Methods and systems for sample extraction

Inventors

Delubac, Daniel

Assignees

Freenome Holdings Inc

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Publication Number

US-11781959-B2

Patent

Publication Date

2023-10-10

Expiration Date


Abstract

The present disclosure provides methods and devices for sample extraction.

Core Innovation

The disclosure describes automated sample extraction using a sample extraction device that includes a pipette with an opening in fluid communication with a reservoir through at least one channel, and at least one sensor in communication with the at least one channel or the reservoir. The sensor outputs one or more signals indicative of viscosity in the at least one channel or the reservoir, while a pressure drop is applied to subject a sample to flow from a container through the pipette opening to the reservoir.

A plurality of samples in the container includes a first sample and a second sample having different viscosities. The method detects a change in viscosity in the at least one channel or the reservoir, where the change is indicative of the second sample flowing from the container through the pipette opening toward the reservoir, and upon detecting the viscosity change terminates the application of the pressure drop to reduce the flow rate of the second sample.

The disclosure further describes automated, robotic, and array-based implementations where the sample extraction device is computer controlled and does not rely on visual inspection or chemical, biochemical, or molecular assays. It can terminate aspiration at blood fraction interfaces by using observed flow-rate and viscosity changes to retain target fractions such as plasma and buffy coat, and barcode/RFID tracking and individually addressable pipettes are also described for handling and operation of multiple extraction devices.

Claims Coverage

The independent claim is directed to viscosity-signal-driven stopping of pressure-drop-driven sample extraction using a pipette-reservoir channel and at least one viscosity sensor. The independent claim contains five core inventive features: device activation with viscosity sensing, directing the pipette into a container holding first and second different-viscosity samples, applying a pressure drop to flow the first sample while monitoring viscosity, detecting viscosity change indicative of second-sample arrival, and terminating the pressure drop to reduce the second-sample flow rate.

Viscosity-sensing pipette with reservoir channel

Activating a sample extraction device having a pipette comprising an opening in fluid communication with a reservoir through at least one channel, and at least one sensor outputting one or more signals indicative of a viscosity in the at least one channel or said reservoir.

Pressure-drop driven flow of different-viscosity samples

Directing the pipette into a container comprising a first sample and a second sample having different viscosities, and subjecting the first sample to flow from the container through the opening of the pipette to the reservoir upon application of a pressure drop while the at least one sensor outputs signals indicative of viscosity.

Viscosity-change detection indicative of second-sample flow

Detecting a change in the viscosity in the at least one channel or the reservoir, wherein the change is indicative of the second sample flowing from the container through the opening of the pipette towards the reservoir.

Terminating the pressure drop to reduce second-sample flow

Upon detecting the change in viscosity, terminating the application of the pressure drop, thereby reducing a flow rate of the second sample from the container through the opening of the pipette towards the reservoir.

Across the independent claim and its dependent refinements described in the provided material, the central inventive concept is to monitor viscosity using sensor signals within a pipette/reservoir channel during pressure-drop aspiration, detect a viscosity change that indicates second sample arrival, and then terminate the pressure drop to reduce or stop second-sample flow. Dependent limitations described further include operating without a density centrifugation medium and additional constraints such as pipette extraction volume limits.

Stated Advantages

Reduces a flow rate of the second sample by terminating the pressure drop upon detecting a viscosity change indicative of second-sample arrival.

Enables automated aspiration and stopping at sample interfaces, including blood fraction interfaces such as air/plasma and plasma/buffy coat, based on detected viscosity changes.

Supports automated, robotic, and array-based sample handling using computer control and individually addressable pipettes.

Avoids reliance on visual inspection and avoids chemical, biochemical, or molecular assays.

Documented Applications

Fractionation of whole blood to obtain plasma and buffy coat by stopping aspiration at interfaces based on viscosity or flow changes.

Extraction from containers holding a plurality of samples including first and second different-viscosity samples, where the second sample flow is detected by viscosity change and aspiration is terminated accordingly.

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