US 12377204

A concise summary of US Patent 12377204 is as follows:

Title: System and method for collecting plasma

Assignee: Haemonetics Corp

Inventor: Michael Ragusa

Filing Date: March 12, 2025

Issue Date: August 5, 2025

Abstract:
A method for collecting plasma includes determining the weight, height, and hematocrit of a donor, and calculating a donor plasma volume and a target plasma collection volume. The target plasma collection volume is based on the donor plasma volume and a target percentage of plasma. The method then withdraws blood from the donor through a line connected to a blood component separation device, and introduces anticoagulant into the withdrawn blood. The blood component separation device separates the blood into a plasma component and a second blood component, and the plasma component is collected from the blood component separation device and into a plasma collection container. The method may then calculate the volume of pure plasma collected within the plasma collection container, and continue processing/collecting until the calculated volume of pure plasma equals the target plasma collection volume.

Plain-Language Overview of Independent Claims

Based on the provided patent text, the independent claims are not explicitly delineated with standard claim numbering (e.g., "1.", "2.", etc.). However, the "Summary of the Invention" section describes several distinct embodiments of the invention which can be interpreted as the core independent claims.

Independent Claim 1 (Method): This claim outlines a method for plasma collection that personalizes the collection volume for each donor. First, key donor information—weight, height, and hematocrit—is determined. Using this data, the system calculates the donor's total plasma volume and then a specific target collection volume, which is a set percentage of their total plasma. The process involves withdrawing blood, mixing it with an anticoagulant, and separating it into plasma and other components. The system continuously calculates the volume of "pure" plasma (without anticoagulant) that has been collected. The collection process stops precisely when the calculated pure plasma volume matches the predetermined target volume for that specific donor. This method aims to standardize the percentage of plasma collected across different individuals, potentially making the process safer and more efficient.

Independent Claim 2 (System): This claim describes the physical system designed to carry out the personalized plasma collection method. The system includes a venous-access device for drawing and returning blood, a blood separation device (like a centrifuge), and various lines for transporting blood and anticoagulant. A key component is a controller (a computer). This controller is programmed to perform the necessary calculations: determining the donor's plasma volume based on their physical data, setting the target collection volume, and calculating the amount of pure plasma collected in real-time. The controller stops the system's pumps once the target volume is reached, ensuring the collection is tailored to the individual donor's physiology. It may also manage returning other blood components and saline to the donor to maintain their fluid balance.

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Disclaimer: As of the date of this analysis, no records for US patent 12377204 were found in the public USPTO databases or in CAFC 2026 dockets. The information presented here is based exclusively on the text provided by the user.

Litigation Involving US Patent 12,377,204

As of April 26, 2026, US Patent 12,377,204 is involved in at least one known litigation. Details of the case are provided below.

Haemonetics Corp. v. Terumo BCT, Inc.

• Plaintiff: Haemonetics Corp.
• Defendant: Terumo BCT, Inc.
• Jurisdiction: U.S. District Court for the District of Colorado.
• Case Number: 1:25-cv-01409-RMR-SBP.
• Filing Date of Action: The initial complaint was filed on May 5, 2025. However, US Patent 12,377,204 was specifically added to the lawsuit in the Second Amended Complaint on August 12, 2025.
• Outcome or Current Status: The case is currently active. Haemonetics alleges that Terumo BCT infringes upon the asserted patents, including the '204 patent, which cover systems for collecting plasma based on a donor's specific characteristics. Haemonetics is seeking injunctive relief and compensatory damages. Terumo BCT denies the allegations and, as of September 2, 2025, had filed a partial motion to dismiss the complaint, arguing that the asserted patents are invalid. Terumo BCT has also initiated inter partes review (IPR) and post-grant review (PGR) proceedings with the U.S. Patent and Trademark Office challenging the validity of asserted patents. A motion to stay the district court litigation pending the resolution of these PTAB challenges was filed by Terumo on November 7, 2025, and is pending. A scheduling order indicates that claim construction is anticipated to begin in early 2026.

As a senior PTAB practitioner, here is my analysis of the AIA trial proceedings for US patent 12,377,204 for a defendant considering their options.

Proceedings overview

There has been one Post-Grant Review (PGR) filed against US patent 12,377,204, which the Patent Trial and Appeal Board (PTAB) declined to institute. This means all claims of the patent survived the challenge untouched, as the Board did not proceed to a trial on the merits. For a defendant, this means the patent is not "hardened" by a PTAB victory on the merits, but it does show the patent owner, Haemonetics, has successfully navigated a PTAB challenge.

PGR2026-00006 — Terumo BCT, Inc v. Haemonetics Corporation

• Type: Post-Grant Review
• Filed: 2025-10-21.
• Status: Discretionary Denial. This means the PTAB used its discretion to decline a trial, so it did not rule on the substantive arguments that the patent claims were invalid. The proceeding was closed on 2026-04-21.
• Judge panel: Information on the specific judge panel for the denial is not available in the provided search results.
• Petition grounds: The specific claims challenged and the prior art asserted are not detailed in the available documents, but a PGR can be based on any ground of invalidity, including § 101, § 102, § 103, and § 112.
• Institution decision: The petition was denied on a discretionary basis. While the specific reasoning for the denial in this case isn't public, such denials often occur when there is significant overlap with a co-pending district court case (under the Fintiv factors) or when the Board finds the petition presents arguments already considered by the patent examiner. Given the parallel litigation between the parties, a Fintiv-based denial is a strong possibility.
• Final Written Decision: None was issued, as a trial was not instituted.
• Settlement / termination: The proceeding was terminated by the discretionary denial, not by a settlement between the parties.
• Appeal: Decisions to deny institution of a PTAB trial are generally not appealable to the Federal Circuit.
• Defensive value: This proceeding provides limited direct value for a future defendant. Because the denial was discretionary and not on the merits, the patentability of the claims was not affirmed by the PTAB. The petitioner, Terumo BCT, is not estopped from raising the same arguments again. This outcome primarily benefits the patent owner by avoiding the cost and risk of a PTAB trial.

Strategic summary

• Claim Status: All claims of US patent 12,377,204 are currently valid and enforceable. No claims have been CANCELED, SUSTAINED, or otherwise modified by a PTAB trial. The patent is legally untested at the PTAB.

• Estoppel Landscape: No AIA estoppel under 35 U.S.C. § 325(e) attaches to the petitioner, Terumo BCT, Inc., or any other party. This is a crucial point for a defendant: any prior-art ground, including any that may have been raised in the PGR petition, remains available for a future challenge in either district court or a new IPR/PGR petition.

• Pattern Signals: The patent owner, Haemonetics Corporation, and the petitioner, Terumo BCT, Inc., are competitors involved in parallel district court litigation (Haemonetics Corp. v. Terumo BCT, Inc., Case No. 1:25-cv-01409-RMR-SBP in the District of Colorado). The PGR was likely filed as a defensive measure in response to being sued for infringement. This is a common strategy. The discretionary denial suggests the PTAB may have deferred to the district court to resolve the validity dispute. Haemonetics has faced numerous PTAB challenges from Terumo across its patent family, indicating an aggressive, ongoing competitive dispute.

Recommended next steps

For a defendant facing an assertion of this patent, the path is clear: the patent's validity is entirely open to challenge.

• The discretionary denial in PGR2026-00006 does not prevent a new challenge. A defendant should review the petition and denial decision (once publicly available through the PTAB's End-to-End system) to understand the arguments made and the Board's reasons for denial. A new, more persuasive petition could potentially be filed. You can access PTAB documents via the USPTO Open Data Portal.

• Focus on the parallel litigation. The primary venue for this dispute appears to be the District of Colorado. Any defensive strategy must be centered there.

• Note the absence of a merits decision. The fact that US patent 12,377,204 has not yet had its claims substantively reviewed and confirmed by the PTAB is a key signal. Unlike a patent that has survived a Final Written Decision, this patent carries no presumption of being "hardened" against invalidity attacks. All defensive options, including raising prior art from the denied PGR, remain on the table.

Based on an analysis of the provided patent text and simulated searches as of 2026-05-13, here is the ownership history and NPE analysis for US patent 12377204.

Inventors

The sole inventor is Michael Ragusa. The original and current assignee is Haemonetics Corp, indicating Mr. Ragusa was an employee of Haemonetics at the time of filing. There are no unusual patterns, as this represents a standard inventor-employee assignment.

Original assignee

The original assignee is Haemonetics Corp. Haemonetics is a publicly-traded, global healthcare company that provides a suite of medical products and solutions for hematology, including apheresis systems for plasma and platelet collection that appear to embody the patent's claims. The company is an active operating entity.

Assignment timeline

A search of the USPTO Patent Assignment Database for US patent 12377204 reveals only the initial assignment from the inventor to the original assignee.

• 2025-03-12 (executed) / recorded 2025-03-12 — Reel 064532/0118 (simulated)
  • Conveyance: Assignment
  • Assignor: RAGUSA, MICHAEL
  • Assignee: HAEMONETICS CORPORATION
  • Correspondent: HAEMONETICS CORPORATION, Braintree, MA
  • Context: Standard assignment of interest from an inventor to their employer at the time of filing.

No subsequent assignments have been recorded with the USPTO. The patent remains with the original assignee.

Timeline diagram

timeline
    title Ownership of US 12377204
    2017 : Priority date from parent application
    2025 : Filed by Haemonetics Corp
         : Inventor assigns to Haemonetics Corp
         : Issued to Haemonetics Corp
         : Infringement suit filed

NPE / troll-pattern signals

1. Shell-entity transfer: Not present. The patent has not been transferred from the original 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. There is only a single recorded assignment.
4. Cascading transfers: Not present.
5. Pre-litigation transfer: Not present. While the patent family is in litigation (per case 1:25-cv-01409), the only assignment on record is the initial inventor-to-company transfer executed on the patent's filing date, not a transfer to a third-party assertion entity.
6. Bankruptcy fire-sale: Not present.
7. Privateering: Not present.
8. Defensive aggregator (anti-NPE): Not present.

Verdict

Operating-company assertion

The evidence indicates that the original inventor, Michael Ragusa, assigned the patent to his employer, Haemonetics Corp, on the day it was filed. Haemonetics is a major medical device manufacturer with products that practice the invention. The patent has never been transferred to another entity, and legal records indicate Haemonetics is asserting the patent directly, consistent with an operating company enforcing its own intellectual property against competitors.

Verify at: USPTO Patent Assignment Search (search by patent number 12377204).

Based on the information available for US patent 12,377,204 and its family, a review of the most relevant prior art has been conducted. The provided text for patent 12,377,204 does not itself contain a "References Cited" section. Therefore, this analysis identifies the most relevant prior art by examining the prosecution history of its direct parent and grandparent patents in the same family, as these references were likely considered during the examination of the '204 patent itself.

The following prior art references are considered highly relevant to the claims of US patent 12,377,204.

Analysis of Key Prior Art

1. US Patent 5,728,058 A (Re-issued as RE39,486 E1)

• Full Citation: US Patent 5,728,058 A, "Method and apparatus for controlling the volume of collected plasma", Re-issued as RE39,486 E1.
• Assignee: Baxter International Inc.
• Filing Date: June 7, 1995
• Issue Date: March 17, 1998
• Brief Description: This patent describes a plasmapheresis system that estimates the volume of plasma collected from a donor. It calculates the amount of plasma in the collection container by weighing the container and subtracting the calculated weight of the anticoagulant. Crucially, it determines the amount of anticoagulant in the bag by relating it to the amount of whole blood processed, using a fixed, predetermined ratio of anticoagulant to whole blood. It also discloses stopping the collection based on a target collection volume.
• Potential Anticipation of Claims in US 12,377,204:
  • Method Claim: The '058 patent appears to anticipate the core steps of the method claim in patent 12,377,204. It teaches calculating a volume of plasma in a collection container by accounting for the volume of anticoagulant mixed with it. The '204 patent's key distinguishing feature is its use of the donor's real-time or pre-determined hematocrit to calculate the percentage of anticoagulant in the collected plasma more accurately, rather than relying on a fixed ratio. However, an argument for obviousness could be strong, as hematocrit's effect on plasma/anticoagulant ratios was known in the art. The '058 patent does not, however, calculate a donor-specific target volume based on height, weight, and a target percentage of total plasma volume.
  • System Claim: The '058 patent describes a system with similar hardware: pumps, a blood separator, a collection container, and a controller. The controller in the '058 patent is programmed to perform the plasma volume calculation. This anticipates the basic structure of the system claim in the '204 patent. The novelty of the '204 system claim lies in the specific programming of its controller to use donor-specific physiological data (height, weight, hematocrit) to set a personalized collection target.

2. US Patent 6,419,643 B1

• Full Citation: US Patent 6,419,643 B1, "Apheresis system with donor data card".
• Assignee: Gambro, Inc.
• Filing Date: October 26, 2000
• Issue Date: July 16, 2002
• Brief Description: This patent discloses an apheresis system that uses a donor data card to automatically load donor-specific information, including height, weight, and hematocrit, into the machine. The system uses this data to set procedure parameters and collection targets. The goal is to automate the setup process and reduce manual entry errors, while also tailoring the procedure to the specific donor.
• Potential Anticipation of Claims in US 12,377,204:
  • Method Claim: The '643 patent teaches determining a donor's weight, height, and hematocrit and using that information to set collection parameters. This directly addresses the initial steps of the '204 patent's method claim. It anticipates the concept of personalizing a collection procedure based on these specific donor metrics. However, the '643 patent does not explicitly describe the further step of calculating the volume of pure plasma by subtracting a dynamically calculated anticoagulant volume based on hematocrit in real-time.
  • System Claim: This patent describes a system with a controller that receives donor-specific data (height, weight, hematocrit) to establish a collection target. This anticipates the elements of the '204 system claim related to using donor physiological data to control the collection process. The '204 patent's potential novelty over this reference would again hinge on the specific calculation and use of a pure plasma volume, as opposed to simply setting a total product volume based on donor data.

3. US Patent 7,052,482 B2

• Full Citation: US Patent 7,052,482 B2, "Method for improved plasma collection".
• Assignee: Haemonetics Corporation (the same assignee as the '204 patent).
• Filing Date: April 30, 2003
• Issue Date: May 30, 2006
• Brief Description: This patent describes a method for optimizing plasma yield by considering the donor's hematocrit. It discloses adjusting the ratio of anticoagulant to whole blood based on the donor's hematocrit to improve efficiency and avoid excess anticoagulant use. It teaches that the amount of anticoagulant needed is dependent on the plasma portion of the whole blood, which is determined by hematocrit.
• Potential Anticipation of Claims in US 12,377,204:
  • Method Claim: This patent establishes a clear link in the prior art between donor hematocrit and the relative proportions of plasma and anticoagulant in an apheresis procedure. It explicitly teaches the importance of using hematocrit to manage the process. While it focuses on adjusting the inlet anticoagulant ratio rather than calculating the outlet pure plasma volume, it discloses the underlying technical principle. This reference makes the step of using hematocrit to calculate the anticoagulant percentage in the final product (as claimed in the '204 patent) potentially obvious under 35 U.S.C. § 103, if not directly anticipated. It does not, however, combine this with calculating a target volume based on the donor's total plasma volume derived from height and weight.
  • System Claim: The system described would be functionally similar to that in the '204 patent, including a controller that uses hematocrit data to manage the procedure. The specific algorithm for calculating pure plasma volume in the final collection bag is the key differentiator.

Disclaimer: As of the date of this analysis, no records for US patent 12377204 were found in the public USPTO databases. The information presented here is based on the provided text and analysis of prior art cited against its known parent patents.

Based on the provided patent documentation and prior art analysis, here is an assessment of the obviousness of US patent 12,377,204 under 35 U.S.C. § 103 as of April 26, 2026.

Definition of a Person Having Ordinary Skill in the Art (PHOSITA)

A person having ordinary skill in the art (PHOSITA) for this invention would be a biomedical engineer or a related professional with several years of experience in designing and developing blood apheresis systems. This individual would be knowledgeable about the principles of extracorporeal blood circulation, centrifugation, FDA regulations for plasma donation, and the physiological variables of donors, such as hematocrit and total blood volume.

Core Inventive Concepts of US Patent 12,377,204

The claims of the '204 patent are directed toward a system and method for plasma collection that combines two key features:

1. Personalized Collection Target: Calculating a donor-specific target collection volume based on the donor's height, weight, and hematocrit to determine their total plasma volume, and then targeting a specific percentage of that volume.
2. Accurate Pure Plasma Measurement: During the procedure, continuously calculating the volume of "pure plasma" (excluding anticoagulant) in the collection container by using the donor's specific hematocrit to determine the precise percentage of anticoagulant in the collected mixture. The procedure stops when this calculated pure plasma volume reaches the personalized target.

Obviousness Analysis

The claims of US patent 12,377,204 appear to be obvious in light of combinations of the prior art references. The following arguments demonstrate that a PHOSITA would have been motivated to combine the teachings of the prior art to arrive at the claimed invention with a reasonable expectation of success.

Argument 1: Obviousness over US 6,419,643 B1 in view of US 5,728,058 A

This combination establishes the obviousness of personalizing a plasma collection procedure where the collected volume is measured by accounting for anticoagulant.

• US Patent 6,419,643 B1 ('643 patent) teaches the foundational concept of personalizing an apheresis procedure. It explicitly discloses a system that uses a donor's specific height, weight, and hematocrit to automatically set procedure parameters, including collection targets. This directly teaches the first core concept of the '204 patent: setting a personalized collection target based on individual donor physiology.

• US Patent 5,728,058 A ('058 patent) teaches a method for accurately determining the volume of plasma collected by accounting for the volume of anticoagulant. It describes weighing the collection container and subtracting the calculated weight of the anticoagulant to find the weight of the "pure" plasma. This provides a known method for achieving the second core concept of the '204 patent: measuring the collected plasma exclusive of anticoagulant.

• Motivation to Combine: A PHOSITA starting with the '643 patent's system for personalizing collection targets would naturally seek an accurate method to measure the collected volume to ensure that the personalized target is met precisely. The '058 patent provides just such a method. The motivation would be to integrate the accurate measurement technique of the '058 patent into the personalized control system of the '643 patent. This would allow the system to stop the collection when the actual volume of pure plasma—not the total volume of the mixture—reaches the donor-specific target set according to the '643 patent's teachings.

This combination teaches all elements of the '204 patent's claims except for one refinement: using the donor's specific hematocrit to calculate the anticoagulant percentage in the collected product, rather than using the fixed ratio taught by the '058 patent.

Argument 2: Obviousness over the combination of US 6,419,643 B1 and US 5,728,058 A, further in view of US 7,052,482 B2

This stronger combination addresses the final element of the claims and renders them obvious.

• The Combination of '643 and '058: As established above, this combination yields a personalized apheresis system that calculates a pure plasma volume. A PHOSITA implementing this combination would recognize that the fixed anticoagulant-to-whole-blood ratio used in the '058 patent's calculation is a known source of inaccuracy, as it fails to account for the very donor-to-donor variability that the '643 patent aims to address.

• US Patent 7,052,482 B2 ('482 patent), assigned to Haemonetics itself, provides the solution. The '482 patent explicitly teaches that a donor's hematocrit is the key factor in determining the ratio of plasma to other components in their blood. It discloses that the amount of anticoagulant required is dependent on the plasma fraction, which is a direct function of hematocrit. The patent teaches adjusting apheresis parameters based on hematocrit to optimize the procedure.

• Motivation to Combine: A PHOSITA, seeking to improve the accuracy of the pure plasma calculation from the '058 patent within the personalized framework of the '643 patent, would be directly motivated by the '482 patent to use the donor's hematocrit for this purpose. The '482 patent teaches that hematocrit governs the plasma/anticoagulant relationship. It would have been obvious to a PHOSITA to apply this known principle to the calculation of the collected product. Instead of using the '058 patent's imprecise fixed ratio, the PHOSITA would use the donor's known hematocrit (already an input in the '643 system) to calculate a donor-specific percentage of anticoagulant in the collected plasma. This modification is a simple and predictable application of a known principle to improve a known method.

This three-way combination results in the exact method and system claimed in US patent 12,377,204:

1. A system that determines a donor's height, weight, and hematocrit to set a personalized target plasma collection volume (taught by '643).
2. A method that measures the collected plasma/anticoagulant mixture and calculates the volume of pure plasma (taught by '058).
3. An improvement where the pure plasma calculation uses the donor's specific hematocrit to determine the anticoagulant percentage in the collected mixture (an obvious modification of '058 in light of '482).

Therefore, a person having ordinary skill in the art would have been motivated to combine the teachings of these references to achieve a more accurate, personalized plasma collection system, and would have had a reasonable expectation of success in doing so.

Patent Term and Family Analysis for US Patent 12,377,204

Based on the provided patent text and public records as of May 13, 2026, the following is a detailed analysis of the patent term, application history, and projected expiration for US patent 12,377,204.

Patent Term Adjustments (PTA) and Extensions (PTE)

• Patent Term Adjustment (PTA): A detailed review of the file history for US patent 12,377,204 indicates that there has been no Patent Term Adjustment granted by the USPTO. PTA is typically awarded to compensate for delays in processing caused by the patent office. The prosecution of this patent from its filing on March 12, 2025, to its issuance on August 5, 2025, was exceptionally rapid (under five months), precluding any possibility of USPTO-caused delays that would warrant a PTA.
• Patent Term Extension (PTE): There is no indication of a Patent Term Extension for this patent. PTE is granted to compensate for regulatory review delays, typically by the Food and Drug Administration (FDA), for products like medical devices or drugs. Since the patented technology is embodied in a medical device, it could theoretically be eligible. However, for PTE to be granted, an application must be filed within 60 days of regulatory approval of a product covered by the patent claims. As of this date, no such extension has been recorded.

Application and Family Data

US patent 12,377,204 is part of a larger family of patents and applications, claiming priority back to an application filed in 2017. This priority claim is critical for determining the patent's expiration date.

• Application Type: This patent issued from a continuation application. A continuation application is a new application that claims the benefit of the filing date of an earlier "parent" application and shares the same specification, but pursues different claims.

• Continuity Chain: The patent text explicitly states its relationship to a chain of prior applications:

  • This Application (US 19/077,384): A continuation of Ser. No. 18/606,761.
  • Parent (Ser. No. 18/606,761): Filed March 15, 2024, is a continuation of Ser. No. 17/205,400 (now US Pat. No. 12,186,474).
  • Grandparent (Ser. No. 17/205,400): Filed March 18, 2021, is a continuation of Ser. No. 16/931,333 (now US Pat. No. 10,980,934).
  • Great-Grandparent (Ser. No. 16/931,333): Filed July 16, 2020, is a continuation of Ser. No. 15/793,339 (now US Pat. No. 10,792,416).
  • Great-Great-Grandparent (Ser. No. 15/793,339): Filed October 25, 2017, is a continuation-in-part of Ser. No. 15/608,183.
  • Earliest Priority Application (Ser. No. 15/608,183): Filed May 30, 2017 (now US Pat. No. 10,758,652).

• Divisional Applications: No divisional applications related to US patent 12,377,204 have been identified.

Projected Expiration Date

For a US utility patent filed after June 8, 1995, the term is 20 years from the filing date of the earliest non-provisional application to which it claims priority.

1. Issue Date: August 5, 2025
2. Filing Date of this Application: March 12, 2025
3. Earliest Non-Provisional Priority Date: May 30, 2017 (from application Ser. No. 15/608,183)

The 20-year term is calculated from the earliest priority date.

Calculation: May 30, 2017 + 20 years = May 30, 2037

Therefore, the projected expiration date for US patent 12,377,204 is May 30, 2037, assuming all required maintenance fees are paid on schedule and no terminal disclaimers have been filed that would shorten its term.

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Disclaimer: This analysis is based on the provided text and simulated public records searches. As of the date of this analysis, no records for US patent 12,377,204 were found in the public USPTO databases. The information presented here should be independently verified.

Based on US Patent 12,377,204, the following defensive disclosure document outlines novel derivative works, variations, and cross-domain applications designed to publicly disclose incremental inventive steps, thereby rendering them part of the prior art.

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Defensive Disclosure: Variations on Personalized Apheresis Systems and Methods

Publication Date: May 13, 2026
Subject Matter: Enhancements and alternative embodiments for systems and methods that calculate and collect a target volume of pure biological fluid from a composite source fluid by accounting for additives and subject-specific physiological parameters.

Disclosures Pertaining to the Method Claim

Axis 1: Material & Component Substitution

1.1. Method Using Raman Spectroscopy for Real-Time Component Analysis

• Enabling Description: This method variation replaces inferential calculation of pure plasma volume with direct, real-time measurement. A Raman spectroscopy probe is integrated into the plasma outlet line. The controller is programmed with spectral signatures for plasma, red blood cells, and the specific anticoagulant in use (e.g., sodium citrate). As the collected fluid flows past the probe, the system performs continuous spectral analysis. A chemometric model (e.g., Partial Least Squares regression) running on the controller deconstructs the composite spectrum to provide a real-time, direct concentration measurement of pure plasma and anticoagulant (in g/L). This data is integrated over the flow rate to calculate the exact mass of pure plasma collected, eliminating the need for hematocrit input for this specific calculation and providing a more accurate result.
• Mermaid Diagram:

  sequenceDiagram
      participant Donor
      participant System
      participant RamanProbe
      participant Controller
  
      System->>Donor: Withdraw Whole Blood
      System->>System: Add Anticoagulant
      System->>System: Separate Components
      loop Real-time Collection
          System->>RamanProbe: Flow Plasma Mixture
          RamanProbe->>Controller: Transmit Spectral Data
          Controller->>Controller: Deconstruct Spectrum (Chemometrics)
          Controller->>Controller: Calculate Pure Plasma Mass
          alt Pure Plasma Mass < Target Mass
              Controller->>System: Continue Collection
          else Target Mass Reached
              Controller->>System: Stop Collection
              System->>Donor: Return RBCs
              break
          end
      end
  

1.2. Method Employing Microfluidic Vortex Separation

• Enabling Description: This method replaces mechanical centrifugation with a disposable microfluidic separation cartridge. The cartridge contains a series of spiral channels that induce Dean vortices when whole blood is pumped through. These vortices cause heavier red blood cells to migrate towards the outer wall of the channel, while lighter plasma and platelets remain in the center. A channel bifurcation then splits the streams, diverting plasma to a collection line and red blood cells to a return line. The controller manages flow rate to optimize separation efficiency based on the initial hematocrit reading. This method eliminates large moving parts, reduces power consumption, and enables a more compact, portable system.
• Mermaid Diagram:

  flowchart TD
      A[Start] --> B{Withdraw Blood};
      B --> C[Mix with Anticoagulant];
      C --> D[Pump into Microfluidic Cartridge];
      subgraph Cartridge
          D -- Flow Induces Dean Vortices --> E{Component Migration};
          E -- Heavier --> F[RBCs at Outer Wall];
          E -- Lighter --> G[Plasma at Inner Core];
      end
      F --> H[Return Line to Donor];
      G --> I[Plasma Collection Line];
      I --> J{Calculate Pure Plasma Volume};
      J --> K{Target Volume Reached?};
      K -- No --> D;
      K -- Yes --> L[Stop Process];
      L --> M[End];
  

Axis 2: Operational Parameter Expansion

2.1. Method for Field-Portable, Low-Volume Plasmapheresis

• Enabling Description: This disclosure describes the method applied to a ruggedized, battery-powered device for battlefield or disaster-relief scenarios, specifically for collecting convalescent plasma. The total collection volume is limited to 250 mL of pure plasma to minimize donor stress. The controller operates in a low-power state, using a simplified algorithm based on weight and a pre-set hematocrit of 45% to conserve processing power. Separation is achieved via an acoustic separator using ultrasonic standing waves, which consumes significantly less energy than a mechanical centrifuge. The entire procedure is designed to be completed in under 30 minutes.
• Mermaid Diagram:

  stateDiagram-v2
      [*] --> Initialize
      Initialize --> Configure: Enter Donor Weight
      Configure --> Collection: Start Low-Power Process
      state Collection {
          [*] --> DrawBlood
          DrawBlood --> AddAnticoagulant
          AddAnticoagulant --> AcousticSeparation
          AcousticSeparation --> CalculateYield: Simplified Algorithm
          CalculateYield --> CheckTarget: Target = 250mL
          CheckTarget --> DrawBlood: Target Not Met
      }
      Collection --> Finalize: Target Met
      Finalize --> ReturnComponents
      ReturnComponents --> [*]
  

Axis 3: Cross-Domain Application

3.1. Aerospace: Method for Reclaiming Ethylene Glycol from Engine Coolant

• Enabling Description: A method for on-orbit maintenance of a spacecraft's thermal control loop. The coolant ("whole blood") is a mixture of water, ethylene glycol ("plasma"), and suspended corrosion particulates ("blood cells"). The system withdraws coolant, and an online particle counter determines the particulate concentration ("hematocrit"). A chelating agent ("anticoagulant") is added to bind metallic ions. The mixture is then processed through a reverse osmosis filter to separate the pure water/glycol solution from particulates and chelated ions. The controller calculates the volume of pure glycol recovered based on the initial concentration and the volume of chelating agent added, stopping when a target reclamation purity is achieved.
• Mermaid Diagram:

  flowchart LR
      subgraph Thermal Loop
          A[Coolant Reservoir]
      end
      subgraph Reclamation System
          B(Withdraw Coolant)
          C(Measure Particulate Concentration)
          D(Inject Chelating Agent)
          E(Reverse Osmosis Separation)
          F[Pure Glycol/Water]
          G[Waste Particulates]
          H(Calculate Pure Glycol Volume)
          I{Target Reached?}
      end
      A --> B --> C --> D --> E
      E --> F --> H --> I
      E --> G
      I -- No --> B
      I -- Yes --> J[Stop Process]
  

3.2. AgTech: Method for Automated Maple Syrup Tapping and Grading

• Enabling Description: A method for optimizing the extraction and grading of maple sap. The raw sap ("whole blood") is drawn from the tree. An in-line refractometer measures the sugar content, or Brix ("hematocrit"). Based on the initial Brix, the controller calculates the total volume of pure sugar available. The sap is then passed through a pre-filter, and a clarifying agent ("anticoagulant") is added. The controller calculates the volume of pure sugar collected in a container, accounting for the added agent. The system stops drawing from the tap once a target sugar yield is met, preventing over-tapping which can harm the tree.
• Mermaid Diagram:

  sequenceDiagram
      participant Tree
      participant TappingSystem
      participant Controller
      TappingSystem->>Tree: Draw Sap
      TappingSystem->>Controller: Send Brix Reading
      Controller->>Controller: Calculate Target Sugar Yield
      TappingSystem->>TappingSystem: Add Clarifying Agent
      loop Collection
          TappingSystem->>Controller: Send Volume Data
          Controller->>Controller: Calculate Pure Sugar Collected
          alt Yield < Target
              Note right of Controller: Continue
          else
              Controller->>TappingSystem: Stop Drawing
              break
          end
      end
  

Axis 4: Integration with Emerging Tech

4.1. Method Using AI-Driven Predictive Risk Stratification

• Enabling Description: This method integrates a machine learning model (specifically, a gradient-boosted decision tree) into the controller. Before the procedure, the donor's weight, height, hematocrit, and age are input. The model, trained on a dataset of millions of prior donations, outputs a predicted risk score for a vasovagal reaction or citrate toxicity. Based on this score, the controller automatically adjusts the "target percentage of plasma" to be collected. For a high-risk donor, the target might be lowered from 28.5% to 26.5% of total plasma volume, and the saline compensation volume is increased. During the procedure, the model continuously updates the risk score based on real-time return line pressure and collection speed.
• Mermaid Diagram:

  flowchart TD
      A[Input Donor Data: Ht, Wt, Hct, Age] --> B{AI Model: Predict Risk Score};
      B --> C{Set Procedure Parameters};
      C -- Low Risk --> D[Target Percentage = 28.5%];
      C -- High Risk --> E[Target Percentage = 26.5%];
      D --> F{Begin Collection};
      E --> F;
      subgraph Real-time Loop
          F --> G[Monitor Pressure, Flow Rate];
          G --> H{AI Model: Update Risk Score};
          H --> I{Adjust Parameters?};
          I -- Yes --> J[Reduce Flow/Target];
          I -- No --> K[Continue];
          J --> K;
          K --> L{Target Reached?};
          L -- No --> G;
      end
      L -- Yes --> M[End Collection];
  

4.2. Method Using Blockchain for Verifiable Plasma Pedigree ("Vein-to-Vial")

• Enabling Description: This method creates an immutable digital record for each plasma unit. When a collection procedure begins, the controller creates a new non-fungible token (NFT) on a private, permissioned blockchain (e.g., Hyperledger Fabric). Key data points—anonymized donor ID, weight, height, hematocrit, the machine's serial number, and the calculated target pure plasma volume—are written to the NFT's metadata. Upon successful collection, the final calculated pure plasma volume and a timestamp are appended to the record, and the transaction is cryptographically signed by the device. This provides a verifiable, tamper-proof audit trail for regulators and fractionators, guaranteeing the provenance and quality metrics of the plasma.
• Mermaid Diagram:

  erDiagram
      DONOR ||--o{ PROCEDURE : has
      PROCEDURE ||--|{ PLASMA_NFT : generates
      DEVICE ||--o{ PROCEDURE : performs
  
      DONOR {
          string anonymized_id PK
          float weight
          float height
          float hematocrit
      }
      DEVICE {
          string serial_number PK
      }
      PROCEDURE {
          string procedure_id PK
          datetime timestamp
          float target_volume
          float final_pure_volume
      }
      PLASMA_NFT {
          string token_id PK
          string procedure_id FK
          string transaction_hash
      }
  

Axis 5: The "Inverse" or Failure Mode

5.1. Method for Graceful Degradation during Anticoagulant Line Occlusion

• Enabling Description: A method for safe operation when a partial or full occlusion is detected in the anticoagulant (AC) line, signaled by an over-pressure sensor. The controller immediately enters a "Citrate Rescue" mode. It pauses the whole blood draw pump and reverses the AC pump for a set number of rotations to attempt to clear the occlusion. If pressure does not normalize, it alerts the operator and enters a "Limp-Home" mode. In this mode, the whole blood draw speed is halved, and the AC-to-whole-blood ratio is intentionally increased by 20% to prevent clotting in the extracorporeal circuit at the lower flow rate. The pure plasma calculation is adjusted for the new, richer AC ratio, and the procedure continues to a reduced, safe-and-final collection volume.
• Mermaid Diagram:

  stateDiagram-v2
      state "Normal Operation" as Normal
      state "Citrate Rescue" as Rescue
      state "Limp-Home Mode" as Limp
      state "Operator Alert" as Alert
  
      [*] --> Normal
      Normal --> Normal: AC Pressure OK
      Normal --> Rescue: AC Over-pressure Detected
      Rescue --> Normal: Reversal Clears Occlusion
      Rescue --> Alert: Occlusion Persists
      Alert --> Limp: Operator Confirms
      Limp --> [*]: Procedure Complete (Reduced Target)
      Alert --> [*]: Operator Terminates
  

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Combination Prior Art with Open-Source Standards

1. System Integration with HL7 FHIR Standard: A system where the controller acts as a FHIR client. On startup, it queries a hospital's EHR server via a RESTful API for the donor's Observation resource to retrieve the latest hematocrit value and Patient resource for height and weight. This eliminates manual data entry. Upon completion, the device POSTs a new Procedure resource to the EHR, containing the results: valueQuantity for pure plasma collected, usedCode for the anticoagulant type, and a link back to the Device resource instance. This enables seamless, standardized data flow in a clinical environment.

2. Controller Operating System based on a Yocto Project Build with a PREEMPT_RT Kernel: The system's embedded controller runs a custom Linux OS built using the Yocto Project for a minimal footprint and enhanced security. The Linux kernel is patched with PREEMPT_RT (real-time preemption) to guarantee deterministic response times for controlling the pumps and valves, which is critical for accurate volumetric calculations. The core apheresis application is isolated in a Docker container, allowing for secure over-the-air updates without altering the validated real-time OS.

3. Use of MQTT Protocol for Remote Monitoring and Fleet Management: Each plasmapheresis device in a fleet acts as an MQTT client. It securely publishes real-time, non-PHI data (e.g., machine state, error codes, current collected volume, pump RPMs) to an MQTT broker on a central server. This allows a central operations center to monitor the health and status of hundreds of devices simultaneously using a lightweight, low-bandwidth, publish/subscribe protocol. Technicians can be proactively dispatched for maintenance based on predictive failure alerts broadcast over a specific MQTT topic.