials. As another example, silicon-based materials may be used in addition to or as an alternative to the metal oxides as dielectric materials, silicon-based materials include polysilicon, amorphous silicon, silicon nitride, silicon carbide, hydrogenated amorphous silicon, and alloys thereof.
The periodicity of the photonic structures may be selected based on a desired feature size at the detection plane. In some embodiments, smaller feature sizes may result in smaller features in the detection plane, while larger features may result in larger features in the detection plane. For example, comparing the features of the field profile illustrated in
At block 1403, the shape of the photonic structures is selected, in accordance with some embodiments. In some applications, the photonic structures may be designed to provide isotropic transmission. For example, the photonic structures may have a cylindrical shape with a circular cross-section. Although the individual photonic structures may have a cylindrical shape to provide isotropic transmission, the overall transmission of light through the photonic structures will also depend on the periodicity and dimensions of the photonic structures.
At block 1404, an initial height for the photonic structures, target wavelength, and dielectric material are initialized. In some embodiments, the dielectric material may be chosen based on a desired feature size, extinction coefficient, manufacturing parameters, and/or refractive index. In some embodiments, the target wavelength may be 570 nm or 650 nm, as described herein. In some embodiments, the initial height may be set to an odd multiple of the half-wavelength of the target wavelength. For example, the initial height may be set to the target wavelength divided by twice the value of the refractive index at the target wavelength.
At block 1405, the optical transmission through the photonic structures in a model integrated device are calculated to provide an actual field profile that results from the modification of the light emitted from the sample as it is transmitted through the photonic structures. In some embodiments, the calculated transmission may be evaluated by the transmission through the iris, absorption by the dielectric material of the photonic structure, and/or feature size. For some applications, transmission through the iris is a desirable parameter and the model may have a minimum acceptable transmission set as an input. For some applications, absorption by the dielectric material of the photonic structure may be an undesired parameter and the model may have a maximum acceptable transmission set as an input parameter. For some applications, the feature size may be based on the periodicity and manufacturing constraints, thus the model may have an input that includes a range of acceptable feature sizes.
In some embodiments, the adjoint state method may be used to calculate the gradients of the transmission parameters with respect to the model parameters. When the simulation performance has not met a target transmission through the iris, absorption by the dielectric material of the photonic structure, and/or feature size, the model parameters may be updated based on the gradient calculation.
Process 1400 ends when the simulated performance has met acceptable performance parameters. The performance parameters may include the transmission through the iris, absorption of the dielectric material of the photonic structures, and/or feature size as described herein.
As described above, the inventors have recognized and appreciated that the size of the photonic features is based at least in part on the refractive index and that taller features may lead to more defects during fabrication. To enable smaller features, the inventors have developed high refractive index materials that have low extinction coefficients.
Process 1600 starts by preparing a top surface 1602 of the background dielectric material for deposition. In some embodiments, the background dielectric is silicon dioxide, as described herein. The background dielectric material may be deposited using chemical vapor deposition (CVD) in accordance with some embodiments. In other embodiments, other deposition techniques such as sputtering, atomic layer deposition, sol-gel, or plasma vapor deposition technique, plasma enhanced chemical vapor deposition, low pressure chemical vapor deposition, evaporation, and other oxide or non-oxide deposition techniques may be used, as aspects of the technology described herein are not limited in this respect.
Preparing the top surface of the background dielectric may involved planarizing or smoothing the top surface using a technique such as chemical mechanical polishing (CMP). Other polishing techniques may be used, as aspects of the technology described herein are not limited in this respect.
Following the preparation of top surface 1602, a layer 1604 of the photonic structure dielectric material is deposited using deposition techniques as described herein. The layer 1604 may be deposited with the desired thickness of the photonic structures.
Next, a layer of pattern resist material 1606 is deposited and patterned above layer 1604. In some embodiments, the pattern resist material may be a photoresist for patterning by exposure to light. In some embodiments, the pattern resist material may be a photoresist for patterning by exposure to an electron beam.
After exposure of the pattern resist material 1606, the exposed regions of layer 1604 are etched to form photonic structures 1608. In some embodiments, etching of the exposed regions of layer 1604 may use a plasma-based etching technique. The remaining resist material following the etch may be removed using a solvent wash.
After formation of photonic structures 1608, an overcoat of background dielectric material is deposited over and between photonic structures 1608. In some embodiments, the overcoat material may be silicon dioxide. The silicon dioxide may be deposited according to the deposition techniques described herein.
Having thus described several aspects of at least one embodiment, it is to be appreciated that various alterations, modifications, and improvements will readily occur to those skilled in the art. Such alterations, modifications, and improvements are intended to be part of this disclosure and are intended to be within the spirit and scope of the principles described herein. Accordingly, the foregoing description and drawings are by way of example only.
The terms “approximately,” “substantially,” and “about” may be used to mean with in ±20% of a target value in some embodiments, within ±10% of a target value in some embodiments, within ±5% of a target value in some embodiments, within ±2% of a target value in some embodiments. The terms “approximately,” “substantially,” and “about” may include the target value.
This application claims the benefit of U.S. Provisional Patent Application Ser. No. 63/254,330, filed Oct. 11, 2021, entitled “LIGHT COUPLING DEVICE,” which is incorporated herein by reference in its entirety.
Number | Date | Country | |
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63254330 | Oct 2021 | US |