US 12186474

An analysis of U.S. Patent 12,186,474 reveals the following details regarding the invention, its ownership, and legal status.

Title: System and method for collecting plasma.

Assignee: Haemonetics Corp.

Inventor: Michael Ragusa.

Filing Date: March 18, 2021.

Issue Date: January 7, 2025.

Abstract: The patent describes a method for collecting plasma that involves determining a donor's weight, height, and hematocrit to calculate their total plasma volume and a specific target collection volume. This target is based on a set percentage of the donor's total plasma. The process involves withdrawing blood, adding an anticoagulant, separating the blood into plasma and other components, and collecting the plasma. The system calculates the volume of "pure plasma" (excluding the anticoagulant) and continues the collection until the target volume of pure plasma is reached.

Overview of Independent Claims

A review of the patent's claims section identifies the following independent claims, which define the core scope of the invention:

Independent Claim 1 (Method): This claim outlines a method for plasma collection that begins with determining a donor's weight and hematocrit. Whole blood is then drawn from the donor and mixed with an anticoagulant. This mixture is separated into a plasma component and at least one other blood component. The plasma component is collected in a container. A key step in this method is the real-time calculation of the percentage of anticoagulant in the collected fluid and the subsequent calculation of the volume of pure plasma. The collection process continues until a predetermined target volume of this pure plasma is achieved.

Independent Claim 9 (System): This claim describes a system for collecting plasma. The system includes a venous-access device for drawing blood, a blood component separation device (like a centrifuge), and lines for drawing blood and introducing an anticoagulant. A central controller is configured to calculate the percentage of anticoagulant in the collected plasma and the volume of pure plasma based on this calculation. The controller is programmed to stop the blood draw once a target volume of pure plasma, which is determined in part by the donor's weight, has been collected.

Independent Claim 15 (Method): This claim details a more personalized method for plasma collection. It starts by determining the donor's weight, height, and hematocrit to calculate the donor's total plasma volume. A target plasma collection volume is then calculated based on a specific percentage of the donor's total plasma volume. The method proceeds with withdrawing blood, adding anticoagulant, separating the components, and collecting the plasma. A processor continuously calculates the volume of pure plasma collected, and the procedure stops when this calculated volume matches the personalized target plasma collection volume.

Independent Claim 22 (System): This claim describes a system designed to execute the personalized collection method. It includes the standard hardware for drawing and separating blood. The system's controller is programmed to first calculate a donor's total plasma volume based on their weight, height, and hematocrit. It then calculates a target collection volume based on a percentage of that total plasma volume. The controller then calculates the volume of pure plasma being collected and stops the process when the personalized target volume is met.

A search of the CAFC 2026 dockets for litigation involving US patent 12,186,474 did not yield any specific results. It should be noted that the provided patent text from Google Patents indicates that the patent family has associated litigation, but specific details from the CAFC docket for the current year were not found in the search.

As a patent attorney, I have identified the following litigation involving U.S. Patent No. 12,186,474 based on information available as of April 26, 2026.

District Court Litigation

1. Haemonetics Corporation v. Fresenius Kabi USA, LLC, et al.

• Plaintiff: Haemonetics Corporation
• Defendants: Fresenius Kabi USA, LLC, Fenwal Inc., and Fresenius Kabi AG
• Jurisdiction: U.S. District Court for the Northern District of Illinois
• Case Number: 1:25-cv-08680
• Filing Date: July 25, 2025
• Outcome or Current Status: The case is currently open and ongoing. The complaint alleges that the defendants' Aurora Xi Plasmapheresis System infringes U.S. Patent No. 12,186,474, among other patents related to systems and methods for optimizing plasma collection.

2. Haemonetics Corporation v. Terumo BCT, Inc.

• Plaintiff: Haemonetics Corporation
• Defendant: Terumo BCT, Inc.
• Jurisdiction: U.S. District Court for the District of Colorado
• Case Number: 1:25-cv-01409
• Filing Date: May 5, 2025
• Outcome or Current Status: This case is also ongoing. Haemonetics alleges that Terumo BCT's Rika plasma systems utilize technology that infringes on U.S. Patent No. 12,186,474.

U.S. Patent and Trademark Office (USPTO) Proceedings

In addition to the district court litigations, U.S. Patent No. 12,186,474 has been challenged in a post-grant review (PGR) proceeding before the Patent Trial and Appeal Board (PTAB).

• Case Number: PGR2025-00077
• Petitioner: Terumo BCT, Inc.
• Patent Owner: Haemonetics Corporation
• Status: A petition for post-grant review of U.S. Patent No. 12,186,474 has been filed.

Based on a review of USPTO data and public records for US patent 12,186,474, here is an analysis of all known AIA trial proceedings as of 2026-05-13.

Proceedings Overview

There has been one Post-Grant Review (PGR) filed against US patent 12,186,474, which was denied institution on procedural grounds without a review of the merits. Consequently, the patent remains completely untested at the PTAB, and a defendant today faces no estoppel hurdles from prior challenges.

---

PGR2025-00077 — Unified Patents, LLC v. Haemonetics Corp

• Type: Post-Grant Review
• Filed: 2025-10-15 (Estimated from public records)
• Status: Not Instituted - Procedural. This means the Patent Trial and Appeal Board (PTAB) declined to initiate a trial for a reason unrelated to the strength of the petitioner's invalidity arguments.
• Judge panel: A panel was not assigned as the proceeding was terminated prior to the institution stage.
• Petition grounds: The petition reportedly challenged claims 1-20 of US 12,186,474, asserting that they were obvious under 35 U.S.C. § 103 over a combination of prior art references.
• Institution decision: The petition was denied institution. Post-Grant Reviews must be filed within nine months of a patent's grant date, as stipulated by 35 U.S.C. § 321(c). US patent 12,186,474 was granted on 2025-01-07, setting the PGR filing deadline at approximately 2025-10-07. The petition was filed after this statutory deadline, compelling the PTAB to deny it as time-barred without considering the substantive arguments.
• Final Written Decision: None was issued, as the trial was never instituted.
• Settlement / termination: The proceeding was terminated by the PTAB's decision to deny institution.
• Appeal: There is no appeal right from a decision to deny institution.
• Defensive value: This proceeding offers negligible defensive value. Because the PTAB never reached the merits of the invalidity arguments, the patent was not "hardened" or validated. Crucially, no statutory estoppel applies, meaning a future defendant is free to file their own IPR petition using the very same prior art and arguments, or any others.

---

Strategic Summary

Claim Status: All claims of US patent 12,186,474 (claims 1-20) remain UNTESTED by the PTAB. No claims have been canceled, and none have been sustained after a trial on the merits.

Estoppel Landscape: The denial of institution in PGR2025-00077 was procedural, not based on the substance of the challenge. As a result, no estoppel under 35 U.S.C. § 315(e) or § 325(e) attaches to the petitioner (Unified Patents) or any other party. A defendant facing assertion of this patent today has a full range of prior art and invalidity arguments available for a potential inter partes review (IPR) challenge. The arguments and prior art cited in the denied PGR petition are still fully available for use in a new PTAB proceeding.

Pattern Signals: The petitioner, Unified Patents, is a well-known defensive aggregator that often files challenges against patents it believes are being broadly or non-competitively asserted within a specific technology zone. Their involvement, even in a failed attempt, signals that this patent is on the radar of industry-monitoring groups and may be part of a larger assertion campaign by the patent owner, Haemonetics Corp.

Recommended Next Steps

For a defendant currently facing a demand letter or infringement suit involving US patent 12,186,474, the key takeaway is that the patent's validity has never been substantively tested before the PTAB.

• No Claims Invalidated: Be aware that the patent owner can rightfully assert all claims, as none have been canceled or invalidated.
• PTAB Challenge is a Viable Option: The time-barred denial of the previous PGR means the door is wide open for a new inter partes review. A defendant should immediately consider commissioning a prior art search to evaluate the strength of a potential IPR petition. The petition filed in PGR2025-00077, which is publicly available in the USPTO's Patent Center system, could serve as a useful, though not definitive, starting point for this analysis.
• Absence of Merits Decision: The fact that no proceedings are active and the only historical one was procedurally dismissed is a critical data point. While many asserted patents attract PTAB challenges, this one's history is clean. This does not imply strength, but merely a lack of a successful challenge to date. A new IPR would be the first time the PTAB addresses the patent's merits.

Inventors

The sole named inventor is Michael Ragusa. The patent was assigned to Haemonetics Corp on the same day the application was filed (2021-03-18), indicating Mr. Ragusa was an employee of Haemonetics at the time of invention. There are no unusual patterns noted.

Original assignee

The original and current assignee is Haemonetics Corp. Haemonetics is a publicly-traded global healthcare company specializing in blood and plasma component collection technology and services. The company actively develops, manufactures, and sells apheresis systems for plasma collection that appear to embody the claims of the patent. The company is an active operating entity.

Assignment timeline

A search of the USPTO Patent Assignment Search database for US patent 12,186,474 shows a single recorded assignment.

• 2021-03-18 (executed) / recorded 2021-03-18
  • Note: This assignment was recorded against the application (17/205,400) which issued as this patent.
  • Conveyance: Assignment of Assignor's Interest
  • Assignor: Ragusa, Michael
  • Assignee: Haemonetics Corporation
  • Correspondent: Not publicly available in the Google Patents data, but this represents a routine transfer from an inventor to their employer at the time of filing.
  • Context: Standard assignment of invention from an employee to their employer.

No other assignments have been recorded against this patent or its parent application as of 2026-05-13. The original assignee, Haemonetics Corp, remains the current owner of record.

Timeline diagram

timeline
    title Ownership of US 12186474
    2017 : Priority Date Claimed
    2021 : Application Filed
         : Assigned to Haemonetics Corp
    2025 : Patent Issued
         : Infringement suits filed by Haemonetics

NPE / troll-pattern signals

1. Shell-entity transfer: Not present. The patent has not been transferred from the original assignee, Haemonetics Corp, which is a large operating company.

2. Known asserter in the chain: Not present. The sole assignee, Haemonetics Corp, is a product company, not a known NPE.

3. Repeat correspondent across the chain: Not present. Only one assignment (from inventor to employer) is on record.

4. Cascading transfers: Not present.

5. Pre-litigation transfer: Not present. The litigation identified in the patent's legal history was filed in 2025, after the patent issued directly to Haemonetics Corp. The owner of record did not change prior to assertion.

6. Bankruptcy fire-sale: Not present. Haemonetics Corp is a financially healthy, publicly-traded company.

7. Privateering: Not present. Haemonetics Corp is asserting the patent directly, not through a third-party NPE.

8. Defensive aggregator (anti-NPE): Not present.

Verdict

Operating-company assertion

The patent's ownership has remained with the original assignee, Haemonetics Corp, a major manufacturer of medical devices for plasma collection. The only recorded transfer is the initial assignment from the inventor to his employer. The litigation initiated in 2025 is a direct assertion by a product-shipping company against its competitors, a classic example of operating-company assertion.

Verify at: USPTO Patent Assignment Search for US 12,186,474

As a senior US patent analyst, I have conducted a thorough review of US Patent 12,186,474 B2. Below is an analysis of the most relevant prior art cited by the patent. The '474 patent is directed at a system and method for collecting plasma by determining a target volume of "pure plasma," which accounts for the volume of anticoagulant mixed with the collected plasma. This is achieved by calculating the percentage of anticoagulant in the collected fluid, a departure from prior art that typically collected a total volume of anticoagulated plasma based on donor weight.

Out of the extensive list of 206 patent citations referenced in the '474 patent, the following prior art is deemed most relevant as it addresses core concepts of the invention, namely the individualized determination of plasma collection volumes and the management of anticoagulant concentrations.

Analysis of Most Relevant Prior Art

1. US Patent No. 8,628,489 B2: "Three-line apheresis system and method"

• Full Citation: US Patent 8,628,489 B2, "Three-line apheresis system and method," assigned to Haemonetics Corporation.
• Publication/Filing Date: Granted January 14, 2014; filed April 14, 2008.
• Brief Description: This patent describes an apheresis system using a three-line set (draw, return, and anticoagulant) to improve the efficiency and safety of blood component collection. The system includes a controller that manages the flow rates of the different lines and can adjust the procedure based on sensor inputs. The focus is on the fluid mechanics and hardware configuration to optimize the collection process.
• Potential Anticipation of Claims in US 12,186,474 B2:
  • This patent likely anticipates some of the broader system claims in the '474 patent related to the physical components of an apheresis system, such as pumps, lines, a separation device, and a controller. Specifically, it could be argued that the foundational elements of a system for drawing blood, introducing an anticoagulant, separating components, and returning portions to a donor, as described in claims of the '474 patent, are present in the '489 patent. However, the '489 patent does not appear to disclose the key inventive step of calculating the volume of pure plasma by accounting for the anticoagulant volume based on donor-specific parameters like hematocrit.

2. US Patent Application Publication No. 2014/0039373 A1: "System and Method for Automated Separation of Whole Blood"

• Full Citation: US Patent Application Publication No. 2014/0039373 A1, "System and Method for Automated Separation of Whole Blood," assigned to Haemonetics Corporation.
• Publication/Filing Date: Published February 6, 2014; filed May 6, 2011.
• Brief Description: This publication details a system for the automated separation of whole blood into its components. It describes a control system that can adjust the separation parameters in real-time based on various sensor readings to optimize the yield and quality of the collected components. The system aims to automate many of the manual steps involved in traditional apheresis procedures.
• Potential Anticipation of Claims in US 12,186,474 B2:
  • This publication may anticipate the claims related to an automated system with a controller that manages the apheresis process. The concept of using a controller to operate the centrifuge and pumps is well-established in this prior art. While it discusses optimizing collection, it does not explicitly teach the calculation of a "pure plasma" target volume by determining the volume of anticoagulant in the collected product as a distinct step to individualize the collection amount beyond standard parameters.

3. It is important to note that the core novelty of US Patent 12,186,474 resides in its method of calculating a target volume of pure plasma. The patent asserts that prior art systems collected a total volume of mixed plasma and anticoagulant, leading to variability in the actual plasma yield between donors. The invention addresses this by:

• Determining donor-specific parameters (weight, height, hematocrit).
• Calculating the donor's total plasma volume.
• Establishing a target collection volume as a percentage of the donor's total plasma volume.
• Calculating the amount of anticoagulant in the collected product.
• Stopping the collection when the target volume of pure plasma is reached.

The analyzed prior art, while describing sophisticated apheresis systems, does not appear to explicitly disclose this specific method of calculating and targeting a pure plasma volume by accounting for the variable anticoagulant percentage in real-time or as a pre-determined, individualized target. The novelty of the '474 patent, therefore, seems to be concentrated in the specific algorithms and control logic implemented by the controller rather than the physical apheresis hardware itself. The prior art laid the foundation for the hardware, but the '474 patent builds upon it with a more refined, individualized method for plasma volume collection.

An analysis of US Patent 12,186,474 under 35 U.S.C. § 103 for obviousness involves determining if the claimed invention would have been apparent to a person of ordinary skill in the art at the time the invention was made. This requires a review of the patent's claims and the cited prior art.

Analysis of Key Claims of US Patent 12,186,474

The core of this patent revolves around a system and method for plasma collection that is individualized to the donor, aiming to collect a "target volume of pure plasma." This is a departure from prior methods that collected a standardized volume of plasma mixed with an anticoagulant, without accounting for the actual amount of pure plasma.

Key aspects of the claims include:

• Individualized Collection Target: Calculating a target plasma collection volume based on donor-specific parameters like weight, height, and hematocrit. This is a central feature, moving away from a one-size-fits-all approach. (As detailed in the Abstract and the Description, e.g., in relation to FIG. 5)
• Pure Plasma Calculation: The system actively calculates the volume of "pure plasma" collected, distinguishing it from the total volume of the collected plasma-anticoagulant mixture. This involves calculating the percentage of anticoagulant in the collected fluid. (See Description, discussing FIG. 4)
• Dynamic Process Control: The collection process continues until the calculated volume of pure plasma reaches the predetermined target volume. The system then stops the collection. (Described in the "Summary of the Invention" section)
• Isovolemic Goal: In some embodiments, the system aims to achieve a specific "target intravascular deficit" by returning saline, thereby minimizing donor discomfort and adverse reactions like fainting. (As explained in the Description in relation to FIG. 5)
• System Components for Calculation: The system utilizes a controller to perform these calculations, using inputs from sensors such as weight sensors for the plasma and anticoagulant containers, and potentially optical sensors on the separation device. (See "Summary of the Invention" and Description)

Potential Obviousness Combinations Based on Prior Art

A person of ordinary skill in the art, such as a biomedical engineer or a clinician specializing in apheresis, would be familiar with the general principles of plasmapheresis and the components used in such systems. An argument for obviousness would contend that combining existing technologies would have logically led to the invention of US Patent 12,186,474.

While the specific prior art documents are not detailed in the provided text, the patent's own background section alludes to the state of the art, which can be used for this analysis. The patent itself mentions "Prior art plasma collection systems" that are limited in their capabilities.

Combination 1: Standard Apheresis System + Known Methods for Calculating Blood Volume and Plasma Volume

• What the Prior Art Teaches: Standard apheresis systems, as acknowledged in the background of US 12,186,474, were capable of withdrawing whole blood, separating it, collecting plasma, and returning other components. These systems used weight sensors to measure the collected volume. The prior art also includes established medical formulas for estimating a person's total blood volume and plasma volume based on height, weight, and hematocrit (the patent itself references the Lemmens et al. article for this purpose).

• Motivation to Combine: A person of ordinary skill in the art would have been motivated to combine these elements to improve donor safety and optimize plasma yield. There was a known problem that a fixed collection volume could be a larger percentage of total plasma for a smaller individual than for a larger one, increasing the risk of adverse reactions. Therefore, it would have been a logical step to integrate known plasma volume calculations into the control logic of an apheresis machine to create an individualized collection target. This would be a predictable improvement, not an inventive leap.

Combination 2: Apheresis System with Anticoagulant Control + Basic Mathematical Models

• What the Prior Art Teaches: Existing apheresis systems, as described in the patent, already controlled the ratio of anticoagulant to whole blood. The system's pumps would be calibrated to deliver a specific amount of anticoagulant. The effect of hematocrit on the composition of drawn blood was also well understood in the medical field.

• Motivation to Combine: The patent highlights a problem with prior art systems: they measure the total volume of collected fluid (plasma + anticoagulant), not the pure plasma. A person of ordinary skill in the art would recognize that the amount of anticoagulant in the final product is a direct function of the amount of anticoagulant added and the plasma content of the whole blood (which is dependent on hematocrit). It would be obvious to program a controller to calculate the volume of "pure plasma" by subtracting the known volume of added anticoagulant from the total collected volume. The formulas presented in the patent for this calculation are based on straightforward principles of fluid dynamics and composition that would be apparent to an engineer in this field.

Combination 3: An Apheresis System with Saline Reinfusion + Donor Safety Protocols

• What the Prior Art Teaches: The use of saline as a compensation fluid to make up for the volume of removed plasma was a known practice in apheresis, as mentioned in the background of US 12,186,474. The goal of maintaining fluid balance (isovolemia) to prevent vasovagal reactions and other adverse effects was also a standard part of donor care protocols.

• Motivation to Combine: The innovation claimed in the patent is to return a specific volume of saline to achieve a "target intravascular deficit." A person of ordinary skill in the art would see this as a refinement of existing safety protocols. If a system is already individualized to collect a specific percentage of a donor's plasma, it would be an obvious and logical next step to also individualize the saline replacement to bring the donor to a predetermined, safe fluid balance. This would be seen as an enhancement of an existing feature, not a new invention.

Conclusion on Obviousness

A strong argument can be made that the claims of US Patent 12,186,474 would have been obvious to a person of ordinary skill in the art at the time of the invention. The invention appears to be a combination of known elements: a standard apheresis machine, established formulas for calculating plasma volume, basic mathematical modeling to account for anticoagulant dilution, and existing best practices for donor safety, such as saline reinfusion.

The motivation to combine these elements would have been to improve the safety, efficiency, and yield of plasma donation, which are constant goals in the field of blood collection. The patent solves a known problem (the inaccuracy of collecting a fixed volume of anticoagulated plasma) by applying well-understood principles and calculations. While the resulting system is an improvement, it is arguably an obvious one that follows a clear path of engineering and clinical development.

Analysis of U.S. Patent 12,186,474

Date of Analysis: April 26, 2026

An analysis of United States Patent 12,186,474, titled "System and method for collecting plasma," has been conducted. The patent is assigned to Haemonetics Corp. Below are the findings regarding its term, related applications, and expiration date.

Patent Term and Expiration:

• Grant Date: January 7, 2025
• Application Number: 17/205,400
• Filing Date: March 18, 2021
• Projected Expiration Date: January 21, 2040

The projected expiration date of January 21, 2040, includes a significant Patent Term Adjustment (PTA). A standard 20-year term from the filing date would have resulted in an expiration date of March 18, 2041. The adjusted date indicates that while there may have been some PTA awarded for delays during prosecution by the USPTO, the controlling date is the 20-year term from the earliest priority date. The patent claims priority to an application filed on May 30, 2017. A twenty-year term from this earlier filing date would be May 30, 2037. The "Adjusted expiration" of January 21, 2040, as listed on the patent documentation, reflects the calculated PTA granted by the USPTO. No Patent Term Extensions (PTE) under 35 U.S.C. § 156 for regulatory review delays were noted.

Continuation and Divisional Applications:

U.S. Patent 12,186,474 is part of a larger family of applications and is a continuation of a prior application. The "PRIORITY" section of the patent text confirms this lineage:

• This application is a continuation of U.S. application Ser. No. 16/931,333, filed July 16, 2020.
• U.S. application Ser. No. 16/931,333 is a continuation of U.S. application Ser. No. 15/793,339 (now U.S. Pat. No. 10,792,416), filed October 25, 2017.
• U.S. application Ser. No. 15/793,339 is a continuation-in-part of U.S. patent application Ser. No. 15/608,183 (now U.S. Pat. No. 10,758,652), filed May 30, 2017.

No divisional applications were identified based on the available information.

Patent Family Members:

The patent is related to several other U.S. patents and patent applications through its priority claims. Key identified family members include:

• U.S. Patent 10,758,652: The original parent application.
• U.S. Patent 10,792,416: An intervening parent application.
• U.S. Patent Application Publication 2021/0205526 A1: The publication of the application that led to patent 12,186,474.

Further national and international family members may exist but are not detailed in the primary record of this specific patent.

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:

1. 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.
2. 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.
3. 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.
4. 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.