US 10758652

Summary of U.S. Patent 10,758,652

A comprehensive analysis of U.S. Patent 10,758,652 reveals the following details:

Title: System and method for collecting plasma.

Assignee: Haemonetics Corporation.

Inventor: Michael Ragusa.

Filing Date: May 30, 2017.

Issue Date: September 1, 2020.

Abstract:
The patent describes a method for collecting plasma from a donor. The process involves determining the donor's weight and hematocrit, then using a venous-access device to withdraw blood. This blood is directed to a blood component separation device where an anticoagulant is introduced. The device separates the blood into a plasma component and a second blood component. The plasma component is collected in a container. The method includes calculating the percentage of anticoagulant in the collected plasma and, based on this, determining the volume of pure plasma. This process continues until a target volume of pure plasma is collected.

Plain-Language Overview of Independent Claims

U.S. Patent 10,758,652 has two independent claims: claim 1 (a method) and claim 11 (a system).

Claim 1 (Method): This claim outlines a specific process for collecting plasma from a donor. The key steps are:

1. Initial Assessment: Determining the donor's weight and hematocrit (the proportion of red blood cells in their blood).
2. Blood Withdrawal and Separation: Drawing whole blood from the donor and separating it into plasma and other blood components using a separation device.
3. Anticoagulant Use: Introducing an anticoagulant to prevent clotting.
4. Calculating Pure Plasma: As the plasma is being collected, the system continuously calculates the volume of anticoagulant that is mixed in with the plasma. This allows for a precise calculation of the volume of "pure plasma" that has been collected.
5. Targeted Collection: The process of drawing, separating, and calculating continues until a predetermined target volume of pure plasma is reached.

In essence, this method aims to collect a more precise and standardized amount of pure plasma from each donor by accounting for the variable amount of anticoagulant in the collected fluid, which is influenced by the donor's specific hematocrit level.

Claim 11 (System): This claim describes the physical system designed to carry out the method of claim 1. The essential components of the system are:

1. Blood Access and Transport: A venous-access device (like a needle) and tubing to draw blood and return other components to the donor, controlled by a pump.
2. Separation Device: A device to separate the whole blood into plasma and other components.
3. Anticoagulant Delivery: A line to introduce anticoagulant into the drawn blood.
4. Controller (the "brain"): A controller that manages the system's operations. This controller is configured to calculate the volume of anticoagulant in the collected plasma in real-time. Based on this, it determines the volume of pure plasma. The controller is programmed to stop the blood collection process once a specific target volume of pure plasma has been collected.

This system is designed to automate the process of collecting a specific, targeted volume of pure plasma, making the collection process more efficient and personalized to the donor's physiological characteristics.

Litigation

As of late 2025, Haemonetics Corp. has filed a complaint against Fresenius Kabi USA LLC, alleging infringement of U.S. Patent 10,758,652. The lawsuit contends that the accused products utilize a system with a controller that determines a target plasma volume based on donor-specific parameters like weight, height, and hematocrit before collection begins. A search for related dockets at the Court of Appeals for the Federal Circuit (CAFC) for 2026 did not yield any specific results for this patent at this time.

As of April 26, 2026, U.S. Patent No. 10,758,652 is involved in at least two known litigation cases.

District Court Litigations:

1. Haemonetics Corp. 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
• Status: Active/Ongoing.
• Details: Haemonetics alleges that Terumo BCT's Rika Plasma Donation System™ infringes on U.S. Patent 10,758,652, along with several other Haemonetics patents. The complaint asserts both direct and indirect infringement, both literally and under the doctrine of equivalents. Terumo BCT has denied the allegations, asserting non-infringement and invalidity of the patent claims. A scheduling order has been issued in the case.

2. Haemonetics Corp. v. Fresenius Kabi USA, LLC

• Plaintiff: Haemonetics Corporation
• Defendant: Fresenius Kabi USA, LLC and Fenwal, Inc.
• Jurisdiction: U.S. District Court for the Northern District of Illinois
• Case Number: 1:25-cv-08680
• Filing Date: The original complaint was filed on July 25, 2025, with a First Amended Complaint filed on October 6, 2025.
• Status: Active/Ongoing.
• Details: Haemonetics alleges that the Aurora Xi Plasmapheresis System infringes on U.S. Patent 10,758,652 and two other patents. The complaint highlights the patent's solution to prior art systems by using a controller to calculate the volume of pure plasma collected, stopping the process only when a target volume of pure plasma is reached.

Patent Trial and Appeal Board (PTAB) Proceedings:

In addition to the district court litigations, a post-grant review (PGR) proceeding has been initiated related to a patent in the same family as the '652 patent.

• Case Name: Terumo BCT, Inc. v. Haemonetics Corporation
• Proceeding Number: PGR2026-00006
• Filing Date: October 20, 2025
• Status: Pending.
• Details: This proceeding was filed by Terumo BCT, Inc. against Haemonetics Corporation. While not directly targeting the '652 patent, it is related to the ongoing dispute between the two companies.

Based on a review of publicly available records, there is one active PTAB proceeding on file for US patent 10,758,652.

Proceedings overview

There is one active inter partes review (IPR) on file, IPR2025-01391, which has been instituted by the Patent Trial and Appeal Board (PTAB). This means the patent is facing a significant validity challenge, as the PTAB has already determined there is a "reasonable likelihood" that the petitioner will prevail in proving at least one of the challenged claims is unpatentable. For a defendant, this proceeding offers substantial defensive leverage against an assertion of this patent.

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IPR2025-01391 — Unified Patents, LLC v. Haemonetics Corp

• Type: Inter Partes Review
• Filed: 2025-08-15
• Status: Pending - Instituted. The PTAB has initiated a trial to review the patentability of the challenged claims. A Final Written Decision is statutorily due one year from the institution date.
• Judge panel: Michael P. Tierney, Georgianna W. Braden, Christopher G. Paulraj
• Petition grounds: The petition challenged claims 1-3, 5, 6, 8, and 11-14.
  • § 103 (Obviousness): Claims 1-3, 5, 6, 8, and 11-14 were alleged to be unpatentable as obvious over the combination of prior art references.
• Institution decision: The trial was instituted on 2026-02-20 against claims 1-3, 5, 6, 8, and 11-14. The Board found that Unified Patents' petition established a reasonable likelihood of prevailing on its obviousness grounds. The PTAB was persuaded that the prior art taught the key limitation of calculating a volume of "pure plasma" by accounting for the volume of anticoagulant, and that combining the references to arrive at the claimed invention would have been obvious to a person of ordinary skill in the art at the time.
• Final Written Decision: Not yet issued. The statutory deadline for the FWD is approximately 2027-02-20.
• Settlement / termination: There is no public record of a settlement. The proceeding remains active.
• Appeal: Not applicable, as no Final Written Decision has been issued.
• Defensive value: This is highly valuable for a defendant. The institution of trial on all challenged claims signals that the validity of a broad swath of the patent is at significant risk. Any defendant should monitor this proceeding closely, as a finding of unpatentability would be binding on the patent owner and could resolve an infringement dispute entirely. The arguments and evidence successfully used by the petitioner can be leveraged in district court litigation, should it run in parallel.

Strategic summary

The validity of US patent 10,758,652 is currently under a serious cloud due to the instituted IPR.

• Claim Status:

  • CHALLENGED & AT RISK: Claims 1-3, 5, 6, 8, and 11-14. These claims are the subject of the instituted IPR trial and could be canceled in the Final Written Decision.
  • UNTESTED: Claims 4, 7, 9, 10, and 15-20. These claims were not challenged in the IPR and remain presumptively valid, though they could be challenged in a future proceeding or in district court.

• Estoppel Landscape: For the petitioner, Unified Patents, and its real parties-in-interest, estoppel under 35 U.S.C. § 315(e) has not yet attached, but it will upon issuance of a Final Written Decision. For any other potential defendant, the prior art grounds raised in this IPR are available to use in litigation. However, given that the PTAB found these grounds persuasive, a defendant would have a strong starting point for its own invalidity contentions.

• Pattern Signals: The petitioner is Unified Patents, a defensive organization that frequently challenges patents it deems to be of low quality, particularly those being asserted by non-practicing entities (NPEs). Their involvement suggests that patent owner Haemonetics Corp. may be actively asserting this patent in the marketplace, and that Unified's membership includes companies targeted by or concerned about this assertion campaign.

Recommended next steps

For a defendant currently facing an assertion of US patent 10,758,652, the active IPR proceeding is the most critical factor in developing a defense strategy.

• Monitor the IPR: Closely track the key upcoming milestones in IPR2025-01391, including the Patent Owner's Response, the Oral Hearing (likely in late 2026), and the Final Written Decision deadline of 2027-02-20. The outcome of this proceeding could be dispositive.

• Review IPR Filings: Obtain and analyze the Petition and the Decision to Institute from the PTAB's E2E portal for case IPR2025-01391. These documents provide a detailed roadmap of the invalidity arguments the PTAB found compelling and can form the core of an invalidity defense in any parallel litigation.

• Consider a Stay: If you are sued in district court, you should strongly consider filing a motion to stay the litigation pending the outcome of the IPR. Courts often grant such stays to conserve judicial resources and simplify the issues, particularly when an IPR has been instituted on a significant number of asserted claims, as is the case here.

Inventors

Based on the patent documentation, the sole inventor is Michael Ragusa. At the time of the application filing on May 30, 2017, the original assignee was Haemonetics Corporation, indicating that Michael Ragusa was likely employed by or had an obligation to assign inventions to Haemonetics Corporation.

Original assignee

The original assignee of US patent 10,758,652 is Haemonetics Corporation. Haemonetics is a global healthcare company that provides a suite of medical products and services for blood and plasma collection, processing, and transfusion. The company's products, including apheresis systems for plasma collection, appear to embody the claims of the patent, which details a "System and method for collecting plasma." Haemonetics Corporation is an active, publicly traded operating company (NYSE: HAE).

Assignment timeline

A search of the USPTO Patent Assignment Search database for US Patent 10,758,652 reveals a single assignment recorded.

• 2018-05-01 (executed) / recorded 2018-05-22 — Reel 044100/0358
  • Conveyance: Assignment of Assignor's Interest
  • Assignor: RAGUSA, MICHAEL
  • Assignee: HAEMONETICS CORPORATION
  • Correspondent: Matthew F. Lambrinos, Wolf, Greenfield & Sacks, P.C., 600 Atlantic Avenue, Boston, MA 02210
  • Context: This is the initial assignment from the inventor to the original assignee, Haemonetics Corporation, formalizing the company's ownership of the invention.

No other assignments have been recorded for this patent as of 2026-05-13. The patent remains with the original assignee.

Timeline diagram

timeline
    title Ownership of US 10758652
    2017 : Application filed
         : Inventor Michael Ragusa assigns to Haemonetics Corp
    2020 : Patent issued

NPE / troll-pattern signals

1. Shell-entity transfer: Not present. The patent has not been transferred from the original operating company assignee.

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

3. Repeat correspondent across the chain: Not present. There is only one recorded assignment.

4. Cascading transfers: Not present. There are no subsequent transfers.

5. Pre-litigation transfer: Not present. The patent has not been assigned post-issuance. According to information on the Google Patents page for US10758652, there is pending litigation, but no pre-litigation transfer is recorded.

6. Bankruptcy fire-sale: Not present. Haemonetics Corporation is a financially active company.

7. Privateering: Not present. The patent has not been transferred to a third-party assertion entity.

8. Defensive aggregator (anti-NPE): Not present. The patent is held by its original operating company assignee.

Verdict

Insufficient data

The USPTO assignment records show only the initial inventor-to-assignee transfer to Haemonetics Corporation (Reel 044100/0358). There is no recorded evidence of any transfer to a non-practicing entity or other assertion-focused vehicle. The patent remains with the original operating company that develops and sells products in the field of the invention. While litigation is noted, without a transfer of ownership, it falls outside the typical NPE pattern.

A direct search can be verified at the USPTO Patent Assignment Search by entering patent number 10758652.

Analysis of Prior Art for U.S. Patent 10,758,652

Based on a review of the prosecution history and the face of the patent, the following patents were cited as prior art during the examination of US 10,758,652. This analysis evaluates their potential relevance to the claims of the '652 patent.

Key Challenge of the Invention

The core novelty asserted in US 10,758,652 is the method and system for collecting a target volume of pure plasma by dynamically calculating and subtracting the volume of anticoagulant mixed with the collected plasma. This addresses the variability in collected "pure plasma" that arises from differences in donor hematocrit when collection is based on total fluid volume. Prior art systems, as described in the '652 patent's background, were "unable to determine the total volume of plasma that has been collected (e.g., because the product collected is a mixture of plasma and anticoagulant)" and therefore collected based on total volume, leading to inconsistent pure plasma yields (US 10,758,652, Col. 1, lines 60-67).

Analysis of Cited Prior Art

The following prior art was cited by the examiner.

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1. US Patent 4,086,924 A - "Plasmapheresis apparatus"

• Full Citation: US 4,086,924 A
• Publication Date: May 2, 1978
• Assignee: Haemonetics Corporation
• Brief Description: This patent describes an early automated plasmapheresis system. It controls the collection of anticoagulated plasma into a container and measures the collected volume. The system uses a weigh scale to monitor the amount of collected fluid and automatically controls draw and return cycles. It also controls the ratio of anticoagulant to whole blood.
• Potential Anticipation of Claims:
  • This reference discloses many foundational elements of a plasmapheresis system, such as withdrawing blood, adding anticoagulant, separating components, and collecting plasma into a container that is weighed (relevant to claims 1(d-g), 6, 11, and 17).
  • However, US 4,086,924 does not appear to anticipate the key steps of claims 1 and 11. It does not teach or suggest calculating a volume of pure plasma by determining the volume of anticoagulant in the collected product and subtracting it from the total collected volume. The system in the '924 patent stops collection based on the total weight/volume of the plasma-anticoagulant mixture. Therefore, it does not disclose the novel elements of claim 1(h), 1(i), and the corresponding functions of the controller in claim 11.

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2. US Patent 5,316,540 A - "Apparatus and method for separating microscopic units in a substantially continuous density gradient solution"

• Full Citation: US 5,316,540 A
• Publication Date: May 31, 1994
• Assignee: Cobe Laboratories, Inc.
• Brief Description: This patent details a centrifugal system for separating blood components. A significant feature is its use of an optical sensor to monitor the location of the interface between different blood components (e.g., the "buffy coat") within the centrifuge. This allows for more precise control over which component is being harvested.
• Potential Anticipation of Claims:
  • The '540 patent discloses the use of an optical sensor to monitor blood components within a separation device. This is directly relevant to dependent claims 7 and 18, which describe determining the donor's hematocrit by "monitoring a volume of red blood cells collected within the blood component separation device" using an optical sensor.
  • While this patent provides a mechanism for determining hematocrit during the procedure, it does not appear to anticipate the core inventive concept of independent claims 1 and 11. The '540 patent does not disclose using this hematocrit value to then calculate the volume of anticoagulant in the final collected plasma product and stop the collection based on a target volume of pure plasma. Its focus is on the precision of the separation process itself.

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3. US Patent 5,651,766 A - "System for controlling a blood processing apparatus"

• Full Citation: US 5,651,766 A
• Publication Date: July 29, 1997
• Assignee: Baxter International Inc.
• Brief Description: This patent describes a sophisticated control system for an apheresis device. The system can estimate or determine various donor-specific physiological parameters (like total blood volume, plasma volume) and use these parameters to optimize the collection procedure, for example, by controlling pump rates to minimize procedure time. It can also estimate the volume of plasma available for collection from a donor.
• Potential Anticipation of Claims:
  • The '766 patent teaches determining donor parameters (like weight, hematocrit) and using them to control the apheresis process. This is relevant to the preliminary steps of claim 1(a-b) and the system's ability in claim 11 to use this information.
  • Crucially, the '766 patent discusses optimizing the procedure based on donor data, but it does not appear to explicitly teach the calculation of pure plasma in the final collection bag in real-time. It does not disclose the steps of calculating the anticoagulant volume within the collected product as it is being collected and using that to determine the pure plasma volume to meet a specific pure plasma target. The control described is more focused on the rate and efficiency of the collection process rather than the precise composition of the final product.

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4. US Patent 6,053,856 A - "Method of and apparatus for controlling a fluid separation process"

• Full Citation: US 6,053,856 A
• Publication Date: April 25, 2000
• Assignee: Baxter International Inc.
• Brief Description: This patent describes a control system for apheresis that predicts the volume of a blood component to be collected based on donor data and process parameters. It can adjust the collection procedure in real-time. The system calculates a target volume of anticoagulated plasma (AC plasma) based on a desired pure plasma yield and the donor's hematocrit.
• Potential Anticipation of Claims:
  • This is a highly relevant prior art reference. The system in the '856 patent calculates a target volume for the anticoagulated mixture before the procedure begins, based on a desired pure plasma target and donor hematocrit. For example, it states, "the desired plasma yield... and the donor HCT are used to calculate the target AC plasma volume" (Col. 14, lines 52-54).
  • However, there is a subtle but important distinction from the claims of the '652 patent. Claims 1 and 11 of the '652 patent specify calculating the volume of pure plasma as the plasma component is being collected and continuing until a target volume of pure plasma is reached. The '856 patent appears to set a target for the total mixture volume at the outset and collects to that volume. It does not describe a dynamic, real-time calculation and subtraction of the anticoagulant volume from the currently collected fluid to determine the current pure plasma volume. The '652 patent claims a method of real-time monitoring of the pure plasma volume itself, rather than collecting to a pre-calculated mixture volume. This distinction, focusing on the dynamic calculation during collection, appears to be what separates the '652 patent from this prior art.

Obviousness Analysis of U.S. Patent 10,758,652 under 35 U.S.C. § 103

This analysis assesses whether the invention claimed in U.S. Patent 10,758,652 would have been obvious to a Person Having Ordinary Skill in the Art (POSA) at the time the invention was made (i.e., prior to the May 30, 2017 priority date). The analysis is based on the prior art references cited within the patent document itself.

A POSA in this context would be a biomedical engineer or a professional with substantial experience in the design and operation of apheresis and blood component separation systems.

Core Inventive Concept

The central inventive concept of US 10,758,652 is not the physical apparatus for apheresis, but rather the control method implemented by its controller. The patent's key contribution is a method and system that calculates the volume of pure plasma being collected in real-time by actively accounting for the volume of anticoagulant mixed with it. The collection process is terminated when a target volume of pure plasma is reached, rather than a target total volume of the plasma-anticoagulant mixture. This is intended to standardize the dose of collected plasma across donors with varying hematocrit levels and maximize collection yields within regulatory limits.

Obviousness Argument Based on a Combination of Prior Art

The independent claims (1 and 11) of patent '652 would have been obvious to a POSA by combining the teachings of a standard automated apheresis system with the well-understood principles of hematology and the clear motivation to optimize plasma collection under existing regulations.

1. The Base System - Automated Apheresis Technology

Numerous prior art references cited in the '652 patent describe the foundational technology for an automated plasmapheresis system. For example:

• US 4,086,924 A (assigned to Haemonetics Corp.): This early reference discloses a plasmapheresis apparatus for separating blood into components, including plasma, which is collected in a container. It establishes the basic process of drawing blood, separating it, and collecting a component.
• US 4,151,844 A (assigned to Baxter Travenol Laboratories, Inc.): This reference teaches a "method and apparatus for separating whole blood into its components and for automatically collecting one component." This establishes the concept of an automated system with a controller that manages the collection process and stops it once a condition is met. Such systems commonly use weight sensors to monitor the collected volume.

These references, and many others cited, establish that by 2017, the concept of a microprocessor-controlled apheresis machine with pumps, sensors (including collection container weight scales), and automated control loops was well-established. These systems had the capability to take donor parameters (like weight) as inputs to determine a target collection volume based on regulatory guidelines. However, this target was typically for the total volume of the anticoagulated plasma product.

2. The Known Problem and Motivation to Combine

The background section of the '652 patent itself articulates the problem that existed in the prior art and the motivation to solve it:

"Prior art plasma collection systems are unable to determine the total volume of plasma that has been collected (e.g., because the product collected is a mixture of plasma and anticoagulant) and, therefore collect based on the total collection volume, even if the total volume of plasma that has been collected is below the limit prescribed by the FDA." (Column 2, Lines 12-19)

A POSA would have been fully aware of this issue. It is a fundamental principle of apheresis that the collected plasma product is diluted by anticoagulant. It is also basic knowledge that the degree of this dilution for a given volume of processed whole blood depends on the donor's hematocrit (the volume percentage of red blood cells).

The motivation to solve this problem is twofold and compelling:

• Regulatory Compliance and Donor Safety: Regulatory bodies like the U.S. FDA set limits on the volume of plasma that can be safely donated. By measuring only the total mixed volume, prior art systems could inadvertently collect more pure plasma than the limit from a low-hematocrit donor or would have to set conservative limits, under-collecting from a high-hematocrit donor.
• Economic Efficiency: Plasma is a valuable commodity. A system that can more accurately collect the maximum allowable amount of pure plasma from every donor is more efficient and profitable.

This creates a strong motivation for a POSA to modify a standard automated apheresis system to account for the anticoagulant volume and thereby measure the "true" volume of collected plasma.

3. The Obvious Solution

Given the base automated system and the clear motivation, the solution claimed in the '652 patent is a predictable and obvious step. A POSA would know that a modern apheresis machine already possesses:

• A controller (microprocessor).
• A means to measure the total collected fluid (e.g., a weight sensor for the plasma collection container, as described in claim 16).
• A precisely controlled anticoagulant pump (where volume can be known from pump rotations, as described in claim 14).
• The ability to accept donor hematocrit as an input.

To implement the invention, a POSA would only need to program the existing controller to perform a simple, real-time calculation:

Volume_of_Pure_Plasma = Total_Monitored_Volume - Volume_of_Anticoagulant_Added

• Total Monitored Volume is provided by the existing weight scale on the plasma container.
• Volume of Anticoagulant Added is known because the system's controller is actively managing the anticoagulant pump. This volume is a direct function of the amount of whole blood processed.

The controller's new instruction would be to compare the calculated Volume_of_Pure_Plasma to the regulatory target volume and stop the procedure when the target is met. This requires no new hardware or non-obvious scientific breakthrough, but rather a straightforward application of programming to solve a known issue using existing system capabilities. The formula presented in the '652 patent specification to calculate the percentage of anticoagulant based on hematocrit is an application of basic principles of mixtures and concentrations that would be routine for a POSA in this field.

Conclusion

The invention of US patent 10,758,652 is rendered obvious under 35 U.S.C. § 103. The combination of a standard automated apheresis system (as taught by numerous prior art references like US 4,151,844 A) with the well-established knowledge of the dilutive effect of anticoagulant provides a clear motivation to create a more accurate collection method. The solution—programming the system's existing controller to subtract the known volume of anticoagulant from the measured total volume to find the pure plasma volume—is a predictable and logical step that would have been obvious to a person of ordinary skill in the art seeking to optimize plasma collection efficiency and regulatory compliance.

Based on a detailed analysis of the provided documentation for U.S. Patent 10,758,652, here are the findings regarding its term, continuation history, and related patent family.

Patent Term and Expiration

• Patent Term Adjustment (PTA): The patent has been granted a patent term adjustment. The standard 20-year term from its filing date of May 30, 2017, would end on May 30, 2037.
• Patent Term Extension (PTE): There is no indication of a Patent Term Extension (PTE) under 35 U.S.C. § 156, which is typically granted for delays in regulatory review by agencies like the FDA.
• Projected Expiration Date: The official adjusted expiration date for U.S. Patent 10,758,652, including all adjustments, is November 20, 2038. This is explicitly stated in the "Legal status" section of the patent's documentation (Source: https://patents.google.com/patent/[US10758652](/patent/US10758652)/en).

Continuation and Divisional Applications

The application that resulted in this patent, US15/608,183, is the parent for several subsequent applications. These are listed as "Related Child Applications" or are part of the broader patent family.

• Continuation-in-Part Application:

  • US15/793,339: Filed on October 25, 2017, which later issued as patent US10792416B2.

• Continuation Applications:

  • US16/866,078: Filed on May 4, 2020, which issued as patent US10980926B2.
  • US17/205,374: Filed on March 18, 2021, which issued as patent US12171916B2.
  • US17/943,410: Filed on September 13, 2022, which issued as patent US11738124B2.
  • US18/955,269: Filed on November 21, 2024, which is expected to issue as patent US12324873B2.
  • US19/202,281: Filed on May 8, 2025, which has been published as US20250269097A1.

• Divisional Applications: There are no applications explicitly identified as "divisional" in the provided documentation for this patent family.

Patent Family Members

U.S. Patent 10,758,652 is part of a large international patent family, indicating that the assignee, Haemonetics Corp., sought protection for this invention in numerous jurisdictions.

• U.S. Family Members (Issued Patents):

  • US10758652B2 (this patent)
  • US10792416B2
  • US10980926B2
  • US11738124B2
  • US12171916B2

• Foreign Family Members (Selected): The invention is also protected or pending in other countries, based on the priority filing.

  • Europe (EP): EP3634524B1, EP4600632A3
  • China (CN): CN110799223B, CN115300698A
  • Japan (JP): JP7257336B2, JP7565389B2
  • Australia (AU): AU2018275198C1, AU2023238237B2
  • Canada (CA): CA3064883A1
  • South Korea (KR): KR102585128B1, KR20230144112A
  • World Intellectual Property Organization (WO): WO2018222441A1

Defensive Disclosure and Prior Art Publication

Title: Derivative Systems and Methods for Controlled, Real-Time Volumetric Fluid Separation
Publication Date: 2026-05-13
Keywords: Apheresis, plasma collection, fluid separation, real-time control, hematocrit, anticoagulant, process control, AI, IoT, microfluidics, cross-domain application.

Abstract: This document discloses novel methods, systems, and applications derived from the core principles of U.S. Patent 10,758,652. The disclosures herein are intended to enter the public domain to serve as prior art against future patent claims on incremental or obvious improvements. The disclosed concepts include alternative component architectures, operation in extreme environments, applications in non-medical fields such as aerospace and agriculture, integration with emerging technologies like artificial intelligence and blockchain, and the implementation of fail-safe and limited-functionality operational modes.

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Part 1: Derivative Methods for Pure Component Collection (Based on Claim 1)

Axis 1: Material & Component Substitution

Derivative 1.1: Method Using Acoustic Microfluidic Separation

• Enabling Description: This method replaces centrifugal separation with an acousto-microfluidic separation chip. Whole blood mixed with anticoagulant is pumped through a microfluidic channel containing piezoelectric transducers. The transducers generate a standing surface acoustic wave (SSAW) across the channel. As blood flows through, the acoustic radiation force directs larger, denser particles (red blood cells) to the pressure nodes of the standing wave, while smaller particles (platelets) and the plasma fluid are less affected. This results in the separation of blood into distinct streams. The controller calculates the volume of pure plasma by monitoring the flow rate in the plasma outlet channel and subtracting the calculated anticoagulant volume based on the known inlet flow rates of blood and anticoagulant, and the donor's hematocrit. The hematocrit is determined pre-procedure using a miniaturized resistive pulse sensor integrated into the fluidic chip.
• Mermaid Diagram:

  flowchart TD
      A[Donor] -->|Whole Blood| B(Micro-Pump);
      C[Anticoagulant] --> D(AC Pump);
      B & D --> E{Mixing Junction};
      E --> F[Acousto-Microfluidic Chip];
      subgraph F
          direction LR
          F1(Inlet) --> F2{SSAW Transducers};
          F2 --> F3(RBC Outlet Stream);
          F2 --> F4(Plasma Outlet Stream);
      end
      F4 --> G[Plasma Collection Container];
      F3 --> H{RBC Reservoir for Return};
      I[Controller] -->|Control SSAW Freq.| F2;
      G -->|Flow Rate| I;
      D -->|AC Flow Rate| I;
      I -->|Stop Pumps| B & D;
      I -- Calculates --> J(Pure Plasma Volume);
  

Derivative 1.2: Method Using Non-Contact Raman Spectroscopy for Hematocrit and Anticoagulant Measurement

• Enabling Description: This method replaces the initial hematocrit determination and the reliance on pump-rotation counting with a non-contact Raman spectroscopy sensor. The sensor is positioned on the exterior of the transparent draw line tubing. It directs a laser (e.g., 785 nm) into the flowing anticoagulated blood. The backscattered light is analyzed for its Raman spectrum. The controller uses a pre-calibrated chemometric model to simultaneously quantify (a) the hematocrit, based on the characteristic peaks of hemoglobin, and (b) the concentration of anticoagulant (e.g., citrate), based on its unique spectral signature. This provides a direct, continuous measurement of the anticoagulant-to-plasma ratio. The controller integrates this ratio against the total volume collected (measured by a weight sensor) to calculate the real-time volume of pure plasma, stopping the collection when the target is met.
• Mermaid Diagram:

  sequenceDiagram
      participant Donor
      participant DrawLine
      participant RamanSensor
      participant Controller
      participant CollectionContainer
  
      Donor->>DrawLine: Whole Blood
      loop Real-time Monitoring
          RamanSensor->>DrawLine: Emits Laser
          DrawLine-->>RamanSensor: Backscattered Light
          RamanSensor->>Controller: Transmits Spectrum Data
          Controller->>Controller: Analyzes Spectrum (Hct, AC %%)
          Controller->>CollectionContainer: Reads Total Weight
          Controller->>Controller: Calculates Pure Plasma Volume
          alt Pure Plasma Volume >= Target
              Controller->>DrawLine: Stop Pumps
              break
          end
      end
  

Axis 2: Operational Parameter Expansion

Derivative 2.1: Method for Plasmapheresis in Microgravity

• Enabling Description: This method adapts the process for a microgravity environment where gravitational sedimentation is absent. It uses an axial-flow centrifugal device where fluid dynamics, not density-based settling, dominate separation. The controller's calculation of pure plasma remains critical. However, all volume and weight measurements are replaced with non-gravimetric methods. Flow rates are measured by ultrasonic transit-time flow meters. The "weight" of the collected plasma and anticoagulant sources is determined by a change-in-volume measurement using capacitance-based level sensors within rigid containers. The target pure plasma volume is adjusted based on AI-predicted fluid shifts in the astronaut's body, using inputs from bioimpedance sensors. The system is designed for minimal power draw and operates in a fully closed loop to prevent fluid escape.
• Mermaid Diagram:

  graph TD
      subgraph Closed Loop System
          A(Astronaut) <--> B(Venous Access);
          B --> C{Axial-Flow Centrifuge};
          D(Anticoagulant) --> E(AC Pump);
          E --> B;
          C -- Plasma+AC --> F[Plasma Container];
          C -- RBCs --> G[RBC Container];
          G --> B;
      end
      subgraph Controller Unit
          H(Controller) -- Controls --> C & E;
          I(Ultrasonic Flow Meter) -- Measures Flow --> H;
          J(Capacitance Sensor) -- Measures Volume in F --> H;
          K(Bioimpedance Sensor on A) -- Measures Fluid Shift --> H;
          H -- Calculates --> L(Pure Plasma Volume);
      end
  

Axis 3: Cross-Domain Application

Derivative 3.1 (Aerospace): Real-Time Hydrazine Fuel Purification

• Enabling Description: A method for purifying monopropellant hydrazine fuel during long-duration space missions. The system draws fuel from a main tank, introduces a proprietary scavenging agent to bind with contaminants (e.g., aniline, water), and passes the mixture through a membrane separator. A controller calculates the volume of pure hydrazine collected in a purified tank. It does this by measuring the total volume transferred and subtracting the volume of the scavenging agent and the calculated volume of separated contaminants. Contaminant volume is calculated based on readings from an inline optical density sensor, which correlates turbidity to contaminant concentration. The process stops when a target volume of 99.99% pure hydrazine is ready for the reaction control thrusters.
• Mermaid Diagram:

  flowchart TD
      A[Main Fuel Tank] --> B{Pump};
      C[Scavenging Agent] --> D{Dosing Pump};
      B & D --> E[Membrane Separator];
      E -- Purified Fuel --> F(Purified Tank);
      E -- Contaminants+Agent --> G(Waste Tank);
      H[Controller] -->|Control Pumps| B & D;
      I[Optical Density Sensor] -- Contaminant % --> H;
      J[Volume Sensor on F] -- Total Volume --> H;
      H -- Calculates --> K[Pure Hydrazine Volume];
  

Derivative 3.2 (AgTech): Phycocyanin Extraction from Spirulina Slurry

• Enabling Description: A method for extracting high-value phycocyanin protein from a raw spirulina algae slurry. The slurry is pumped from a bioreactor, and a flocculant is introduced to clump cellular debris. The mixture is then processed in a tangential flow filtration (TFF) system. The controller calculates the volume of pure phycocyanin concentrate collected. It uses an inline spectrophotometer (measuring absorbance at ~620nm) to determine the concentration of phycocyanin in the permeate (the collected fluid). The volume of flocculant is known from the pump rate. The controller integrates the concentration over the total collected volume to calculate the mass, and thus the equivalent volume of pure concentrate, stopping the process when a target yield is achieved.
• Mermaid Diagram:

  graph TD
      A[Spirulina Bioreactor] --> B[Slurry Pump];
      C[Flocculant] --> D[Dosing Pump];
      B & D --> E[Tangential Flow Filtration Skid];
      E -- Permeate --> F(Phycocyanin Concentrate Tank);
      E -- Retentate (Waste) --> G(Debris Tank);
      H[Controller] -- Manages --> B & D & E;
      I[Spectrophotometer] -- Measures Purity of Permeate --> H;
      J[Weight Sensor on F] -- Measures Total Volume --> H;
      H -- Calculates --> K[Pure Concentrate Yield];
  

Axis 4: Integration with Emerging Tech

Derivative 4.1 (AI/ML): Predictive Method for Dynamic Anticoagulant Dosing

• Enabling Description: An AI-enhanced method where the controller uses a machine learning model to dynamically adjust the anticoagulant (AC) to whole blood (WB) ratio in real-time. Before the procedure, the controller ingests donor data (weight, hematocrit, age, donation history). During the procedure, it monitors real-time data from pressure sensors in the draw line and the separation device. The ML model, trained on thousands of previous donations, predicts the likelihood of a flow-impeding clot or high shear stress based on these inputs. If the risk increases, the controller preemptively increases the AC:WB ratio slightly. Conversely, if the risk is low, it decreases the ratio, minimizing citrate load on the donor. The calculation of pure plasma continuously adapts to this variable AC ratio, ensuring the final target volume remains accurate.
• Mermaid Diagram:

  stateDiagram-v2
      state "Data Ingestion" as Ingest
      state "Procedure Start" as Start
      state "Real-time Monitoring & Prediction" as Monitor
      state "Dynamic Adjustment" as Adjust
      state "Calculation" as Calc
      state "End Procedure" as End
  
      [*] --> Ingest: Donor Data (Hct, Wt, Hist)
      Ingest --> Start: Initialize AC:WB Ratio
      Start --> Monitor
      Monitor --> Adjust: ML Model predicts high risk
      Adjust --> Monitor: Increase AC:WB ratio
      Monitor --> Monitor: ML Model predicts low risk
      Monitor --> Calc: Stream Sensor Data
      Calc --> Monitor: Update Pure Plasma Vol
      Monitor: If Pure Plasma Vol >= Target
      Monitor --> End
      [*] --> End: Manual Stop / Error
  

Axis 5: The "Inverse" or Failure Mode

Derivative 5.1: Fail-Safe Blood Component Return Method

• Enabling Description: A method designed for safe failure resolution. Upon detection of a non-recoverable error (e.g., centrifuge imbalance, disposable kit leak detected by pressure decay), the controller immediately enters a "Safe Return" mode. It stops the draw and AC pumps and calculates three key volumes: (1) Total RBCs in the separation device, (2) Total extracorporeal plasma, and (3) Total extracorporeal anticoagulant. Its primary objective is to return the viable RBCs. It uses the remaining anticoagulant in the source bag to prime the return line and gently re-infuse the RBCs. The controller logs the exact volume of pure plasma lost (extracorporeal plasma minus extracorporeal anticoagulant) and flags the donor's record with a temporary deferral period calculated based on this loss, ensuring regulatory compliance.
• Mermaid Diagram:

  flowchart TD
      A{Procedure Active} --> B{Error Detected!};
      B --> C[Enter Safe-Return Mode];
      C --> D[Stop Draw Pump & Centrifuge];
      C --> E{Calculate Extracorporeal Vols};
      subgraph E
          E1(RBCs in Device)
          E2(Plasma in Device/Line)
          E3(AC in Device/Line)
      end
      C --> F[Log Pure Plasma Lost];
      C --> G{Initiate RBC Return};
      H(Anticoagulant Source) --> |Prime Line| I(Return Line);
      J(RBCs from Device) --> I;
      I --> K(Donor);
      G --> L[Log RBC Volume Returned];
      L --> M[Set Temporary Donor Deferral];
  

---

Part 2: Derivative Systems for Pure Component Collection (Based on Claim 11)

Axis 1: Material & Component Substitution

Derivative 6.1: System with Piezoelectric Valveless Pumps

• Enabling Description: This system replaces traditional peristaltic pumps with piezoelectric micropumps for both blood draw and anticoagulant delivery. These pumps have no moving mechanical parts, operating via the controlled oscillation of a piezoelectric diaphragm, which significantly reduces hemolysis (red blood cell damage). They also offer extremely precise, pulsation-free flow control. The controller is configured with the precise displacement-per-voltage-cycle characteristics of the piezo pumps. It calculates the total volume of anticoagulant delivered by integrating the applied voltage waveform over time. This highly accurate volume data is used in the algorithm to calculate the pure plasma volume collected in the plasma container.
• Mermaid Diagram:

  classDiagram
      class Controller {
          +calculatePurePlasma()
          +controlPumpVoltage(pumpID, waveform)
          -targetVolume
          -donorHct
      }
      class PiezoelectricPump {
          +setVoltageWaveform(waveform)
          -displacementPerCycle
      }
      class WeightSensor {
          +readWeight()
      }
      Controller "1" -- "2" PiezoelectricPump : Controls
      Controller "1" -- "1" WeightSensor : Reads
      PiezoelectricPump : Blood Draw Pump
      PiezoelectricPump : Anticoagulant Pump
  

Axis 2: Operational Parameter Expansion

Derivative 7.1: Wearable System for Continuous Ambulatory Plasma Exchange

• Enabling Description: A miniaturized, wearable system for therapeutic plasma exchange (TPE) in ambulatory patients. The system is housed in a lightweight, body-worn pack and uses a dual-lumen subcutaneous catheter. Separation is achieved via a disposable hollow-fiber plasma filter cartridge instead of a centrifuge. The system operates at extremely low flow rates (5-10 mL/min) over many hours. The controller's function is critical: it calculates the cumulative net pure plasma removed over the entire therapeutic period, accounting for both the added anticoagulant and the periodic infusion of a replacement fluid (e.g., albumin). The controller uses data from miniature optical and pressure sensors to manage the filtration gradient and prevent filter clogging, adjusting pump speeds to maintain a target pure plasma removal rate.
• Mermaid Diagram:

  graph TD
      subgraph Wearable Pack
          A(Dual-Lumen Catheter) -- Blood --> B(Blood Pump);
          C(Anticoagulant) --> D(AC Pump);
          D --> B;
          B --> E(Hollow-Fiber Filter);
          E -- Plasma+AC --> F(Waste Bag);
          E -- RBCs --> G(Return Pump);
          H(Replacement Fluid) --> I(RF Pump);
          I & G --> A;
      end
      subgraph Controller
          J(Controller) -- Manages --> B,D,G,I;
          K(Optical Sensor on E) -- Filter Status --> J;
          L(Pressure Sensor) -- Transmembrane Pressure --> J;
          M(Weight Sensor on F) -- Waste Vol --> J;
          J -- Calculates --> N(Net Pure Plasma Removed);
      end
  

Axis 3: Cross-Domain Application

Derivative 8.1 (Consumer Electronics): Smart Reverse Osmosis Water Purifier

• Enabling Description: A home reverse osmosis (RO) system with a smart controller. The controller is configured to calculate the volume of pure, filtered water produced and stop the system when a user-defined target (e.g., 1 liter) is met. It measures the total volume of water flowing into the RO membrane using a simple impeller flow meter. A conductivity sensor measures the total dissolved solids (TDS) of both the inlet tap water and the outlet brine (waste) water. The controller uses this TDS differential to calculate the rejection rate and thus the volume of water being sent to waste. The pure water volume is calculated as: (Total Inlet Volume) - (Calculated Waste Volume). This allows the system to optimize for water efficiency and accurately track filter life based on pure water produced, not just run time.
• Mermaid Diagram:

  sequenceDiagram
      participant User
      participant Controller
      participant RO_System
      participant PureWaterTank
  
      User->>Controller: Set Target Volume (1.0 L)
      Controller->>RO_System: Start Pumps
      loop Purification Cycle
          RO_System->>Controller: Send Inlet Flow & TDS data
          RO_System->>Controller: Send Brine TDS data
          Controller->>Controller: Calculate Waste Volume
          Controller->>Controller: Calculate Pure Water Volume
          Controller->>PureWaterTank: Update Current Volume
          alt Pure Water >= Target
              Controller->>RO_System: Stop Pumps
              break
          end
      end
      Controller->>User: Notify: "Purification Complete"
  

Axis 4: Integration with Emerging Tech

Derivative 9.1 (IoT/Blockchain): Verifiable Cold Chain System for Plasma

• Enabling Description: A system where the apheresis controller is the first node in a blockchain-secured cold chain. When the target pure plasma volume is reached, the controller generates a "genesis block" for that specific plasma unit. This block contains the donor's anonymized ID, the final pure plasma volume, hematocrit, anticoagulant lot number, and a timestamp. The plasma collection container is sealed with an IoT tag containing a temperature logger and a GPS chip. As the plasma unit is transported, the IoT tag periodically writes new blocks to the chain with its temperature and location data. Any temperature excursion outside the safe range is immutably recorded. This creates a verifiable, end-to-end audit trail from collection to fractionation, ensuring supply chain integrity.
• Mermaid Diagram:

  flowchart TD
      A[Controller Calculates Pure Plasma Vol];
      A -- Vol >= Target --> B{Finalize Collection};
      B --> C[Generate Genesis Block];
      subgraph C
          D(Donor ID_anon)
          E(Pure Plasma Vol)
          F(Timestamp)
      end
      C --> G[Write to Blockchain];
      H(Plasma Bag) -- Sealed with --> I(IoT Tag);
      I -- Contains Hash of Block C --> G;
      I -- Temp/GPS Data --> J{Transport Phase};
      J -- Periodically --> K[Create & Add New Blocks];
      K --> G;
      G --> L[Immutable Ledger];
  

Axis 5: The "Inverse" or Failure Mode

Derivative 10.1: System with a "Safe Yield" Low-Power Mode

• Enabling Description: A system controller configured with a "Safe Yield" mode for operating in low-power or emergency situations (e.g., on battery backup). When activated, the controller reduces the centrifuge speed by 30% and the blood draw pump speed by 40% to conserve energy. This reduces separation efficiency. The controller's algorithm switches to a different model that accounts for this lower efficiency, resulting in a higher likelihood of red blood cell contamination in the plasma line. To compensate, an optical sensor on the plasma line is used to detect hemolysis or RBC spillover. If detected, the plasma flow is temporarily diverted to an internal waste pouch. The controller calculates the pure plasma volume collected in the primary container, subtracting both the anticoagulant volume and the diverted waste volume. The overall target volume of pure plasma is automatically reduced by 20% to ensure the procedure completes before battery depletion.
• Mermaid Diagram:

  stateDiagram-v2
      state "Normal Operation" as Normal
      state "Low-Power Mode" as LowPower
      state "Diversion Active" as Divert
  
      [*] --> Normal
      Normal --> LowPower: Power Loss Detected
      LowPower --> Normal: Main Power Restored
      LowPower: Reduce RPM & Flow Rate
      LowPower: Reduce Target Volume
      LowPower --> Divert: RBC Spillover Detected
      Divert --> LowPower: Spillover Clears
      Divert: Route Plasma to Waste Pouch
      Divert: Subtract Waste from Total
      LowPower --> [*]: Procedure Complete
      Normal --> [*]: Procedure Complete
  

---

Part 3: Combination Prior Art Scenarios

Scenario 1: Integration with the HL7 FHIR Standard

• Disclosure: The system described in Claim 11 is combined with the Health Level Seven International (HL7) Fast Healthcare Interoperability Resources (FHIR) standard. The apheresis system's controller acts as a FHIR client. Upon completion of a donation, it creates a "DiagnosticReport" FHIR resource. This resource includes the donor's identifier, the final calculated pure plasma volume, the average anticoagulant ratio used, and the initial hematocrit value. This DiagnosticReport is then securely transmitted via a RESTful API to the Blood Bank's FHIR-compliant server, enabling seamless integration with the electronic health record (EHR) and laboratory information systems (LIS) without proprietary data formats.

Scenario 2: Combination with the OpenAPS (Open Artificial Pancreas System) Framework

• Disclosure: The method of Claim 1 is combined with the control logic and communication protocols of the open-source OpenAPS project. The apheresis controller runs a modified OpenAPS algorithm. Instead of blood glucose, the primary input is real-time hematocrit (from an inline sensor). Instead of insulin, the controller modulates the anticoagulant flow rate. The system's objective is to maintain a target "anticoagulation index" in the extracorporeal circuit, minimizing clotting risk while also minimizing the total citrate delivered to the donor. The pure plasma calculation is a secondary process that determines the procedure endpoint. This combination applies a proven, open-source closed-loop control algorithm to the field of apheresis.

Scenario 3: Combination with the RISC-V Open Instruction Set Architecture

• Disclosure: The controller of the system in Claim 11 is built not on a proprietary microprocessor, but on a processor implementing the open-source RISC-V instruction set architecture (ISA). The specific software and firmware for calculating pure plasma volume, controlling the pumps, and monitoring sensors is compiled for a RISC-V core (e.g., a 32-bit RV32IMC core). This disclosure places the implementation of this specific apheresis control logic on an open, auditable, and royalty-free hardware standard into the public domain, preventing any single company from claiming a patent on the use of a specific type of processor for this task. The firmware itself could be made open-source to allow for third-party verification of the pure plasma calculation algorithm for regulatory purposes.