IMAGING SYSTEM AND RELATED METHODS

Abstract

An imaging system and related methods are disclosed. According to one implementation, the system includes a flow cell receptacle for receiving a flow cell that receives a sample, and an imaging system having a light source assembly and an imaging device. The light source assembly forms a substantially collimated beam. The optical assembly includes an asymmetric beam expander group including one or more asymmetric or anamorphic elements disposed along an optical axis. The optical assembly receives the substantially collimated beam from the light source assembly and converts the substantially collimated beam into a shaped sampling beam having an elongated cross-section at a far field at or near a focal plane of the optical assembly for optically probing the sample. The imaging device acquires image data associated with the sample in response to optically probing the sample with the sampling beam.

Description

[Technical Field]

[0001] (Related Applications Section) This application claims the benefit of and priority to U.S. Provisional Patent Application No. 62 / 294,968, filed December 30, 2021, the entire contents of which are incorporated herein by reference for all purposes. [Background technology]

[0002] An instrument such as a sequencing instrument may image the sample on the flow cell. Summary of the Invention

[0003] Advantages and benefits over the prior art may be achieved through the provision of imaging systems and related methods, as described hereinafter in this disclosure. Various implementations of the devices and methods are described below, and the devices and methods, including and excluding the additional implementations listed below, in any combination (provided that such combinations are not inconsistent), can overcome these disadvantages and achieve the benefits described herein.

[0004] According to a first implementation, an apparatus comprises or includes a flow cell and a system. The flow cell receives a sample. The system comprises or includes a flow cell receptacle and an imaging system. The flow cell receptacle receives the flow cell. The imaging system comprises or includes a light source assembly, an optical assembly, and an imaging device. The light source assembly forms a substantially collimated beam. The optical assembly comprises or includes an asymmetric beam expander group comprising or including one or more asymmetric or anamorphic elements arranged along an optical axis. The optical assembly receives the substantially collimated beam from the light source assembly and converts the substantially collimated beam into a shaped sampling beam comprising or having an elongated cross-section at or near a focal plane of the optical assembly in a far field for optically probing a sample in the flow cell. The imaging device acquires image data associated with the sample in response to optically probing the sample with the shaped sampling beam.

[0005] According to a second implementation, the system comprises or includes a flow cell receptacle and an imaging system. The flow cell receptacle receives a flow cell for receiving a sample, and the imaging system comprises or includes a light source assembly and an imaging device. The light source assembly forms a substantially collimated beam. The optical assembly comprises or includes an asymmetric beam expander group comprising or including one or more asymmetric or anamorphic elements arranged along an optical axis. The optical assembly receives the substantially collimated beam from the light source assembly and transforms the substantially collimated beam into a shaped sampling beam comprising or having an elongated cross-section at or near a focal plane of the optical assembly in a far field for optically probing the sample in the flow cell. The imaging device acquires image data associated with the sample in response to optically probing the sample with the sampling beam.

[0006] According to a third implementation, a method comprises or includes generating a collimated beam using a light source assembly and converting the collimated beam using an optical assembly into a shaped sampling beam with or having an elongated cross-section in a far field at a focal plane of the optical assembly. The optical assembly has an asymmetric beam expander group with or including one or more asymmetric or anamorphic elements arranged along an optical axis. The method also comprises or includes optically probing a sample using the shaped sampling beam.

[0007] Furthermore, in accordance with the first, second, and / or third implementation forms described above, the apparatus and / or method may further comprise or include any one or more of the following:

[0008] According to one implementation, the substantially collimated beam has a first aspect ratio and the shaped sampling beam has a second aspect ratio.

[0009] According to another implementation, the first aspect ratio of the substantially collimated beam is at most 4:1 and the second aspect ratio of the shaped sampling beam is at least 8:1.

[0010] According to another implementation, the asymmetric beam expander group provides a first magnification in a first axis and a second, different magnification in a second, different axis.

[0011] According to another implementation, the first magnification is at least twice the second magnification.

[0012] According to another implementation, the optical assembly comprises or includes an asymmetric beam expander group and an objective lens group, where the asymmetric beam expander group asymmetrically or anamorphically expands a substantially collimated beam with or having a first aspect ratio to form a shaped beam with or having a second, different aspect ratio, and the objective lens group is disposed along the optical axis to receive the shaped beam from the asymmetric beam expander group and convert the shaped beam into a shaped sampling beam at or near a focal plane of the optical assembly.

[0013] According to another implementation, the light source assembly comprises or includes a beam source for providing input radiation and a collimator for substantially collimating the input radiation to form a substantially collimated beam comprising or having a first aspect ratio.

[0014] According to another implementation, the collimator comprises or includes a waveguide that comprises or has a first aspect ratio.

[0015] According to another implementation, the waveguide comprises or includes at least one of a rectangular optical fiber or a light pipe comprising or having a first aspect ratio.

[0016] According to another implementation, the collimator comprises or includes at least one of a spherical lens or an aspherical lens arranged to collimate the output of the optical fiber.

[0017] According to another implementation, the optical assembly comprises or includes a beam shaping group, an asymmetric beam expander group, and an objective lens group. The beam shaping group comprises or includes one or more optical elements arranged along the optical axis to receive a substantially collimated beam from the collimator and convert the substantially collimated beam into a first shaped beam with or having a first aspect ratio. The asymmetric beam expander group asymmetrically or anamorphically expands the first shaped beam with or having a first aspect ratio to form a second shaped beam with or having a second, different aspect ratio. The objective lens group is arranged along the optical axis to receive the second shaped beam from the asymmetric beam expander group and convert the second shaped beam into a shaped sampling beam at or near a focal plane of the optical assembly.

[0018] According to another implementation, the imaging device comprises or includes a time domain integration (TDI) image sensor that comprises or has an aspect ratio that corresponds to the aspect ratio of the sampling beam.

[0019] According to another implementation, the asymmetric beam expander group comprises or includes one or more pairs of crossed cylindrical lenses disposed along the optical axis.

[0020] According to another implementation, each pair of one or more crossed cylindrical lenses comprises or includes two cylindrical lenses having different powers and oriented on different axes.

[0021] According to another implementation, the asymmetric beam expander group comprises or includes a cylindrical telescope disposed along the optical axis.

[0022] According to another implementation, the cylindrical telescope comprises or includes a singlet lens.

[0023] According to another implementation, the cylindrical telescope comprises or includes an afocal doublet lens.

[0024] According to another implementation, the doublet lens is achromatic.

[0025] According to another implementation, the cylindrical telescope is at least one of a Kepler telescope, a Galilean telescope, or a hybrid Kepler-Galilean telescope.

[0026] According to another implementation, the asymmetric beam expander group comprises or includes a second cylindrical telescope.

[0027] According to another implementation, the cylindrical telescope and the second cylindrical telescope are at least one of tandem, nested, or interleaved.

[0028] According to another implementation, the cylindrical telescope and the second cylindrical telescope magnify by different amounts in different axes.

[0029] According to another implementation, the asymmetric beam expander group comprises or includes one or more anamorphic prisms arranged along the optical axis such that magnification is provided substantially in one axis.

[0030] According to another implementation, the one or more anamorphic prisms comprise or include a first prism comprising or including a first glass type and a second prism comprising or including a second glass type.

[0031] According to another implementation, the asymmetric beam expander group includes one or more diffractive elements disposed along the optical axis.

[0032] According to another implementation, the one or more diffractive elements comprise or include at least one of a refractive homogenizer, a refractive diffuser, or a cylindrical microlens array.

[0033] According to another implementation, the asymmetric beam expander group comprises or includes a lens disposed along the optical axis, and the imaging system moves the lens along the optical axis to switch the asymmetric beam expander group between a high irradiance mode and a low irradiance mode.

[0034] According to another implementation, the imaging system further comprises or includes an actuator and a reflective element, wherein the actuator positions the reflective element to sweep the shaped sampling beam across the flow cell within the exposure time.

[0035] According to another implementation, the asymmetric beam expander group further comprises or includes at least one of a crossed pair of cylindrical lenses, a cylindrical telescope, an anamorphic prism, or a diffractive element to provide anamorphic expansion along a first axis, and an actuator positions the reflective element to sweep the shaped sampling beam along a second, different axis.

[0036] According to another implementation, the actuator positions the reflective element within a range to sweep the shaped sampling beam across the flow cell.

[0037] According to another implementation, the range is from about 39 degrees to about 41 degrees.

[0038] According to another implementation, generating the collimated beam comprises or includes passing the input beam through a waveguide.

[0039] According to another implementation, the waveguide comprises or includes at least one of a rectangular optical fiber or a light pipe.

[0040] According to another implementation, converting the collimated beam into a shaped sampling beam comprises or includes asymmetrically or anamorphically expanding a substantially collimated beam with or having a first aspect ratio using an asymmetric beam expander group to form a shaped beam with or having a second aspect ratio.

[0041] According to another implementation, converting the collimated beam into a shaped sampling beam comprises or includes converting the shaped beam into the shaped sampling beam at or near a focal plane of the optical assembly using an objective lens group arranged along the optical axis.

[0042] According to another implementation, asymmetrically or anamorphically expanding the substantially collimated beam comprises or includes passing the substantially collimated beam through at least one of: 1) one or more pairs of crossed cylindrical lenses; 2) one or more cylindrical telescopes; 3) one or more anamorphic prisms; or 4) one or more diffractive elements.

[0043] According to another implementation, asymmetrically or anamorphically expanding the substantially collimated beam comprises or includes moving lenses of the asymmetric beam expander group along the optical axis to switch the asymmetric beam expander group between a high irradiance mode and a low irradiance mode.

[0044] According to another implementation, the method also comprises or includes sweeping the shaped sampling beam across the sample.

[0045] According to another implementation, sweeping the shaped sampling beam across the sample comprises or includes directing the shaped beam to a reflective element and rotating the reflective element using an actuator.

[0046] According to another implementation, converting the collimated beam into a shaped sampling beam includes converting the substantially collimated beam into a first shaped beam having a first aspect ratio using a beam shaping group having one or more optical elements arranged along an optical axis, and asymmetrically or anamorphically expanding the first shaped beam having the first aspect ratio using an asymmetric beam expander group to form a second shaped beam having a second, different aspect ratio.

[0047] According to another implementation, converting the collimated beam into a shaped sampling beam comprises or includes converting the second shaped beam into the shaped sampling beam at or near a focal plane of the optical assembly using an objective lens group arranged along the optical axis.

[0048] According to another implementation, asymmetrically or anamorphically expanding the first shaped beam expands the first shaped beam by a first magnification in a first axis and by a second, different magnification in a second, different axis.

[0049] According to another implementation, the first magnification is at least twice the second magnification.

[0050] According to another implementation, asymmetrically or anamorphically expanding the first shaped beam comprises or includes passing the first shaped beam through one or more pairs of crossed cylindrical lenses.

[0051] According to another implementation, asymmetrically or anamorphically expanding the first shaped beam includes passing the first shaped beam through one or more cylindrical telescopes.

[0052] According to another implementation, asymmetrically or anamorphically expanding the first shaped beam includes passing the first shaped beam through one or more anamorphic prisms.

[0053] According to another implementation, asymmetrically or anamorphically expanding the first shaped beam includes passing the first shaped beam through one or more diffractive elements.

[0054] According to another implementation, asymmetrically or anamorphically expanding the first shaped beam comprises or includes passing the first shaped beam through a lens and moving the lens along the optical axis to switch the asymmetric beam expander group between a high irradiance mode and a low irradiance mode.

[0055] According to another implementation, the method comprises or includes sweeping the shaped sampling beam across the sample by directing the second shaped beam to a reflective element and rotating the reflective element using an actuator.

[0056] According to another implementation, the method comprises or includes acquiring image data associated with the sample in response to optically probing the sample with the shaped sampling beam.

[0057] It is understood that all combinations of the foregoing concepts and additional concepts, described in more detail below (provided such concepts are not mutually inconsistent), are considered to be part of the subject matter disclosed herein and / or can be combined to achieve particular benefits of particular embodiments. In particular, all combinations of claimed subject matter appearing at the end of this disclosure are considered to be part of the subject matter disclosed herein. [Brief explanation of the drawings]

[0058] The accompanying drawings, together with the following detailed description, referencing identical or functionally similar elements through separate views, are incorporated in and form a part of this disclosure, and further illustrate exemplary implementations, including the claimed invention, and serve to explain various principles and advantages of those examples. Moreover, the figures show only specific details relevant to understanding the examples of the disclosure, so as not to obscure the disclosure with details that will be readily apparent to those skilled in the art having the benefit of the description herein. [Figure 1] 1 shows a schematic diagram of an exemplary implementation of a system according to the teachings of the present disclosure. [Figure 2] 2 is a schematic diagram of portions of an exemplary imaging system that may be used to implement the imaging system of FIG. 1. [Figure 3] FIG. 3 is a schematic diagram of an example asymmetric beam expander group that can be used to implement the asymmetric beam expander group of FIGS. 1 and / or 2. [Figure 4] FIG. 3 is a schematic diagram of another example asymmetric beam expander group that can be used to implement the asymmetric beam expander group of FIGS. 1 and / or 2. [Figure 5] FIG. 3 is a schematic diagram of another example asymmetric beam expander group that can be used to implement the asymmetric beam expander group of FIGS. 1 and / or 2. [Figure 6] 6 shows an exemplary illumination pattern produced using the asymmetric beam expander group of FIG. 5 when each of the prisms is formed from the same type of glass. [Figure 7] 6 shows an exemplary illumination pattern produced using the asymmetric beam expander group of FIG. 5 when the prisms are formed of more than one type of glass. [Figure 8] FIG. 3 is a schematic diagram of another example asymmetric beam expander group that can be used to implement the asymmetric beam expander group of FIGS. 1 and / or 2. [Figure 9] FIG. 3 is a schematic diagram of another example asymmetric beam expander group that can be used to implement the asymmetric beam expander group of FIGS. 1 and / or 2. [Figure 10]10 illustrates a high irradiance elongated beam pattern that can be generated with the asymmetric beam expander group of FIG. 9 in a first position. [Figure 11] 10 illustrates a broader beam pattern at low irradiance that can be produced with the asymmetric beam expander group of FIG. 9 in a second position. [Figure 12] FIG. 3 is a schematic diagram of another asymmetric beam expander group that can be used to implement the asymmetric beam expander group of FIGS. 1 and / or 2, with the reflective element in a first position. [Figure 13] FIG. 13 is a schematic diagram of the asymmetric beam expander group of FIG. 12 showing the reflective element in a second position. [Figure 14] FIG. 13 is a schematic diagram of the asymmetric beam expander group of FIG. 12 showing the reflective element in a third position. [Figure 15] 13 shows an illumination pattern illustrating a sampling beam produced using the asymmetric beam expander group of FIG. 12 with the reflective element in a first position. [Figure 16] 14 shows an illumination pattern illustrating a sampling beam produced using the asymmetric beam expander group of FIG. 13 with the reflective element in a second position. [Figure 17] 15 shows an illumination pattern illustrating a sampling beam produced using the asymmetric beam expander group of FIG. 14 with the reflective element in a third position. [Figure 18] 1, 2, 3, 4, 5, 8, 9, and / or 12. FIG. 1 is a flow chart of an exemplary process for using the system of FIG. 1, the imaging system of FIG. 1 and FIG. 2, the optical assembly of FIG. 1 and / or FIG. 2, and / or the asymmetric beam expander group of FIG. 1, FIG. 2, FIG. 3, FIG. 4, FIG. 5, FIG. 8, FIG. 9, and / or FIG. 12.

[0059] The components of the apparatus and methods have been represented, where appropriate, by conventional symbols in the drawings that show only the specific details relevant to understanding the implementation of the present disclosure, so as not to obscure the present disclosure with details that will be readily apparent to those skilled in the art having the benefit of the description herein. DETAILED DESCRIPTION OF THE INVENTION

[0060] Although the following description discloses detailed descriptions of implementations of methods, apparatus, and / or articles of manufacture, it should be understood that the legal scope of ownership is defined by the claims at the end of this patent. Accordingly, the following "Detailed Description" should be construed as exemplary only and does not describe every possible implementation, as describing every possible implementation would be impractical, if not impossible. Numerous alternative implementations may be implemented using either current technology or technology developed after the filing date of this patent. It is contemplated that such alternative implementations would still fall within the scope of the claims.

[0061] At least one aspect of the present disclosure is directed to an instrument, such as a line-scan sequencing instrument, that can be used to perform analyses on one or more target samples (e.g., biological samples). The instrument includes an optical assembly designed to receive an input beam from a beam source and convert the input beam into a sampling beam for optically probing the sample. While a laser, laser diode, diode-pumped solid-state laser, coherent light source, light-emitting diode, or any other laser-like source can be used to form the input beam, such sources often output a narrowly focused, non-uniform, high-irradiance beam. However, the use of such a narrowly focused, non-uniform, high-irradiance beam to illuminate the sample can cause photobleaching of the sample, photodamage to the sample, photodamage to reagents used to perform chemical reactions, and / or photodamage to a substrate used to support the sample.

[0062] The disclosed optical assembly thus converts an input beam into a larger, shaped beam for optically probing a sample. An exemplary shaped beam has a thin, or otherwise elongated, substantially rectangular cross-section in the far field, with the shaped beam having substantially uniform irradiance across the cross-section. By spreading the irradiance of the input beam over a wider area, sample photobleaching, photodamage to the sample, photodamage to reagents used to perform chemical reactions, and / or photodamage to substrates used to support the sample can be reduced. However, the irradiance provided by such a larger shaped beam can be sufficient to generate sufficient fluorescence emission from the sample to enable sequencing of the sample. Furthermore, because the substantially more uniform excitation illumination results in illumination of the edge of the area of ​​excitation illumination, the irradiance provided by such a shaped beam allows the instrument to operate at increased speeds. Such shaped beams also often enable the use of time-delay-integration (TDI) line scanners with large aspect ratios (e.g., at least 8:1). Although examples are described herein as generating a sampling beam having an elongated substantially rectangular cross-section, the technique may be used to form any number of elongated cross-sectional shapes in the far field, including ellipses, parallelograms, etc.

[0063] Most optical assemblies for containing and transporting light from a light source have aspect ratios close to 1 (e.g., 1:1). However, line-scan sequencing systems often use time-delay-integrated (TDI) imaging devices with large aspect ratios (e.g., at least 8:1). While waveguides with aspect ratios up to 4:1 are available and can be used as collimators to form substantially collimated beams, aspect ratios greater than this are not readily available. Thus, shaped beams formed from collimated beams produced by readily available collimators do not have aspect ratios that match the aspect ratio of TDI imaging devices.

[0064] Thus, in various implementations herein, an optical assembly for a line scan sequencing system includes an asymmetric beam expander group including one or more asymmetric or anamorphic elements arranged along the optical axis to asymmetrically or anamorphically expand a shaped beam. In some implementations, the shaped beam is formed from a collimated beam by a beam shaping group of the optical assembly. The asymmetric beam expander group expands or expands the width of the shaped beam and the height of the shaped beam by different amounts. That is, the asymmetric beam expander group expands or expands the shaped beam by different amounts in the x-axis and y-axis, with the z-axis being parallel to the optical axis of the optical assembly. The asymmetric beam expander group may, for example, expand the shaped beam in the x-axis by an amount that is at least twice the amount of expansion in the y-axis. However, in some implementations, the shaped beam is expanded in only one axis. The asymmetric beam expander group, in some implementations, may include one or more pairs of crossed cylindrical lenses, one or more cylindrical telescopes, one or more anamorphic prisms, or one or more diffractive optical elements.

[0065] The asymmetric beam expander group can also be selectively controllable to switch the optical assembly between a high irradiance mode and a low irradiance mode to asymmetrically or anamorphically expand the shaped beam in various implementations. The asymmetric beam expander group can include a lens or a lens group.

[0066] In further implementations, the asymmetric beam expander group sweeps the shaped sampling beam across the sample to controllably expand the shaped beam asymmetrically or anamorphically. In such implementations, the asymmetric beam expander group may include an actuator for controlling the angle of the reflective element to sweep the sampling beam across the sample. The sampling beam may be swept across the sample during a sampling interval of the imaging device. The asymmetric beam expander group may further include one or more pairs of crossed cylindrical lenses, one or more cylindrical telescopes, one or more anamorphic prisms, or one or more diffractive elements to aid in shaping the sampling beam.

[0067] FIG. 1 shows a schematic diagram of an exemplary implementation of a system 100 according to the teachings of the present disclosure. System 100 can be used to perform analysis on one or more target samples. The one or more samples may include one or more DNA clusters linearized to form single-stranded DNA (sstDNA). In the illustrated implementation, system 100 is adapted to receive a pair of flow cell assemblies 102, 104 including corresponding flow cells 106. System 100 includes, in part, one or more sample cartridges 107, an imaging system 108, and a flow cell interface 110 having flow cell receptacles 112, 114 that support the corresponding flow cell assemblies 102, 104. Flow cell interface 110 may be associated with and / or referred to as a flow cell deck structure. System 100 also includes a stage assembly 116, a pair of reagent selector valve assemblies 118, 120, and a controller 122. The reagent selector valve assemblies 118, 120 each include a reagent selector valve 124 and a valve drive assembly 126. The reagent selector valve assemblies 118, 120 may be referred to as mini-valve assemblies. The controller 122 is electrically and / or communicatively coupled to the imaging system 108, the reagent selector valve assemblies 118, 120, and the stage assembly 116 and adapted to cause the imaging system 108, the reagent selector valve assemblies 118, 120, and the stage assembly 116 to perform various functions as disclosed herein.

[0068] 1, in the illustrated implementation, includes a light source assembly 128, an optical assembly 129, and an imaging device 130. The imaging device 130 may be implemented as a scanner, detector, sensor, camera, and / or solid-state TDI line scanner. Other types of imaging device 130 may prove suitable.

[0069] The optical assembly 129 includes an asymmetric beam expander group 132, which in the illustrated implementation includes one or more asymmetric or anamorphic elements 133 disposed along the optical axis of the optical assembly 129. The light source assembly 128 forms a substantially collimated beam of illumination 131. In operation, the optical assembly 129 receives the substantially collimated beam 131 from the light source assembly 128 and converts the substantially collimated beam 131 into a shaped sampling beam 134 having an elongated cross-section 210 in a far field at or near a focal plane 135 of the optical assembly 129. The shaped sampling beam 134 can optically probe a sample 211 in the flow cell 106. The imaging device 130 acquires image data associated with the sample 211 in response to optically probing the sample 211 with the sampling beam 134.

[0070] The substantially collimated beam 131 has a first aspect ratio, and the shaped sampling beam 134 has a second aspect ratio. The shaped sampling beam 134 results in less damage and / or photobleaching to the sample 211 in the flow cell 106. In some implementations, the first aspect ratio of the substantially collimated beam is at most 4:1, and the second aspect ratio of the shaped sampling beam is at least 8:1. However, the first aspect ratio and / or the second aspect ratio may vary.

[0071] The asymmetric beam expander group 132 provides a first magnification in a first axis and a second, different magnification in a second, different axis. The first axis can be the x-axis, and the second axis can be the y-axis. Thus, the asymmetric beam expander group 132 can convert a high irradiance, elongated beam into a low irradiance, wider beam, as discussed further below. The first magnification can be at least twice the second magnification. However, the first magnification and / or the second magnification can be in different ratios.

[0072] The optical assembly 129 also includes an objective lens group 136. The asymmetric beam expander group 132 asymmetrically or anamorphically expands the substantially collimated beam 131 having a first aspect ratio to form a shaped beam 137 having a second, different aspect ratio. The objective lens group 136 is disposed along the optical axis and receives the shaped beam 137 from the asymmetric beam expander group 132 and converts the shaped beam 137 into an elongated sampling beam 134 at or near a focal plane 135 of the optical assembly 129. The focal plane 135 of the optical assembly 129 may be the same as the focal plane of the objective lens group 136.

[0073] Asymmetric beam expander group 132 may expand or expand the width of shaped beam 137 and the height of shaped beam 137 by different amounts. That is, asymmetric beam expander group 132 can expand shaped beam 137 by different amounts in the x-axis and y-axis. The z-axis is parallel to the optical axis of optical assembly 129. Shaped beam 137 is expanded in only one axis in some implementations.

[0074] Light source assembly 128, in the illustrated implementation, also includes a beam source 138 and a collimator 139. In operation, beam source 138 provides input radiation, and collimator 139 substantially collimates the input radiation from beam source 138 to form substantially collimated beam 131. Substantially collimated beam 131 can have a first aspect ratio.

[0075] Collimator 139 is shown to include a waveguide 140 having or associated with a first aspect ratio. Waveguide 140 may include a fiber, such as an optical fiber, a rectangular optical fiber, and / or a rigid light pipe, having or associated with a first aspect ratio. The rectangular optical fiber may have an aspect ratio of 4:1. However, other aspect ratios may prove suitable. Collimator 139 may additionally or alternatively include a spherical lens and / or an aspherical lens arranged to collimate the output of waveguide 140. Other methods of forming collimated beam 131 may also prove suitable.

[0076] 1 also includes, in the illustrated implementation, a sipper manifold assembly 150, a sample loading manifold assembly 152, a pump manifold assembly 154, a drive assembly 156, and a waste reservoir 158. Controller 122 is electrically and / or communicatively coupled to sipper manifold assembly 150, sample loading manifold assembly 152, pump manifold assembly 154, and drive assembly 156 and adapted to cause sipper manifold assembly 150, sample loading manifold assembly 152, pump manifold assembly 154, and drive assembly 156 to perform various functions as disclosed herein.

[0077] Each of the flow cells 106 includes a plurality of channels 160 in the illustrated implementation. Each of the channels 160 has a first channel opening positioned at a first end of the flow cell 106 and a second channel opening positioned at a second end of the flow cell 106. Depending on the direction of flow through the channels 160, either of the channel openings can act as an inlet or an outlet. Although the flow cell 106 is shown in FIG. 1 as including two channels 160, any number of channels 160 (e.g., 1, 2, 6, 8) can be included.

[0078] Each of the flow cell assemblies 102, 104 also includes a flow cell frame 162 and a flow cell manifold 148 coupled to a first end of the corresponding flow cell 106. As used herein, a flow cell (also referred to as a flowcell) can include a device having a lid extending over a reaction structure to form a flow channel between the flow cells that communicates with multiple reaction sites of the reaction structure. Some flow cells can also include a detection device that detects a specified reaction occurring at or adjacent to the reaction site. As shown, the flow cell 106, the flow cell manifold 148, and / or any associated gaskets used to establish a fluid connection between the flow cell 106 and the system 100 are coupled to or otherwise supported by the flow cell frame 162. While the flow cell frame 162 is shown included in the flow cell assemblies 102, 104 in FIG. 1 , the flow cell frame 162 can be omitted. In this manner, the flow cell 106 and associated flow cell manifold 148 and / or gaskets may be used in the system 100 without the flow cell frame 162 .

[0079] 1 are shown once as being coupled to both of the flow cells 106, it is noted that in some implementations, these components may be duplicated such that each flow cell 106 has its own corresponding component, and the system 100 may include three or more flow cell receptacles 112, 114 and corresponding components. For example, each flow cell 106 may be associated with a separate sample cartridge 107, sample loading manifold assembly 152, pump manifold assembly 154, etc. In other implementations, the system 100 may include a single flow cell 106 and corresponding components.

[0080] The system 100 includes a sample cartridge receptacle 164 that receives a sample cartridge 107 carrying one or more samples of interest (e.g., analytes). The system 100 also includes a sample cartridge interface 166 that establishes a fluid connection with the sample cartridge 107.

[0081] The sample loading manifold assembly 152 includes one or more sample valves 167, and the pump manifold assembly 154 includes one or more pumps 168, one or more pump valves 170, and a cache 172. One or more of the valves 167, 170 may be implemented by rotary valves, pinch valves, flat valves, solenoid valves, check valves, piezoelectric valves, and / or three-way valves. However, different types of fluid control devices may be used. One or more of the pumps 168 may be implemented by syringe pumps, peristaltic pumps, and / or diaphragm pumps. However, other types of fluid transfer devices may be used. The cache 172 may be a serpentine cache and may temporarily store one or more reaction components, for example, during a bypass operation of the system 100 of FIG. 1. While the cache 172 is shown included in the pump manifold assembly 154, in other implementations, the cache 172 may be located in a different location. For example, cache 172 may be included in shipper manifold assembly 150 or in a separate manifold downstream of bypass fluid line 173 .

[0082] In the illustrated implementation, the sample loading manifold assembly 152 and the pump manifold assembly 154 flow one or more samples of interest from the sample cartridge 107 through fluid lines 174 toward the flow cell assemblies 102, 104. In some implementations, the sample loading manifold assembly 152 can individually load / address a sample of interest into each channel 160 of the flow cell 106. The process of loading a sample of interest into the channels 160 of the flow cell 106 can occur automatically using the system 100 of FIG. 1 .

[0083] The sample cartridge 107 and the sample loading manifold assembly 152 are positioned downstream of the flow cell assemblies 102, 104, as shown in the system 100 of FIG. 1 . The sample loading manifold assembly 152 can load a sample of interest into the flow cell 106 from the rear of the flow cell 106. Loading a sample of interest from the rear of the flow cell 106 can be referred to as “rear loading.” Rear-loading the sample of interest into the flow cell 106 can reduce contamination. In some implementations, the sample loading manifold assembly 152 is coupled between the flow cell assemblies 102, 104 and the pump manifold assembly 154.

[0084] To draw the sample of interest from the sample cartridge 107 toward the pump manifold assembly 154, the sample valve 167, the pump valve 170, and / or the pump 168 can be selectively actuated to urge the sample of interest toward the pump manifold assembly 154. The sample cartridge 107 can include multiple sample reservoirs that are selectively fluidly accessible via corresponding sample valves 167. Thus, each sample reservoir can be selectively isolated from the other sample reservoirs using the corresponding sample valve 167.

[0085] The sample valve 167, the pump valve 170, and / or the pump 168 can be selectively actuated to force the sample of interest toward the flow cell assembly 102 and into each channel 160 of the corresponding flow cell 106 to individually flow the sample of interest toward the corresponding channel of one of the flow cells 106 and away from the pump manifold assembly 154. In some implementations, each channel 160 of the flow cell 106 receives a sample of interest. In other implementations, one or more of the channels 160 of the flow cell 106 selectively receive the sample of interest, while others of the channels 160 of the flow cell 106 do not receive the sample of interest. The channels 160 of the flow cell 106 that cannot receive the sample of interest can instead receive a wash buffer, for example.

[0086] The drive assembly 156 interfaces with the shipper manifold assembly 150 and the pump manifold assembly 154 to flow one or more reagents that interact with the sample in the corresponding flow cell 106. Reversible terminators may be attached to the reagents to allow incorporation of a single nucleotide onto the growing DNA strand. In some such implementations, one or more of the nucleotides have a unique fluorescent label that emits a color upon excitation. The color (or lack thereof) is used to detect the corresponding nucleotide. In the illustrated implementation, the imaging system 108 excites one or more of the distinguishable labels (e.g., fluorescent labels) and then acquires image data for the distinguishable labels using the imaging device 130. The labels may be excited by incident light and / or a laser, and the image data may include one or more colors emitted by each label in response to excitation. The image data (e.g., detection data) may be analyzed by the system 100. The imaging system 108 may be a fluorescence spectrophotometer including an objective lens and / or the imaging device 130. The imaging device 130 may include a charge coupled device (CCD) and / or a complementary metal oxide semiconductor (CMOS) device. However, other types of imaging system 108 and / or optical instruments may be used. For example, the imaging system 108 may be or be associated with a scanning electron microscope, a transmission electron microscope, an imaging flow cytometer, high-resolution optical microscopy, confocal microscopy, epifluorescence microscopy, two-photon microscopy, differential interference contrast microscopy, etc.

[0087] After the image data is acquired, the drive assembly 156 interfaces with the sipper manifold assembly 150 and the pump manifold assembly 154 to flow another reaction component (e.g., a reagent) through the flow cell 106, which is then received by the waste reservoir 158 via the main waste fluid line 166 and / or otherwise discharged by the system 100. Some reaction components perform a flushing action that chemically cleaves the fluorescent label and reversible terminator from the sstDNA. The sstDNA is then ready for another cycle.

[0088] A main waste fluid line 166 is coupled between the pump manifold assembly 154 and the waste reservoir 158. Pumps 168 and / or pump valves 170 of the pump manifold assembly 154 can selectively flow reaction components from the flow cell assemblies 102, 104 through fluid line 174 and the sample loading manifold assembly 152 to the main waste fluid line 166.

[0089] The flow cell assemblies 102, 104 are coupled to a central valve 175 via a flow cell interface 110. An auxiliary waste fluid line 173 is coupled to the central valve 175 and to a waste reservoir 158. In some implementations, the auxiliary waste fluid line 173 receives excess fluid of the target sample from the flow cell assemblies 102, 104 via the central valve 175 when the target sample is rear-loaded into the flow cell 106, as described herein, and directs the excess fluid of the target sample to the waste reservoir 158. That is, the target sample can be loaded from the rear of the flow cell 106, and any excess fluid of the target sample can exit from the front of the flow cell 106. By rear-loading the flow cells 106 with the samples of interest, different samples can be separately loaded into corresponding channels 160 of corresponding flow cells 106, and a single flow cell manifold 148 can couple the front of the flow cells 106 to a central valve 175 to direct excess fluid from each sample of interest to an auxiliary waste fluid line 173. Once the samples of interest are loaded into the flow cells 106, the flow cell manifold 148 can be used to deliver a common reagent from the front (e.g., upstream) of the flow cell 106 to each channel 160 of the flow cell 106, with this common reagent exiting the rear (e.g., downstream) of the flow cell 106. In other words, the sample of interest and the reagent can flow in opposite directions through the channels 160 of the flow cell 106.

[0090] The sipper manifold assembly 150, in the illustrated implementation, includes a shared line valve 178 and a bypass valve 180. The shared line valve 178 may be referred to as a reagent selector valve. The reagent selector valve 124 of the reagent selector valve assemblies 118, 120, the central valve 175, and / or the valves 178, 180 of the sipper manifold assembly 150 may be selectively actuated to control fluid flow through fluid lines 182, 184, 186, 188, 190. One or more of the valves 124, 170, 175, 178, 180 may be implemented by rotary valves, pinch valves, flat valves, solenoid valves, check valves, piezoelectric valves, etc. Other fluid control devices may prove suitable.

[0091] The sipper manifold assembly 150 may be coupled to a corresponding number of reagent reservoirs 192 via reagent sippers 193. The reagent reservoirs 192 may contain fluids (e.g., reagents and / or other reaction components). The sipper manifold assembly 150 may include multiple ports. Each port of the sipper manifold assembly 150 may receive one of the reagent sippers 193. The reagent sippers 193 may be referred to as a fluid line.

[0092] The shared line valve 178 of the sipper manifold assembly 150 is coupled to the central valve 175 via a shared reagent fluid line 182. Different reagents may flow through the shared reagent fluid line 182 at different times. When performing a flushing operation before changing one reagent for another, the pump manifold assembly 154 may draw a wash buffer through the shared reagent fluid line 182, the central valve 175, and the corresponding flow cell assemblies 102, 104. Thus, the shared reagent fluid line 182 may be involved in the flushing operation. Although one shared reagent fluid line 182 is shown, any number of shared fluid lines may be included in the system 100.

[0093] The bypass valve 180 of the sipper manifold assembly 150 is coupled to the central valve 175 via reagent fluid lines 184, 186. The central valve 175 may have one or more ports that correspond to the reagent fluid lines 184, 186.

[0094] Dedicated fluid lines 188, 190 are coupled between the sipper manifold assembly 150 and the reagent selector valve assemblies 118, 120. Each of the dedicated reagent fluid lines 188, 190 may be associated with a single reagent. Fluids that may flow through the dedicated reagent fluid lines 188, 190 may be used during sequencing operations and may include cleavage reagents, incorporation reagents, scanning reagents, cleavage wash solutions, and / or wash buffers. Because only a single reagent may flow through each of the dedicated reagent fluid lines 188, 190, the dedicated reagent fluid lines 188, 190 themselves may not be flushed when performing a wash operation before switching between one reagent and another. Including dedicated reagent fluid lines 188, 190 may be advantageous when the system 100 uses reagents that may have adverse reactions with other reagents. Furthermore, reducing the number of fluid lines or the length of the fluid lines flushed when changing between different reagents can reduce reagent consumption and flush volumes, thereby decreasing the cycle time of the system 100. Although four dedicated reagent fluid lines 188 , 190 are shown, any number of dedicated fluid lines may be included in the system 100 .

[0095] The bypass valve 180 is also coupled to the cache 172 of the pump manifold assembly 154 via a bypass fluid line 176. One or more reagent priming, hydration, mixing, and / or transfer operations may be performed using the bypass fluid line 176. The priming, hydration, mixing, and / or transfer operations may be performed independently of the flow cell assemblies 102, 104. Thus, operations using the bypass fluid line 176 may be performed, for example, during incubation of one or more samples of interest in the flow cell assemblies 102, 104. That is, the shared line valve 178 may be utilized independently of the bypass valve 180, such that the bypass valve 180 may utilize the bypass fluid line 176 and / or the cache 172 to perform one or more operations while the shared line valve 178 and / or the central valve 175 perform other operations simultaneously, substantially simultaneously, or offset-synchronously. Thus, the system 100 may perform multiple operations at once, thereby reducing execution time.

[0096] In the illustrated implementation, drive assembly 156 includes a pump drive assembly 194 and a valve drive assembly 196. Pump drive assembly 194 may be adapted to interface with one or more pumps 168 to pump fluid through and / or load one or more samples of interest into flow cell 106. Valve drive assembly 196 may be adapted to interface with one or more of valves 167, 170, 175, 178, 180 to control the position of the corresponding valves 167, 170, 175, 178, 180.

[0097] In the illustrated implementation, controller 122 includes a user interface 195, a communication interface 196, one or more processors 197, and a memory 198 that stores machine-readable instructions executable by the one or more processors 197 to perform various functions, including the disclosed implementations. User interface 195, communication interface 196, and memory 198 are electrically and / or communicatively coupled to the one or more processors 197.

[0098] The user interface 195 may be adapted to receive input from a user and provide the user with information associated with the operation of the system 100 and / or the analyses performed. The user interface 195 may include a touchscreen, a display, a keyboard, a speaker, a mouse, a trackball, and / or a voice recognition system. The touchscreen and / or the display may display a graphical user interface (GUI).

[0099] The communications interface 196 may be adapted to enable communication between the system 100 and a remote system (e.g., a computer) over a network. The network may include the Internet, an intranet, a local-area network (LAN), a wide-area network (WAN), a coaxial cable network, a wireless network, a wired network, a satellite network, a digital subscriber line (DSL) network, a cellular network, a Bluetooth connection, a near field communication (NFC) connection, etc. Some of the communications provided to the remote system may be associated with analysis results, imaging data, etc. generated or otherwise acquired by the system 100. Some of the communications provided to the system 100 may be associated with fluid analysis operations, patient records, and / or protocols performed by the system 100.

[0100] One or more processors 197 and / or system 100 may include one or more of a processor-based system or a microprocessor-based system. In some implementations, one or more processors 197 and / or system 100 include one or more of a programmable processor, a programmable controller, a microprocessor, a microcontroller, a graphics processing unit (GPU), a digital signal processor (DSP), a reduced-instruction set computer (RISC), an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), a field programmable logic device (FPLD), a logic circuit, and / or another logic-based device that performs various functions, including those described herein.

[0101] The memory 198 may be a semiconductor memory, a magnetically readable memory, an optical memory, a hard disk drive (HDD), an optical storage drive, a solid-state storage device, a solid-state drive (SSD), a flash memory, a read-only memory (ROM), an erasable programmable read-only memory (EPROM), an electrically erasable programmable read-only memory (EEPROM), a random-access memory (RAM), a non-volatile RAM (NVRAM) memory, a compact disc (CD), a compact disc read-only memory (CD-ROM), a digital versatile disk (DVD), a Blu-ray disc, a redundant array of independent disks, This may include one or more of: a storage device, a RAID (repeated array of independent disks), a cache, and / or any other storage device or disk on which information is stored for any duration (e.g., permanently, temporarily, long-term, for buffering, for caching).

[0102] Figure 2 is a schematic diagram of a portion of an exemplary imaging system 200 that may be used to implement the imaging system 108 of Figure 1. The imaging system 200 is similar to the imaging system 108 of Figure 1 in that the imaging system 200 of Figure 2 includes a beam source 138, a collimator 139, an asymmetric beam expander group 132, and an objective lens group 136. However, the imaging system 200 of Figure 2, in contrast, includes an optical assembly 201 having a beam shaping group 202 having one or more optical elements 203. The optical element 203 is disposed along an optical axis 204 of the optical assembly 201 and receives the substantially collimated beam 131 from the collimator 139. The beam shaping group 202 converts the substantially collimated beam 131 into a first shaped beam 206 having a first aspect ratio.

[0103] In the illustrated implementation, the asymmetric beam expander group 132 receives the first shaped beam 206 and asymmetrically or anamorphically expands the first shaped beam 206 to form a second shaped beam 208 having a second, different aspect ratio. The shaped beam 137 and the second shaped beam 208 can be the same or substantially the same. The asymmetric beam expander group 132 expands or expands the width of the first shaped beam 206 and the height of the first shaped beam 206 by different amounts. That is, the asymmetric beam expander group 132 expands or expands the first shaped beam 206 by different amounts in the x-axis and y-axis. The z-axis is parallel to the optical axis 204. The objective lens group 136 is disposed along the optical axis 204 and receives the second shaped beam 208 from the asymmetric beam expander group 132. Objective lens group 136 transforms second shaped beam 208 into elongated sampling beam 134 at or near focal plane 135 of optical assembly 129 .

[0104] The imaging system 200 is generally configured to form a sampling beam 134 having an elongated cross-section 210 onto a sample 211 in the flow cell 106 of FIG. 1 or onto another substrate. The exemplary elongated cross-section 210 is substantially rectangular in the illustrated implementation; however, other cross-sections may prove suitable. The sample 211 being exposed to the shaped sampling beam 134 causes the sample 211 to fluoresce. The imaging device 130 of FIG. 1 can detect, sense, and / or image the fluorescent illumination and / or radiation emitted by the sample 211.

[0105] The light source assembly 128 includes a beam source 138 that generates an input beam 212 and a collimator 139 positioned to receive the input beam 212. The input beam 212 may be referred to as input radiation. The collimator 139 and the beam source 138 are shown disposed along an optical axis 204 of the imaging system 200.

[0106] Beam source 138 may be implemented using any number and / or type of laser, laser diode, diode-pumped solid-state laser, coherent light source, light-emitting diode, blackbody source, optical amplifier, filter, and / or amplification stage. However, beam source 138 may be implemented in different ways. In some implementations, beam source 138 emits light in the blue region of visible light. In other implementations, beam source 138 may emit light in the ultraviolet spectrum or another spectrum to excite fluorescence from the probed sample. While often described herein as a beam, the light or beam may additionally be referred to as radiation or illumination. Although described herein as a single beam and single beam source 138, multiple beam sources may provide multiple beams individually, pulse-interleaved, or simultaneously to elements of the systems and devices described herein.

[0107] The collimator 139, in the illustrated implementation, is disposed along the optical axis 204 between the beam source 138 and the beam shaping group 202 and receives the input beam 212 from the beam source 138. The collimator 139 generates a substantially collimated beam 131 from the input beam 212. The system 139 may include one or more optical components 214.

[0108] Beam shaping group 202 formats substantially collimated beam 131 into first shaped beam 206 having an elongated cross-section according to a first aspect ratio. Beam shaping group 202 may include any number and / or types of optical elements 203 arranged along optical axis 204.

[0109] The optical elements 203 of the beam shaping group 202 may include focusing surfaces, lenses, reflective surfaces or mirrors, diffractive elements, filters, polarizers, wave plates, apertures, spatial light modulators, and / or microlens arrays. The beam shaping group 202 may include Powell lenses, beam shaping lenses, diffractive elements, and / or scattering elements. Although the asymmetric beam expander group 132 is shown separate from and following the beam shaping group 202, the beam shaping group 202 and the asymmetric beam expander group 132 may be implemented differently. The asymmetric beam expander group 132 may, for example, precede the beam shaping group 202 or be integrated into the beam shaping group 202. The beam shaping group 202 may alternatively be omitted.

[0110] The objective lens group 136 has one or more optical elements 216 and is disposed along the optical axis 204. The objective lens group 136 can focus the second shaped beam 208 so that the shaped sampling beam 134 propagates and is focused, for example, toward the sample 211. The objective lens group 136 can have a focal plane 135 that can be at the sample 211, in a region of the sample 211, in a region along the optical axis 204 upstream of the sample 211, or in a region along the optical axis 204. However, the imaging device 130 can be in a location different from that shown.

[0111] FIG. 3 is a schematic diagram of an exemplary asymmetric beam expander group 300 that may be used to implement the asymmetric beam expander group 132 of FIGS. 1 and / or 2. The asymmetric beam expander group 300 asymmetrically or anamorphically expands or expands a beam, such as the substantially collimated beam 131 and / or the first shaped beam 206. The asymmetric beam expander group 300 of FIG. 3 includes a pair 302 of cylindrical lenses 304 and 306 disposed along the optical axis 204. The cylindrical lenses 304, 306 may have different powers and are shown oriented on different axes 308, 310. The longitudinal axis of cylindrical lens 304 is shown aligned with axis 308, and the longitudinal axis of cylindrical lens 306 is shown aligned with axis 310. Axis 308 may be parallel to the x-axis and / or the x-axis, axis 310 may be parallel to the y-axis and optical axis 204 may be parallel to the z-axis. The cylindrical lenses 304, 306 of Figure 3 are arranged perpendicular to one another, with cylindrical lens 304 parallel to the x-axis 308 and cylindrical lens 306 parallel to the y-axis 310. One of the cylindrical lenses 304, 306 may have twice the power, magnification, or effective focal length of the other cylindrical lens 304, 306. The asymmetric beam expander group 300 and beam shaping group 202 of Figure 2 can be used to generate a sampling beam 134 with a larger aspect ratio.

[0112] The cylindrical lenses 304, 306 may alternatively be crossed such that the cylindrical lenses 304, 306 are aligned at different angles relative to the x-axis and / or y-axis of the asymmetric beam expander group 300. The cylindrical lenses 304, 306 can expand the beam by different amounts along different axes when the cylindrical lenses 304, 306 are crossed and have different powers. Multiple cylindrical lenses aligned to the same axis may be implemented to provide additional expansion along a particular axis. The cylindrical lenses 304 and / or 306 may expand the first shaped beam 206 differently along different axes 308, 310, such as the x-axis and / or y-axis. While FIG. 3 shows two lenses 304, 306 being provided, two or more pairs 302 of crossed cylindrical lenses 304, 306 or any number of lenses 304, 306 may be included in series and / or a single cylindrical lens may be included. A single cylindrical lens 304 and / or 306 and / or multiple aligned cylindrical lenses 304, 306 may expand the first shaped beam 206 differently along different axes, such as the x-axis and / or the y-axis.

[0113] Figure 4 is a schematic diagram of another example asymmetric beam expander group 400 that may be used to implement the asymmetric beam expander group 132 of Figures 1 and / or 2. The asymmetric beam expander group 400 asymmetrically or anamorphically expands or expands a beam, such as the substantially collimated beam 131 or the first shaped beam 206. The asymmetric beam expander group 400 of Figure 4 includes a pair of cylindrical telescopes 402 and 404 disposed on the optical axis 204. However, other numbers of cylindrical telescopes 402, 404 may be used.

[0114] In the illustrated implementation, the first cylindrical telescope 402 includes a singlet lens 406 that includes a single lens 408, and the second cylindrical telescope 404 includes a doublet lens 410 that includes a pair of lenses 412, 414. However, in other implementations, other combinations of singlet and / or doublet lenses may be implemented. The doublet lens 410 may be an afocal doublet and may be achromatic. The lenses 412, 414 of the doublet lens 410 may alternatively be spaced apart to provide an air gap between the lenses 412, 414. The air gap between the lenses 412, 414 reduces the distance light travels through the lenses 410, 412 and the likelihood that the lenses 412, 414 will absorb heat. The cylindrical telescopes 402, 404 may be tandem, nested, or interleaved. The cylindrical telescopes 402, 404 may, in some implementations, be Keplerian, Galilean, and / or hybrid Keplerian-Galilean telescopes. The cylindrical telescopes 402, 404 may expand the beams 131 and / or 206 by different amounts along different axes, such as along the x-axis and / or y-axis. One of the cylindrical telescopes 402, 404 may, for example, anamorphically expand the beams 131 and / or 206 by a factor of two along one axis.

[0115] The asymmetric beam expander group 400 and beam shaping group 202 of Figure 2 can be used to generate a sampling beam 134 with a larger aspect ratio. While Figure 4 shows two cylindrical telescopes 402, 404 being provided, for example, three or more cylindrical telescopes may be provided and aligned with respect to axis 204, and / or one cylindrical telescope may be included.

[0116] The cylindrical telescopes 402, 404 may alternatively be crossed such that the cylindrical telescopes 402, 404 are aligned at different angles relative to the x-axis and / or y-axis of the asymmetric beam expander group 400. The z-axis of the asymmetric beam expander group 400 may be parallel to the optical axis 204. The cylindrical telescopes 402, 404 may expand the beam by different amounts along different axes when the cylindrical telescopes 402, 404 are crossed and have different powers.

[0117] FIG. 5 is a schematic diagram of another exemplary asymmetric beam expander group 500 that can be used to implement the asymmetric beam expander group 132 of FIGS. 1 and / or 2 . The asymmetric beam expander group 500 asymmetrically or anamorphically expands or expands a beam, such as the substantially collimated beam 131 or the first shaped beam 206. The asymmetric beam expander group 500 of FIG. 5 includes multiple anamorphic prisms 502, 504, 506, 508, and 510. In the illustrated implementation, the prisms 502, 504, 506, 508, and 510 are arranged along the optical axis 204 so as to provide expansion in substantially only one axis, such as the x-axis or the y-axis. The beam 512 can be, or can be associated with, the collimated beam 131 from the light source assembly 128 and / or the first shaped beam 206 from the beam shaping group 202. Each of the prisms 502, 504, 506, 508, and 510 results in asymmetric or anamorphic expansion or magnification of the beam 512 in only one axis. In other words, the prisms 502, 504, 506, 508, and 510 expand the beam 512 along one axis, such as the x-axis, and do not expand the beam 512 along another axis, such as the y-axis or z-axis.

[0118] A series of anamorphic prisms 502, 504, 506, 508, and 510 may be implemented to successively expand or magnify the beam 512 shown in FIG. The prisms 502, 504, 506, 508, and 510 may be made of the same material or different materials. Each prism 502, 504, 506, 508, and 510 may be made of the same glass, such as, for example, N-SF11. Alternatively, one or more of the prisms 502, 504, 506, 508, and 510 may be made of a first glass, such as, for example, N-BK7, and one or more others of the prisms 502, 504, 506, 508, and 510 may be made of a second glass, such as, for example, N-FK56. Thus, the first prism 502 may include a first type of glass, and the second prism 504 may include a second type of glass. The material selection for the anamorphic prisms 502, 504, 506, 508, and 510 may allow dispersion caused by an earlier one of the prisms 502, 504, 506, 508, and 510 to be compensated for by a later one of the prisms 502, 504, 506, 508, and 510 in the asymmetric beam expander group 500.

[0119] Although five anamorphic prisms 502, 504, 506, 508, and 510 are shown, in other implementations, fewer or more anamorphic prisms may be included with the asymmetric beam expander group 500. The beam shaping group 202 with a first aspect ratio may be used to generate a shaped sampling beam 134 with a larger aspect ratio when the asymmetric beam expander group 500 is used in the imaging system 108, 200 in some implementations.

[0120] Prisms 502, 504, 506, 508, and 510 have surfaces 514, 516, 518, 520, and 522 that define angles 524, 526, 528, 530, and 532 relative to corresponding bases 534 of prisms 502, 504, 506, 508, and 510 that are the same or substantially the same. As described herein, substantially the same means having angles of about + / - 2° relative to each other, or taking into account manufacturing tolerances. Surfaces 514, 516, 518, 520, and 522 may be referred to as entrance faces. However, one or more of angles 524, 526, 528, 530, and 532 may differ.

[0121] In operation, beam 512 propagates through prisms 502, 504, 506, 508, and 510 and strikes surfaces 514, 516, 518, 520, and 522 of each of prisms 502, 504, 506, 508, and 510 at the same or nearly the same angle in the implementation shown. Beam 512 may strike surfaces 514, 516, 518, 520, and 522 of each of prisms 502, 504, 506, 508, and 510 at corresponding Brewster angles to reduce light loss. However, beam 512 may strike prisms 502, 504, 506, 508, and 510 at different angles. One or more surfaces 514, 516, 518, 520, 522 of the prisms 502, 504, 506, 508, and 510 may be coated with an anti-reflective coating.

[0122] Figure 6 shows an example illumination pattern 600 produced using the asymmetric beam expander group 500 of Figure 5 when each of the prisms 502, 504, 506, 508, and 510 are formed from the same type of glass. The illumination pattern 600 of Figure 6 includes two lines 602, 604, one of which corresponds to blue light and the other of which corresponds to green light.

[0123] 5 through anamorphic prisms 502, 504, 506, 508, and 510, which separate beam 512 into its corresponding component colors, referred to as dispersion. In some implementations, when prisms 502, 504, 506, 508, and 510 are formed from the same type of glass, the different colors of light form distinct illumination patterns at different locations in the far field.

[0124] FIG. 7 shows an example illumination pattern 700 produced using the asymmetric beam expander group 500 of FIG. 5 when the prisms 502, 504, 506, 508, and 510 are formed of two or more types of glass. The illumination pattern 700 of FIG. 7 includes one line 702 that has higher irradiance and contains all the colors of the beam 512. The lines 602 and 604 of FIG. 6 may overlap each other to form the line 702 of FIG. 7. The prisms 502, 504, 506, 508, and 510 used to form the illumination pattern 700 of FIG. 7 allow light of different colors to collectively overlap and form a single region of high irradiance in the far field, shown as line 702. The light of different colors overlaps even if it diverges within the asymmetric beam expander group 500. Prisms 502 , 504 , 506 , 508 , and 510 having different material types can therefore allow light of at least two wavelengths to diverge and then overlap at focal plane 135 .

[0125] Figure 8 is a schematic diagram of a further exemplary asymmetric beam expander group 800 that may be used to implement the asymmetric beam expander group 132 of Figures 1 and / or 2. The asymmetric beam expander group 800 asymmetrically or anamorphically expands or expands a beam, such as the substantially collimated beam 131 and / or the first shaped beam 206. The asymmetric beam expander group 800 of Figure 8 includes diffractive elements 802 and 804 disposed along the optical axis 204. The diffractive elements 802, 804 may be referred to as diffractive optical elements and may be configured to perform one-dimensional (1D) shaping.

[0126] The diffractive elements 802, 804 shape the collimated beam 131 and / or the first shaped beam 206 in one axis, for example, by causing the beam 131 and / or 206 to diverge in only one axis. The diffractive elements 802, 804 may include a refractive homogenizer, a refractive diffuser, and / or a cylindrical microlens array. In some implementations, the diffractive elements 802, 804 may be diffusers designed with a substantially or pseudo-random non-periodic surface such that the resulting beam has a substantially uniform flat-top illumination profile. While two diffractive elements 802, 804 are shown in FIG. 8 , in other implementations, fewer or more optical elements may be included with the asymmetric beam expander group 800.

[0127] Figure 9 is a schematic diagram of another exemplary asymmetric beam expander group 900 that may be used to implement the asymmetric beam expander group 132 of Figures 1 and / or 2. The asymmetric beam expander group 900 asymmetrically or anamorphically expands or expands a beam, such as the substantially collimated beam 131 or the first shaped beam 206. The asymmetric beam expander group 900 of Figure 9 includes a lens 902 disposed along the optical axis 204. The lens 902 may include a lens group.

[0128] During operation, the imaging system 108, 200 or an associated actuator can move the lens 902 along the optical axis 204 to switch the asymmetric beam expander group 900 between a high irradiance mode and a low irradiance mode. The imaging system 108, 200 can selectively position the lens 902 along the optical axis 204. That is, the imaging system 108, 200 can selectively move the lens 902 back and forth along the optical axis 204 between a first position associated with the high irradiance mode and a second position associated with the low irradiance mode. The high irradiance mode is associated with the asymmetric beam expander 900 generating the elongated beam pattern 1000 with high irradiance shown in FIG. 10 , and the low irradiance mode is associated with the asymmetric beam expander 900 generating the wider beam pattern 1100 with low irradiance shown in FIG. 11 .

[0129] Asymmetric beam expander group 900 can thus be used to selectively asymmetrically or anamorphically expand the shape of sampling beam 134 differently along different axes, such as the x-axis and / or the y-axis. Asymmetric beam expander group 900 of Figure 9 can include and / or be used in conjunction with any of asymmetric beam expander groups 132, 300, 400, 500, and 800. Asymmetric beam expander groups 132, 300, 400, 500, 800 can thus use asymmetric expansion to form an elongated beam of high irradiance that asymmetric beam expander group 900 accepts and converts into a wider beam of lower irradiance.

[0130] FIG. 10 shows a high irradiance elongated beam pattern 1000 produced with the asymmetric beam expander group 900 of FIG. 9 in a first position.

[0131] FIG. 11 shows a broader beam pattern 1100 of low irradiance produced with the asymmetric beam expander group 900 of FIG. 9 in a second position.

[0132] FIG. 12 is a schematic diagram of another asymmetric beam expander group 1200 that can be used to implement the asymmetric beam expander group 132 of FIGS.

[0133] Asymmetric beam expander group 1200 includes actuator 1202, reflective element 1204, optical dogleg 1208 having reflective elements 1210 and 1212, and objective lens group 136. Asymmetric beam expander group 1200 may also include cylindrical lens 1213 or any of asymmetric beam expander groups 300, 400, 500, and 800, allowing for independent control of magnification in each direction, such as along the x-axis and / or along the y-axis. Actuator 1202 may be a servo, galvanometer, or any other actuator, and reflective elements 1204, 1210, and 1212 may be mirrors. Although asymmetric beam expander group 1200 is shown including three reflective elements 1204, 1210, and 1212, asymmetric beam expander group 1200 may include more or fewer reflective elements.

[0134] The use of a high irradiance sampling beam with an elongated cross-section (e.g., generated as described above in connection with Figures 2, 3, 4, and 8) can be beneficial for photoinduced damage to absorbing molecules or DNA via energy transfer. However, imaging devices with lower aspect ratios (e.g., 1:1) that illuminate the entire field of view of the imaging device may be implemented.

[0135] In operation, the asymmetric beam expander group 1200 receives the beam 1214, and the actuator 1202 redirects the beam 1214. The objective lens group 136 may focus the beam 1214 onto the focal plane 135 of the sample 211. The reflective element 1204 in FIG. 12 is angled at approximately 39 degrees with respect to the optical axis of the asymmetric beam expander group 1200. However, the actuator 1202 may position the reflective element 1204 to tilt at any other angle. The beam 1214 may be, or may be associated with, the collimated beam 131 and / or the first shaped beam 206. 12 can sweep a shaped beam 137, 208 having a high irradiance and elongated cross-section generated using one of the asymmetric beam expander groups 300, 400, 500, 800, so that the shaped sampling beam 134 sweeps across the sample 211. In some implementations, the asymmetric beam expander group 1200 can sweep the sampling beam within the exposure time of the imaging device 130.

[0136] One or more of the asymmetric beam expanders 300, 400, 500, 800 can, in some implementations, shape the beam 1214 to have an elongated, substantially rectangular cross-section. Illuminating the entire field of view of such an imaging device can reduce the irradiance of the sampling beam.

[0137] Figure 13 is a schematic diagram of the asymmetric beam expander group 1200 of Figure 12, showing the reflective element 1204 in a second position. The reflective element 1204 is at an angle of approximately 40 degrees relative to the optical axis of the asymmetric beam expander group 1200 in the illustrated implementation.

[0138] Figure 14 is a schematic diagram of the asymmetric beam expander group 1200 of Figure 12, showing the reflective element 1204 in a third position. The reflective element 1204 is at an angle of approximately 41 degrees relative to the optical axis of the asymmetric beam expander group 1200 in the illustrated implementation.

[0139] Figure 15 shows an illumination pattern 1500 illustrating a sampling beam 1502 generated using the asymmetric beam expander group 1200 of Figure 12 with the reflective element 1204 in a first position. The sampling beam 1502 is shown approximately at the top of the illumination pattern 1500 in Figure 15. Varying the angle of the reflective element 1204 can also change the location of the sampling beam 1502 within the field of view of the imaging device 130, for example.

[0140] Figure 16 shows a pattern of illumination 1600 illustrating a sampling beam 1502 generated using the asymmetric beam expander group 1200 of Figure 13 with the reflective element 1204 in a second position. The sampling beam 1502 is shown approximately in the center of the pattern of illumination 1600 in the illustrated implementation.

[0141] Figure 17 shows an illumination pattern 1700 illustrating a sampling beam 1502 generated using the asymmetric beam expander group 1200 of Figure 14 with the reflective element 1204 in a third position. The sampling beam 1502 is shown approximately below the illumination pattern 1600.

[0142] FIG. 18 is a flowchart of an example process 1800 using the system 100 of FIG. 1 , the imaging systems 108, 200 of FIG. 1 and FIG. 2 , the optical assemblies 129, 201 of FIG. 1 and FIG. 2 , and / or the asymmetric beam expander groups 132, 300, 400, 500, 900, 1200 of FIG. 1 , FIG. 2 , FIG. 3 , FIG. 4 , FIG. 5 , FIG. 8 , FIG. 9 , FIG. 12 . In the flowchart of FIG. 18 , blocks surrounded by solid lines may be included in an implementation of the process 1800, and blocks surrounded by dashed lines may be optional in an implementation of the process. However, regardless of how the block boundaries are presented in FIG. 18 , the order of execution of the blocks may be changed, and / or some of the described blocks may be changed, deleted, combined, and / or subdivided into multiple blocks.

[0143] 18 begins with the light source assembly 128 generating a collimated beam 131 (block 1802). In some implementations, the collimated beam 131 may be generated by passing the input beam 212 through a waveguide 140. The waveguide 140 may include at least one of a rectangular optical fiber or a light pipe. However, the optical fiber may have another cross section, and other types of waveguides 140 may prove suitable.

[0144] The collimated beam 131 is transformed (block 1804) using an optical assembly 129, 201 into a shaped sampling beam 134 having an elongated cross section 210 in the far field at a focal plane 135 of the optical assembly 129. The optical assembly 129, 201 includes an asymmetric beam expander group 132, 300, 400, 800, 900, 1200 that includes one or more asymmetric or anamorphic elements 133 disposed along an optical axis 204.

[0145] In some implementations, the collimated beam 131 is converted into a shaped sampling beam 137 by asymmetrically or anamorphically expanding the substantially collimated beam 131 having a first aspect ratio using an asymmetric beam expander group 132, 300, 400, 800, 900, 1200 to form a shaped beam 134, 208 having a second aspect ratio. In some implementations, the collimated beam 131 is converted into a shaped sampling beam 134 by using an objective lens group 136 disposed along the optical axis 204 to convert the shaped beam 137, 208 into a shaped sampling beam 134 at or near a focal plane 135 of the optical assembly 129, 201. The substantially collimated beam 131 may be asymmetrically or anamorphically expanded by passing the substantially collimated beam 131 through at least one of: 1) one or more pairs of crossed cylindrical lenses 304, 306; 2) one or more cylindrical telescopes 402, 404; 3) one or more anamorphic prisms 502, 504, 506, 508, 510; or 4) one or more diffractive elements 802, 804. The substantially collimated beam 131 may additionally or alternatively be asymmetrically or anamorphically expanded by moving the lens 902 of the asymmetric beam expander group 900 along the optical axis 204 to switch the asymmetric beam expander group 900 between a high irradiance mode and a low irradiance mode.

[0146] In some implementations, the collimated beam 131 is converted into a shaped sampling beam 134 by using an asymmetric beam expander group 132, 300, 400, 800, 900, 1200 having one or more optical elements 203 arranged along an optical axis 204 to convert the substantially collimated beam 131 into a first shaped beam 206 having a first aspect ratio, and then using the asymmetric beam expander group 132, 300, 400, 800, 900, 1200 to asymmetrically or anamorphically expand the first shaped beam 206 having the first aspect ratio to form a second shaped beam 208 having a second, different aspect ratio. The collimated beam 131 may be converted into a shaped sampling beam 134 by converting the second shaped beam 208 into a shaped sampling beam 134 at or near a focal plane 135 of the optical assembly 129, 201 using an objective lens group 136 disposed along the optical axis 204. The first shaped beam 206 may be expanded asymmetrically or anamorphically by expanding the first shaped beam 206 by a first magnification factor in a first axis and by a second, different magnification factor in a second, different axis. In some implementations, the first magnification factor is at least twice the second magnification factor.

[0147] In some implementations, the first shaped beam 206 may be asymmetrically or anamorphically expanded by passing the first shaped beam 206 through one or more pairs 302 of crossed cylindrical lenses 304, 306. In some implementations, the first shaped beam 206 may be asymmetrically or anamorphically expanded by passing the first shaped beam 206 through one or more cylindrical telescopes 402, 404. In some implementations, the first shaped beam 206 may be asymmetrically or anamorphically expanded by passing the first shaped beam 206 through one or more anamorphic prisms 502, 504, 506, 508, 510. In some implementations, the first shaped beam 206 may be asymmetrically or anamorphically expanded by passing the first shaped beam 206 through one or more diffractive elements 802, 804. In some implementations, the first shaped beam 206 can be expanded asymmetrically or anamorphically by passing the first shaped beam 206 through a lens 902 and moving the lens 902 along the optical axis 204 to switch the asymmetric beam expander group 900 between a high irradiance mode and a low irradiance mode.

[0148] The sample 211 is optically probed with the shaped sampling beam 134 (block 1806). Image data associated with the sample 211 is acquired in response to optically probing the sample 211 with the shaped sampling beam 134 (block 1808). The shaped sampling beam 134 is swept across the sample 211 (block 1810). In some implementations, the shaped sampling beam 134 is swept across the sample 211 by directing a shaped beam 137, 208 to the reflective element 1204 and rotating the reflective element 1204 with the actuator 1202. In some implementations, the shaped sampling beam 134 is swept across the sample 211 by directing a second shaped beam 208 to the reflective element 1204 and rotating the reflective element 1204 with the actuator 1202. The shaped beam 137, 208 may pass through at least one of the crossed pair of cylindrical lenses 304, 306, the cylindrical telescopes 402, 404, the anamorphic prisms 502, 504, 506, 508, 510, and / or the diffractive elements 802, 804 to anamorphically expand the shaped beam 137, 208 along a first axis, and the reflective element 1204 may rotate to sweep the shaped sampling beam 134 along a second, different axis. The first axis may be the x-axis and the second axis may be the y-axis.

[0149] An apparatus comprising: a flow cell for receiving a sample; and a system, the system comprising: a flow cell receptacle for receiving the flow cell; and an imaging system, the imaging system comprising: a light source assembly for forming a substantially collimated beam; and an optical assembly including an asymmetric beam expander group including one or more asymmetric or anamorphic elements arranged along an optical axis, the optical assembly receiving the substantially collimated beam from the light source assembly and transforming the substantially collimated beam into a shaped sampling beam having an elongated cross-section at or near a focal plane of the optical assembly in a far field for optically probing a sample in the flow cell; and an imaging device for acquiring image data associated with the sample in response to optically probing the sample with the shaped sampling beam.

[0150] The apparatus of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the substantially collimated beam has a first aspect ratio and the shaped sampling beam has a second aspect ratio.

[0151] An apparatus described in any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the first aspect ratio of the substantially collimated beam is at most 4:1 and the second aspect ratio of the shaped sampling beam is at least 8:1.

[0152] The apparatus of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the asymmetric beam expander group provides a first magnification in a first axis and a second, different magnification in a second, different axis.

[0153] The apparatus of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the first magnification is at least twice the second magnification.

[0154] The apparatus of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the optical assembly comprises: an asymmetric beam expander group for asymmetrically or anamorphically expanding a substantially collimated beam having a first aspect ratio to form a shaped beam having a second, different aspect ratio; and an objective lens group disposed along the optical axis to receive the shaped beam from the asymmetric beam expander group and convert the shaped beam into a shaped sampling beam at or near a focal plane of the optical assembly.

[0155] The apparatus of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the light source assembly includes a beam source for providing input radiation and a collimator for substantially collimating the input radiation to form a substantially collimated beam having a first aspect ratio.

[0156] The apparatus of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the collimator includes a waveguide having a first aspect ratio.

[0157] The device of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the waveguide comprises at least one of a rectangular optical fiber or a light pipe having a first aspect ratio.

[0158] The apparatus of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the collimator includes at least one of a spherical lens or an aspherical lens arranged to collimate the output of the optical fiber.

[0159] The apparatus of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the optical assembly comprises: a beam shaping group having one or more optical elements arranged along the optical axis to receive a substantially collimated beam from the collimator and convert the substantially collimated beam into a first shaped beam having a first aspect ratio; an asymmetric beam expander group that asymmetrically or anamorphically expands the first shaped beam having the first aspect ratio to form a second shaped beam having a second, different aspect ratio; and an objective lens group arranged along the optical axis to receive the second shaped beam from the asymmetric beam expander group and convert the second shaped beam into a shaped sampling beam at or near a focal plane of the optical assembly.

[0160] An apparatus described in any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the imaging device includes a time-domain integration (TDI) image sensor having an aspect ratio corresponding to the aspect ratio of the sampling beam.

[0161] The apparatus of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the asymmetric beam expander group includes one or more pairs of crossed cylindrical lenses arranged along the optical axis.

[0162] The apparatus of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein each pair of one or more crossed cylindrical lenses includes two cylindrical lenses having different powers and oriented on different axes.

[0163] The apparatus of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the asymmetric beam expander group includes a cylindrical telescope disposed along the optical axis.

[0164] The apparatus of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the cylindrical telescope includes a singlet lens.

[0165] The apparatus of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the cylindrical telescope includes an afocal doublet lens.

[0166] The apparatus of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the doublet lens is achromatic.

[0167] The apparatus of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the cylindrical telescope is at least one of a Kepler telescope, a Galilean telescope, or a hybrid Kepler-Galilean telescope.

[0168] The apparatus of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the asymmetric beam expander group includes a second cylindrical telescope.

[0169] The apparatus of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the cylindrical telescope and the second cylindrical telescope are at least one of serially arranged, nested, or interleaved.

[0170] The apparatus of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the cylindrical telescope and the second cylindrical telescope magnify by different amounts in different axes.

[0171] The apparatus of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the asymmetric beam expander group includes one or more anamorphic prisms arranged along the optical axis such that magnification is provided substantially in one axis.

[0172] The apparatus of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the one or more anamorphic prisms comprise a first prism including a first glass type and a second prism including a second glass type.

[0173] An apparatus comprising: a system, the system comprising: a flow cell receptacle for receiving a flow cell that receives a sample; and an imaging system, the imaging system including: a light source assembly for forming a substantially collimated beam; and an optical assembly including an asymmetric beam expander group including one or more asymmetric or anamorphic elements arranged along an optical axis, the optical assembly receiving the substantially collimated beam from the light source assembly and converting the substantially collimated beam into a shaped sampling beam having an elongated cross-section at a far field at or near a focal plane of the optical assembly for optically probing a sample in the flow cell; and an imaging device for acquiring image data associated with the sample in response to optically probing the sample with the sampling beam.

[0174] The apparatus of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the asymmetric beam expander group includes one or more diffractive elements arranged along the optical axis.

[0175] The apparatus of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the one or more diffractive elements comprise at least one of a refractive homogenizer, a refractive diffuser, or a cylindrical microlens array.

[0176] The apparatus of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the asymmetric beam expander group includes a lens arranged along an optical axis, and the imaging system moves the lens along the optical axis to switch the asymmetric beam expander group between a high irradiance mode and a low irradiance mode.

[0177] An apparatus described in any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the imaging system further includes an actuator and a reflective element, and the actuator positions the reflective element to sweep the shaped sampling beam across the flow cell within the exposure time.

[0178] The apparatus of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the asymmetric beam expander group further includes at least one of a crossed pair of cylindrical lenses, a cylindrical telescope, an anamorphic prism, or a diffractive element to provide anamorphic expansion along a first axis, and the actuator positions the reflective element to sweep the shaped sampling beam along a second, different axis.

[0179] An apparatus described in any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein an actuator positions a reflective element within a range to sweep a shaped sampling beam across the flow cell.

[0180] The device of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the range is from about 39 degrees to about 41 degrees.

[0181] 1. A method comprising: generating a collimated beam using a light source assembly; converting the collimated beam using an optical assembly into a shaped sampling beam having an elongated cross-section in a far field at a focal plane of the optical assembly, the optical assembly having an asymmetric beam expander group including one or more asymmetric or anamorphic elements arranged along an optical axis; and optically probing a sample using the shaped sampling beam.

[0182] The method of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein generating the collimated beam includes passing the input beam through a waveguide.

[0183] The method of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the waveguide comprises at least one of a rectangular optical fiber or a light pipe.

[0184] The method of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein converting the collimated beam into a shaped sampling beam includes using an asymmetric beam expander group to asymmetrically or anamorphically expand a substantially collimated beam having a first aspect ratio to form a shaped beam having a second aspect ratio.

[0185] A method as in any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein converting the collimated beam into a shaped sampling beam includes converting the shaped beam into a shaped sampling beam at or near a focal plane of the optical assembly using an objective lens group arranged along the optical axis.

[0186] The method of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein asymmetrically or anamorphically expanding the substantially collimated beam includes passing the substantially collimated beam through at least one of: 1) one or more pairs of crossed cylindrical lenses; 2) one or more cylindrical telescopes; 3) one or more anamorphic prisms; or 4) one or more diffractive elements.

[0187] The method of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein asymmetrically or anamorphically expanding the substantially collimated beam includes moving lenses of the asymmetric beam expander group along the optical axis to switch the asymmetric beam expander group between a high irradiance mode and a low irradiance mode.

[0188] The method of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, further comprising sweeping the shaped sampling beam across the sample.

[0189] A method as in any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein sweeping the shaped sampling beam across the sample includes directing the shaped beam to a reflective element and rotating the reflective element using an actuator.

[0190] The method of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein converting the collimated beam into a shaped sampling beam includes: using a beam shaping group having one or more optical elements arranged along an optical axis to convert the substantially collimated beam into a first shaped beam having a first aspect ratio; and using an asymmetric beam expander group to asymmetrically or anamorphically expand the first shaped beam having the first aspect ratio to form a second shaped beam having a second, different aspect ratio.

[0191] A method as in any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein converting the collimated beam into a shaped sampling beam includes converting the second shaped beam into the shaped sampling beam at or near a focal plane of the optical assembly using an objective lens group arranged along the optical axis.

[0192] The method of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein asymmetrically or anamorphically expanding the first shaped beam expands the first shaped beam by a first magnification in a first axis and by a second, different magnification in a second, different axis.

[0193] The method of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the first magnification is at least twice the second magnification.

[0194] The method of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein asymmetrically or anamorphically expanding the first shaped beam includes passing the first shaped beam through one or more pairs of crossed cylindrical lenses.

[0195] The method of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein asymmetrically or anamorphically expanding the first shaped beam includes passing the first shaped beam through one or more cylindrical telescopes.

[0196] The method of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein asymmetrically or anamorphically expanding the first shaped beam includes passing the first shaped beam through one or more anamorphic prisms.

[0197] The method of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein asymmetrically or anamorphically expanding the first shaped beam includes passing the first shaped beam through one or more diffractive elements.

[0198] The method of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein asymmetrically or anamorphically expanding the first shaped beam includes passing the first shaped beam through a lens and moving the lens along the optical axis to switch the asymmetric beam expander group between a high irradiance mode and a low irradiance mode.

[0199] The method of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, further comprising sweeping the shaped sampling beam across the sample by directing the second shaped beam to a reflective element and rotating the reflective element using an actuator.

[0200] A method as in any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, further comprising acquiring image data associated with the sample in response to optically probing the sample with the shaped sampling beam.

[0201] The foregoing description is provided to enable one skilled in the art to practice the various configurations described herein. While the subject technology has been particularly described with reference to various diagrams and configurations, it should be understood that these are for illustrative purposes only and should not be construed as limiting the scope of the subject technology.

[0202] As used herein, elements or steps described in the singular and followed by the words "a" or "an" should be understood as not excluding a plurality of those elements or steps, unless such exclusion is expressly stated. Furthermore, references to "one implementation" are not intended to be interpreted as excluding the existence of additional implementations that also incorporate the recited features. Furthermore, unless expressly stated to the contrary, implementations that "comprising," "including," or "having" an element or elements having a particular characteristic may include additional elements whether or not they have that characteristic. Furthermore, the terms "comprising," "including," "having," etc. are used interchangeably herein.

[0203] As used throughout this specification, the terms "substantially," "approximately," and "about" are used to describe and take into account small variations due to processing variations, etc. For example, small variations can refer to ±5% or less, such as ±2% or less, such as ±1% or less, such as ±0.5% or less, such as ±0.2% or less, such as ±0.1% or less, such as ±0.05% or less.

[0204] There may be many other ways to implement the subject technology. The various functions and elements described herein may be divided differently than shown without departing from the scope of the subject technology. Various modifications to these implementations may be readily apparent to those skilled in the art, and the general principles defined herein may be applied to other implementations. Accordingly, many changes and modifications may be made to the subject technology by those skilled in the art without departing from the scope of the subject technology. For example, a different number of given modules or units may be used, different types or multiple types of given modules or units may be used, given modules or units may be added, or given modules or units may be omitted.

[0205] Underlined and / or italicized headings and subheadings are used for convenience only, do not limit the subject technology, and are not referred to in connection with interpreting the description of the subject technology. All structural and functional equivalents to the elements of the various implementations described throughout this disclosure that are known or later become known to those skilled in the art are expressly incorporated herein by reference and are intended to be encompassed by the subject technology. Furthermore, nothing disclosed herein is intended to be publicly exclusive, regardless of whether such disclosure is explicitly set forth in the description above.

[0206] It is understood that all combinations of the foregoing concepts and additional concepts described in more detail below (provided such concepts are not mutually inconsistent) are considered to be part of the subject matter disclosed herein. In particular, all combinations of claimed subject matter appearing at the end of this disclosure are considered to be part of the subject matter disclosed herein.

Claims

1. 1. An apparatus comprising: a flow cell for receiving the sample; a system, the system comprising: a flow cell receptacle for receiving the flow cell; an imaging system, a light source assembly for forming a substantially collimated beam; an optical assembly including an asymmetric beam expander group including one or more asymmetric or anamorphic elements disposed along an optical axis, the optical assembly receiving the substantially collimated beam from the light source assembly and converting the substantially collimated beam into a shaped sampling beam having an elongated cross-section in a far field at or near a focal plane of the optical assembly for optically probing the sample in the flow cell; an imaging device for acquiring image data associated with the sample in response to the optically probing the sample with the shaped sampling beam.

2. 2. The apparatus of claim 1, wherein the substantially collimated beam has a first aspect ratio and the shaped sampling beam has a second aspect ratio, the first aspect ratio of the substantially collimated beam being at most 4:1 and the second aspect ratio of the shaped sampling beam being at least 8:

1.

3. 10. The apparatus of claim 1, wherein the asymmetric beam expander group provides a first magnification in a first axis and a second, different magnification in a second, different axis, the first magnification being at least twice the second magnification.

4. the optical assembly the asymmetric beam expanders for asymmetrically or anamorphically expanding the substantially collimated beam having a first aspect ratio to form a shaped beam having a second, different aspect ratio; 10. The apparatus of claim 1, further comprising: an objective lens group disposed along the optical axis to receive the shaped beam from the asymmetric beam expander group and convert the shaped beam into the shaped sampling beam at or near the focal plane of the optical assembly.

5. the light source assembly a beam source for providing input radiation; a collimator for substantially collimating the input radiation to form the substantially collimated beam having a first aspect ratio.

6. 6. The apparatus of claim 5, wherein the collimator includes a waveguide having the first aspect ratio, the waveguide comprising at least one of a rectangular optical fiber or a light pipe having the first aspect ratio, and the collimator includes at least one of a spherical lens or an aspherical lens arranged to collimate an output of the optical fiber.

7. the optical assembly a beam shaping group having one or more optical elements disposed along the optical axis to receive the substantially collimated beam from the collimator and transform the substantially collimated beam into a first shaped beam having a first aspect ratio; the asymmetric beam expanders asymmetrically or anamorphically expanding the first shaped beam having the first aspect ratio to form a second shaped beam having a second, different aspect ratio; 10. The apparatus of claim 1, further comprising: an objective lens group disposed along the optical axis to receive the second shaped beam from the asymmetric beam expander group and convert the second shaped beam into the shaped sampling beam at or near the focal plane of the optical assembly.

8. The apparatus of claim 1 , wherein the imaging device comprises a time domain integration (TDI) image sensor having an aspect ratio corresponding to an aspect ratio of the sampling beam.

9. 10. The apparatus of claim 1, wherein the asymmetric beam expander group comprises one or more pairs of crossed cylindrical lenses disposed along the optical axis, each pair of the one or more crossed cylindrical lenses comprising two cylindrical lenses having different powers and oriented on different axes.

10. The apparatus of claim 1 , wherein the asymmetric beam expander group comprises a cylindrical telescope disposed along the optical axis.

11. The apparatus of claim 10 , wherein the cylindrical telescope comprises a singlet lens or an achromatic afocal doublet lens.

12. 10. The apparatus of claim 1, wherein the asymmetric beam expander group includes a second cylindrical telescope, the cylindrical telescope and the second cylindrical telescope expanding by different amounts in different axes.

13. 13. The apparatus of claim 12, wherein the cylindrical telescope and the second cylindrical telescope are at least one of tandem, nested, or interleaved.

14. 10. The apparatus of claim 1, wherein the asymmetric beam expander group comprises one or more anamorphic prisms arranged along the optical axis such that magnification is provided substantially in one axis.

15. 15. The apparatus of claim 14, wherein the anamorphic prism comprises a first prism including a first glass type and a second prism including a second glass type.

16. 1. An apparatus comprising: a system, the system comprising: a flow cell receptacle for receiving a flow cell for receiving a sample; an imaging system, a light source assembly for forming a substantially collimated beam; an optical assembly including an asymmetric beam expander group including one or more asymmetric or anamorphic elements disposed along an optical axis, the optical assembly receiving the substantially collimated beam from the light source assembly and converting the substantially collimated beam into a shaped sampling beam having an elongated cross-section in a far field at or near a focal plane of the optical assembly for optically probing the sample in the flow cell; an imaging device for acquiring image data associated with the sample in response to the optically probing the sample with the sampling beam.

17. 17. The apparatus of claim 16, wherein the asymmetric beam expander group includes one or more diffractive elements disposed along the optical axis, the one or more diffractive elements comprising at least one of a refractive homogenizer, a refractive diffuser, or a cylindrical microlens array.

18. 17. The apparatus of claim 16, wherein the asymmetric beam expander group includes a lens disposed along the optical axis, and wherein the imaging system moves the lens along the optical axis to switch the asymmetric beam expander group between a high irradiance mode and a low irradiance mode.

19. 17. The apparatus of claim 16, wherein the imaging system further comprises an actuator and a reflective element, the actuator positioning the reflective element to sweep the shaped sampling beam across the flow cell within an exposure time.

20. 20. The apparatus of claim 19, wherein the asymmetric beam expander group further comprises at least one of a crossed pair of cylindrical lenses, a cylindrical telescope, an anamorphic prism, or a diffractive element to provide anamorphic expansion along a first axis, and wherein the actuator positions the reflective element to sweep the shaped sampling beam along a second, different axis.

21. 20. The apparatus of claim 19, wherein the actuator positions the reflective element within a range to sweep the shaped sampling beam across the flow cell.

22. 1. A method comprising: generating a collimated beam using a light source assembly; converting the collimated beam into a shaped sampling beam having an elongated cross-section in a far field at a focal plane of the optical assembly using the optical assembly, the optical assembly having an asymmetric beam expander group including one or more asymmetric or anamorphic elements disposed along an optical axis; and optically probing a sample with the shaped sampling beam.

23. 23. The method of claim 22, wherein generating the collimated beam comprises passing the input beam through a waveguide, the waveguide comprising at least one of a rectangular optical fiber or a light pipe.

24. 23. The method of claim 22, wherein converting the collimated beam into the shaped sampling beam comprises using the asymmetric beam expanders to asymmetrically or anamorphically expand the substantially collimated beam having a first aspect ratio to form a shaped beam having a second aspect ratio.

25. 25. The method of claim 24, wherein converting the collimated beam into the shaped sampling beam comprises converting the shaped beam into the shaped sampling beam at or near the focal plane of the optical assembly using an objective lens group disposed along the optical axis.

26. 25. The method of claim 24, wherein asymmetrically or anamorphically expanding the substantially collimated beam comprises passing the substantially collimated beam through at least one of: 1) one or more pairs of crossed cylindrical lenses; 2) one or more cylindrical telescopes; 3) one or more anamorphic prisms; or 4) one or more diffractive elements.

27. 25. The method of claim 24, wherein asymmetrically or anamorphically expanding the substantially collimated beam comprises moving lenses of the asymmetric beam expander group along the optical axis to switch the asymmetric beam expander group between a high irradiance mode and a low irradiance mode.

28. 25. The method of claim 24, further comprising sweeping the shaped sampling beam across the sample.

Images