Obviousness

Obviousness Analysis of US Patent 12174107 Under 35 U.S.C. § 103

This analysis addresses the obviousness of US Patent 12174107, titled "Flow Cytometer," under 35 U.S.C. § 103, considering the effective prior art date of May 30, 2012, based on the earliest priority date cited in the patent. The patent broadly claims an improved flow cytometer comprising several enhanced subassemblies: a laser diode (LD) based optical subsystem, a composite microscope objective, a pulseless fluidic subsystem, a pulseless peristaltic pump, and a wavelength division multiplexer (WDM). Each of these components is presented as addressing known problems in the field of flow cytometry.

Identified Prior Art References and Their Publication Dates

The following prior art references are cited within US12174107 or were found during the analysis, all published before May 30, 2012:

• U.S. Pat. No. 5,788,927: Published August 3, 1998. Discusses collimating and expanding a Gaussian beam for flow cytometry.
• U.S. Pat. No. 6,713,019: Published March 30, 2004. Describes an LD-based optical subsystem for flow cytometry.
• U.S. Pat. No. 7,385,682: Published June 10, 2008. Mentions aspheric lenses for LD collimation.
• U.S. Pat. No. 7,561,267: Published July 14, 2009. Mentions aspheric lenses for LD collimation.
• U.S. Pat. No. 4,727,020: Published February 23, 1988. Discloses multi-laser excitation in flow cytometers and branched WDM configurations.
• U.S. Pat. No. 6,683,314: Published January 28, 2003. Mentions a "star configuration" for WDM.
• U.S. Pat. No. 6,510,007: Published December 23, 2002. Describes a microscope objective.
• U.S. Pat. No. 7,110,192: Published November 14, 2006. Describes a microscope objective.
• WO 01/27590: Published April 19, 2001. Discloses a spherical concave mirror objective.
• U.S. Provisional Patent Application Ser. No. 61/653,245: Filed May 30, 2012, entitled "Pulseless Peristaltic Pump."
• U.S. Provisional Patent Application Ser. No. 61/653,328: Filed May 30, 2012, entitled "Composite Microscope Objective with a Dispersion Compensation Plate."
• Practical Flow Cytometry, Howard M. Shapiro, Wiley (2003) ISBN 0471411256: A foundational text on flow cytometry.

Obviousness of Individual Subsystems

A person having ordinary skill in the art (PHOSITA) in flow cytometry would possess a strong motivation to improve various aspects of flow cytometer design to enhance performance, reliability, and ease of use.

1. LD-based Optical Subsystem
US12174107 claims an LD-based optical subsystem that directs an elliptical beam with its minor axis parallel to the flow direction, using a beam-compressing element for the major axis and a cylindrical focusing element (axis perpendicular to flow) to focus the minor axis. This configuration aims to provide a Gaussian-like intensity profile along the minor axis and an optimized width along the major axis, overcoming issues like "fringes" from LDs and astigmatism in prior art.

• Prior Art: U.S. Pat. No. 6,713,019 ("the '019 patent") addresses LD beam quality by orienting the slow axis (minor axis) parallel to the flow, then diffusing the beam perpendicular to the flow with a cylindrical lens before focusing with a spherical lens. However, this leads to astigmatic and wide beams. U.S. Pat. No. 5,788,927 teaches general collimation and focusing to an elliptical Gaussian beam.
• Motivation for Combination: A PHOSITA would be keenly aware of the problems with LD beam quality, specifically the fringes along the fast axis and the astigmatism/width issues introduced by the approach of U.S. Pat. No. 6,713,019. Given the general knowledge of cylindrical lenses for anamorphic beam shaping and focusing, it would be obvious to reconfigure the optical train. The PHOSITA would be motivated to exploit the smoother profile of the LD's slow axis along the flow direction (as recognized by the '019 patent) while actively focusing this axis with a cylindrical lens positioned for precise control, and using a separate element for the major axis, to produce a tight, non-astigmatic elliptical spot. This is an application of known optical principles to overcome specific, identified deficiencies in existing LD-based flow cytometer illumination systems.

2. Composite Microscope Objective
The patent describes a composite microscope objective with a concave mirror and an aspheric aberration corrector plate, where the viewing zone is located between them. This design is intended to provide a long working distance, large numerical aperture (NA), large field of view (FOV), and minimal chromatic aberration.

• Prior Art: WO 01/27590 discloses an objective design based on a spherical concave mirror, offering large NA and good on-axis image quality but poor off-axis characteristics. U.S. Pat. Nos. 6,510,007 and 7,110,192 describe objectives using modified apochromats with gel-coupled or epoxy bonded lenses, which sacrificed image quality. Aspheric lenses are generally known for aberration correction in optical systems, as indicated by their mention in U.S. Pat. Nos. 7,385,682 and 7,561,267 for LD collimation.
• Motivation for Combination: To address the "poor off-axis characteristics" of mirror-based objectives like that in WO 01/27590, a PHOSITA would be motivated to employ known aberration correction techniques. The use of aspheric lenses for correcting various optical aberrations, including off-axis aberrations, is a well-established optical design principle. Combining the light-gathering capability of a concave mirror with an aspheric corrector plate to improve image quality, particularly off-axis performance for applications requiring a large FOV (e.g., multiple laser spots as taught by U.S. Pat. No. 4,727,020), would be an obvious design choice. Placing the viewing zone between the mirror and the corrector plate is a specific geometric arrangement that an optical designer would explore for compactness and optical performance. The details of the aspheric lens's power zones (negative outer, positive inner) represent a specific application of known aspheric design principles to achieve the desired correction.

3. Fluidic Subsystem for Pulseless Sheath Flow
US12174107 details a fluidic subsystem using a liquid pump, a T-coupling with a bypass conduit back to the reservoir (lower fluidic resistance), and a sheath route to the viewing zone that includes a particle filter. Critically, the system is designed to trap air within the particle filter inlet and in a reservoir capsule (or tubing) between the T-coupling and the filter, where this trapped air acts as a fluidic capacitor to reduce pulsations.

• Prior Art: The problem of pulsations in liquid flow within flow cytometers is well-known (implicitly addressed by the very title of U.S. Provisional Patent Application Ser. No. 61/653,245, "Pulseless Peristaltic Pump," filed on the same priority date). General fluid dynamics teaches that compressible elements, such as trapped air, can act as accumulators or dampeners to reduce pulsations. Bypass loops are standard engineering practice for flow and pressure regulation in fluid systems.
• Motivation for Combination: A PHOSITA tasked with creating a "pulsation-free" or "pulseless" liquid flow for flow cytometry (a stated goal of the '245 provisional) would immediately consider methods to dampen pulsations, especially those from common pumps like peristaltic pumps. Recognizing that air is compressible and can serve as a fluidic capacitor, it would be obvious to incorporate air chambers or deliberately design components to trap air to exploit this property. Designing a bypass loop to relieve excess pressure and further stabilize flow is a straightforward fluidic engineering solution. Combining these elements – a pump, a T-coupling, a bypass loop, and air-containing components (like a filter inlet or dedicated reservoir capsule/tubing) to act as fluidic capacitors – to achieve a stable, pulseless sheath flow would be obvious to a fluidics engineer.

4. Peristaltic Pump for Pulseless Liquid Flow
The peristaltic pump claimed in US12174107 includes rollers, a rotor, and a compressible tube against an arcuate track. The inventive feature lies in modifying the track with recesses that cause the tube to progressively decompress and then compress, maintaining a substantially invariant total fluid volume from the recess to the pump outlet. Alternatively, programmable motor speed is used to compensate for tube expansion.

• Prior Art: Peristaltic pumps are known, and their inherent pulsation is a widely recognized problem. The very existence of U.S. Provisional Patent Application Ser. No. 61/653,245, filed May 30, 2012, and titled "Pulseless Peristaltic Pump," strongly indicates that the problem of peristaltic pump pulsations and solutions for achieving pulseless flow were known and being actively developed at the priority date.
• Motivation for Combination: A PHOSITA in pump design would be motivated to address the known pulsation problem of peristaltic pumps. Modifying the geometry of the pump track to precisely control the compression and decompression of the tube and thus regulate fluid displacement is a direct application of mechanical design principles to achieve a desired flow characteristic. Similarly, using a variable-speed motor and programming its speed to counteract known pulsations or volume changes at the exit section is a standard application of control systems engineering. These solutions are predictable modifications of existing peristaltic pump designs aimed at solving a well-known problem.

5. Wavelength Division Multiplexing (WDM) System
US12174107 describes a WDM system featuring a cascaded unit-magnification image relay architecture with multiple optical elements to extend the collimated path without significant beam expansion. Dichroic filters are placed along this path, potentially in a zig-zag configuration, and are designed for consistent optical alignment via bonding to a holder with a reference surface.

• Prior Art: WDM techniques are "well-established in the optical communication industry" and were known to be "readily adapted for fluorescence light detection". U.S. Pat. No. 4,727,020 and U.S. Pat. No. 6,683,314 already disclose WDM configurations for flow cytometers (branched and star configurations, respectively). Unit-magnification image relay systems are a known optical principle for propagating beams or images over distances while maintaining beam characteristics.
• Motivation for Combination: A PHOSITA in optical design for flow cytometry would be motivated to create a WDM system that is more efficient, versatile, compact, and easily reconfigurable for separating multiple fluorescence signals. Recognizing the limitations of simply cascading dichroic filters in a non-relay system (e.g., beam expansion), it would be obvious to apply known unit-magnification image relay optics to extend the collimated path, allowing for the insertion of more filters (e.g., in a zig-zag configuration for compactness). The use of reference surfaces and templates for bonding optical filters to holders to ensure precise and repeatable alignment is a standard manufacturing and assembly practice for optical systems, aiming to improve manufacturability and serviceability.

Obviousness of the Overall Flow Cytometer System

The claims of US12174107 cover a flow cytometer that integrates these five improved subsystems. Flow cytometers are inherently complex systems that combine optical, fluidic, and detection components to analyze particles in a fluid stream.

• Motivation for Combination: A PHOSITA in the field of flow cytometry would understand that the performance of the overall system is dependent on the performance of its individual critical components. Therefore, there would be a strong and obvious motivation to integrate the best available or newly improved versions of each subsystem into a single flow cytometer to achieve a cumulative advantage in overall system performance. For instance, improved illumination from the LD optical subsystem, better light collection from the composite microscope objective, stable particle delivery from the pulseless fluidic system and peristaltic pump, and efficient signal separation from the WDM system all contribute to the well-understood goals of more accurate, reliable, and high-throughput flow cytometry. The integration of such improved components, each addressing a recognized challenge in its specific domain, into a comprehensive flow cytometer system would be a predictable result of routine engineering optimization and design choices to improve an existing technology.

In summary, while each subsystem of US12174107 presents specific engineering solutions, these solutions generally build upon known principles and address known problems in flow cytometry and related fields (optics, fluidics, pump design). The motivation to combine these individually improved components into a unified flow cytometer system would be clear to a PHOSITA seeking to enhance the performance and capabilities of such devices.