Derivative works — US Patent 12186474

Defensive Disclosure: System and Method for Collecting Plasma

Publication Date: April 26, 2026
Reference Patent: US 12,186,474

This document discloses novel and non-obvious variations, extensions, and applications of the core technologies described in US Patent 12,186,474. The intent of this disclosure is to establish prior art for the described concepts, thereby precluding subsequent patenting of these incremental improvements by third parties. The following sections detail derivative inventions based on the foundational claims of the reference patent.

Core Claim Analysis (Inferred)

The foundational technology of US 12,186,474 pertains to a system and method for apheresis, specifically for collecting plasma. The key inventive steps appear to be:

Calculating Pure Plasma Volume: A method to distinguish the volume of "pure plasma" from the total volume of collected fluid, which includes an anticoagulant. This calculation is based on donor-specific parameters like weight and hematocrit.
Personalized Collection Target: Establishing a target collection volume for pure plasma that is a percentage of the donor's total plasma volume, which is calculated using the donor's height, weight, and hematocrit.
Dynamic Process Control: A controller-driven system that continuously calculates the collected pure plasma volume and terminates the procedure upon reaching the personalized target volume.
Isovolemic Compensation: A method for returning saline to the donor to achieve a target intravascular deficit, minimizing adverse reactions.

Derivative Disclosures

I. Material & Component Substitution

1. Perfluorocarbon-Based Anticoagulant Emulsion

Enabling Description: The standard citrate-based anticoagulant is replaced with a perfluorocarbon (PFC) emulsion. PFCs have a significantly higher density than both plasma and citrate solutions. This high density differential allows for more rapid and precise separation of the anticoagulant from the plasma-anticoagulant mixture within a secondary, smaller centrifugal or acoustic separation chamber integrated downstream of the primary separation bowl. An in-line densitometer or optical sensor tuned to the refractive index of the PFC emulsion measures the residual PFC concentration in the collected plasma, allowing the controller to calculate pure plasma volume with greater than 99.5% accuracy. The PFC, being an efficient oxygen carrier, also provides the secondary benefit of oxygenating the returned blood components.

Mermaid Diagram:

graph TD
    A[Whole Blood Draw] --> B{Primary Centrifuge};
    B --> C[Packed RBCs/Buffy Coat];
    C --> D[Return to Donor];
    B --> E[Plasma + PFC Anticoagulant];
    E --> F{Secondary Acoustic Separator};
    F --> G[Pure Plasma -> Collection Bag];
    F --> H[PFC Emulsion -> Recirculation/Waste];
    I[PFC Reservoir] --> A;
    J[Controller] --> B;
    J --> F;
    K[Densitometer] --> J;
    G -- Monitored by --> K;

2. Magnetorheological Fluid Pumps

Enabling Description: The peristaltic pumps (e.g., blood pump 232, anticoagulant pump 234) are replaced with valveless magnetorheological (MR) fluid pumps. These pumps use an electromagnet to change the viscosity of an MR fluid in a diaphragm-based pumping chamber. This allows for pulseless, continuous flow, which reduces shear stress on red blood cells (hemolysis). The flow rate is controlled with extreme precision by modulating the magnetic field strength, enabling micro-liter adjustments to the anticoagulant-to-blood ratio in real-time based on feedback from an in-line hematocrit sensor. This eliminates the need for calculating ratios based on discrete pump rotations and provides a more responsive system.

Mermaid Diagram:

sequenceDiagram
    participant C as Controller
    participant H as Hematocrit Sensor
    participant MRP as MR Fluid Pump (Anticoagulant)
    participant D as Donor Line

    C->>MRP: Set Base Flow Rate
    loop Real-time Adjustment
        H->>C: Report Hematocrit Value (Hct)
        C->>C: Calculate new AC_ratio = f(Hct)
        C->>MRP: Modulate Magnetic Field to achieve new AC_ratio
    end
    MRP-->>D: Inject Anticoagulant

3. Graphene-Coated Centrifuge Bowl

Enabling Description: The interior surfaces of the blood component separation device (centrifuge bowl 214) are coated with a monolayer of medical-grade graphene. This coating provides an ultra-smooth, biocompatible, and protein-repellent surface. The anti-thrombogenic properties of graphene reduce the required volume of anticoagulant by up to 15%, as less is needed to prevent clotting on the device surfaces. This lower anticoagulant volume simplifies the pure plasma calculation and reduces the physiological load on the donor. Furthermore, the graphene surface reduces friction, allowing the centrifuge motor to operate with lower energy consumption.

Mermaid Diagram:

classDiagram
  class CentrifugeBowl {
    +volume: float
    +rpm: int
    +surfaceMaterial: Material
  }
  class Material {
    <<interface>>
    +biocompatibility: float
    +thrombogenicity: float
  }
  class Polycarbonate {
    +biocompatibility: 0.8
    +thrombogenicity: 0.7
  }
  class GrapheneCoatedPolycarbonate {
    +biocompatibility: 0.98
    +thrombogenicity: 0.2
  }
  CentrifugeBowl o-- Material
  Material <|.. Polycarbonate
  Material <|.. GrapheneCoatedPolycarbonate

II. Operational Parameter Expansion

1. Microfluidic Apheresis for Neonatal Applications

Enabling Description: The entire system is scaled down to a microfluidic chip-based apheresis device for neonatal or small animal applications. Whole blood volumes of less than 50 mL are processed. The centrifugal bowl is replaced by a serpentine microchannel that uses deterministic lateral displacement (DLD) pillars to separate cells based on size. Red blood cells are shunted into one channel while plasma and platelets proceed to another. Anticoagulant is introduced via a micro-dosing piezoelectric pump. Pure plasma volume is calculated based on the known channel geometry and flow rates measured by micro-Doppler sensors, with a target collection volume as low as 5-10 mL.

Mermaid Diagram:

graph LR
    subgraph Microfluidic Chip
        A[Blood Inlet] --> B(DLD Pillar Array);
        B --> C[RBC Outlet];
        B --> D[Plasma/Platelet Outlet];
        E[AC Inlet] --> B;
    end
    F[Piezoelectric Pump] --> E;
    G[Micro-Doppler Sensor] -- Measures Flow --> D;
    H[Controller] --> F;
    G --> H;
    D --> I[Plasma Collection < 10mL];
    C --> J[RBC Return];

2. High-G Force, Continuous Flow System for Bio-Manufacturing

Enabling Description: The system is adapted for industrial-scale bio-manufacturing to continuously harvest therapeutic proteins from large-volume cell cultures (e.g., 1000-liter bioreactors). The centrifuge operates at extremely high rotational speeds (>10,000 RPM) to handle the high throughput. The "donor" is the bioreactor, and the "blood" is the cell culture medium. The system separates viable cells from the protein-rich supernatant (the "plasma"). No anticoagulant is needed; instead, temperature and pH are tightly controlled. The "pure plasma" calculation is adapted to be a "pure supernatant" calculation, accounting for priming fluids and media additives. The target is not a fixed volume but a target protein concentration, monitored in real-time by an in-line UV-Vis spectrophotometer.

Mermaid Diagram:

stateDiagram-v2
    [*] --> Priming
    Priming --> Running: System Primed
    Running --> Running: Process Culture Medium
    state Running {
        [*] --> Separating
        Separating --> Harvesting: Protein Conc. < Target
        Harvesting --> Separating: Continue Flow
        Harvesting --> Flushing: Protein Conc. >= Target
    }
    Flushing --> [*]: Cycle Complete

III. Cross-Domain Application

1. Aerospace: In-Flight Astronaut Plasma Collection for Research

Enabling Description: A compact, ruggedized version of the system is designed for use on the International Space Station (ISS) or future long-duration space missions. The system must operate reliably in microgravity. Centrifugal separation is maintained, but fluid management is handled by a closed-loop system of bladder-based reservoirs and pumps to prevent free-floating liquids. The "pure plasma" calculation algorithm is augmented with a variable for fluid shifts experienced by astronauts in space, which alters their baseline plasma volume and hematocrit. The system's primary purpose is to collect regular plasma samples for ground-based analysis of physiological changes during spaceflight, with the remaining blood components immediately returned to the astronaut to minimize biological impact.

Mermaid Diagram:

graph TD
    subgraph Zero-G Module
        A[Astronaut Arm Interface] --> B{Micro-Centrifuge};
        C[Anticoagulant Bladder] --> A;
        B --> D[Packed Cells -> Return Line];
        B --> E{Plasma/AC Mix};
        E --> F[Sample Cassette for Analysis];
        E --> G[Excess Plasma -> Waste Bladder];
    end
    H[Mission Controller] --> I(Onboard Computer);
    I -- Controls --> B;
    I -- Controls --> C;
    J[Biometric Sensors] -- Fluid Shift Data --> I;

2. AgTech: Automated Bovine Colostrum Fractionation

Enabling Description: The system is applied in the agricultural technology sector to automatically fractionate bovine colostrum ("first milk") on dairy farms. The goal is to separate high-value immunoglobulin G (IgG) from fat and other components. The "whole blood" is fresh colostrum. The centrifuge separates it into a fat layer, a casein/cell layer, and a whey/IgG fraction (the "plasma"). The "pure plasma" calculation is repurposed to be a "pure IgG fraction" calculation, accounting for dilution with buffer solutions. An in-line nephelometer measures IgG concentration to determine the endpoint of the collection, maximizing the yield of this critical component for calf health supplements.

Mermaid Diagram:

flowchart LR
    A[Raw Colostrum Tank] --> B(Pump);
    B --> C{High-Speed Centrifugal Separator};
    C --> D[Fat/Casein -> Animal Feed];
    C --> E[IgG-rich Whey];
    F[Buffer Solution] --> B;
    E --> G[Nephelometer];
    G -- IgG Concentration --> H{Controller};
    H -- Controls --> B;
    H -- Controls --> C;
    G --> I{Collection Tank};
    I -- When Full/Target Met --> J[Packaging];

3. Consumer Electronics: Water Purification and Contaminant Isolation

Enabling Description: The core principle of separating a primary fluid from a mixture is applied to a point-of-use water purification device. The device uses a high-speed centrifugal chamber to separate suspended solids, microplastics, and certain immiscible liquid contaminants from water. The "whole blood" is contaminated influent water. The "anticoagulant" is a flocculant, automatically dosed based on turbidity measured by an optical sensor. The "plasma" is purified drinking water, and the "red blood cells" are the concentrated contaminants, which are flushed to a waste cartridge. The "pure plasma" (pure water) calculation accounts for the volume of flocculant added and determines when the waste cartridge is full.

Mermaid Diagram:

sequenceDiagram
    participant User
    participant Device
    participant TurbiditySensor as TS
    participant FlocculantPump as FP
    participant Centrifuge as C

    User->>Device: Activate Purification
    Device->>TS: Measure Influent Turbidity
    TS->>Device: Report Turbidity (NTU)
    Device->>FP: Dose Flocculant based on NTU
    Device->>C: Spin to Separate
    loop Until Target Volume Reached
        C-->>Device: Output Purified Water
        C-->>Device: Output Concentrated Waste
    end
    Device->>User: Dispense Water

IV. Integration with Emerging Tech

1. AI-Driven Donor Hemolysis Prediction and Prevention

Enabling Description: The system controller is integrated with a machine learning model (a recurrent neural network or RNN) trained on historical apheresis data. The model takes real-time inputs from IoT sensors in the system: blood flow rate, pump pressure, line temperature, and the donor's initial hematocrit and blood pressure. It continuously predicts the likelihood of shear-induced hemolysis (red blood cell rupture) in the next 60 seconds. If the predicted probability exceeds a safety threshold, the AI automatically modulates the pump speed and centrifuge RPM to less aggressive settings, preventing hemolysis before it occurs and preserving the quality of both the collected plasma and the returned cells.

Mermaid Diagram:

graph TD
    A[IoT Sensors: Pressure, Flow, Temp] --> B(ML Model);
    C[Donor Vitals: Hct, BP] --> B;
    B -- Hemolysis Probability --> D{Decision Logic};
    D -- >0.9 Threshold --> E[Adjust Pump/RPM];
    D -- <0.9 Threshold --> F[Maintain Current Params];
    E --> G{Apheresis System};
    F --> G;
    A -- Placed on --> G;

2. Blockchain-Verified "Vein-to-Vial" Supply Chain

Enabling Description: Each disposable collection set is tagged with a unique, tamper-proof NFC chip. When a procedure begins, the system reads the kit's unique ID, the donor's anonymized ID, and the machine's ID. A new block is created on a private blockchain. Throughout the procedure, critical parameters (start time, end time, final pure plasma volume, operator ID) are added to the transaction data. When the plasma collection bag is sealed, its own unique NFC tag is written with the corresponding block hash. This creates an immutable, auditable "vein-to-vial" record, ensuring traceability and preventing counterfeiting or commingling of plasma products in the pharmaceutical supply chain.

Mermaid Diagram:

sequenceDiagram
    participant Donor
    participant ApheresisSystem as AS
    participant Blockchain
    participant CollectionBag as Bag

    Donor->>AS: Start Donation
    AS->>Blockchain: Create Block (DonorID, KitID, MachineID)
    AS->>AS: Collect Plasma
    AS->>Blockchain: Append Data (Volume, Timestamp)
    AS->>Bag: Seal Bag & Write Block Hash to NFC
    Bag->>Blockchain: Later Scans Verify Hash

V. The "Inverse" or Failure Mode

1. "Safe Return" Gravity-Fed Failsafe Mode

Enabling Description: In the event of a catastrophic power failure, all electrically actuated valves default to a specific "safe return" configuration. The blood pump disengages, and a gravity-feed return line is opened. The centrifuge, still containing the separated blood components, is allowed to spin down naturally. Due to its orientation and the force of gravity, the higher-density red blood cells settle at the bottom and are passively returned to the donor through the dedicated, large-bore gravity line. This ensures that the donor receives their own red cell mass back even without system power, preventing acute anemia. The lower-density plasma remains in the bowl and is disposed of with the kit. This prioritizes donor safety over product collection in a failure scenario.

Mermaid Diagram:

stateDiagram-v2
    state "Normal Operation" as Normal {
        [*] --> Drawing
        Drawing --> Separating
        Separating --> Returning
        Returning --> Drawing
    }
    state "Power Failure Mode" as Failure {
        [*] --> OpenGravityValves
        OpenGravityValves --> PassiveRBCReturn: Gravity Feed
        PassiveRBCReturn --> ProcedureEnd
    }
    Normal --> Failure: Power Loss Detected

2. "Low Yield" Anticoagulant-Free Mode

Enabling Description: A limited-functionality mode is designed for situations where the correct anticoagulant is unavailable or the anticoagulant pump fails. The system uses a highly accelerated draw-separate-return cycle. A very small volume of whole blood (e.g., 30-50 mL) is drawn and immediately processed in the centrifuge at high speed, and the red cells are returned in under 90 seconds, before significant clotting can occur within the specially heparin-coated disposable set. This process is repeated. The resulting "plasma" yield is low, and its quality is compromised, but it allows for the collection of a small, critical sample for diagnostic testing when a full, standard donation is not possible. The controller's software enforces a maximum cycle time and total procedure time to ensure safety.

Mermaid Diagram:

flowchart TD
    A{Start Low Yield Mode} --> B[Draw 40mL WB];
    B --> C{Process < 90s};
    C --> D[Return RBCs];
    D --> E[Collect ~20mL Plasma];
    E --> F{Cycle < 10?};
    F -- Yes --> B;
    F -- No --> G[End Procedure];

Combination Prior Art Scenarios

1. Integration with HL7 FHIR for EMR Integration

Scenario: The plasma collection system is integrated with the Health Level Seven (HL7) Fast Healthcare Interoperability Resources (FHIR) open standard.
Description: The system's controller acts as a FHIR client. Before the procedure, it queries the healthcare facility's Electronic Medical Record (EMR) server for the donor's recent lab results, specifically retrieving their latest hematocrit value via a standardized FHIR Observation resource. This eliminates the need for a separate pre-donation blood test, streamlining the workflow. Upon completion, the system generates a new FHIR Procedure resource and linked Observation resources detailing the exact volume of pure plasma collected, anticoagulant used, and total processing time. This data is then securely transmitted back to the donor's EMR, creating a seamless, interoperable health data record.

2. Combination with Data Distribution Service (DDS) for Real-Time Monitoring

Scenario: The internal communication architecture of the apheresis system and its connection to a central monitoring station utilize the Data Distribution Service (DDS) open standard from the Object Management Group (OMG).
Description: Each component within the system (blood pump, AC pump, centrifuge motor, weight sensors) acts as a DDS "Publisher," broadcasting its status, speed, and readings onto a DDS "Topic." The central controller subscribes to these topics to get real-time data for its calculations. Simultaneously, a dashboard in a central monitoring room can also subscribe to these topics from multiple machines, allowing a single technician to oversee a fleet of apheresis devices. The DDS standard's Quality of Service (QoS) policies ensure reliable, low-latency delivery of this critical data without the need for custom-coded networking protocols.

3. Use of OPC Unified Architecture (OPC UA) for Industrial Control

Scenario: The system, when used in the "Cross-Domain Application" for bio-manufacturing, integrates into the larger factory control system using the OPC Unified Architecture (OPC UA) open standard.
Description: The apheresis machine's controller exposes its data and functions as an OPC UA server. The factory's SCADA (Supervisory Control and Data Acquisition) system acts as an OPC UA client. The SCADA system can read variables like "CurrentSupernatantPurity" and "CellViability," and can write to variables to "StartProcess," "StopProcess," or "SetTargetProteinConcentration." This allows the plasma separation process to be fully automated and integrated into the overall manufacturing batch record, adhering to a widely adopted, secure, and platform-independent standard for industrial automation.