CN116783448A - OCT design of miniature experiment table - Google Patents

Abstract

The present invention relates to an OCT system built on a micro optical bench or a semiconductor optical bench. The OCT system can use free space optics and avoid the use of fiber optics.

Description

OCT design of miniature experiment table

Technical Field

The present invention relates generally to the field of Optical Coherence Tomography (OCT) and Optical Coherence Domain Reflectometer (OCDR) systems. More particularly, the present invention relates to the use of micro-optics in the design/construction of low cost and/or compact OCT and OCDR systems.

Background

There is a great need for a compact, low cost Optical Coherence Tomography (OCT) and Optical Coherence Domain Reflectometer (OCDR) system. The OCDR system measures optical scattering/reflectivity in the sample along the optical sampling beam axis, while the OCT system combines a plurality of such measurements along a direction orthogonal to the axial illumination to produce a cross-sectional image or tomogram of the sample. Typically, the sample is biological tissue, but other types of materials are also possible.

To date, there have been two main approaches to achieving lower cost systems; classical "macroscopic" OCDR/OCT systems (e.g., bulk optical systems using separate bulk optics and/or fiber optics) are redesigned to reduce size and cost, and research is conducted into implementing OCDR/OCT systems in semiconductor chips called "OCT on chip". The redesign of macroscopic OCDR/OCT systems, which typically consists of a set of components (e.g., light sources, beam splitters, etc.) connected by fiber optics, has not heretofore achieved the desired cost reduction goals due to the cost of the individual components and the overall manufacturing cost of the system. While having the potential to achieve the size and cost reduction goals, the "on-chip OCT" system has prohibitively expensive non-recurring costs (NREs), such as high initial investment costs, such as research and development of optical sub-array circuit (PIC) design and fabrication, and investment in development and construction of large-scale semiconductor chip (e.g., PIC) manufacturing facilities.

An alternative to photonic integrated circuits is the use of so-called micro-optical or semiconductor optical benches. In a manner similar to a typical optical bench (or optical bench or optical circuit board) that can be a straight rigid rod or mount (usually marked with graduations) to which lenses, light sources and other optical components can be attached, a micro optical bench is a substrate mount (such as a ceramic bench or other mount material) upon which a location (e.g., cavity or pit) for receiving or attaching a micro optical device is constructed.

The potential of micro-optical benches in optical system construction has been recognized. For example, light sources (e.g., glance source light sources) have been implemented on micro-optical labs, and these light sources have been used to construct macroscopic (e.g., bulk-optical-based) glance source OCT systems. In addition to providing the glance source illumination light, a micro-optical bench is used to implement a k-clock interferometer that interferes the glance source light with itself with a small optical delay to produce a modulated signal that can be used to trigger an OCT detection system or to correct for non-linearities in the glance rate of the glance source. Optical coherence tomography and coherence domain optics methods in biomedical XXIII, 1086706 (2019, 2 months 22 days) in Bart Johnson, walid Atia, seungbum wo, carlos Melendez, mark Kuznetsov, tim Ford, nature Kemp, joey Jabbour, ed Mallon, peter Whitney, "tunable 1060nm VCSEL"Proc.SPIE 10867 for OCT and lidar co-packaged with pumps and SOAs; doi: an example of this embodiment is described in 10.1117/12.2510395.

Semiconductor optical benches are built/grown on PIC-type substrates (e.g., monocrystalline silicon or other semiconductor wafers). In addition to having openings on the surface (e.g., cavity or pit) for receiving discrete components, the semiconductor optical bench can also include integrated circuits. Semiconductor optical benches have been used for telecommunication applications (e.g., as optical transceivers). It is believed that the use of a semiconductor optical bench can potentially enable a reduced size and cost-effective lidar module for autonomous vehicles. However, to the best of the inventors' knowledge, semiconductor optical laboratories have not been used in the field of medical imaging or OCT.

It is an object of the present application to reduce the cost and size of OCT/OCDR systems.

It is another object of the present application to simplify the design and construction of OCT/OCDR systems, such as minimizing the use of fiber optics and maximizing the use of micro-optics.

It is another object of the application to provide parallelization of OCT and integration of scanning into a compact design.

It is a further object of the application to simplify the calibration of OCT/OCDR systems.

Disclosure of Invention

The above objects are achieved in an OCT/OCDR system that determines and maximizes the advantages of constructing an OCT/OCDR system on a micro-optical bench or a semiconductor optical bench. The present application uses a miniature or semiconductor optical bench to achieve a compact low cost Optical Coherence Tomography (OCT) and Optical Coherence Domain Reflectometer (OCDR) system. Both the micro-optical bench and the semiconductor optical bench can be described as supporting and aligning (e.g., separate) the (typically rigid) mounts of the micro-optical devices, but the semiconductor optical bench is generally smaller than the micro-optical bench and can differ in terms of build materials and manufacturing processes. Micro-optical benches are typically rigid carriers (such as ceramic benches or other base materials) that house several micro-optical elements that are placed by a robot and are typically actively aligned. Typical lens diameters are in the range of 0.5mm to 2.5 mm. Common packages used to house micro-optics benches are standard (e.g., 14 pin) butterfly packages or Surface Mount Device (SMD) packages (or other micro-packages/integrated circuit packages). Semiconductor optical benches are typically smaller than micro-optical benches and consist of a (e.g., grown) substrate (e.g., a silicon wafer) with recessed openings (e.g., receptacles, cavities, or pits) on the surface, wherein the recessed openings are designed to receive and hold micro-optics or other (e.g., discrete) components at predetermined (X, Y, Z) positions and orientations. This can eliminate (or reduce) the need for active alignment of the received components. Optionally, in accordance with the present application, the semiconductor optical bench can also have Integrated Circuits (ICs) and/or photonic integrated optical devices (PICs) (e.g., integrated optical circuits) built/grown/built in/on the semiconductor optical bench. Although the present application uses the term micro-optical bench (or micro-bench) for a slightly larger, generally rigid and/or relaxed alignment-based variation as described above, to distinguish from semiconductor optical benches, it should be appreciated that semiconductor optical benches are sometimes referred to in the art as micro-optical benches.

Implementing OCT/OCDR on a micro-optical bench or semiconductor optical bench can replace the bulk optics and fiber optics of conventional bulk optics (e.g., macroscopic) systems with micro-optics, thereby greatly reducing cost. The semiconductor optical bench approach also eliminates the need for active alignment, much like the "on-chip OCT" approach discussed above, and thus should be able to achieve the expected cost similar to "on-chip OCT". While the semiconductor optical bench concept can require more non-recurring costs (NRE) than the micro optical bench approach, both of these approaches can be implemented with lower development effort from the state of the art than the "on-chip OCT" concept, while still achieving greater cost reduction and reliability improvement compared to redesign of the "macro" OCDR/OCT system. The micro optical bench approach also provides greater flexibility in component integration because the components do not need to be composed of chip material.

Some features/innovations of the present invention include implementing an OCDR/OCT system on a micro-optical bench or semiconductor optical bench with micro-components (e.g., micro-optics), and/or eliminating fiber optics. Bulk optical components (such as used in "macroscopic" or "bulk optical" OCDR/OCT systems) are expensive and have additional significant costs associated with solving alignment problems between components. Fiber optics reduces system stability by increasing temperature dependent and motion sensitive polarization effects while solving many of the alignment challenges in bulk optical systems, variability in fiber length complicates the design and manufacturing process. The present method (particularly using a semiconductor optical bench) allows for the creation of a reliable free space optics OCT/OCDR system with minimal alignment/calibration problems.

Other objects and achievements of the present invention and a more complete understanding will become apparent and appreciated by referring to the following description and claims in conjunction with the accompanying drawings.

Several publications can be cited or referenced herein to facilitate an understanding of the present invention. All publications cited or referred to herein are incorporated by reference in their entirety.

The embodiments disclosed herein are merely examples and the scope of the present disclosure is not limited to them. Any feature of an embodiment mentioned in one claim category, e.g. system, can also be claimed in another claim category, e.g. method. The dependencies or references in the appended claims are chosen for form reasons only. However, any subject matter resulting from an intentional reference to any preceding claim, such that the claim and any combination of features thereof are disclosed and can be claimed regardless of the dependency chosen in the appended claims.

Drawings

In the drawings, like reference numerals/characters designate like parts:

fig. 1A shows a generalized frequency domain optical coherence tomography (FD-OCT) system.

Fig. 1B shows an example of a facial blood vessel image.

Fig. 1C shows an exemplary B-scan of a blood vessel (OCTA) image.

Fig. 1D shows OCT with orthogonal polarization states that use polarizers to create interference between light returning from the reference arm and the sample arm.

FIG. 1E illustrates an exemplary computer system (or computing device or computer).

Fig. 2A shows an exemplary OCT system 11 on a semiconductor optical bench 13 (or alternatively on a micro optical bench).

Fig. 2B shows an alternative embodiment of the OCT system of fig. 2A, wherein a window W (or other transmissive element) is used as an interface between the hermetically sealed laboratory bench 13 and the outside world, instead of using fiber optics.

Fig. 2C shows another alternative embodiment in which the reference arm (RefArm) is fully integrated on the optical bench 13, eliminating the need for a reference arm interface between the optical bench 13 and the outside world.

Fig. 2D shows an example of PS-OCT with two detection paths (PthA) and (PthB) implemented on a micro optical bench or a semiconductor optical bench 13.

Fig. 2E shows a quadrature detector approach, where the light in the detection arm (below the pinhole P) is first split by a non-polarizing beam splitter other than PBS before traveling to two separate polarizing beam splitters PBS2 and PBS 3.

Fig. 2F shows an alternative embodiment of an OCT system that uses a window W to connect between the laboratory table and the sample and reference arms, and fiber optic couplings (31 and 33) to connect detectors 38 and 40.

Fig. 2G and 2H illustrate two embodiments that address the problem of nonlinearity in the frequency sweep of a light source that can be found in a swept source OCT system.

Fig. 3 shows an example of a polarizing beam splitter PBS adapted to receive light in a detection arm and redirect it to the silicon wafer surface, and thus to integrated detectors D1 and D2.

Fig. 4A illustrates one method of combining multiple VCSELs (41/43) using a beam splitter 45.

Fig. 4B shows the use of another beamsplitter 51 to separate the light at the detection end of the OCT to a different detector (47/49), such as if the VCSELs 41/43 of fig. 4A are operated simultaneously.

Fig. 5 shows an alternative way of scanning a given location in a sample tissue with a plurality of VCSELs covering different wavelength bands.

Fig. 6 illustrates an exemplary guidance system for aiming an OCT imaging module (according to the present invention) at the pupil center.

Fig. 7A illustrates a pivot system for scanning an imaging module and illustrates a structure for moving the imaging module along a spherical surface using one or more pivot points.

Fig. 7B illustrates the displacement of the imaging platform of fig. 7A as the structure rotates or pivots.

Fig. 7C illustrates another pivot system for the scanning imaging module and shows a mechanism for mechanically moving the effective pivot point of fig. 7A.

Fig. 7D illustrates the displacement of the imaging platform of fig. 7C as the structure rotates or pivots.

Fig. 8 shows that the present invention can eliminate or reduce the need for a very limited area called a "pupil box" and optionally also an ophthalmic lens.

FIG. 9A illustrates another method of physically moving the scanning system (or "OCT component" OA 1) to scan the eye by using a polar coordinate-based system.

Fig. 9B shows a close-up front view of radial slider RS1 relative to the patient's eye.

Fig. 9C shows an exemplary scan pattern suitable for use with a sphere scan assembly, and in particular for use with an OCTA scan.

Figure 10 illustrates the placement of a fixation target behind the sphere plane traversed by the present imaging system.

Fig. 11 shows sequentially acquiring a limited field of view by translating the present scan module.

Fig. 12 shows an arrangement in which the light beam incident on the scan mirror is a beam line, all of which hit the scan mirror at the same location, but enter from different angles along the line.

Fig. 13A shows another way of converting a 2D array into a set of points with equal spacing in the vertical direction by slightly rotating the array.

Fig. 13B shows another way of achieving an effect similar to that of fig. 13A with a VCSEL array in the form of a parallelogram, in which each row or column is shifted slightly perpendicular to the scan direction.

Fig. 13C shows that the number of VCSELs in the vertical and horizontal directions can be significantly different.

Fig. 14A and 14B illustrate passing an array of light beams through a lenslet array (or lens array) to adjust the amount of numerical aperture multiplied by the pitch, thereby optimizing imaging on the retina.

Fig. 15 shows an exemplary OCT B-scan image of a normal retina of a human eye, and exemplary determinations of retinal layers and boundaries of various specifications.

Detailed Description

The OCDR system measures optical scattering/reflectivity in the sample axially along the optical sampling beam, while the OCT system combines a plurality of such measurements in a direction orthogonal to the axial illumination to produce a cross-sectional image or tomogram of the sample. OCT angiography (OCTA) is an extension of OCT that recognizes (e.g., presents in image format) blood flow in a tissue layer. The OCTA can identify blood flow by identifying time-varying differences (e.g., contrast differences) in a plurality of OCT images of the same retinal region and designate the differences that satisfy a predetermined criterion as blood flow. Since OCDR, OCT, and OCTA are similar in construction and share many components, this discussion focuses on OCT, while those skilled in the art will be able to apply this discussion to OCDR and OCTA. It is to be understood that the present invention is similarly applicable to OCDR and OCTA, unless otherwise indicated.

In general, optical Coherence Tomography (OCT) uses low coherence light to produce two-dimensional (2D) and three-dimensional (3D) internal views of biological tissue or other samples. Examples of OCT systems provided in U.S. Pat. nos. 6,741,359 and 9,706,915, which are incorporated herein by reference in their entirety.

Fig. 1A shows a generalized frequency domain optical coherence tomography (FD-OCT) system OCT-1 suitable for use in the present invention for collecting 3D image data of an eye E. The FD-OCT system OCT-1 comprises a light source LtSrc1. Typical light sources include, but are not limited to, broadband light sources with short coherence lengths or glancing laser sources. Sample light (SLt) from a light source LtSrc1 is typically transmitted along the sample arm through an optical fiber (Fbr 1) to illuminate the sample, e.g. the eye E; a typical sample is tissue in the human eye. In the case of spectral domain OCT (SD-OCT), the light source LtSrc1 can for example be a broadband light source with a short coherence length, or in the case of swept source OCT (SS-OCT), it can be a wavelength-tunable laser source. The sample light can typically be scanned with a scanner Scnr1 located between the output end of the optical fiber Fbr1 and the sample E such that the light beam (dashed line Bm) is scanned laterally over the sample area to be imaged. The light beam from the scanner Scnr1 can pass through the scanning lens SL and the ophthalmic lens OL and be focused onto the imaged sample E. The scanning lens SL is capable of receiving the sample beam SLt from the scanner Scnr1 at a plurality of angles of incidence and producing substantially collimated light, which the ophthalmic lens OL is then capable of focusing onto the sample. The present example shows a scanning beam Bm that needs to be scanned in two lateral directions (e.g., X and Y directions in a cartesian plane) to scan a desired field of view (FOV). An example of this is point field OCT, which uses a point field beam (a beam focused to a point) to scan a sample. Thus, the scanner Scnr1 is illustratively shown as comprising two sub-scanners: a first sub-scanner Xscn for scanning a spot field beam through the sample in a first direction (e.g., a horizontal X-direction); and a second sub-scanner Yscn for scanning the spot field beam on the sample in a direction transverse to the second direction (e.g., the vertical Y direction). If the scanning beam is a line field beam (a beam focused into a line), such as line field OCT, which is capable of sampling the entire line portion of the sample at one time, only one scanner can be required to scan the line field beam through the sample to span the desired FOV. If the scanning beam is a full field beam (e.g., full field OCT), then the scanner is not required and the full field beam can be applied over the entire desired FOV at once.

Regardless of the type of beam used, light scattered from the sample (SctL) is collected. In the present example of fig. 1A, the scattered light SctL returned from the sample is collected into the same optical fiber Fbr1, which is used to guide the illuminating light SLt.

The reference light RefL from the same light source LtSrc1 travels together with the sample light SLt until separated into a separate reference path (e.g., reference arm) by the optical splitter LSpltr1 (implemented herein as a fiber coupler Cplr 1). It should be appreciated that different types of optical splitters are known. The reference path includes an optical fiber (Fbr 2) and a retroreflector (RR 1) with adjustable optical delay. Those skilled in the art will recognize that a transmissive reference path can also be used and that the adjustable delay device can be placed in the sample or reference arm of the interferometer. The collected scattered light from the sample (e.g., scattered light SctL returned from the sample arm) is combined with reference light RefL returned from the reference arm by an optical combiner LCmbnr1, embodied herein as a fiber-optic coupler Cplr1. Also, it should be understood that different types of light combining mechanisms are known in the art. The reference light RefL and the scattered light SctL then travel together to an OCT light detector dttr 1 (e.g., a photodetector array, a digital video camera, etc.), wherein interference between the reference light RefL and the scattered light SctL produces an OCT signal OS, which can be passed to an electronic processor Cmp1 (or a computer system) that converts the observed interference into depth information of the sample. The depth information can be stored in a memory associated with the processor Cmp1 and/or displayed on a display (e.g., computer/electronic display/screen) scr 1 (e.g., a scanned image such as shown in fig. 1B and 1C). The processing and storage functions can be located within the OCT instrument, or the selection functions can be offloaded onto (e.g., executed on) an external processor (e.g., an external computing device at a local or remote site) to which the collected data can be transferred (e.g., by a peer-to-peer connection or wired or wireless via a computer network such as a local area network, wide area network, the internet, etc.).

In this example, the interference between the reference light RefL and the scattered light SctL occurs at the optical combiner LCmbnr1 (implemented as a fiber coupler Cplr 1), but can also occur at the optical component between the optical combiner LCmbnr1 and the detector dttr 1. For example, if the reference light RefL and the scattered light SctL have orthogonal polarization states when combined by the light combiner LCmbnr1, interference can be generated by a polarizer (not shown) at 45 degrees relative to the polarization states of RefL and SctL, as described in U.S. Pat. No. 7,126,693B 2, which is incorporated herein by reference in its entirety. For purposes of illustration, the system 700B of U.S. patent No. 7,126,693B 2 is reproduced herein as fig. 1D, and the polarizer is identified as component 752B. For discussion purposes, the component that generates interference will be referred to hereinafter as the interference generator IG.

Returning to FIG. 1A, while a single fiber port is shown leading to detector Dtctr1, one skilled in the art will recognize that various designs of interferometers can be used for balanced or unbalanced detection of an interference signal. Alternatively, the output analog OCT signal AOS from detector dttr 1 can be converted to a digital OCT signal DOS by an analog-to-digital converter (ADC) AD1 and then provided to a processor (e.g., an internal or external computing device) Cmp1.

An example of a computing device (or computer system) is shown in FIG. 1E. This unit can be dedicated to data processing or to perform other tasks which are very versatile and not dedicated to OCT devices. The processor (computing device) Cmp1 can comprise, for example, a Field Programmable Gate Array (FPGA), a Digital Signal Processor (DSP), an Application Specific Integrated Circuit (ASIC), a Graphics Processing Unit (GPU), a system on a chip (SoC), a Central Processing Unit (CPU), a General Purpose Graphics Processing Unit (GPGPU), or a combination thereof, that can perform some or all of the processing steps in a serial and/or parallel manner with one or more host processors and/or one or more external computing devices. A more complete discussion of an exemplary computing device is provided below.

The sample and reference arms in the interferometer can consist of bulk optics, fiber optics, or a hybrid optical system, and can have different architectures such as Michelson, mach-Zehnder, or common path based designs as understood by those skilled in the art. A light beam as used herein can be any carefully oriented light path. Instead of mechanically scanning the beam, the light Field can illuminate a one-or two-dimensional region of the retina To produce OCT data (see, e.g., U.S. Pat. No. 9332902; D. Hillmann et al, "Holographic Optical Coherence Tomography," Optics Letters,36 (13): 2390 2011;Y.Nakamura et al, "High-Speed Three Dimensional Human Retinal Imaging by Line Field Spectral Domain Optical Coherence Tomography," Optics Express,15 (12): 7103 2007;Blazkiewicz et al, "Signal-To-Noise Ratio Study of Full-Field Fourier-Domain Optical Coherence Tomography," Applied Optics,44 (36): 7722 (2005)). In time domain systems, the reference arm needs to have a tunable optical delay to produce interference. Typically, balanced detection systems are used in TD-OCT and SS-OCT systems, while spectrometers are used at the detection ports of SD-OCT systems.

The present invention can be applied to any type of OCT/OCTA/OCDR system, such as those discussed above, but is herein fully or partially constructed on micro and/or semiconductor optical tables, or similar devices with specially configured/shaped grooves, each groove designed to receive and hold a particular micro-optical device (or other (e.g., discrete) component) at a predetermined location, preferably at a predetermined height and orientation. For ease of discussion, one or more features of the invention are described as applied to a semiconductor optical bench, it being understood that the same features can be applied to a micro optical bench unless otherwise indicated. Other fiducials commonly found in photolithography processes can also be used to place a particular micro-optic device in a predetermined location. Aspects of the present invention can be applied to any type of OCT/OCTA/OCDR system or other type of ophthalmic diagnostic system and/or a variety of ophthalmic diagnostic systems including, but not limited to, fundus imaging systems, field of view testing devices, and scanning laser polarimeters.

In SS-OCT system configurations that use light sources with long instantaneous coherence lengths, variable delays (e.g., adjusting the optical path length of the reference arm according to the depth/axial position of the sample region to be imaged, as described elsewhere herein) can eliminate the need to position the sample within a depth imaging window (of the system). Alternatively, a large optical path length mismatch between the reference light and the sample light can be tolerated. For example, a large imaging depth can be generated that is large enough that in a typical imaging scene, the sample is always within the depth imaging window. The acquired image can then be cropped to display only the region of interest (e.g., the desired depth range). The region of interest can be dynamically changed during acquisition, for example to compensate for sample motion. However, this clipping method requires sufficiently fast digitizing electronics (e.g., analog-to-digital converters) to resolve the high frequency interference signal corresponding to the maximum imaging depth, which can be difficult to achieve using a stand-alone video card, video capture card, daughter board, and other discrete components, particularly in a cost-effective manner. However, high speed detection and/or digitizing electronics (circuitry) can be implemented by integrating the detection and/or digitizing electronics (circuitry) directly onto the same substrate/mount as the semiconductor optical bench (or onto an IC on the same substrate/mount as the micro optical bench, e.g., in a manner similar to a system on chip, SOP, or integrated circuit board approach), on which the OCT system of the present invention is configured. Higher operating speeds can be achieved at least in part due to the smaller traces (and optionally lower rail-to-rail voltage swings) associated with common integrated circuits, which avoids/mitigates high frequency interference problems between long traces/leads/wires and large capacitive loads, large signal propagation delays, and general timing problems associated with routing traces/leads/wires for interconnection with external discrete components.

Alternatively, the analog OCT signal can be downmixed (or modulated or down-converted or mixed or frequency shifted) with a frequency corresponding to one edge of the desired imaging window (minimum or maximum path length mismatch), thereby creating a downmixed OCT signal having a spectral content corresponding to that obtained when the reference arm path length is adjusted to that imaging depth. Such downmixing is typically accomplished by frequency mixing the OCT signal with a downmixing frequency to produce a frequency at the OCT signal plus or minus the downmixing frequency, and then filtering to remove (or select or separate) the summed (or modulated or mixed or frequency shifted) frequencies. The down-mix frequency can be selected such that the zero frequency is slightly beyond the sweep range of interest to avoid noise around the zero frequency and/or to provide a buffer whereby the down-mix frequency can be adjusted if the signal is present in this frequency band around the zero frequency; in standard SS-OCT systems, a similar effect can be achieved by making the reference arm length slightly beyond the sample depth range of interest. Mixing OCT signals down in this manner can provide a number of advantages. Most relevant for the present optical bench (semiconductor optical bench or micro optical bench) design is that the down-mixing allows for a significant mismatch of the (optical) path length between the reference arm and the sample arm, enabling the integration of a short reference arm (e.g. shorter than the distance to the sample (e.g. retina) location) on the micro bench (or semiconductor optical bench) which does not leave the micro package, and enabling the down-mixing frequency to be adjustable to enable the elimination of the need for mechanical or optical adjustment of the reference arm or sample arm path length.

To quickly find the appropriate downmixing frequency, the source can first be swept slowly, generating a large scan range at a relatively slow a scan rate, and then, once the desired scan depth is identified, switched to a faster scan rate and corresponding a scan rate, with the appropriate downmixing frequency to properly set the scan depth to obtain a more limited scan range.

Electronic adjustment of the downmix frequency provides a fast adjustment of the depth (axial position) of the imaging window, enabling adjustment of the scan depth to follow the sample (e.g. retina) (e.g. its curvature) during acquisition, even moving the scan depth to follow the sample between a scans within B scans or during acquisition (e.g. adjusting the path length to follow the total sample position, sample surface or specific layers in the sample during acquisition). Various methods can be used to track a surface or layer, examples of which include adjusting the down-mixing frequency based on the spectrum of the OCT signal or based on the identification of specific layers or boundaries in the OCT image found by signal processing of OCT. In the case of retinal imaging, the surface that can be followed will be the RPE, or the entire retina can be tracked. To track the entire retina, the OCT digitally acquired spectrum can be kept near the midpoint of the digitally supported bandwidth range, while to track the RPE, the peak spectral signal, which can correspond to the RPE, can be kept at a fixed frequency.

The down-mixing method for moving the scan depth has the advantage of not adding a doppler shift to the OCT signal, such as the doppler shift produced by moving the reference mirror to adjust the scan depth. This doppler shift is undesirable because it affects the image, resulting in phase washout and axial position displacement in SD-OCT systems or axial Point Spread Function (PSF) broadening in swept source systems. Electronic adjustment of the down-mix frequency can be achieved by using a voltage controlled oscillator.

As an alternative to electronically implementing the down-mixing, the same effect can also be achieved by shifting the optical frequency of the sample light or the reference light. To generate the corresponding frequency shift, an optical modulator, such as an acousto-optic modulator or an electro-optic modulator, can be used. In a hybrid mini-bench/PIC system, such modulation can be provided in the PIC.

One possible complication that can occur during angiographic imaging is the variation of the down-mixing frequency during acquisition, where two OCT scans taken at slightly different times are compared, the difference between the scans being indicative of motion typically due to blood flow. If the down-mix frequency is adjusted between two such sweeps, it can be necessary to correct for this down-mix frequency variation before calculating the difference between the sweeps so as not to create artifacts.

In some embodiments, the above-described downmixing concept can be selected to achieve a large optical path length mismatch between the sample arm and the reference arm, but the optical path length adjustment can be selected to be optically implemented for alignment of the sample in the axial direction. This can still be done within a miniature package without moving parts. For example, a scanning delay line can be implemented using an electro-optic deflector in combination with a grating and a mirror.

In a preferred embodiment, the OCT system described above is implemented on a semiconductor optical bench, i.e., the grooves (recesses) of the micro-optics are etched in the semiconductor and the micro-optics are placed without the need for an active alignment process. Such a system is particularly suited for mass production because it benefits from the scalability of the semiconductor manufacturing process. By patterning the entire semiconductor wafer using photolithography, grooves of micro-optical devices can be etched in parallel for hundreds or thousands of devices. The micro-optics can then be robotically assembled over the entire wafer at a time, followed by a wafer level packaging step in which a cap wafer is bonded on top of the base layer, creating a hermetic seal. Alternatively, another semiconductor optical bench can be used instead of the cap wafer. The "lid" semiconductor optical bench can be configured with corresponding/complementary grooves (or patterns) configured to receive a portion of the micro-optics extending above the surface of the opposing "base" semiconductor optical bench. In this configuration, the micro-optics are sandwiched between two semiconductor optical benches and maintained in alignment by two opposing semiconductor optical benches. The cover wafer does not necessarily have to be made of a semiconductor material, but can also be made of glass or ceramic, for example, without semiconductor properties. This is beneficial in the case of operating wavelengths where typical semiconductor materials (e.g., silicon) are opaque. Having at least one of a transparent bench wafer or a transparent cover wafer is desirable because the bench or cover typically serves as a window through which light can be coupled out of and/or into the micro-package. The hermetically sealed package can contain a vacuum to allow elements within the package, such as MEMS elements of a Vertical Cavity Surface Emitting Laser (VCSEL) or MEMS-based beam steering mirrors, to move faster. Alternatively, it can contain a specific gas that prevents or reduces degradation of the active semiconductor optical material, for example, damage due to oxidation at the face of the gain chip.

Because photolithographic patterning of semiconductor wafers produces grooves and/or other alignment fiducials with nanometer precision, semiconductor optical tables are particularly advantageous for applications requiring precise control of optical path length. These include, for example, multi-beam OCT systems, in which a sample is scanned with multiple parallel beams and no imaging depth mismatch between the individual imaging channels is desired, or, for example, for quadrature detectors, in which the interference signals to be detected are separated and acquired with a relative phase shift of 90 degrees in order to reconstruct a complex signal.

Fig. 2A shows an exemplary OCT system 11 on a base, such as a semiconductor optical bench 13 (or alternatively on a micro optical bench). In this example, light from light source LtSrc1 passes through half-wave plate (or retarder) 15 (denoted herein by symbol λ as a wave plate, which is an optical device that changes the polarization state of the light wave passing through it) to first polarizing beam splitter (or beam splitter) PBS0. The separated light then leaves the laboratory bench through the first quarter-wave plate 17 to the sample (along the sample arm) and leaves the laboratory bench 13 through the second quarter-wave plate 19 to the reference arm. The return light from the sample arm (SctL) and from the reference arm (RefL) is combined at the first polarization beam splitter PBS0 and passed through the second half wave plate 21, the first lens 23 (denoted herein by the symbol L) the (optional) pinhole P and the second lens 25 to reach the second polarization beam splitter PBS1, which is preferably at 45 degrees with respect to the polarization states of the return light SctL and RefL, and is used as an interference generator IG (e.g. which generates interference). The interference signal is then sent to detectors 27 and 29 (the detectors are denoted herein by the symbol D). The purpose of the various half-wave plates in this specification is to change the polarization state such that a portion of the light passes through the polarizing beam splitter and a portion of the light is reflected by the polarizing beam splitter. The same function can be performed by waveplates having different amounts of phase retardation. For example, although the polarization state can be rotated 45 degrees using a half-wave plate of 22.5 degrees so that half of the light is reflected by the polarization beam splitter and half of the light is transmitted through the polarization beam splitter, the same 50/50 beam splitting can be achieved with a quarter-wave plate rotated 45 degrees, thereby obtaining circularly polarized light. One advantage of this approach is that all of the waveplates can be quarter waveplates, reducing the number of different parts required. Possibilities for microlenses used in the system include, but are not limited to, spherical lenses, GRIN lenses, spherical lenses, aspherical lenses, or freeform lenses.

Fig. 2B illustrates an alternative embodiment of the OCT system of fig. 2A. Elements similar to those in fig. 2A have similar reference numerals and are described above. In fig. 2B, a window 18A/18B (herein denoted by the symbol W) or other transmissive element is used as an interface between the hermetically sealed laboratory bench 13 and the outside world, instead of using fiber optics.

Fig. 2C shows another embodiment of an OCT system according to the present invention. Elements similar to those in fig. 2A and 2B have similar reference numerals and are described above. In fig. 2C, the reference arm RefArm is fully integrated on the optical bench 13 (semiconductor optical bench or micro optical bench), eliminating the need for a reference arm interface (e.g., 18B in fig. 2B) between the optical bench 13 and the outside world. In this example, the retroreflector (e.g., similar to RR1 of fig. 1) is implemented as a mirror 20 (denoted herein by symbol M). Since interference is obtained when the reference path length matches the sample path length to within the coherence length of the light, several ways in which this can be achieved are contemplated herein. A reference arm path length can be created on the optical bench 13 that is approximately (or substantially) equal to the sample arm path length. Alternatively, a light source with a long coherence length can be used in a glance source system, and then only a limited scan depth can be used by not displaying the full scan depth, or by down-mixing/demodulating the OCT signal prior to digitizing, as described above.

Another embodiment can eliminate the need for external sample arm optics. Alternatively, the sample can be placed in contact with or in the vicinity of the micro-optical package. In such an embodiment, all of the sample arm optics are part of a micro-package. For example, focusing optics can be used to simultaneously act as an exit/entrance window for the sample beam.

Since most of the costs in micro-optical bench and/or semiconductor optical bench solutions are in NRE and packaging, the complexity of OCT solutions can be increased without significantly increasing the overall cost, thereby making more complex designs such as Polarization Sensitive (PS) OCT viable. Fig. 2D shows an example of PS-OCT with two detection paths PthA and PthB implemented on a micro-optical bench or semiconductor optical bench 13. Elements similar to those discussed above have similar reference numerals, and repeated examples of similar elements have similar reference numerals with the letter "b" appended at their ends. In this example, PBS0 and PBS0b deflect light into their corresponding reference arms RefArm and RefArmb, each containing a quarter wave plate 19/19b, rotating the polarization state of the light 90 degrees in two passes, so that all reference light is returned through PBS0 and PBS0b into the corresponding detector paths PthA and PthB. The two polarization states returned from the sample (e.g., scattered light SctL through window 18A) are separated by PBS0b, the first polarization state passing through polarizer PBS0 to detector path PthA, and the second polarization state being reflected by PBS0b to detector path PthB. Light returning from the sample to the detector path PthA is reflected by PBS0 because its polarization state is rotated 90 degrees by the combination of half-wave plate 15b and Faraday rotator 22 (Faraday rotator, which is a type of polarization rotator, is denoted herein by symbol FR). This combination of half-wave plate and faraday rotator also slightly rotates the polarization of the light propagating towards the sample arm so that some of the source light is deflected into the reference arm RefArmb. As previously described, balanced detection is achieved in each detection path by rotating the polarization state 45 degrees before it is incident on the polarizing beam splitters PBS1/PBS1b in front of their corresponding detectors 27/29 and 27b/29 b.

Fig. 2E illustrates another approach involving quadrature detection. In this method, the light in the detection arm (under the pinhole P) passes through the half-wave plate 21 and is first split by the non-polarizing beam splitter non-PBS24 before it travels to the two separate polarizing beam splitters PBS2 and PBS3, which reflect their signals to the corresponding detectors 30/32 and 34/36. In one of the paths between non-PBS24 and PBS3, a quarter wave plate (λ/4) 26 is added to introduce a quarter wave retardation. Quadrature detection enables the system to distinguish between negative and positive differences in path length between the reference arm and the sample by suppressing the complex conjugate mirror of FD-OCT, thereby expanding the viable scan range over a distance where the reference arm path is equal to the sample arm path.

It is also desirable to integrate other aspects of the clinical OCT system into a micro-optical or semiconductor optical bench to further miniaturize the system and reduce cost. Examples of possible include:

1) A second imaging modality, such as a scanning laser ophthalmoscope for imaging or tracking the retina or both, is integrated.

2) Providing a fixation target to the eye, a microelectromechanical system (MEMS) mirror can be used to direct the fixation target to different locations on the back of the eye to change the fixation position of the patient.

3) Focusing and/or aberration correction of OCT samples to account for differences in optical characteristics of different eyes. Such correction can be accomplished by, for example, a moving lens within the package, a tunable mirror (e.g., also within the package), an Alvarez micro lens, or an electrically tunable lens.

Another advantage of implementing OCT on a semiconductor optical bench (or micro optical bench) is that OCT can then be packaged in, for example, a dual in-line package (DIP) or a Surface Mount Device (SMD) (or other micro package or integrated circuit package) and soldered onto a printed circuit board along with other chips, such as processing electronics for OCT signals.

In one or more of the above embodiments, the polarizing beam splitters PBS output their respective two light beams to corresponding detectors, which can be integrated within (on) the optical bench 13. Fig. 3 shows an example of a polarizing beam splitter PBS adapted to receive light in a detection arm and redirect it to the surface of a silicon wafer. In this example, detectors D1 and D2 are integrated into a semiconductor optical bench.

Fig. 2F shows an alternative embodiment of an OCT system according to the present invention. All similar elements as described above have similar reference numerals. Similar to the case of fig. 2B, windows W18A/18B are provided to connect from the laboratory bench 13 to the sample arm and the reference arm. In this case, fiber optic couplings (31 and 33) are used to connect with detectors 38 and 40. However, as previously mentioned, it is highly desirable to eliminate fiber optics in OCT systems to improve stability and manufacturability. Fiber optics in a typical OCT system provides two main advantages: alignment and spatial mode filtering are simplified to ensure single mode interference between light from the reference arm and the sample arm. The present micro optical bench and semiconductor optical bench technique addresses the need for alignment, but does not directly address the need to achieve single mode interference of the return signal. To limit the light reaching the detector to a single mode, or at least close enough to a single mode to achieve good performance of OCT, the return light from the sample and reference arms can pass through one or more pinholes P (not shown in fig. 2F) prior to detection, as shown in fig. 2A-2E. Moreover, to simplify alignment, and to ensure that the reference light and the sample light are confined to the same single mode, it is desirable that the sample light and the reference light pass together through the same pinhole after being combined. By combining the two light beams on the same optical path using a polarizing beam splitter, rather than having them interfere at the beam splitter as in classical systems, which provides a shared path for the light source and reference light, such pinholes can be placed therein, as shown in fig. 2A to 2E.

Nonlinearity in the frequency sweep of the light source can be a problem in a swept source OCT system. Fig. 2G and 2H illustrate two embodiments that address this non-linearity problem. All elements similar to those in fig. 2C have similar reference numerals and are described above. The embodiment of fig. 2G and 2H incorporates a second (on-board) interferometer 12, illustratively shown as including a beam splitter 14 (denoted herein by the symbol "BS"), two mirrors 20A and 20B, and a detector 16. By directing a portion of the light from light source LtSrc1 to interferometer 12 (e.g., a gauge or michelson interferometer), a k-clock can be generated for triggering SS-OCT acquisition, or a reference signal can be acquired. Any of these configurations can be used to linearize the sweep (e.g., by a sweep signal), where the k-clock flip-flop directly linearizes the acquisition and the reference signal can be used to determine the nonlinearity and thus correct it. The light used to generate the k-clock or reference signal can be picked up immediately after the source using the PBS and half-wave plate. For example, in fig. 2G, a part of the light from the light source LtScr1 is guided to the interferometer 12 through the half-wave plate 15A and the polarization beam splitter PBS 4. Alternatively, as shown in fig. 2H, a portion of the light from the light source LtScr1 can be directed to the interferometer 12, followed by the michelson interferometer 12, through a partially transmissive mirror 20C (and optionally another quarter wave plate 19A) in the reference arm RefArm, which eliminates several components compared to the design shown in fig. 2G.

To avoid additional components for spatial filtering, the active area of the photodiode can be used as a spatial filter if the size of the photodiode is selected accordingly. In this case one would focus the collected light onto the detector and use a small detector, typically less than a few times the focused beam size.

Depending on the application, the light beam coming out of the micro-optics package can be coupled to additional optics (e.g., mirror scanner, beam expander, relay optics to the sample). To avoid reflections from these optical surfaces back to the detector in the interferometer, a quarter wave plate (17 in FIG. 2A) in the sample path can be placed outside the micro-bench, one option being between the last optics and the sample. In this configuration, reflections from any component in the sample path before the quarter wave plate will be directed away from the detector due to its polarization state.

Reflections from various optical components in the system can lead to detector saturation, VCSEL or optical amplifier damage, and/or artifacts or ghosts in the OCT signal. These undesirable reflections can be reduced or eliminated in a variety of ways, including but not limited to: using pinholes and pore sizes; limiting the effective area of the detector; the components are bonded to reduce index mismatch, anti-reflective coatings, tilted components, and polarization isolation.

The OCT systems described in fig. 2A-2E (and fig. 2G and 2H) can avoid the use of optical fibers and/or semiconductor waveguides. The absence of the optical fiber avoids signal fluctuations due to birefringence changes that occur when the optical fiber moves or changes in temperature, and the absence of a semiconductor waveguide, which typically has a submicron diameter, improves collection and propagation efficiency and alignment stability, for example if the probe is dropped or vibrated.

In conventional OCT systems, light in the reference path is reflected back to the interferometer using corner retroreflectors. Corner retroreflectors direct incident light over a wide range of angles of incidence, making it ideal for reliably redirecting reference light in the presence of systematic tolerances and misalignments. However, corner retroreflectors are expensive and difficult to manufacture in sizes less than 1 mm. If the beams are directed towards the centre of the component they can also change the polarisation on the wavefront. The main advantage of the described micro-optic system is the tight tolerances on the mounting of the optical components, which can allow the use of flat mirrors instead of retroreflectors (20 in fig. 2C and 2D). If the system is unable to ensure adequate alignment of the sample and reference in a test using this configuration, the system can instead include a lens (i.e., cat-eye retroreflector) with a mirror at its back focal plane in the reference path.

As previously mentioned, the cost of the system can be very low. However, the cost of an SS-OCT system is typically determined by the cost of a tunable light source. It is therefore desirable to use a particularly inexpensive light source in order to achieve an overall low system cost. Vertical Cavity Surface Emitting Lasers (VCSELs) are popular in many high capacity applications such as data centers, optical computer mice, distance and proximity sensors, biometric facial recognition, and so forth, and are therefore typically very inexpensive. It has been previously shown that their center wavelengths can be tuned by adjusting their laser drive currents. Thus, a source or a combination of a plurality of such sources is well suited for use in the presently described system. One problem with VCSELs, particularly thermally driven VCSELs, is the limited range of wavelengths over which they can scan. Since the axial resolution of OCT systems is determined by the swept bandwidth of the light, it can be desirable to combine multiple VCSELs with different center wavelengths to achieve an increased combined bandwidth and, in some cases, an increased total optical output power.

Fig. 4A illustrates one method of combining multiple VCSELs (e.g., glancing sources) 41/43 using a beam splitter 45. In this method, light from the glance source 41 passes through the beam splitter 45 and light from the glance source 43 is reflected by the beam splitter 45. In this way, the two VCSELs 41/43 are combined to define a combined beam 46.

Referring to fig. 4B, if VCSELs 41/43 of fig. 4A are operated simultaneously, which is desirable from the standpoint of optical output power, it is desirable to split their light to different detectors (47/49) at the detection end of OCT by using another beamsplitter 51.

Alternatively, multiple VCSELs can be operated sequentially, and then light from each VCSEL (e.g., two or more VCSELs) can be detected on the same detector. For example, if the VCSEL has a limited duty cycle, it can be beneficial to operate the VCSELs sequentially. The limited duty cycle can be due to the need for the VCSEL to cool between thermally driven sweeps, or in the case of MEMS VCSEL, the need for the MEMS to return to its original position to begin the next sweep.

Fig. 5 shows an alternative way of scanning a given location in a sample tissue with a plurality of VCSELs covering different wavelength bands. In this example, a plurality of different VCSELs (e.g., VCSEL-1, VCSEL-2, VCSEL-3, and VCSEL-4) sequentially illuminate the same location on a (tissue) sample by focusing the different VCSELs along the line and moving the scan with the distance between the focused VCSELs. Fig. 5 shows a graph of time versus (illuminated) position on a tissue sample. In this way, a plurality (e.g., four) of VCSELs sequentially scan the same given location (e.g., location Loc 1) on the sample. Alternatively, a combination of multiple current-tuned VCSELs can be used. For example, more than two VCSELs and pairs/groups of saccades with large spectral intervals can be used spectrally in parallel, then the second group is used sequentially. The VCSELs can be linearized and the VCSEL array can be inserted into a slot in a micro optical bench (or semiconductor optical bench). Alternatively, one or more VCSELs can be integrated into a semiconductor wafer used to construct the semiconductor of the optical bench substrate/mount, just like an electronic device or detector. The use of VCSELs is particularly advantageous in this regard, because they emit out of the laboratory bench vertically, directly, and thus simple mirrors or turning prisms can be used to redirect the VCSEL light along the plane of the semiconductor-based laboratory bench.

Another problem with VCSELs is their limited optical output power. For high quality OCT imaging of biological samples, they can therefore be used in combination with semiconductor optical amplifiers. However, three aspects unique to the OCT systems described herein enable VCSELs to be used for high quality OCT imaging of biological samples without an optical amplifier, which has not been demonstrated yet:

1. high optical efficiency of free space micro-optics interferometers. Similar optical efficiencies are not feasible for fiber-based designs, at least in the 800nm and 1060nm wavelength ranges, because there is no effective circulator at these wavelengths and therefore a large amount of power is always lost on the path to the sample.

2. The use of a low noise detector instead of a balanced detector based on P-i-n and a transimpedance amplifier. Because the performance of the systems described herein can be significantly limited by the amount of reference light required to overcome detector noise, it is desirable to use a very low noise detector compared to prior art OCT systems that do not typically lack source power. This allows shot noise to have limited sensitivity at low reference power. Thus, by adjusting the wave plate in front of the first polarizing beam splitter accordingly, a large part of the available optical power can be transmitted to the sample. A low noise detector suitable for use in the systems described herein is an electron injection detector (E-I detector). They exhibit low noise because their inherent amplification is less dependent on their RF signal bandwidth.

The Relative Intensity Noise (RIN) of the light source is also typically not a problem if only a small reference power is required to overcome the detector noise as the primary noise source. Thus, balance detection in such a system can be omitted and still be limited by shot noise. However, because balance detection not only suppresses RIN, but also common mode signals, such as autocorrelation signals, it is often desirable to still use a balance detection arrangement.

3. A VCSEL array and thus a plurality of parallel beams are used. This will multiply the total optical sample power by the number of VCSELs in the array. Thus, the same or higher sample power can be achieved as in prior art OCT systems using, for example, MEMS tunable VCSELs and optical amplifiers. The concept of multiplexing by using VCSEL and detector arrays will be described in more detail in the later section of this document.

Another embodiment can add a partially transmissive element to the sample arm that produces a reflection that then interferes with the reference light. Since the above embodiments already have multiple optical surfaces in the sample arm, reflection from one of these optical surfaces can be used instead of introducing additional elements. Because the reflection will in any case be closer than the sample, its interference signal will have a lower frequency than the OCT signal. It can thus be separated from the OCT signal, for example, by separating the signals and high-pass/low-pass filtering the two copies accordingly. For example, a low frequency can be used for the reference interference signal and a high frequency can be used for the OCT signal. The reference interference signal will then be digitized in parallel and used to correct for the wavenumber nonlinearity of the glance and for phase-stabilizing the OCT data. Alternatively, the reference signal and OCT signal can be digitized together and separated in digital space. This would avoid the need for a second data acquisition channel.

The invention also envisages other aspects of the OCT system implemented on or actually integrated into a micro-optical bench or a semiconductor optical bench. For example, a MEMS mirror scanning the OCT beam can be implemented on a laboratory bench, or integrated onto a semiconductor-based laboratory bench by lithography. The MEMS mirror can provide the OCT system with complete lateral scanning capability or be a component of the system. In particular, the MEMS mirror is capable of providing a fast scan over a limited field of view, with a more extended field of view provided by the secondary scanning system. Limiting the field of view of a MEMS scanning system integrated on a micro-optical bench and/or a semiconductor optical bench (i.e., e.g., to less than the desired/intended/target full (or more extended) scanning FOV of the system, e.g., a wide field scanning system) has several advantages. First, the angular range of MEMS mirrors is typically on the order of +/-6 degrees, making it difficult to handle the full field of view required for typical OCT systems. In classical (e.g., bulk optical) OCT systems, a relatively large MEMS mirror can be used and the MEMS imaged as a reduced spot to increase the field of view, but for both the mirror and OCT system this is more difficult for the limited space within the DIP (or other typical semiconductor package). Furthermore, by limiting the size of the MEMS mirror, the scan speed can be increased, but at the cost of not being able to further shrink the beam to increase the field of view. Note that the scanning speed of the MEMS mirror can be further increased by resonant scanning about one scanning axis. Finally, the scanning behavior resulting from a fast scan of a small region that moves relatively slowly across the retina is beneficial. The fact that the region of interest moves relatively (or relatively) slowly over the retina enables the optimal performance of the OCT system to be maintained, adjusting the axial scan depth, focus, and/or other aberrations such as astigmatism to match the characteristics of the retina at a given location.

One challenge in this configuration is to relay the beam from the scanner to the patient's pupil while maintaining a large working distance and compact design of the OCT module. The introduction of a converging beam onto a MEMS scanner provides design flexibility including the possibility of relaying the scanner with a single lens positioned at a distance slightly greater than the focal length of the lens. The vergence of the beam can also be adjusted by translating the lens before the scanner, providing a focusing element for the design. This configuration provides a compact design with minimal components for pupil relay and focusing.

The need to address fast scanning using mirrors integrated on micro/semiconductor optical benches also means that wide field scanning systems can scan at slower rates, providing more flexibility in their design. Examples of options implemented by reduced scan speed requirements include mirrors driven by galvanometers or by motors, or indeed moving OCT systems including MEMS mirrors over the field of view. The ultra-compact OCT interferometer design implemented by micro-optical bench and semiconductor optical bench solutions makes moving the entire OCT interferometer more feasible, but can also use this combination of small field-of-view fast scan (on micro-bench) plus wide field-of-view slower scan in more classical fiber-optic based OCT systems, where the OCT sample arm fiber tip, MEMS scanner, and small field-of-view optics move as a set over the entire field of view.

If wide field imaging is provided by moving the OCT system or fiber tip, it is desirable that the system move along a sphere centered around the pupil (e.g., spherical surface/plane) in order to maintain a fixed working distance relative to the pupil. In addition to the advantage of maintaining the working distance, the mechanism for generating motion on the sphere can also be designed to have elements that remain parallel to the spherical surface as it moves along the sphere. The OCT/optical imaging system can then be mounted with its optical axis perpendicular to the element parallel to the sphere, ensuring that the imaging system remains pointed toward the center of the sphere where the pupil is located as the system scans over the field of view.

For a number of reasons, it can be desirable to slightly deviate the center of the sphere from the pupil during scanning. Possible reasons include, but are not limited to:

1) Alignment is simplified by allowing flexibility in pupil position relative to the scan center.

2) The center of the sphere is moved back from the eye to move the mechanism for driving the OCT system's position on the sphere away from the face and the eye.

3) The center of the sphere is moved toward the eye to minimize the change in distance to the retina as it is scanned across the field of view.

In the case of a shift in the center of the sphere relative to the pupil position, it can become important to maintain additional angular alignment capability between the surface parallel to the sphere and the axis of the OCT imaging system, which must be directed toward the pupil during scanning. To maintain this alignment with the pupil, it can also be desirable to have a pupil tracking component with an OCT imaging system mounted that monitors the alignment axis of the OCT system relative to the pupil and adjusts the angular alignment system to maintain the OCT system directed toward the pupil.

Fig. 6 shows an example of such a system with a camera pointing along an axis or parallel axis to the OCT system. That is, fig. 6 provides an example of a guidance system for aiming the OCT imaging module at the pupil center of the eye 67. In this illustration, a pupil camera and scanning module (e.g., OCT system) are shown that are collectively implemented by element 61. Feedback from this camera will then be used to adjust the alignment system to align the camera to the pupil and thus also the OCT system to the pupil. That is, the pupil camera is able to track the center of the eye pupil and drive (e.g., provide a feedback signal to) for example, a two-axis gimbal 63 that provides a tilting function to maintain alignment of the camera and OCT imaging module 61. In this example, the gimbal 63 is attached to a movable scan module platform (or imaging module plate) 65, which preferably provides spherical motion (e.g., motion conforming to a spherical surface). In summary, the pupil camera tracks the pupil center, driving a two-axis gimbal to maintain alignment of the camera and OCT imaging module 61. Thus, pupil tracking can account for eye movement and misalignment due to the wide FOV pivot system. Thus, the present system is capable of maintaining alignment over a predetermined area (e.g., a 2 x 2 inch area), which is a much larger area than is conventionally required, where the patient's eye needs to be placed to achieve effective imaging (e.g., pupil box).

If the alignment system is sufficiently calibrated, the camera can also be mounted directly onto the parallel surface and then feedback can be used to align the OCT system without affecting the camera system. In the event of cataracts or other clouding of the pupil portion, such a system can be maintained in alignment with a particular location on the pupil to optimize image quality. Without such turbidity, the system would be very well able to maintain alignment of the OCT system with the pupil center.

Fig. 7A illustrates a transport system that defines spherical motions for an imaging module (e.g., pupil camera and/or scanning module and/or medical imaging device). The transport system of this embodiment comprises a pivot system for scanning an imaging module according to the invention, wherein the acquisition angle is driven/defined by one or more rotating structures (or rods) 72/73, the rotation of which defines a sphere (or sphere) plane/surface 70 (e.g. defines a sphere motion). Fig. 7A shows a particularly simple method of moving the imaging system (e.g., attached to the imaging module plate 65) along the surface of the sphere (or a portion of the sphere) by using pivot points 71A on the sphere, e.g., displaced 90 degrees relative to the axis of the eye, wherein the curved structure 72 extends from this pivot point 71A along the surface of the sphere to a second pivot point 71B on the opposite side of the sphere. The structure 72 is then rotated relative to the two pivot points 71A/71B to sweep the structure 72 across the surface of the sphere. As shown, if the second structure 73 is mounted on a sphere at 90 degrees rotation relative to the first structure 72, and also rotates in a similar manner, the intersection of the two structures 72/73 can be placed at any point on the sphere. Thus, by mounting the imaging module plate (or scanning module platform) 65 to the intersection of (e.g., between) the two structures 72/73, a desired behavior of the platform 65 can be created, which platform 65 can be translated to all points on the sphere portion, the surface on the platform 65 always being parallel to the sphere surface and thus having a point perpendicular to the sphere center where the pupil is located. Note that although it would be desirable to obtain optimal mechanical properties if the two structures 72/73 were rotated 90 degrees relative to each other on a sphere, the positions of the rotation points need not be separated by 90 degrees. If the structures are not separated by 90 degrees, all points on the sphere can still be reached, but the force generated by rotating one will not propagate directly along the axis of the other structure, creating some additional friction.

It can be undesirable for the pivot point to lie in the same plane as the center of the sphere in which the pupil lies. Since the patient's face and body can also be in this plane, it is difficult to place the pivot points in these locations without striking the human body. As previously mentioned, one solution is to move the sphere away from the body, thereby moving the pivot point and sphere center to the front of the eye and body. If so, the OCT axis alignment system can need to correct the offset to maintain alignment with the pupil. This can be achieved by a tracking system that keeps the optical axis of the system aligned with the pupil, or by compensating for such displacement by applying an angle-dependent offset on the alignment system, or both. This ability to tilt and point to the scan module is shown in fig. 7B. That is, fig. 7B shows the displacement of the stage when one of the structures rotates.

Alternatively, the effective pivot point can be mechanically moved. Fig. 7C shows one such example of mechanical movement to a pivot point. In this way, the clearance with the face 74 can be increased by moving the pivot point. In this schematic illustration, the effective pivot point (e.g., pivot point 75) is moved a given distance 77 relative to position 76. Moving the pivot point in this or a similar manner enables the use of a smaller portion of the sphere while also moving the rotation mechanism away from the face 74. Fig. 7D shows the displacement of the platform when one of the structures is rotated.

This approach has the added advantage that a small FOV system moves in an arc around the pupil while maintaining alignment with the pupil, as it greatly reduces the need to place the pupil in a very limited area (referred to as a "pupil box") defined by the optics of the system. Fig. 8 shows that the present system 80 eliminates the need for a wide field ophthalmic lens 81 and corresponding pupil box 82 of a conventional optical system 83. Pupil box 81 can conventionally define a three-dimensional region of space (relative to the ophthalmic device) in which the patient's pupil should be located for effective imaging. While it is theoretically possible to increase pupil tracking of mobile optics in a conventional wide field system 83, the size and weight of the optics required to support wide FOV imaging makes this impractical. In contrast, the present system provides no optics near the eye (indicated by arrow 84), and the flexible pointing of the optics eliminates the pupil box (as indicated by arrow 85). The above method makes use of limited FOV optics, which are lighter in weight, capable of tracking the pupil by moving the optical system. It is particularly useful for wide field (> 50 degrees) imaging systems where movement of a heavy-duty optical head for pupil tracking becomes impractical.

Fig. 9A illustrates another transport system for defining spherical motion of an imaging module according to the present invention. As described above, the present transport system physically moves the scanning system/imaging module (or "OCT assembly" OA 1) with respect to sphere planes/motions to scan the eye, but the present embodiment includes a polar coordinate based system. In this example, the above-described spherical motion of OCT assembly OA1 is provided by a spherical (or partially dome-shaped) surface or frame (Sphr) within housing H1. Alternatively, the surface Sphr can be minimally of sufficient size to receive the patient's eye, and thus can be relatively small compared to typical macroscopic OCT systems. In this example, the housing H1 is shown schematically as being 5 inches (12.7 cm) high. Fig. 9A provides an interior side view (or cut-out view) v1 of housing H1, a front view v2 of housing H1, and an exploded view v3, showing that a portion of OCT assembly OA1 extends from the exterior of surface Sphr to the interior thereof along a curved radial slide (or guide) (RS 1) that can be disposed along an interior, curved plane of surface Sphr. The rotor Rtr or other rotating armature/mechanism is capable of rotating the surface Sphr (e.g., about the axial center of the patient's pupil), as indicated by arrow r 1. In this way, OCT assembly OA1 can be rotated unidirectionally or bidirectionally along a circular path (e.g., azimuthal direction) at a given radial distance from the center of surface Sphr. Additionally, OCT assembly OA1 can be moved radially (outwardly or inwardly) from the center of surface Sphr along radial slider RS1 (or other radially movable carriage/holding assembly or rail system), as indicated by arrow rd 1. By the combination of rotor Rtr (rotating surface Sphr) and radial slider RS1, OCT assembly OA1 can be positioned anywhere along the sphere plane defined by the interior of surface Sphr.

Fig. 9B provides close-up, frontal and contour views of radial slider RS1 relative to a patient's eye. In this example, OCT assembly OA1 is shown having a rectangular frontal profile, while in the example of fig. 9A, OCT assembly OA1 is shown having a circular frontal profile. It should be appreciated that OCT assembly OA1 is not limited to any one configuration. As shown, radial slide RS1 can be azimuthally rotated (e.g., by rotor Rtr or other rotational axis, as indicated by arrow r 1) about the center of the patient's pupil (as indicated by dashed line Cntr) such that OCT assembly OA1 can be moved to any position within the spherical surface defined by surface Sphr. In this way, OCT assembly OA1 can be maintained at a fixed distance (e.g., two inches or 5.08 cm) from the pupil of the patient. In this example, a fixed target Fx1 (e.g., mirror, light emitting diode, micro electronic display, etc.) is fixed to the center of the spherical surface aligned with the patient's pupil. Alternatively, the fixation target Fx1 can be moved to (or fixed at) any other desired position along the surface Sphr.

Returning to fig. 9A, a fixed target Fx1, which can be a mirror, is shown at the center of the surface Sphr and can be provided by a fixed laser FL1, which eliminates the need for focusing adjustment of the fixed target Fx 1. The fixed laser FL1 can project a still or moving image (e.g., a movie) onto the fixed target Fx 1. Alternatively, the fixation target Fx1 can be attached to the surface Sphr and rotate therewith, or be held in fixed rotation relative to the eye. Furthermore, the stationary laser FL1 can be independent of the surface Sphr and project the stationary target Fx1 at any internal location on the surface Sphr, such as if the interior of the surface Sphr is reflective, e.g., has a mirror surface. In this way, the stationary laser FL1 can project a stationary target Fx1 at a plurality of stationary positions relative to the patient's pupil, or can define a stationary path Pth1, such as a radial path opposite the radial path rd1 of the OCT assembly OA1, as the surface Sphr rotates. Other elements, such as pupil alignment cameras P1, P2, and P3, can be attached to and rotate with spherical surface Sphr.

Fig. 9C shows an exemplary scan pattern suitable for use with a sphere scanning assembly, particularly, but not limited to, an OCTA scanning application. Multiple scan areas or patches (Ptch 1, ptch 2) can be created in radial and azimuthal steps to define a composite circular scan area. For example, if the OCT assembly has a limited scan field of view of, for example, ±6 degrees, each scan patch can have a limited scan width (LS 1) of 12 degrees. As shown, the scan patch can be composed of a shorter scan patch Ptch1 and a longer scan block Ptch2, which are radially oriented and overlap each other to define an effective (e.g., compound, such as by clipping) larger field of view of, for example, 100 degrees. As indicated by inwardly and outwardly directed arrows A1, some scan patches (e.g., shorter scan patches Ptch 1) can be scanned when the OCT assembly is moved radially inward toward the center of the spherical surface, while other scan patches (e.g., longer scan patches Ptch 2) can be scanned when the OCT assembly is moved radially outward from the center of the spherical surface. In this way, successive azimuthal and radial scans can be achieved by one or more scanning beams. Alternatively, if the entire scan area/region defined by the patch Ptch1/Ptch2 is defined by the scan field of view of the (e.g., stationary) OCT assembly, the scan patch Ptch1/Ptch2 can be scanned while the OCT assembly is in the corresponding rest position before the OCT assembly is moved to the next scan position to capture the next scan patch. As described above, the OCT assembly can include one or more single point scanners, line scanners, or full field scanners. If the OCT assembly comprises a plurality of scanning beams operating in parallel, as described above, the effective scanning speed of the system can be increased.

Although any combination of radial and azimuthal movements can be made to scan the eye, if the OCT system is parallelized such that there are multiple OCT scanning beams into the eye, and one is interested in OCT angiography, one can expect a series of radial scans with azimuthal rotations between them, as shown in fig. 9C, to keep the rotation of the array fixed during each radial scan. In particular, this will ensure that there is no rotation between repeated vascular scans, as such rotation will change the horizontal and vertical spacing between the collimated light beams, and thereby make it difficult to repeat the a-scan pattern (at the same location) for angiography.

In some aspects, the above method is similar to clipping, in which a person manually captures a set of images with a limited field-of-view instrument, and then combines them to produce a wide field-of-view image. In such manual methods, the patient is typically required to look at a fixed target and then take a series of images with the fixed target at different locations. The eye then views each image in a different direction, so the photograph shows different parts of the eye, which can then be clipped. The method described herein differs in that the fixed target does not move between sets of subfields and all subfields are acquired sequentially without an alignment step between the subfield acquisitions.

One challenge in cropping images is to fix the target within the imaging field of view of the center image, rather than the peripheral image. This can result in the need for two fixed target systems, one within the field of view of the optic and one outside the optic. In the present system, this problem can be avoided, and only one fixed target system is required to cover the central and peripheral subfields. As shown in fig. 10, this can be accomplished by placing a fixed target 86 behind the sphere plane 70 traversed by an imaging system (e.g., a scanning module or scanning head) 87. The small scan module 87 can briefly block the fixed target 86 as the scan module 87 passes in front of the fixed target 86. That is, the fixed target 86 is blocked occasionally as the imaging system 87 passes in front of it, but since the fixed target is typically designed to blink, a blinking pattern can be set so that the fixation is turned off when the imaging system 87 briefly blocks it. The method also simplifies the system by eliminating the need for optics to combine the fixed target with the imaging system. It is also possible to have multiple fixed targets (not shown) at different locations behind the scanning optics to produce a more classical montage image in which multiple images are acquired in different fixed ways and then combined. This can be done by making a separate complete acquisition of each image, or illuminating one target during acquisition followed by illuminating the next target. If there are different fixed positions to be present during a single image acquisition, a preferred approach can be to have a single fixed target that moves during acquisition to expand the field of view obtained by the system. This is made possible by a single fixed target within and outside the field of view for the image optics.

Fig. 11 shows a scan pattern 90 in which the scan (or acquisition) field of view of the scan module defines a region of interest 92 and arrow 91 shows translation of the scan module to define the region of interest scan to achieve optimized OCT imaging. This shows another advantage of the present system over classical scanning systems in that the limited field of view is sequentially acquired (scanned) by the translational scanning module, the system moving relatively slowly over the retina, enabling adjustment of imaging parameters of the system during acquisition to account for variations in the optical characteristics of the retina over the field of view. Parameters that can be adjusted during acquisition include, but are not limited to, scan depth, focus, astigmatism, polarization, aberrations, and scan range.

Since OCT typically uses near infrared light for imaging, which does not significantly disturb the patient, data can be acquired for significant periods of time up to 30 seconds or more. However, movement of the retina during acquisition can be challenging, creating distortion in the image and/or in the region of the eye with missing OCT data. To address this problem, people often use a second imaging system to track the retina, such as in the Heidelberg spectra ^TM And Zeiss Cirrus ^TM As in OCT instruments. There is also a relatively advanced development in OCT, known as OCT angiography, whereby the movement of blood is detected by repeated scanning to image micro-blood vessels in the eye. It is proposed herein that both of these capabilities can be combined with current new scanning methods by using repeated scans to detect blood flow in the eye and to measure the overall movement of the retina. Historically, OCT angiography was accomplished by repeating a single B-scan, each consisting of a long (10-60 degrees) line scan across the retina, where each B-scan took about 5 milliseconds to acquire. When the retina moves, these acquisitions do not overlap, and then the information from the secondary tracking system is used to correct the position of the OCT scan and reacquire the data. In the present case, the eye is acquired by taking over the 5 millisecond period rather than a 1D (one-dimensional) lineA limited 2D (two-dimensional) region of the eye, the present system is capable of detecting motion in 2D by determining an a-scan in the 2D region that matches the repeat scan. As a simple example, if there is a 500k A scan/second system with a delay of 5 milliseconds between repeated scans, a 50×50A scan area can be scanned, corresponding to an area of approximately 50×20um=1 mm×lmm, thus enabling tracking of movements up to 1mm every 5 milliseconds. Thus, the present scanning method enables the same repeated scanning to be used for OCT angiography and retinal tracking, thereby enabling retinal tracking without the need for a secondary tracking system.

In some cases, it can also be desirable to have a micro-optics based OCT system that does not have lateral scanning capabilities, where lateral scanning would be provided by moving or rotating the micro-optics OCT. For example, a micro-optic OCT module without an on-board beam scanner can be configured to instead drag/move the micro-optic OCT module (and its unscanned OCT beam) across the skin surface in order to produce a B-scan of the skin tissue. Such a system can include optics external to the micro or semiconductor optical bench for coupling light into the sample, or can directly illuminate the sample without any additional optics. Similarly, there are applications in which micro-optics systems can be used without scanning in optical coherence domain reflectometer mode. An example of such an application can be measuring the distance to a sample in a microscope in order to optimize the focus of the microscope.

Another aspect of OCT systems that can be integrated as part of a micro-package is focus adjustment. Tunable lenses, sometimes referred to as liquid lenses, have proven to provide very fast focus adjustment, but are generally limited by their clear aperture. Thus, the beamlet diameter inside or near the micro-package is very matched to such a tunable lens. In a preferred embodiment, the focus tunable lens will be placed in the pupil conjugate plane.

The use of MEMS tunable VCSELs enables a wider spectral tuning bandwidth. These devices are tuned by means of MEMS elements by adjusting their cavity length. They are in the form of optical and electrical pumps. The optical pump tunable MEMS VCSEL typically includes at least a laser diode and MEMS VCSEL for optical pumping. The electrically pumped tunable MEMS VCSEL typically includes at least MEMS VCSEL having an electrically driven active gain section. Electrically and optically pumped VCSELs are typically combined with optical amplifiers to increase optical power. Alternatively, the MEMS tunable VCSEL can be co-packaged with an aligned optical amplifier. Silicon (e.g., semiconductor) optical tables can use different alignment methods. For example, microscopy and image recognition can be used, and/or laser beams can be sent through the system and their position or intensity optimized. These components are typically packaged individually and fiber-coupled to each other, or are packaged together on a micro-bench within a butterfly package. Their manufacturing process includes multiple active alignment steps and fiber coupling and packaging steps for each device. To further reduce the size and cost of these devices and to be able to manufacture larger volumes of these devices, it would be beneficial to construct such devices on silicon (semiconductor) optical tables that rely on passive placement and alignment steps in order to benefit from the scalability of the wafer-level fabrication and packaging process.

VCSELs, detectors and pinholes can all be fabricated as arrays at the wafer level with sub-millimeter/micron spacing between elements of the array. Thus, a parallel micro or semiconductor optical bench OCT system can be configured, wherein the VCSEL, detector and/or pinhole is an array, and an array of beams from the VCSEL propagate in parallel through the individual optics of the micro/silicon bench (multiple OCT optical beams through the same optical component, with each beam having at least one corresponding detector for generating OCT signals). For example, assuming a 3 x 3 array of VCSELs with corresponding detector and pinhole arrays, one can go from one acquisition channel to 9 acquisition channels, all 9 channels sharing the same lenses and mirrors, thus no additional optics are required in the OCT interferometer. This can also be done with a 1D array of VCSELs, which can be a more natural pattern for scanning, but is less efficient in filling the lens, which typically has a circular aperture for the optical beam to pass through. It is desirable to package as many beams as possible into a set of optics of a given size, giving maximum filling regardless of the pattern. For example, hexagonal packing with 2,3, 2=7 lines of beams, or 3,4,5,4,3 =19 lines of beams can be desired. As mentioned above, the optimal arrangement of the light beams through the optics can be different from the arrangement of the light beams required for scanning. In this case, the beam arrangement between the OCT interferometer and the scan mirror can be changed with one or more optics that appropriately deflect each beam.

Fig. 12 shows a configuration for converting a 2D array (e.g., a 3x3 array) of light beams 101 (black dots 103 representing focused light beams) into a 1D array (e.g., represented by black dots 105) of light beams. The (collimated) beam 107 incident on the scan mirror 109 is a beam line, all of which hit the scan mirror 109 at the same location, but enter from different angles along the line. As shown in fig. 12, given the 2D array of beams 101 in the OCT interferometer, optics between the OCT interferometer and the scan mirror 107 are expected to convert the 2D array of beams 101 to a 1D array. In this example, a 2D array of lenses (with beam deflection) 111, a 1D array of lenses (with beam deflection) 113, and a lens 115 provide this conversion. Converging/diverging beam 117 is transmitted between the 2D array of beams 101 and the 2D array of lenses 111. The collimated beam 115 is transmitted between the 2D array of lenses 111 and the 1D array of lenses 113, and the converging/diverging beam 105 is transmitted between the 1D array of lenses 113 and the lenses 115.

Referring to fig. 13A, another way to convert a 2D rectangular array of dots 121 into a set of dots with equal spacing in the vertical (transverse to the scan) direction is to simply slightly rotate the array relative to the scan direction, as shown. Black dots represent a rotated 4 x 4 array of dots 121, gray dots 123 represent scan dots (e.g., resulting scan pattern), and arrows 125 indicate the scan direction. Referring to fig. 13B, another way to achieve a similar effect is to arrange the array of VCSELs 127 in a parallelogram, each row or column moving slightly perpendicular to the scan direction 129. Likewise, gray points 128 indicate scan points. Referring to fig. 13C, a parallelogram array 131 with different horizontal and vertical VCSEL spacing is shown. As previously described, gray points 132 indicate scan points. Arrow 133 indicates the scanning direction. To maximize the use of clear circular apertures for the lenses, it is desirable that the 2D array be approximately square (the height and width of the array are nearly equal). Since the spacing between VCSELs 131 can be significantly different in the horizontal and vertical directions, the number of VCSELs can be significantly different in the vertical and horizontal directions to achieve this.

The VCSEL array will have a given pitch (spacing between VCSELs) and beam numerical aperture (e.g., a dimensionless number that characterizes the angular range over which the system can accept or emit light). Numerical aperture times pitch remains a conservation when imaging VCSELs with single element optics. Fig. 14A provides an example of a VCSEL array 141 (e.g., 200 μm by 300 μm in size), with a single lens 143 located between the VCSEL array 141 and the scanner 145. However, the required "pitch" or "sampling interval" times the "beam numerical aperture" on the retina can be mismatched with the amount of conservation from the VCSEL array. To address this problem, it can be necessary to pass the beam array 146 (e.g., from the 500 μm x 600 μm VCSEL array 147) through the lenslet array (or lens array) 148, as shown in fig. 14B, to adjust this amount of conservation to optimize imaging on the retina. In the example of fig. 14B, the lens array 148 reduces the divergence of the beam, increasing the distance to the lens. The lateral spacing between the beams at the lens array is constant, but the lens focal distance and distance from the lens to the scanner (mirror) 145 increases.

The use of VCSEL arrays increases the total optical sample power of the device depending on the number of VCSELs in the array. This allows each individual channel to use lower sample power than typical single beam OCT systems, and still achieve equal or better image quality and/or imaging speed. In particular, it has not been demonstrated to enable the use of VCSELs for high quality OCT imaging of biological samples without an optical amplifier.

Although omitting all fiber optics or other waveguide optics is described as advantageous in the several embodiments described above, some micro-optics OCT systems can include waveguides, for example as part of an edge-emitting laser, semiconductor optical amplifier, or optical modulator. The micro-optical OCT system can further be an assembly of multiple planar waveguides and/or Photonic Integrated Circuits (PICs) coupled together using micro-optics. For example, semiconductor optical bench assembled using wafer level assembly and packaging steps can represent a cost-effective way to combine and package multiple optical components made of different materials in a miniature hermetically sealed package. This is particularly desirable in cases where different components cannot be integrated on a single PIC due to material incompatibility, for example when lasers or amplifiers made of gallium arsenide are combined with a passive silicon nitride PIC. The micro-optical OCT system can be further adapted to the electronics included in the same package, discrete analog electronics, and electronic integrated circuits. In particular, systems built on silicon optical tables (i.e., silicon wafers) are capable of achieving specific depth electronic and optical integration, as the same silicon wafer can be processed to include electronic integrated circuits. Such systems can include not only passive and active optical components, but also electronic integrated circuits for driving light sources, signal conditioning, analog-to-digital conversion, signal processing (e.g., image reconstruction), data transmission, and data storage.

In hybrid PIC/micro-optical devices, the micro-optics are not only able to function as a coupling between waveguides and/or photonic integrated circuits as described above. In some systems, it can be desirable to use micro-optics to perform some of the functions of the system, while other systems use optical sub-integration circuits, which would then be on a common substrate and co-packaged.

Further situations where fiber optics can be desirable include optical fibers that couple to an external light source of the micro-optic assembly or optical fibers that collect light in the detection arm and direct it to an external photodetector. The optical fiber in these cases can be, for example, a single mode optical fiber, a polarization maintaining optical fiber, a polarizing optical fiber, or a double clad optical fiber.

Although the micro-optics described herein are shown as propagating light in only a single plane, it can be desirable to direct at least one optical beam, for example, in a direction perpendicular to that plane. For example, it is desirable that the sample arm or sample and reference arm exit through the lid of the package rather than its side walls. In this case, the cover is transparent at the operating wavelength or comprises a window or lens integrated in the cover.

In summary, some of the innovations/features provided in the present application include:

1) Various aspects of the OCT/OCDR system are implemented on a micro optical bench or a semiconductor optical bench.

2) Implementation of a hybrid system, wherein some macroscopic aspects of the OCT/OCDR (e.g., sample arm and reference arm) are external to the micro-or semiconductor optical bench, and the rest of the OCT/OCDR system is bonded to the micro-bench.

3) Components, including for example scanning capabilities, can be included on a micro or semiconductor optical bench other than OCT/OCDR interferometers alone, by using micro-electromechanical systems (MEMS) mirrors mounted on the bench, or integrated into the semiconductor bench through semiconductor fabrication processes.

4) The optical components of the OCT/OCDR system are used as part of the hermetic seal of a micro-or semiconductor optical bench to minimize optical surfaces. For example, if the transmission of light from a micro or semiconductor optical bench to the outside is not done by fiber optics, the light must pass through the transmissive element in the transition from the hermetically sealed OCT/OCDR engine to the outside. Instead of using a window for the transmissive element as shown in W in fig. 2B, a quarter wave plate can be placed at this transition between the hermetically sealed OCT/OCDR engine and the external sample and reference arm, as shown in fig. 2A. The quarter wave plate can then be made part of the hermetic seal, eliminating the need for window W, as shown in fig. 2B. Other optical components required for operation of the OCT/OCDR can also be used for hermetic sealing at this transition point for different configurations of OCT/OCDR.

5) The creation of free space optics OCT/OCDR systems is also shown without active alignment (any parts other than that located at the laboratory bench, such as viable reference and sample arms). This can be achieved in particular with semiconductor optical tables, in which the precision of the component placement is extremely high. The socket opening of the semiconductor optical bench can be designed to hold the component in a predetermined alignment orientation with high precision.

6) Components of multiple semiconductor optical bench OCT/OCDR systems can be packaged and/or tested at the wafer level.

7) Integrating additional IC electronics (e.g., detector electronics and analog-to-digital converters) into a (e.g., silicon substrate) semiconductor optical bench package can further reduce costs such that ultra-short electrical paths can enable the high-speed electronics required for ultra-fast OCT/OCDR systems. For example, integrated circuits built on the substrate of the semiconductor optical bench itself can avoid signal propagation delay and timing problems associated with routing traces/wires for interconnecting external discrete components, thereby achieving higher clock speeds.

8) If the detector is to be integrated into a wafer, the polarizing beam splitter can be configured to deflect the detection path beam downward from the horizontal into the integrated detector, as shown in FIG. 3. Also, VCSELs integrated onto a semiconductor laboratory bench can emit light directly vertically onto the laboratory bench and couple back to the OCT/OCDR system on the laboratory bench through a turning prism.

9) The mixing of the analog OCT/OCDR signal with an adjustable frequency (e.g., modulation reference frequency) oscillator will enable fast all-electronic path length adjustment. For example, the analog output from the detector can be mixed with a self-adjusting oscillator to demodulate the analog output to a target frequency range to establish a desired image detection range. The self-adjusting oscillator can be digitally set (and/or controlled by a feedback mechanism) to achieve the target mixing frequency and thus fast Z-tracking. This approach also avoids the occurrence of doppler shifts when the sampling depth is changed.

10 Transmission of return light from the reference arm and/or sample arm can pass through one or more pinholes to eliminate unwanted light (particularly multiple scattered light from the sample) that would not interfere properly.

11 Transmission of light returned from the reference and sample arms through a common pinhole. This results in a pattern match between the reference and sample arm light to maximize interference between the arms. This can be done before or after interference occurs (e.g., before or after PBS1 in fig. 2A). As shown in fig. 2A, an advantage to having a balanced detection system before interference is that only one pinhole is required, rather than one pinhole in front of each of the two detectors. In addition to reducing the number of pinholes required, this can also improve balanced detection, since the use of the same pinholes for light reaching both detectors produces consistency in the spatial filtering of light reaching both detectors. Alternatively, the photodiode itself can act as a pinhole. To achieve this, for example, the diameter of the active region of the photodiode can be made close to the diameter of the focused light spot.

12 Quadrature detectors can be implemented on the present micro or semiconductor optical bench without active alignment.

13 Micro or semiconductor optical bench OCT/OCDR systems can form a handheld OCT/OCDR system without fiber optics or semiconductor waveguides.

14 A micro-or semiconductor optical bench can contain all the optical components of the OCT system except for aspects of the sample arm, eliminating the need to pass optical beams other than the sample beam out of the micro-or semiconductor optical bench, and optionally enabling component placement tolerances to be relied upon to align the reference arm.

Fig. 2A, 2B, 2E and 2F show a hybrid solution with external sample and reference arms. Additionally, FIG. 2A shows the use of a 1/4 wave plate as part of a hermetic seal at the edge of a micro or semiconductor optical bench.

Descriptions of various hardware and architectures suitable for use with the present invention are provided below.

Optical coherence tomographic imaging system

As described above, FIG. 1A illustrates a generalized optical coherence tomography system suitable for use with the present invention. Various ways of creating cross-sectional images (e.g., B-scans) are known in the art, including, but not limited to: along a horizontal or X-direction, along a vertical or Y-direction, along a diagonal of X and Y, or in a circular or spiral pattern. The B-scan can be in the X-Z dimension, but can be any cross-sectional image including the Z-dimension. Fig. 15 shows an exemplary OCT B-scan image of a normal retina of a human eye. OCT B-scans of the retina provide a view of the retinal tissue structure. For purposes of illustration, fig. 15 determines retinal layers and layer boundaries for various specifications. The identified retinal boundary layer includes (from top to bottom): inner Limiting Membrane (ILM) Lyer1, retinal nerve fiber layer (RNEL or NFL) Layr2, ganglion Cell Layer (GCL) Layr3, inner Plexiform Layer (IPL) Layr4, inner Nuclear Layer (INL) Layr5, outer Plexiform Layer (OPL) Layr6, outer Nuclear Layer (ONL) Layr7, junctions between Outer Segment (OS) and Inner Segment (IS) of photoreceptors (indicated by reference symbol Layr 8), outer or outer membrane (ELM or OLM) Layr9, retinal Pigment Epithelium (RPE) Layr10, and Bruch's Membrane (BM) Layr11.

In OCT angiography or functional OCT, analysis algorithms can be applied to OCT data collected at the same or approximately the same sample location on the sample at different times (e.g., cluster scanning) to analyze motion or flow (see, e.g., U.S. patent publication nos. 2005/0171438, 2012/0307014, 2010/0027857, 2012/0277579, and U.S. patent nos. 6,549,801, the entire contents of which are incorporated herein by reference). The OCT system can use any of a variety of OCT angiography processing algorithms (e.g., motion contrast algorithms) to determine blood flow. For example, a motion contrast algorithm can be applied to intensity information derived from image data (intensity-based algorithm), phase information from image data (phase-based algorithm), or complex image data (complex-based algorithm). The facial image is a 2D projection of the 3D OCT data (e.g., by averaging the intensities of each individual a-scan such that each a-scan defines a pixel in the 2D projection). Similarly, facial vascular images are images that display motion contrast signals in which the data dimension corresponding to depth (e.g., along the z-direction of an a-scan) is displayed as a single representative value (e.g., a pixel in a 2D projection image), typically by summing or integrating all or isolated portions of the data (see, e.g., U.S. patent No. 7,301,644, the entire contents of which are incorporated herein by reference). OCT systems that provide angiography imaging functionality can be referred to as OCT angiography (OCTA) systems.

Fig. 1B shows an example of a facial blood vessel image. After processing the data to highlight the motion contrast using any motion contrast technique known in the art, pixel ranges corresponding to a given tissue depth from the Inner Limiting Membrane (ILM) surface in the retina can be summed to produce a facial (e.g., frontal view) image of the blood vessel. Fig. 1C shows an exemplary B-scan of a blood vessel (OCTA) image. As shown, the structural information can be not explicitly defined, as blood flow can pass through multiple retinal layers, making their definition inferior to that in structural OCT B scans, as shown in fig. 15. However, OCTA provides a non-invasive technique for imaging the microvasculature of the retina and choroid, which can be critical for diagnosing and/or monitoring various pathologies. For example, OCTA can be used to determine diabetic retinopathy by determining microaneurysms, neovascular complexes, and quantifying foveal avascular and non-perfused areas. Furthermore, OCTA has been shown to be well consistent with Fluorescein Angiography (FA), a more traditional but invasive technique that requires injection of dye to observe vascular flow in the retina. Additionally, in dry age-related macular degeneration, OCTA has been used to monitor the overall reduction in choroidal vascular layer blood flow. Similarly, in wet age-related macular degeneration, OCTA can provide qualitative and quantitative analysis of choroidal neovascularization. OCTA is also used to study vascular occlusions, for example to evaluate the integrity of non-perfused areas and superficial and deep vascular plexuses.

Computing device/system

FIG. 1E illustrates an exemplary computer system (or computing device or computer device) in accordance with the present invention. In some embodiments, one or more computer systems are capable of providing the functionality described or illustrated herein and/or performing one or more steps of one or more methods described or illustrated herein. As described above, the computer system can be integrated into the substrate of the semiconductor optical bench, or can take any suitable physical form. For example, the computer system can be an embedded computer system, a System On Chip (SOC), a single board computer System (SBC), such as a Computer On Module (COM) or a System On Module (SOM), a desktop computer system, a laptop or notebook computer system, a grid of computer systems, a mobile phone, a Personal Digital Assistant (PDA), a server, a tablet computer system, an augmented/virtual reality device, or a combination of two or more of these. Where appropriate, the computer system can be located in a cloud, which can include one or more cloud components in one or more networks.

In some embodiments, the computer system can include a processor Cpnt1, a memory Cpnt2, a storage Cpnt3, an input/output (I/O) interface Cpnt4, a communication interface Cpnt5, and a bus Cpnt6. The computer system can also optionally include a display Cpnt7, such as a computer monitor or screen.

The processor Cpnt1 includes hardware for executing instructions, such as those comprising a computer program. For example, processor Cpnt1 can be a Central Processing Unit (CPU) or a general purpose computing (GPGPU) on a graphics processing unit. Processor Cpnt1 is capable of retrieving (or fetching) instructions from an internal register, internal cache, memory Cpnt2 or store Cpnt 3; decoding and executing the instruction; and write one or more results to an internal register, an internal cache, memory Cpnt2, or storage Cpnt3. In particular embodiments, processor Cpnt1 may include one or more internal caches for data, instructions, or addresses. The processor Cpnt1 may include one or more instruction caches, one or more data caches, such as to hold a data table. The instructions in the instruction cache can be copies of instructions in memory Cpnt2 or in memory Cpnt3, and the instruction cache can speed up retrieval of those instructions by processor Cpnt1. Processor Cpnt1 can include any suitable number of internal registers and can include one or more Arithmetic Logic Units (ALUs). Processor Cpnt1 can be a multicore processor; or may include one or more processors Cpnt1. Although this disclosure describes and illustrates a particular processor, this disclosure contemplates any suitable processor.

Memory Cpnt2 can include main memory for storing instructions for processor Cpnt1 to execute or hold temporary data during processing. For example, the computer system may be capable of loading instructions or data (e.g., a data table) from memory Cpnt3 or from another source (such as another computer system) to memory Cpnt2. The processor Cpnt1 is capable of loading instructions and data from the memory Cpnt2 into one or more internal registers or internal caches. To execute instructions, the processor Cpnt1 may be able to retrieve and decode instructions from internal registers or internal caches. During or after execution of the instructions, processor Cpnt1 may be able to write one or more results (which may be intermediate or final results) to an internal register, internal cache, memory Cpnt2, or store Cpnt3. Bus Cpnt6 may include one or more memory buses (which may each include an address bus and a data bus), and may couple processor Cpnt1 to memory Cpnt2 and/or store Cpnt3. Optionally, one or more Memory Management Units (MMUs) facilitate data transfer between processor Cpnt1 and memory Cpnt2. The memory Cpnt2 (which can be a fast volatile memory) can include Random Access Memory (RAM), such as Dynamic RAM (DRAM) or Static RAM (SRAM). Storage Cpnt3 can include long term or mass storage for data or instructions. The storage Cpnt3 may be internal or external to the computer system and includes one or more of a disk drive (e.g., hard disk drive HDD or solid state drive SSD), flash memory, ROM, EPROM, optical disk, magneto-optical disk, magnetic tape, a Universal Serial Bus (USB) accessible drive, or other type of non-volatile memory.

The I/O interface Cpnt4 can be software, hardware, or a combination of both, and includes one or more interfaces (e.g., serial or parallel communication ports) for communicating with I/O devices, which enable communication with a person (e.g., a user). For example, the I/O device can include a keyboard, a keypad, a microphone, a monitor, a mouse, a printer, a scanner, a speaker, a still camera, a stylus, a tablet, a touch screen, a trackball, a camera, another suitable I/O device, or a combination of two or more of these.

The communication interface Cpnt5 can provide a network interface for communicating with other systems or networks. The communication interface Cpnt5 can include a bluetooth interface or other type of packet-based communication. For example, the communication interface Cpnt5 can include a Network Interface Controller (NIC) and/or a wireless NIC or wireless adapter for communicating with a wireless network. The communication interface Cpnt5 may be capable of providing communication with a WI-FI network, an ad hoc network, a Personal Area Network (PAN), a wireless PAN (e.g., bluetooth WPAN), a Local Area Network (LAN), a Wide Area Network (WAN), a Metropolitan Area Network (MAN), a cellular telephone network (such as a Global System for Mobile communications (GSM) network), the Internet, or a combination of two or more of these.

Bus Cpnt6 may be capable of providing a communication link between the aforementioned components of the computing system. For example, bus Cpnt6 may include an Accelerated Graphics Port (AGP) or other graphics bus, an Enhanced Industry Standard Architecture (EISA) bus, a Front Side Bus (FSB), a HyperTransport (HT) interconnect, an Industry Standard Architecture (ISA) bus, an InfiniBand bus, a Low Pin Count (LPC) bus, a memory bus, a Micro Channel Architecture (MCA) bus, a Peripheral Component Interconnect (PCI) bus, a PCI-Express (PCIe) bus, a Serial Advanced Technology Attachment (SATA) bus, a video electronics standards Association local (VLB) bus, or other suitable bus or combination of two or more of these.

Although this disclosure describes and illustrates a particular computer system having a particular number of particular components in a particular arrangement, this disclosure contemplates any suitable computer system having any suitable number of any suitable components in any suitable arrangement.

Herein, a computer-readable non-transitory storage medium or media can include one or more semiconductor-based or other Integrated Circuits (ICs) (such as a Field Programmable Gate Array (FPGA) or Application Specific IC (ASIC)), a Hard Disk Drive (HDD), a hybrid hard disk drive (HHD), an Optical Disk Drive (ODD), a magneto-optical drive, a Floppy Disk Drive (FDD), a magnetic tape, a Solid State Drive (SSD), a RAM drive, a secure digital card or drive, any other suitable computer-readable non-transitory storage medium, or any suitable combination of two or more of these. The computer-readable non-transitory storage medium can be volatile, nonvolatile, or a combination of volatile and nonvolatile where appropriate.

While the invention has been described in conjunction with several specific embodiments, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art in light of the foregoing description. Accordingly, the invention described herein is intended to embrace all such alterations, modifications, applications and variations that fall within the spirit and scope of the appended claims.

Claims (30)

1. A system for medical optical tomography imaging a sample, such as an eye, the system comprising:

hermetically sealed micro-package housing:

i) A base supporting a light source and a beam splitter, wherein the light source produces a light beam, the beam splitter directs a first portion of the light into a reference arm and a second portion of the light into a sample arm;

ii) a transmissive element providing an interface between the interior and the exterior of the micro-package, the transmissive element being along the sample arm and being at least partially transparent to the second portion of the light;

a detector for receiving light returned from the sample arm and the reference arm and generating a signal in response; and

And a processor for converting the signals into image data.

2. The system of claim 1, wherein:

the optical tomography system is a swept source Optical Coherence Tomography (OCT) system and produces an imaging depth large enough that the sample is always within the depth imaging window of the system;

accommodating the detector within the micro-package;

the mount is a semiconductor substrate and includes digitizing circuitry integrated onto the mount and configured for digitizing signals from the detector;

the image data is cropped to display a desired depth range within the depth imaging window on an electronic display, wherein the desired depth range dynamically changes during a data acquisition scan.

3. The system of claim 2, wherein the depth range is changed to follow the curvature of the sample.

4. The system of claim 2, wherein the depth range changes during an a-scan within a B-scan.

5. The system of any one of claims 1-4, wherein:

the system generates an imaging depth that is large enough so that the sample is always within the depth imaging window of the system;

The reference arm is completely enclosed within the micro-package and has an optical path length that does not match the optical path length of the sampling arm; and

the system further includes an optical modulator supported by the base and configured to shift an optical frequency of one of the first portion of the light or the second portion of the light to define a modulated OCT signal having a spectral content corresponding to a spectral content obtained when the optical path length of the reference arm more closely matches the imaging depth.

6. The system of any one of claims 1-5, wherein:

the system generates an imaging depth that is large enough so that the sample is always within a depth imaging window;

the reference arm is completely enclosed within the micro-package and has an optical path length that does not match the optical path length of the sampling arm; and

the system further includes a mixer supported by the base and configured to frequency mix the signal from the detector with a frequency corresponding to an edge of the depth imaging window to create a down-mix OCT signal having a spectral content corresponding to a spectral content obtained when the optical path length of the reference arm more closely matches the imaging depth.

7. The system of claim 5 or 6, wherein a frequency corresponding to an edge of the depth imaging window is determined by using a preliminary scan sweep having a slow a-scan rate, and a faster scan sweep is performed at a faster a-scan rate after determining a frequency corresponding to an edge of the depth imaging window from the preliminary scan sweep.

8. The system of any of claims 1-7, wherein the hermetically sealed micro-package comprises a vacuum.

9. The system of any of claims 1-7, wherein the hermetically sealed micro-package contains a gas that mitigates degradation of active semiconductor optical material.

10. The system of any one of claims 1-9, wherein,

the beam splitter is a first polarizing beam splitter;

the detector that receives light returned from the sample arm and the reference arm is a first detector; and

the base also supports:

a first waveplate optically coupling the light source to the first polarization beam splitter;

a second wave plate in the sample arm and a third wave plate in the reference arm;

a fourth wave plate and a second polarization beam splitter, light returned from the sample arm and the reference arm being combined at the first polarization beam splitter and sent through the fourth wave plate to the second polarization beam splitter serving as an interference generator; and

A second detector, the first detector and the second detector coupled to the second polarization beam splitter to produce a signal in response.

11. The system of claim 10, wherein the base further supports a pinhole in the optical path between the first and second polarizing beamsplitters.

12. The system of claim 10 or 11, wherein the second wave plate is the transmissive element.

13. The system of any of claims 10-12, wherein the first, second, third, and fourth wave plates all have the same phase retardation.

14. The system of any of claims 10-12, wherein:

the first wave plate and the fourth wave plate are half wave plates; and

the second and third waveplates are quarter waveplates.

15. The system of any of claims 1-14, wherein all sample arm optics are part of the micro-package.

16. The system of any one of claims 1-9, wherein:

the beam splitter is a first polarizing beam splitter;

The detector receiving light returned from the sample arm and the reference arm is supported by the base and is a first detector;

the base also supports:

a first waveplate optically coupling the light source to the first polarization beam splitter;

a second wave plate in the sample arm and a third wave plate in the reference arm;

a fourth wave plate and a second polarization beam splitter, light returned from the sample arm and the reference arm being combined at the first polarization beam splitter and sent through the fourth wave plate to the second polarization beam splitter serving as an interference generator;

a second detector, the first detector and the second detector coupled to the second polarization beam splitter to generate a signal in response;

a Faraday rotator, a fifth wave plate, a sixth wave plate, a third polarization beam splitter, a fourth polarization beam splitter, a third detector, and a fourth detector;

wherein:

the faraday rotator and the second wave plate are in the optical path between the first polarization beam splitter and the third polarization beam splitter;

the third polarization beam splitter directs a first portion of the light received by the third polarization beam splitter from the first polarization beam splitter through the fifth wave plate to a second reference arm and directs a second portion of the light received by the third polarization beam splitter from the first polarization beam splitter to a second sample arm;

The sixth waveplate optically couples the third polarization beam splitter to the fourth polarization beam splitter;

the third detector and the fourth detector receive light returned from the second reference arm and the second sample arm from the fourth polarizing beam splitter and generate a signal in response.

17. The system of any one of claims 1-9, wherein:

the beam splitter is a first polarizing beam splitter;

the detector receiving light returned from the sample arm and the reference arm is supported by the base and is a first detector;

the base also supports:

a first waveplate optically coupling the light source to the first polarization beam splitter;

a second wave plate in the sample arm and a third wave plate in the reference arm;

a fourth wave plate and a non-polarizing beam splitter, light returned from the sample arm and the reference arm being combined at the first polarizing beam splitter and sent to the non-polarizing beam splitter through the fourth wave plate;

a second polarizing beam splitter and a second detector, said second polarizing beam splitter receiving a portion of said light received by said non-polarizing beam splitter, said first detector and said second detector coupled to said second polarizing beam splitter to produce a signal in response;

A third polarizing beam splitter, a fifth wave plate, a third detector, and a fourth detector, the third polarizing beam splitter receiving a portion of the light received by the non-polarizing beam splitter through the fifth wave plate, the third detector and the fourth detector coupled to the third polarizing beam splitter to generate a signal in response.

18. The system of any one of claims 1 to 17, wherein the base further supports a fiber optic coupler for interfacing the beam splitter with the detector.

19. The system of any one of claims 1 to 18, wherein:

the beam splitter, the reference arm, and the sample arm are part of a first interferometer;

the base also supports a second interferometer that includes a second beam splitter, a first mirror, and a second mirror, a portion of the light from the light source being directed to the second interferometer to generate a clock to linearize a scanning sweep of the OCT system.

20. The system of claim 19, wherein the second interferometer is optically coupled to the reference arm of the first interferometer by a partially transmissive mirror.

21. The system of any one of claims 1 to 20, wherein:

the light source comprises a plurality of lasers, each of the lasers having a different center frequency and a limited range of wavelengths;

the mount also supports at least one beam splitter for combining the light from the plurality of lasers to define a combined glance bandwidth that is greater than the individual wavelength ranges of each of the lasers.

22. The system of any one of claims 1 to 20, wherein:

the light source comprising a plurality of lasers, each of the lasers having a different center frequency and a limited range of wavelengths, the plurality of lasers being sequentially operated to sequentially scan the same region on the sample; and

as the plurality of lasers are operated sequentially, the detector sequentially detects sequential light returned from the sample arm and the reference arm.

23. The system of any of claims 1 to 22, wherein the micro-package is part of an imaging module, the system further comprising:

a transport system defining a spherical motion;

the imaging module coupled to the transport system and movable in the spherical motion by the transport system;

A gimbal providing a tilting function for the imaging module for aligning the imaging module to a target point on the sample.

24. The system of claim 23, wherein the sample is an eye and the target point is an eye pupil, the system further comprising:

a pupil camera tracks the center of the eye pupil and provides feedback signals to the gimbal to maintain alignment of the imaging module.

25. The system of claim 23, wherein the transport system comprises a rotatable structure, rotation of which at least partially defines the spherical motion.

26. The system of claim 23, wherein the transport system comprises a rotatable spherical surface with radial guides to move the imaging module radially inside the spherical surface.

27. The system of any one of claims 1 to 26, wherein the base is one of a micro-optical bench and a semiconductor optical bench.

28. The system of any one of claims 1 to 27, wherein the system is one of an Optical Coherence Tomography (OCT) system, an OCT angiography system, and an Optical Coherence Domain Reflectometer (OCDR) system.

29. The system of any one of claims 1 to 28, wherein the base has a recessed opening on a surface configured to receive a micro-optical device at a predetermined position, height, and orientation to achieve a predetermined alignment of the micro-optical device.

30. The system of claim 29, wherein the micro-package comprises a cover coupled to the base, the cover having a corresponding opening on a surface facing the surface of the base, the opening on the cover configured to receive the micro-optical device to maintain the predetermined alignment of the micro-optical device.