Obviousness

The obviousness of US patent 11703443 under 35 U.S.C. § 103 can be analyzed by identifying combinations of prior art references that would render the claimed inventions obvious to a person having ordinary skill in the art (PHOSITA). The patent describes several improved subsystems for a flow cytometer, including an LD-based optical subsystem, a composite microscope objective, a fluidic system, a peristaltic pump, and a wavelength division multiplexer (WDM). The prior art date for the patent is May 30, 2012.

Analysis of Obviousness for Subsystems of US11703443

1. LD-based Optical Subsystem

• Inventive Concept (US11703443): Directing an elliptically shaped beam from a Laser Diode (LD) into a viewing zone where its minor axis is parallel to the flow direction. The system uses a collimating lens, a beam compressing optical element to reduce the major axis width (perpendicular to flow) to be less than the sheath flow, and a cylindrical focusing element (axis perpendicular to flow) to tightly focus the minor axis at the viewing zone, resulting in a smooth, elliptical beam profile.
• Prior Art References:
  • U.S. Pat. No. 6,713,019 (the '019 patent): Discloses orienting an LD by 90 degrees such that its slow axis (corresponding to the minor axis of US11703443) is parallel to the direction of flow. This was done to overcome problematic fringes along the fast axis. However, the '019 patent's approach produced a highly astigmatic beam and a width perpendicular to flow that was comparable to or wider than the sheath flow, leading to reduced signal and increased background noise.
  • General knowledge of optics: A PHOSITA would be aware of cylindrical lenses for independently manipulating beam dimensions along different axes and for correcting astigmatism.
• Motivation to Combine: A PHOSITA would be motivated to address the drawbacks of the '019 patent while retaining its benefit of mitigating fringe effects. Specifically, the motivation would be to eliminate the astigmatism and reduce the excessive beam width perpendicular to flow, which diminished the amount of laser energy on the particle and increased undesirable background scattering.
• Obvious Combination: Combining the LD orientation from the '019 patent with known optical elements (a beam compressing element and a cylindrical focusing element) to refine the beam profile would be obvious. The beam compressing optical element (e.g., plano-convex lens 504 in US11703443) would reduce the major axis width perpendicular to the flow, and a high-power cylindrical focusing element (505 in US11703443), with its axis perpendicular to the flow, would selectively focus the minor axis along the flow. This combination directly solves the astigmatism and beam width problems identified in the '019 patent, resulting in an optimized, fringe-free elliptical spot suitable for flow cytometry.

2. Composite Microscope Objective

• Inventive Concept (US11703443): An objective including a concave mirror and an aberration corrector plate (an aspheric lens with a first zone of negative optical power outside a neutral zone and a second zone inside with positive optical power). The viewing zone is located between the mirror and the plate, allowing for a compact design and single-sided illumination/detection.
• Prior Art References:
  • U.S. Provisional Patent Application Ser. No. 61/653,328 (priority document): This provisional application, filed on May 30, 2012, explicitly describes a "Composite Microscope Objective with a Dispersion Compensation Plate," indicating that the inventors considered this specific objective design to be novel at the priority date.
  • General knowledge of catadioptric optics: Systems combining mirrors and lenses are known for achieving high numerical aperture, long working distances, and improved aberration correction.
  • General knowledge of aspheric lenses: Aspheric lenses are well-known for their ability to correct spherical and other aberrations in optical systems.
  • U.S. Pat. Nos. 7,385,682 and 7,561,267: Disclose using large numerical aperture aspheric lenses, though in the context of LD collimation.
• Motivation to Combine: Optical engineers are constantly motivated to design microscope objectives with improved imaging quality, longer working distances, larger numerical apertures, and reduced aberrations, especially for applications like flow cytometry requiring high precision. A compact design with single-sided access is also a desirable feature.
• Obviousness Argument: While the specific optical prescription and arrangement (concave mirror, aspheric plate with defined power zones, and viewing zone positioned between them) for a flow cytometer objective, as described in US11703443, may not be explicitly found in the cited prior art, the general principle of combining reflective (mirror) and refractive (aspheric corrector) elements to achieve a high-performance, aberration-corrected objective is known in optical design. A PHOSITA would be motivated to employ such combinations to address the limitations of purely refractive or reflective designs. Without more specific prior art detailing this exact configuration for a flow cytometer objective, this particular aspect might present a stronger case against obviousness, especially given its presence in a priority provisional application.

3. Fluidic System

• Inventive Concept (US11703443): A fluidic system for supplying pulsation-free sheath flow, utilizing a T-coupling with a bypass conduit (lower fluidic resistance) returning a fraction of liquid to the reservoir. An air-filled inlet portion of a particle filter acts as a fluidic capacitor, and a reservoir capsule or tubing is included to store air ejected from the filter when the pump is turned off.
• Prior Art References:
  • U.S. Provisional Patent Application Ser. No. 61/653,245 (priority document): This provisional application describes a "Pulseless Peristaltic Pump," indicating a prior focus on reducing pulsations in fluid delivery.
  • General fluidics engineering: Bypass loops are commonly used for flow regulation, pressure control, and coarse pulsation dampening. The use of compressible elements, such as trapped air, as fluidic capacitors to dampen pulsations is a well-known technique in fluid dynamics. Managing air within fluidic systems (e.g., preventing air locks or cavitation) is a standard design consideration.
• Motivation to Combine: The accuracy of flow cytometry is critically dependent on stable, pulsation-free sheath flow. A PHOSITA in fluidics system design for cytometry would be highly motivated to eliminate or significantly reduce pulsations, especially when using less expensive or higher-pulsation-frequency pumps, and to address practical operational issues like air management.
• Obvious Combination: Given the known need for stable flow, a PHOSITA would routinely combine standard components like a pump and T-coupling with a bypass loop for primary flow regulation and coarse pulsation dampening. Intentionally designing the particle filter inlet to trap air or selecting a filter that does so, and then utilizing this trapped air as a fluidic capacitor, is an obvious application of known pulsation-dampening principles. Furthermore, foreseeing the issue of air ejection from the filter when the pump stops, adding a dedicated reservoir (capsule or tubing) to store this air to prevent it from entering critical parts of the system is a straightforward engineering solution to a predictable operational problem. The design choice for the bypass to have lower resistance is an optimization to allow for higher pump flow rates and higher pulsation frequencies, which are easier to attenuate.

4. Pulseless Peristaltic Pump

• Inventive Concept (US11703443): A peristaltic pump designed for minimal pulsation. Two main approaches are described:
  1. Mechanical Compensation: The arcuate curved track of the pump housing includes recesses that cause the compressible tube to progressively decompress and then re-compress as rollers pass, maintaining a substantially invariant total volume of liquid in certain sections to minimize pulsation.
  2. Programmable Speed Control: A variable speed motor programmatically speeds up when a roller reaches the exit section to compensate for tube expansion.
• Prior Art References:
  • U.S. Provisional Patent Application Ser. No. 61/653,245 (priority document): Entitled “Pulseless Peristaltic Pump,” this provisional application highlights the inventors' focus on addressing peristaltic pump pulsations as of May 30, 2012.
  • General peristaltic pump technology: Pulsation is a well-known inherent characteristic and drawback of peristaltic pumps. Various methods for reducing pulsation are known, such as increasing the number of rollers or using dampeners.
  • General mechanical engineering: Modifying cam profiles or track geometries to achieve specific displacement characteristics to smooth motion or fluid delivery is a known design principle.
  • General control systems engineering: The use of variable speed motors and programmatic control to compensate for known, predictable variations in mechanical systems (e.g., flow rate fluctuations) is a standard application of control theory.
• Motivation to Combine: The critical need for stable, pulsation-free fluid flow in flow cytometry provides a strong motivation for a PHOSITA to improve peristaltic pump designs to minimize pulsations.
• Obvious Combination:
  • For Mechanical Compensation: A PHOSITA would understand the volumetric changes that cause pulsation in peristaltic pumps. They would be motivated to modify the pump's mechanical design (e.g., the shape of the arcuate track) to counteract these changes. Designing recesses or modified track profiles to maintain a substantially invariant fluid volume in critical sections, thereby smoothing the flow, is a direct and logical engineering solution to a known problem.
  • For Programmable Speed Control: Knowing that tube expansion near the exit section is a source of pulsation, a PHOSITA would be motivated to implement active control. Using a variable speed motor (a common feature in modern pumps) to programmatically adjust the rotor speed (e.g., speed up during tube expansion) to maintain a constant flow rate is a straightforward application of feedforward control to compensate for a predictable system characteristic.

5. Wavelength Division Multiplexing (WDM) System

• Inventive Concept (US11703443): A WDM system that separates light into multiple colored bands, featuring a cascaded unit-magnification image relay architecture to extend the collimated optical path length without large beam expansion. Dichroic filters (potentially in zig-zag or branched configurations) are used to separate light, which is then focused onto small semiconductor photodetectors. The system may also include precision alignment techniques for dichroic filters using templates.
• Prior Art References:
  • U.S. Provisional Patent Application Ser. No. 61/715,819 (priority document): Entitled “Wavelength Division Multiplexing for Extended Light Source,” filed on Oct. 18, 2012, this highlights the inventors' prior work in this area.
  • "WDM techniques well-established in the optical communication industry": The patent explicitly states this, acknowledging that WDM itself is not new.
  • U.S. Pat. No. 6,683,314: Discusses a "star configuration" for WDM.
  • U.S. Pat. No. 4,727,020: Discusses a "branched configuration" for WDM.
  • General optical design principles: Unit-magnification image relay systems are known in optics to transport images or beams over distances while preserving their characteristics and minimizing expansion. Dichroic filters are standard components for wavelength separation. Precision manufacturing and assembly techniques (e.g., using templates and reference surfaces for alignment) are common in high-precision optics.
• Motivation to Combine: A PHOSITA in optical engineering for flow cytometry would be motivated to efficiently separate multiple fluorescence signals for detection, requiring an optical system that can handle multiple wavelengths, be reconfigurable, maintain beam quality over an extended path, and deliver light efficiently to small detectors.
• Obvious Combination: Given that WDM techniques are "well-established" and specific configurations (star, branched) are known, a PHOSITA would be motivated to adapt these for flow cytometry. Combining these known WDM principles (using dichroic filters in zig-zag or branched paths) with a unit-magnification image relay architecture is an obvious engineering choice to efficiently extend the optical path for wavelength separation without significant beam expansion, allowing for greater flexibility and potentially more channels. The use of templates for accurate and consistent alignment of dichroic filters is a routine manufacturing practice to ensure reconfigurability and maintain optical performance in a complex WDM system.

In summary, while US11703443 describes an integrated flow cytometer system with several improved subsystems, many of these improvements, when analyzed against the explicitly cited prior art and general engineering knowledge, appear to be combinations of known elements or techniques that a PHOSITA would be motivated to employ to solve known problems or improve performance in flow cytometry. The strongest argument for non-obviousness might reside in the specific design of the composite microscope objective, particularly its unique configuration of the mirror, aspheric plate with distinct power zones, and the viewing zone's placement, provided that this precise combination was not explicitly taught or suggested by prior art.