Derivative works — US Patent 12174106

DEFENSIVE DISCLOSURE: DERIVATIVE EMBODIMENTS AND APPLICATIONS OF FLOW CYTOMETRY SYSTEMS

Publication Date: May 13, 2026
Reference Patent: US 12,174,106 B2

This document discloses novel and non-obvious variations, applications, and integrations of the flow cytometer technology described in US Patent 12,174,106 B2. The purpose of this disclosure is to establish prior art for subsequent inventions that may be considered incremental or obvious extensions of the foundational technology.

Disclosure Area 1: Composite Microscope Objective

The core concept involves a composite microscope objective with a concave mirror and a specific aspheric aberration corrector plate. The following are derivative embodiments:

1.1. Material & Component Substitution

Enabling Description: The concave mirror (601) and the aberration corrector plate, described as being made of optically transparent materials like glass or plastic, can be fabricated from advanced ceramic composites such as Aluminum Oxynitride (ALON) or Spinel (MgAl₂O₄). These materials offer superior scratch resistance, a higher refractive index for more compact designs, and enhanced thermal stability, making the objective suitable for harsh environments. The optical coupling, currently achieved with gel or adhesive, can be replaced by a van der Waals bonding process or by using a cured, index-matched fluoroelastomer, providing a more permanent and contamination-resistant interface.
```
graph TD
    A[Illuminated Object in Viewing Zone] --> B(Scattered/Fluoresced Light);
    B --> C{Concave Mirror (Spinel/ALON)};
    C --> D{Aberration Corrector Plate (Sapphire/ALON)};
    D --> E[Image Plane];
    F(Van der Waals Bonding) --> C;
    F --> D;
```

1.2. Operational Parameter Expansion

Enabling Description: For cryogenic flow cytometry applications (e.g., analyzing cells preserved in liquid nitrogen), the objective components are designed to operate at temperatures down to -196°C. The mirror and corrector plate are made from fused silica with a near-zero coefficient of thermal expansion. The housing is constructed from Invar 36 alloy to prevent mechanical stress due to thermal contraction. The optical coupling medium is a low-temperature-grade silicone fluid that remains transparent and viscous at cryogenic temperatures, ensuring stable optical performance during analysis of cryopreserved samples.
```
stateDiagram-v2
    [*] --> Operating
    Operating --> Cryogenic_Mode: Temperature < -150C
    Cryogenic_Mode --> Operating: Temperature > -100C
    Cryogenic_Mode: Fused Silica Optics
    Cryogenic_Mode: Invar 36 Housing
    Operating: Standard Glass/Plastic
```

1.3. Cross-Domain Application: Aerospace

Enabling Description: The microscope objective design is adapted for real-time monitoring of microbial contamination in spacecraft water recycling systems. The flow cell (cuvette 603) is integrated into a bypass line of the water system. The objective's high numerical aperture and aberration correction are critical for detecting and identifying single-celled organisms or biofilms at low concentrations. The entire assembly is ruggedized to withstand launch vibrations (up to 20 Grms) and space radiation, using rad-hardened glass for the optical elements and a titanium housing.
```
flowchart LR
    subgraph Spacecraft Water System
        A[Main Water Line] --> B{Bypass Valve};
        B --> C[Micro-Flow Cell];
        C --> D[Return to System];
    end
    subgraph Contaminant Detection Module
        E(Laser Diode) --> C;
        C -- Light --> F(Composite Objective);
        F -- Signal --> G(WDM & Detector);
        G -- Data --> H(Onboard Computer);
    end
```

1.4. Cross-Domain Application: AgTech (Agricultural Technology)

Enabling Description: The objective is integrated into a portable soil analysis device for in-field quantification of microbial populations and spore viability. A microfluidic chip replaces the cuvette, into which a soil suspension is injected. The objective's large field of view allows for simultaneous imaging of multiple microfluidic channels. Illumination is provided by a battery-powered LED array, and the collected fluorescence data is processed by an embedded system to provide farmers with immediate feedback on soil health and pathogen load.
```
sequenceDiagram
    participant Farmer
    participant Device
    participant SoilSample
    participant Cloud
    Farmer->>Device: Inject Soil Suspension
    Device->>SoilSample: Illuminate with LED
    SoilSample-->>Device: Emit Fluorescence
    Device->>Device: Image via Composite Objective
    Device->>Cloud: Transmit Processed Data
    Cloud-->>Farmer: Display Soil Health Report
```

1.5. Integration with Emerging Tech: AI-Driven Adaptive Optics

Enabling Description: The aberration corrector plate is replaced with a deformable mirror (DM) controlled by an artificial intelligence algorithm. A wavefront sensor is placed at the image plane to detect residual aberrations in real-time. The AI, a trained convolutional neural network (CNN), analyzes the sensor data and continuously adjusts the DM's surface profile to correct for thermal drift, minor misalignments, or variations in the refractive index of the sample fluid. This creates an adaptive optical system that maintains diffraction-limited performance under changing operating conditions. An IoT sensor on the objective housing monitors temperature and vibration, feeding this data to the AI as additional input for predictive aberration correction.
```
graph TD
    A[Light from Concave Mirror] --> B(Deformable Mirror);
    B --> C[Image Plane];
    C --> D{Wavefront Sensor};
    D -- Aberration Data --> E(AI Control Unit);
    F{IoT Temp/Vibration Sensor} -- Environmental Data --> E;
    E -- Control Signals --> B;
```

1.6. The "Inverse" or Failure Mode: Fail-Safe Athermal Design

Enabling Description: The objective is designed for low-power, field-deployable applications where reliability is paramount. It employs a passive athermal design. The housing is made of a material with a coefficient of thermal expansion that precisely matches the thermo-optic coefficient (dn/dT) of the primary optical elements (e.g., a PMMA lens with an aluminum housing). This ensures that as temperature changes, the expansion or contraction of the housing adjusts the spacing between the mirror and corrector plate to maintain focus without any active electronic intervention. In case of severe shock causing misalignment, the components are kinematically mounted to return to a pre-defined, slightly defocused "safe mode" that still allows for basic particle counting, albeit with reduced resolution, preventing total system failure.
```
stateDiagram-v2
    state "Optimal Focus" as Optimal
    state "Athermal Drift" as Drift
    state "Fail-Safe Defocus" as Failsafe

    [*] --> Optimal
    Optimal --> Drift: Temperature Change
    Drift --> Optimal: Passive Compensation
    Optimal --> Failsafe: High-G Shock Event
    Failsafe --> [*]: Requires Reset
```

Disclosure Area 2: Pulsation-Free Fluidic Subsystem

The core concept involves a fluidic system using a T-coupling bypass and an air-trapping filter to dampen pulsations from a pump.

2.1. Material & Component Substitution

Enabling Description: The T-coupling and conduits are fabricated from perfluoroalkoxy alkanes (PFA) for extreme chemical inertness, allowing the use of aggressive solvents for system cleaning or sample preparation. The particle filter, which doubles as a fluidic capacitor, uses a hydrophilic PVDF membrane with a precisely engineered pore structure to control the volume of trapped air. The reservoir capsule is replaced with a bank of parallel, flexible silicone micro-tubes, which act as distributed, low-volume fluidic capacitors, providing more effective high-frequency pulsation damping.
```
graph TD
    A[Liquid Pump (PFA Diaphragm)] --> B{T-Coupling (PFA)};
    B --> C[Bypass to Reservoir];
    B --> D(Silicone Micro-tube Capacitor Bank);
    D --> E{Particle Filter (Hydrophilic PVDF)};
    E --> F[Flow Cell];
    subgraph Air Trap
        G[Trapped Air Bubble]
    end
    E --- G;
```

2.2. Cross-Domain Application: Consumer Electronics (Inkjet Printing)

Enabling Description: The pulsation-damping principle is applied to high-resolution, multi-material 3D inkjet printing. A high-throughput peristaltic pump supplies ink to a manifold (equivalent to the T-coupling). A bypass line returns excess ink to the reservoir, while the primary line feeds the printhead. Before the printhead, a micro-machined filter with a gas-trapping chamber is installed. This ensures that the ink pressure at the nozzle plate is exceptionally stable, eliminating pressure fluctuations that cause inconsistent droplet volume and placement errors ("banding") in the printed object.
```
sequenceDiagram
    participant Pump
    participant Manifold
    participant Ink_Reservoir
    participant Filter_Capacitor
    participant Printhead
    Pump->>Manifold: Pulsating Ink Flow
    Manifold->>Ink_Reservoir: Divert excess ink (Bypass)
    Manifold->>Filter_Capacitor: Forward main flow
    Filter_Capacitor->>Printhead: Deliver Stable-Pressure Ink
    Printhead->>: Print Layer
```

2.3. Integration with Emerging Tech: IoT-Monitored Smart Fluidics

Enabling Description: The fluidic system is equipped with MEMS-based pressure sensors before and after the T-coupling, and at the inlet of the flow cell. These IoT-enabled sensors stream real-time pressure data to a central controller. The controller uses a machine learning model to detect anomalies in the pressure differential, which can indicate a clog in the particle filter, a leak in the bypass line, or degradation of the pump tubing. The system can then auto-adjust the pump speed to compensate or trigger a maintenance alert. The blockchain is used to log every maintenance event and component replacement, creating an immutable service record for regulatory compliance (e.g., in clinical diagnostics).
```
flowchart LR
    Pump --> T_Coupling;
    T_Coupling --> Bypass;
    T_Coupling --> Main_Line;
    Main_Line --> Filter;
    Filter --> Flow_Cell;

    subgraph IoT Monitoring
        Sensor1[Pressure Sensor] --> T_Coupling;
        Sensor2[Pressure Sensor] --> Main_Line;
        Sensor3[Pressure Sensor] --> Flow_Cell;
        Controller(AI Controller) -- adjusts --> Pump;
        Sensor1 -- data --> Controller;
        Sensor2 -- data --> Controller;
        Sensor3 -- data --> Controller;
        Controller -- log event --> Blockchain;
    end
```

2.4. The "Inverse" or Failure Mode: Controlled Pulsation Mode for Micro-mixing

Enabling Description: The system is designed to operate in an alternative "pulsation-on" mode for applications requiring in-line mixing of a sample with a reagent. The bypass line is closed via a solenoid valve, and the air-trapping filter is replaced with a solid-state damper that has minimal capacitance. The pump controller is programmed to introduce specific, high-frequency pressure oscillations (e.g., 100-500 Hz). These controlled pulses induce chaotic advection within the flow channel immediately prior to the viewing zone, ensuring rapid and complete mixing of the sample and sheath fluid (now containing a reagent) without the need for a separate mechanical mixer. This mode is useful for kinetic studies of cellular reactions.
```
stateDiagram-v2
    state "Stable Flow Mode" as Stable {
        direction LR
        Bypass_Valve: OPEN
        Filter: Air-Trap Engaged
    }
    state "Pulsatile Mixing Mode" as Mixing {
        direction LR
        Bypass_Valve: CLOSED
        Filter: Solid-State Damper
        Pump: Frequency-Modulated
    }
    [*] --> Stable
    Stable --> Mixing: Activate Reagent Mixing
    Mixing --> Stable: End Kinetic Analysis
```

Disclosure Area 3: Wavelength Division Multiplexer (WDM)

The core concept is a WDM with a cascaded image relay architecture to create a long, collimated beam path for inserting dichroic filters.

3.1. Component Substitution & Miniaturization

Enabling Description: The entire WDM assembly is miniaturized onto a silicon photonics chip. The "extended light source" is the output of a multi-mode optical fiber pigtailed to the chip. The collimating and relay optical elements are replaced with integrated graded-index (GRIN) lenses fabricated directly into the silicon substrate. The dichroic filters are replaced by thin-film interference filters deposited in sequence along a trench etched into the silicon. The light is guided by silicon nitride waveguides from the filters to on-chip avalanche photodiodes (APDs). This creates a monolithic, alignment-free WDM that is orders of magnitude smaller and more robust.
```
graph TD
    subgraph Silicon Photonics Chip
        A[Fiber Input] --> B(GRIN Collimator);
        B -- Collimated Beam --> C{Trench with Dichroic Filter 1};
        C -- Transmitted --> D(GRIN Relay Lens);
        C -- Reflected --> E(Waveguide);
        E --> F[On-Chip APD 1];
        D --> G{Dichroic Filter 2};
        G -- Reflected --> H(Waveguide);
        H --> I[On-Chip APD 2];
    end
```

3.2. Cross-Domain Application: Telecommunications

Enabling Description: The cascaded image relay architecture is adapted for a free-space optical (FSO) communication de-multiplexer. A received broadband laser signal from a telescope is treated as the extended light source. The first optical element collimates this light. The long, collimated path allows for the insertion of highly sensitive, temperature-controlled, narrow-band dichroic filters. Each filter peels off a specific data channel (wavelength) and directs it to a high-speed photodetector. The unit-magnification relay stages prevent beam divergence over the required path length, ensuring that each channel can be focused onto a small-area, low-noise detector, which is critical for maximizing signal-to-noise ratio in long-range FSO links.
```
flowchart LR
    A[Telescope Receiver] --> B(Collimating Optics);
    B --> C[Relay Stage 1];
    C -- Path --> D{Dichroic 1 (λ1)};
    D -- Reflected λ1 --> E[Detector 1];
    D -- Transmitted --> F[Relay Stage 2];
    F -- Path --> G{Dichroic 2 (λ2)};
    G -- Reflected λ2 --> H[Detector 2];
    G -- Transmitted --> I[...];
```

3.3. Integration with Emerging Tech: AI-Reconfigurable WDM

Enabling Description: The static dichroic filters are replaced with dynamically tunable optical filters, such as acousto-optic tunable filters (AOTFs) or liquid crystal-based filters, placed along the collimated beam path. An AI-powered spectrometer constantly analyzes the incoming light spectrum. Based on the specific fluorescent dyes detected in a sample, the AI controller reconfigures the WDM in real-time by programming the center wavelengths of each AOTF. This "smart WDM" automatically optimizes the light separation for the specific assay being run, eliminating the need for manual filter changes and enabling the use of novel or custom fluorophores without hardware modification.
```
sequenceDiagram
    participant Spectrometer
    participant AI_Controller
    participant AOTF_Bank
    participant Detectors

    Spectrometer->>AI_Controller: Transmit Full Spectrum Data
    AI_Controller->>AI_Controller: Identify Fluorophore Peaks
    AI_Controller->>AOTF_Bank: Send New Wavelength Config
    AOTF_Bank->>Detectors: Route Separated Wavelengths
```

Combination Prior Art Scenarios

Combination with OPC-UA (Open Platform Communications Unified Architecture): The flow cytometer's control system, including the LD power control, peristaltic pump speed, and fluidic valve states, is integrated using an OPC-UA server. This open standard allows the cytometer (as described in US 12,174,106) to be seamlessly integrated into a larger laboratory automation system. A central scheduler can control the cytometer, a robotic sample handler, and a data analysis server using a standardized communication protocol. This combination would be obvious to one skilled in the art of laboratory automation seeking to create an interoperable diagnostic workflow.
Combination with FIJI/ImageJ (Open-Source Image Processing): The digital imaging capabilities of the flow cytometer, which can capture images of individual cells, are combined with the open-source FIJI/ImageJ software platform. The cytometer's output is a stream of TIFF images with associated metadata (FSC, SSC, fluorescence intensity). A custom ImageJ plugin is developed to automate the analysis of these images, performing cell segmentation, morphological feature extraction, and fluorescence colocalization analysis. This leverages a widely used, free platform to enhance the analytical power of the hardware, a step that would be an obvious development for researchers using the instrument.
Combination with a Luer-Lok Standard (ISO 80369-7): The fluidic connections to and from the flow cell, sample inlet, and sheath fluid reservoir of the fluidic subsystem in US 12,174,106 are all implemented using standard Luer-Lok connectors. This allows the cytometer to be used with standard, off-the-shelf syringes, tubing sets, and sample preparation devices from any manufacturer. This modification, while simple, makes the system universally compatible and would be an obvious design choice for anyone aiming to commercialize the described fluidic system for use in clinical or research laboratories where such standards are ubiquitous.