Patent Application
20110216401
This invention relates to scanning systems, and more particularly to light scanning systems that transmit collimated light between a fixed source/receiver and an orbiting (rotating) element, such as a microscope objective.
There are several technical fields having a need for an apparatus capable of scanning large areas with high resolution and high efficiency. One such technical field involves the identification of a relatively low number of rare cells in blood or other body fluids using a fluorescent material that selectively attaches to the rare cells, and then a smear treated in this manner is optically analyzed to identify rare cells of the targeted type by the presence of the fluorescent material in the smear. For statistical accuracy it is important to obtain as large a number of cells as required for a particular process, in some studies at least ten rare cells should be identified, requiring a sampling of at least ten million cells, for a one-in-one-million rare cell concentration. Another technical field requiring an apparatus capable of scanning large areas with high resolution and high efficiency is in the solar industry, where there is need to quickly ablate solar cells to make vias to interconnect to an external circuit. In production, solar cells may have a nitride layer insulating and protecting the top junction. If there were a way to quickly and efficiently produce these vias through laser ablation in a laser scanner, a high throughput production of solar cells could be achieved. For some laser ablation applications, a femto-second laser may be required. For a femto-second laser to work properly, chromatic and other types of aberrations can adversely affect the pulse quality. These aberrations occur because the scanning lenses curve and distort the beam during scanning to produce linear movement, flat field and constant scanning velocity. This invention solves this problem by eliminating the intermediate scan lenses to provide a simple and lens free intermediate light-path during the scanning process.
Currently, the various technical fields requiring high resolution, high efficiency scanning apparatus either employ a microscope, which is capable of providing high resolution, or a scanning apparatus, which provides high efficiency. With respect to high resolution, microscopes have an advantage over conventional scanning systems in that the microscope's objective lens can be completely filled by collimated light to produce a tightly focused beam with a high numerical aperture (NA). The resulting steep cone angle inside the microscope objective is what makes high resolution possible. On the other hand, conventional scanning systems, such as those used for laser ablation (discussed above), inherently suffer degraded resolution because the scanning beam must have a smaller diameter than the field lens to avoid truncation as it scans across the lens, and therefore necessarily presents a shallower cone angle onto the object plane.
An obvious approach to achieving high resolution and high efficiency would be to repeatedly move a microscope objective over a sample in a selected raster (scanning) pattern. Utilizing a rectilinear format raster pattern (i.e., moving the objective back and forth over a sample) could provide a workable solution, but due to the significant mass of the microscope objective, moving the objective in a oscillating format raster pattern (i.e., back and forth) over a sample is problematic because the resulting momentum would limit the raster speed. On the other hand, the objective could revolve about a central axis passing over the sample once every revolution. A processor could remap the sector-shaped rasters into linear format rasters enabling a large area and high resolution, but the light gathering efficiency would be low because samples only occupy a small fraction of the scanned circumference. To increase the light gathering efficiency, several sample stations could be placed around the revolved circumference to increase the time spent gathering light. But for the majority of applications where there is only one sample to scan, this approach yields only the lowest efficiency, perhaps 10%. A better way to increase the light gathering efficiency would be to scan one sample station with multiple objectives. This approach would also yield high efficiency, but there is a problem with coupling the collimated light down the axis of each orbiting objective during scanning that has heretofore prohibited this method. That is, in designing a single-axis rotating objective system that has more than one objective there has always been a problem of the laser beam “walking” along the facet during each scan. In particular, the reflected light could not be made parallel to the optical axis without lenses which would cause optical aberrations.
What is needed is a scanning system that can be used to produce large area, high resolution, high efficiency apparatus such as, for example, a high speed scanning microscope or a laser ablation device. More particularly, what is needed is a scanning system that is capable of transferring collimated light to or from a fixed device (e.g., a source such as a laser or a receiver such as an image sensor) in a manner that allows the collimated light to be reliably and accurately multiplexed down the axis of one or more orbiting elements (e.g., microscope objectives) without using lenses that cause optical aberration, thereby facilitating, for example, a large field, high resolution, high efficiency rotary microscope or laser ablation device.
The present invention is generally directed to a low cost scanning system in which two rotating units cooperatively interact to continuously transfer collimated light along a light path between a fixed device (e.g., a source such as a laser or a receiver such as an image sensor) and one or more orbiting elements (e.g., filters, lenses, or microscope objectives), thereby eliminating the intermediate scan lenses to provide a simple and unchanging light path during the scanning process. The scanning system is utilized, for example, in a scanning microscope by positioning the orbiting microscope objectives over a flat surface at a constant height and capturing the scanned image using an image sensor as the fixed device. Alternatively, the scanning system is utilized as a laser ablation device in which the scanning system is used to direct laser pulses from a fixed laser to an orbiting lens disposed to pass over a solar cell at a constant height.
The first rotating unit of the scanning system (referred to herein as a conveyor unit) utilizes one or more pairs of flat-plate surfaces that are spaced apart by a predetermined distance and inclined at an angle (e.g., 45°) relative to the first axis, and orbit the first axis in a fixed parallel relationship. With this arrangement, collimated light directed parallel to the first axis along a fixed portion of the light path onto the first surface is redirected (i.e., reflected or refracted) by way of the second surface onto a scanning portion of the light path, where the scanning light path portion is parallel to the fixed portion and pivots around the fixed path at a fixed offset distance. According to an aspect of the present invention, the resulting arrangement is low cost because the optical surfaces of the conveyor unit are implemented using flat plate optics, thereby avoiding the high production expenses typically associated with curved optical surfaces. Moreover, because flat plate optics are used, the scanning system of the present invention facilitates transferring collimated light between a stationary device disposed in the fixed light path portion and a moving element (e.g., a microscope objective) disposed in the scanning path portion without the aberration or distortion produced by curved optical surfaces.
The second rotating unit of the scanning system (referred to herein as a revolver unit) includes at least one orbiting element (e.g., a microscope objective) rotated around a second axis. According to another aspect of the invention, the revolver unit is positioned relative to the conveyor unit such that the first and second axes maintain a fixed parallel and non-collinear orientation, the second axis is arranged to be collinear with the fixed light path portion, and the orbiting element is maintained at a fixed radial distance from the second axis that is equal to the fixed offset distance separating the fixed and scanning light path portions. With this arrangement, the orbiting element is easily positioned to receive collimated light transmitted from the fixed light path portion to the scanning light path portion by the conveyor unit simply by rotating the orbiting element around the second axis (i.e., with the conveyor unit in a stationary state) until the scanning light path portion intersects (e.g., passes through) the orbiting element.
According to another aspect of the invention, the conveyor unit and the revolver unit are rotated at a common rotational speed (e.g., 100 rotations per minute) such that, while the collimated light is directed along the fixed light path portion onto the first surface, the collimated light redirected by the second surface onto the scanning light path portion remains intersected with said element. That is, because the orbiting element travels along the same circular path traced by the scanning light path portion, by rotating the conveyor unit around the first axis at the same rotational speed as the revolver unit is rotated around the second axis, the collimated light directed along the scanning light path portion remains intersected with the orbiting element. In this way, the present invention provides a scanning system that is capable of transferring collimated light to or from a fixed device (e.g., a source such as a laser or a receiver such as an image sensor) in a manner that allows the collimated light to be directed along the optical axis of one or more orbiting elements.
According to an embodiment of the invention, the orbiting element is implemented by a microscope objective disposed between the scanning light path portion and a predetermined sample, whereby the collimated light directed along the light path is focused by the microscope objective onto the sample. By utilizing a microscope objective as the orbiting element in the above-scanning system, the present invention facilitates the production of large area, high resolution, high efficiency apparatus such as, for example, a high speed scanning microscope or a laser ablation device. That is, because the microscope objective is rotated around a fixed axis at a constant speed, and because collimated light transferred from the fixed light path portion to the scanning portion remains aligned with the optical axis of the microscope objective as it orbits around the second axis, the present invention successfully combines the high resolution of a microscope objective with the high efficiency of a scanning system. This arrangement enables the extension of microscopy into large area with high efficiency and high resolution, and with all the microscope functions still intact.
According to alternative embodiments of the present invention, the collimated light is redirected by the conveyor unit using either refracted or reflected light. Refracted light is achieved, for example, using a solid optical (e.g., clear glass) element having the parallel refracting surfaces formed on opposite sides of the element, where a benefit of this arrangement is that the surfaces are automatically aligned by the solid optical element, thereby reducing assembly and maintenance costs. Reflected light is achieved using parallel mirrors that face each other and are disposed at a 45° angle with respect to the fixed light path. In one specific embodiment, the parallel mirrors are maintained in the proper orientation by a support structure having an opening to allow passage of collimated light. In an alternative embodiment, the parallel mirrors are formed on opposite sides of a solid optical element (i.e., such that the mirrors face into the element), thereby providing the self-alignment benefits mentioned above.
According to another specific embodiment of the invention, a multiplexed scanning system is produced by proving the conveyor unit including a multifaceted optical element including multiple outward-facing first mirror (reflecting) surfaces, and a ring structure concentrically integrally connected to the optical element and including multiple inward-facing second mirror surfaces that are disposed around the multifaceted optical element and positioned such that each of the first mirror surfaces reflects light from the fixed light path portion to an associated second mirror surface when the first mirror surface is positioned to intersect the fixed light path portion. That is, the multifaceted optical element and the ring structure are disposed to rotate around the first axis in a fixed relationship. The multiplexed scanning system also includes revolver unit including multiple orbiting elements disposed in a circular pattern around a second axis, where the number of orbiting elements is the same as the number of first mirror/second mirror pairs and arranged such that, as each first mirror surface rotates into a position that intersects the fixed light beam portion, light is reflected between the fixed light beam portion and a corresponding one of the orbiting elements by way of an associated second mirror surface. In a manner similar to that described above, simultaneous rotation of the conveyor and revolver units at the same speed causes light reflected by each first mirror surface to remain on-axis with its corresponding orbiting element as both units rotate through a predetermined range of rotation, thereby causing light acted upon (e.g., focused) by the corresponding orbiting element to trace across the surface of a sample along a curved path. By periodically moving the sample relative to the scanning apparatus (e.g., using an X-Y table), the multiplexed scanning system facilitates the production of a large field, high resolution, high efficiency rotary microscope or laser ablation device.
According to an embodiment of the present invention, a large field, high resolution, high efficiency rotary microscope or scanning device is produced utilizing any of the scanning apparatus described herein by providing a light source/receiver (e.g., a laser or an images sensor) in the fixed light path portion and providing a sample positioning mechanism (e.g., an X-Y table) below the revolver unit such that light passing through one or more orbiting elements is scanned across a sample in a systematic pattern.
These and other features, aspects and advantages of the present invention will become better understood with regard to the following description, appended claims, and accompanying drawings, where:
The present invention relates to an improvement in scanning systems that can be utilized to produce, for example, a large field, high resolution, high efficiency rotary microscope. The following description is presented to enable one of ordinary skill in the art to make and use the invention as provided in the context of a particular application and its requirements. As used herein, directional terms such as “above” and “below” are intended to provide relative positions for purposes of description, and are not intended to designate an absolute frame of reference. In addition, the phrases “integrally connected” and “integrally molded” is used herein to describe the connective relationship between two portions of a single molded or machined structure, and are distinguished from the terms “connected” or “coupled” (without the modifier “integrally”), which indicates two separate structures that are joined by way of, for example, adhesive, fastener, clip, or movable joint. Various modifications to the preferred embodiment will be apparent to those with skill in the art, and the general principles defined herein may be applied to other embodiments. Therefore, the present invention is not intended to be limited to the particular embodiments shown and described, but is to be accorded the widest scope consistent with the principles and novel features herein disclosed.
Referring to the upper portion of
According to an embodiment of the present invention, first surface 130 and second surface 140 are formed on opposite sides of a solid optical element 120 comprising, e.g., a low iron glass or clear plastic produced as an integrally molded or otherwise integrally connected structure. Utilizing optical element 120 in this manner provides several benefits. First, because optical element 120 is solid, first surface 130 and second surface 140 remain permanently aligned relative to each other in the desired fixed parallel relationship, thus maintaining optimal optical operation while minimizing assembly and maintenance costs. Moreover, the loss of light at the gas/solid interfaces is minimized because only solid optical element material (e.g., low-iron glass) is positioned between first surface 130 and second surface 140. In alternative embodiments, one or more solid optical elements may be assembled to provide first surface 130 and second surface 140, but such a multiple part arrangement might require additional assembly and regular maintenance to assure optimal performance.
Those skilled in the art will recognize that a collimated light beam transmitted onto surface 130 in a direction that is parallel to axis Z1 (e.g., along fixed light path portion LP1) will be refracted inside optical element 120 toward second surface 140 (i.e., along intermediate light path portion LP2) at refraction angle a determined by the index of refraction of optical element 120, the index of refraction of the medium outside the optical element (air), and the inclination angle e, and then refracted again by second surface 140 and emerge from optical element 120 as collimated light traveling in a direction that is parallel to but offset from the input direction by offset distance R (i.e., along scanning light path portion LP3), where offset distance R is determined by the refraction angle a and the spacing distance S between first surface 130 and second surface 140.
Referring to the lower portion of
According to another aspect of the invention, a mechanism (e.g., motor 180) is operably connected to conveyor unit 110 and revolver unit 150 using known techniques in order to rotate conveyor unit 110 and revolver unit 150 at a common rotational speed (e.g., conveyor unit 110 and revolver unit 150 are locked in synchronous rotation such that both conveyor unit 110 and revolver unit 150 rotate at 100 rotations per minute). By rotating conveyor unit 110 and revolver unit 150 at a common rotational speed after aligning orbiting element 160 with scanning light path portion LP3, the light transmitted on scanning light path portion LP3 continuously remains on-axis (e.g., passes through) orbiting element 160. That is, because orbiting element 160 orbits second axis Z2 (i.e., travels along a circular path C2 shown in
According to the present embodiment, scanning system 100A differs from generalized scanning system 100 in that the orbiting element of revolver unit 150A comprises a microscope objective lens (microscope objective) 160A, such as a 40× objective, mounted on a suitable rotating structure (e.g., a plate 170A) such that an optical axis OA of microscope objective 160A is disposed collinear with scanning light path portion LP3, and such that microscope objective 160A focuses the collimated light of scanning portion LP3 in a focused region LP4 that traces a circular scan path C3 over the surface of sample 60A. That is, similar to previous embodiments, microscope objective 160A is disposed at radial distance R from second axis Z2 that is equal to the lateral offset distance between fixed light path portion LP1 and scanning light path portion LP3, microscope objective 160A is rotated around second axis Z2 while first surface 130A and second surface 140A are rotated around first axis Z1 at the same rotational speed, and microscope objective 160A is aligned such that scanning light path portion LP3 is collinear with optical axis OA of microscope objective 160A during at least a portion of the circular path C2 traveled by microscope objective 160A around second axis Z2. This arrangement enables the extension of microscopy into large area with high efficiency and high resolution, and with all the microscope functions still intact. That is, because the transfer of light between the fixed and scanning light paths portions is entirely accomplished with flat-plate optics (i.e., there are no lenses or curved surfaces that would introduce chromatic or dispersive aberrations in the pristine microscope light path), light collimation, polarization, phase, spectral content, axial performance and virtually all objectives made for standard microscopes remain unaffected by the scanning system of the present invention, so all of the imaging methods that are available to standard microscopes are also available for exploitation in a rotary microscope utilizing the scanning system of the present invention. In particular, the present invention facilitates the production of large field microscopes that permit any number of fluorescence channels, support all microscope resolutions that do not involve oil emersion including confocal resolutions, exhibit low noise void of autofluorescence problems, allow all types of microscope illumination techniques such as Kohler, Darkfield, Rheinberg, Phase Contrast, Polarized, DIC, and Spectral, and finally, facilitate large scan-fields with light capture efficiencies so high that the image capture rate may be limited only by the capacity and throughput of the electronic subsystems. Moreover, scanning system 100A can be utilized to produce a laser ablation device that addresses the problems associated with conventional laser ablation devices by eliminating the intermediate scan lenses needed in conventional systems, thereby providing a simple and unchanging light-path between the laser and the target substrate during the scanning process.
According to the present embodiment, scanning system 100B differs from the previously described scanning systems in that first surface 130B and second surface 140B are reflecting (i.e., mirror) surfaces instead of refracting surfaces. In particular, both first mirror surface 1308 and second mirror surface 140B are arranged in parallel 45° angles with respect to axis Z1, and are supported in fixed parallel relationship by a support structure 120B, where support structure 120B defines an opening 122B to allow the passage of collimated light reflected by second mirror surface 140B from intermediate light path portion LP2 to scanning light path portion LP3. Similar to the refracted light embodiments mentioned above, the flat-plate optical system produced by first mirror surface 130B and second mirror surface 140B facilitate the transmission of collimated light between fixed light path portion LP1 and scanning light path portion LP3 (as indicated by the parallel lines along the light path).
Although scanning system 100B utilizes support structure 120B to maintain first mirror surface 130B and second mirror surface 140B, other arrangements are also possible. For example, parallel mirror surfaces 130B and 140B may be formed on opposite sides of a solid optical element (e.g., a prism) similar to that described above with reference to
Referring to
Referring to
When used as a light multiplexer for either input or output scanning, intermediate light path LP2 can be split into multiple light paths. For example, as indicated by the simplified diagram in
For applications where different light qualities are required per aperture station each arm (LP2 or LP3) of the apparatus can be unique; for applications where there are common light qualities required, the light qualifier optics can be placed in the common path LP1.
By repeating the operation described with reference to
Although the present invention has been described with respect to certain specific embodiments, it will be clear to those skilled in the art that the inventive features of the present invention are applicable to other embodiments as well, all of which are intended to fall within the scope of the present invention.
For example, although the multiplexing scanning microscope is described with reference to eight microscope objectives, any number of objectives may be utilized (e.g., two, ten, twenty-five, etc.).
In addition, from
Moreover, the scanning system can be utilized to make a large field movie microscope. This would include setting a camera in LP1 in drift scanning mode, or time-delay-imaging (TDI) (well known in the art) and staggering the arm lengths to sweep out adjacent portions of a large field image during one revolution. Then by rotating at 30 revolutions per second, a set of real-time images of a large field at high resolution can be produced suitable for animated viewing or storage.
Another possible modification to the invention could be to make a large field interlaced confocal microscope (limited to air-gap imaging; no oil emersion). This configuration would extend the resolution to about 0.3 um @ 60×, 0.95 NA. An image can be passed through pinholes to create a confocal microscope. By both staggering the arms and/or staggering the focus of a respective arm, a 3-D volume could be defined and imaged.
Furthermore, a 2-D array of 0.3 um pinholes can be defined and placed in the return portion of fixed light path LP1. The pinholes would be arranged 0.15 um apart in the slow direction to achieve Niquist criteria but staggered in the fast direction to maintain at least 10 hole diameters between any adjacent holes. An array of 1024 holes would cover 154 um of the sample in the slow scan direction. The resultant light could be imaged onto the face of a 1024×1280 video CCD in drift scanning or TDI mode for readout.
Another possible application for the rotary microscope is a Semiconductor and PC Board Inspection Microscope.
Another possible application for the invention is to provide a Kohler illumination system for a rotary microscope by mounting a secondary and synchronous undercarriage conveyor/rotator from below with Kohler illumination characteristics.
Another possible application for the invention is to provide a Differential Interference Contrast Microscopy (DICM) illumination system for a rotary microscope by mounting a secondary and synchronous undercarriage conveyor/rotator from below with DCIM illumination characteristics.
Another possible application for the invention is a Spatially Resolved Spectral Analysis Rotary Microscope. This application would use a grating in the fixed part of the light path to array light onto a multi-cathode pmt to acquire a spectrum for each point scanned.
Another possible adaptation of the rotary microscope is a Wide Field Scanning Profilimeter. This could be accomplished by staggering the z-axis focal heights of each objective around the circumference of the rotator unit. A single revolution would capture several focal depths, while multiple revolutions could capture more depths; image processing would acquire peak contrast versus depth over a wide field to obtain depth information vs position.
Another possible use for the rotary microscope is to make an extended depth of focus microscope by staggering the z-axis focal heights of each objective around the circumference of the rotator unit to image different slices of a specimen. A single revolution would capture several focal depths, while multiple revolutions could capture more depths; image processing would acquire peak contrast versus depth over a wide field to display an in-focus image regardless of the depth.
A possible modification to the invention involves placing a 45 degree mirror at the output of the revolver, redirecting the optical path radially outward from the axis of revolution. Such a system would resemble the characteristics of a galvo-scanner but have an efficiency and scan rate far in excess of current galvo scanners.
Another possible modification to the invention involves replacing the microscope objectives with optics compatible with projection optics and single or multi-colored light sources compatible with color displays. Such a combination may provide optical efficiencies and multiplexing flexibility beyond that of conventional galvo-based designs.
Another possible modification to the invention involves replacing the microscope objectives with telescope optics. Such an input device could provide optical efficiencies and multiplexing flexibility beyond that of conventional galvo-based designs.
Another possible modification to the invention involves placing a beam splitter into the output pathway and redirecting a fraction of the light into a grating clock that can be used to clock data into or out of image buffers. This could help eliminate motor hunting, scan non-linearity, or scan line jitter that plagues many raster systems.
Another possible use of the invention involves placing light sources along the arc of the scan of the revolver unit directed into the input aperture of the rotating light path. The fixed portion of the light path will repeatedly access these sources in the order placed at a high rate of speed and throughput. If the light sources are modulated, that too will be transferred to the single optical path. The light sources can be the output of fiber optics or fiber bundles as well as lasers.
Another possible modification to the invention is to stop the rotation of the unit and use it as a stationary light path. This would allow, for instance, the use of a high quality microscope and a rotary microscope in the same form factor.
Another possible modification to the invention is to place two or more axis Z2 with associated rotary optics at alternate points around axis Z1. Two axes Z2 would allow, for instance, a stereo scanner or two sample inspection stations around the periphery of the conveyor unit.
Another possible application of the invention is to use it for a scanning cytometer to find rare cells. A laser emitting at 488 nm, for instance, can be inserted into the fixed path with a dichroic mirror to illuminate the sample through a microscope objective with an 8 micron spot in a raster pattern. Subsequent fluorescent light emitted from any rare cell target is simultaneously collected by the microscope objective and transferred back to a photomultiplier tube (PMT) through the dichroic splitter and an emission filter to detect a rare cell. Several PMT's can be used to capture multiple emission frequencies from multiple targets using standard fluorescence microscope techniques. This system would eliminate any auto fluorescence caused by fiber bundle capture techniques and be much faster than flow cytometers.
Moreover, a Multiple Laser Stimulation and Emission Fluorescence Rotary Microscope could be implemented by inserting several different laser frequencies at LP1 and selectively allowing/blocking the stimulation and return frequencies on the sample by placing unique stimulation and return filters on the individual arms.
