Obviousness

US Patent 4151844 describes a method and apparatus for separating whole blood into at least three components (red blood cells, a buffy coat of white blood cells, and plasma with platelets) using centrifugation. The core of the invention lies in the automatic monitoring of the composition or optical density of the collected component (specifically the buffy coat of white blood cells) using an optical sensing device. Based on this sensing, the apparatus automatically adjusts the rates of withdrawal of the other two components (red blood cells and plasma) in opposite directions to maintain the desired composition of the collected component and minimize contamination. One component (e.g., buffy coat) is withdrawn at a fixed rate, while the other two are withdrawn at variable rates.

The patent states that the invention "overcomes this operator monitoring requirement by providing a method and apparatus wherein the composition or optical density of the buffy coat of white blood cells being withdrawn from a centrifuge device is automatically monitored and when changes occur therein an optical sensing device is operable to cause an adjustment in the rates of withdrawal of the red blood cells and the plasma containing platelets so as to maintain a desired composition or optical density of the white blood cells being withdrawn."

Prior Art References and their Disclosures:

1. US Patent 3,986,442 (U.S. Pat. No. 3,986,442): This patent is explicitly identified as prior art in the description of US4151844. It discloses a centrifugal liquid processing apparatus for separating whole blood into components (red blood cells, buffy coat, and plasma). It teaches the use of outlets at different radii for withdrawing these components via pumps. However, US4151844 highlights a significant drawback: "The rates of withdrawal by the various pumps depend upon the concentration of these components in the blood and upon changes in the radius at which these components collect during centrifugation." It further explains that "an operator must carefully observe the blood components while they are being withdrawn" and manually adjust pump speeds, which "requires constant attention by an operator and is somewhat tedious when the processing extends up to an hour or more." Thus, US3986442 provides the foundational centrifugal separation and component withdrawal, but requires manual intervention.

2. US Patent 4,086,924 (Haemonetics Corporation): This patent, titled "Plasmapheresis apparatus," has a priority date of 1976-10-06, which predates the filing date of US4151844 (1977-11-11) and thus constitutes prior art. The abstract for US4086924 states: "An automatic control system for regulating the withdrawal of plasma from a centrifugal separation system used in plasmapheresis includes an optical detector for sensing red blood cells at the plasma withdrawal port, and a pump control system for maintaining the interface of red cells and plasma below the withdrawal port."

Obviousness Analysis under 35 U.S.C. § 103:

The independent claims of US4151844, such as Claim 1 (method) and Claim 7 (apparatus), cover the concept of automatically sensing the composition of a withdrawn blood component (e.g., buffy coat) and adjusting the withdrawal rates of other components (red blood cells and plasma) in response to this sensing to minimize contamination.

A combination of US3986442 and US4086924 would render the claims of US4151844 obvious to a person having ordinary skill in the art (PHOSITA).

Motivation for Combination:

1. Established Need for Automation: US3986442 explicitly identifies the problem of manual monitoring and adjustment during blood component separation as "tedious" and requiring "constant attention." This patent, therefore, itself provides a strong motivation for a PHOSITA to seek methods and apparatus for automating the process.
2. Known Solution for Contamination Control: US4086924 teaches an "automatic control system for regulating the withdrawal of plasma" in a centrifugal separation system. Crucially, this system "includes an optical detector for sensing red blood cells at the plasma withdrawal port, and a pump control system for maintaining the interface of red cells and plasma below the withdrawal port." This demonstrates that:
   • Optical sensing was a known technique for detecting blood components (specifically red blood cells to prevent their withdrawal with plasma).
   • Automatic pump control based on optical sensing was a known solution for maintaining component purity (preventing contamination) during centrifugal blood separation.
3. Predictable Application: Given the problem of manual monitoring described in US3986442 and the existing automatic optical sensing and pump control solutions shown in US4086924 for maintaining component purity during plasmapheresis, a PHOSITA would have been motivated to combine these teachings. The specific application in US4151844 involves sensing the buffy coat (instead of the plasma/RBC interface) and adjusting red blood cell and plasma pumps, but this is a straightforward application of known principles. The problem is a lack of automatic control to maintain a precise separation interface, and the solution from US4086924 is precisely that: automatic optical sensing coupled with pump control to maintain an interface.

Specific Obviousness Argument for Claim 1 and 7:

• Primary Reference (US3986442): Discloses the basic method and apparatus for centrifuging whole blood to separate it into three components (red blood cells, buffy coat, plasma), withdrawing each component, and recombining two for return to the donor. It also sets forth the problem of manual adjustment.
• Secondary Reference (US4086924): Teaches the use of an optical detector to sense blood components (e.g., red blood cells) at a withdrawal port during centrifugation and a pump control system that automatically adjusts pump speeds in response to the optical sensing to maintain a desired interface and prevent contamination.

A PHOSITA, facing the tedious manual adjustment problem explicitly noted in US3986442, would look for ways to automate the process. US4086924 provides a clear teaching of how to automatically monitor a blood component boundary using optical sensing and how to automatically adjust a pump (or pumps, by extension) to maintain component purity in a continuous flow centrifugal system. Extending this known automation technique to monitor the buffy coat (rather than plasma) and control the adjacent red blood cell and plasma pumps in a coordinated, inverse manner (as disclosed in US4151844) would be a logical and predictable step for a PHOSITA. The principle of using optical density to detect component boundaries and then using that information to automatically adjust pump rates to maintain separation is present in US4086924. Applying this principle to different component interfaces or to adjust multiple pumps in an inverse fashion would be an obvious design choice to solve the known problem of manual intervention.

Therefore, claims such as Claim 1 (method) and Claim 7 (apparatus) of US4151844 would be rendered obvious by a combination of the teachings of US3986442 and US4086924.