Fluidic devices and systems for sample preparation or autonomous analysis

Inventors

Ismagilov, Rustem F. • Shen, Feng • Li, Liang • Hsu, Yu-Hsiang • Begolo, Stefano • Karymov, Mikhail • Selck, David • McCalla, Stephanie • Homewood, Philip James

Assignees

California Institute of Technology • Talis Biomedical Corp

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Publication Number

US-9822356-B2

Patent

Publication Date

2017-11-21

Expiration Date


Abstract

The present invention relates to fluidic devices for preparing, processing, storing, preserving, and/or analyzing samples. In particular, the devices and related systems and methods allow for preparing and/or analyzing samples (e.g., biospecimen samples) by using one or more of capture regions and/or automated analysis.

Core Innovation

The invention relates to a multilayer sample preparation device for receiving a sample and performing washing and eluting using a fluidic arrangement with a first layer, a second layer, and an intermediate layer. The first layer includes a plurality of first chambers, including a sample chamber, a washing chamber comprising a washing buffer, and an eluting chamber comprising an elution buffer. The second layer includes one or more second chambers disposed with the first layer, enabling sample handling across multiple chambers.

An intermediate layer is disposed between the first and second layers, and the intermediate layer comprises a membrane matrix. The membrane matrix is used as part of the connection between chamber regions and intermediate matrix regions. The device is configured so that at least one of the plurality of first chambers, at least one of the one or more second chambers, and the membrane matrix are able to be connected by relative movement, indicating controlled engagement and disengagement among these components.

The disclosed multilayer architecture is associated with sample processing and preservation, including rapid drying using desiccant and reversible vapor contact via bridges or membranes, together with sample partitioning and selective rehydration and recovery. The described systems and methods support sample processing for nucleic acids and proteins, including filtering, lysis, binding, washing, and elution, with downstream analysis such as gel electrophoresis and qPCR/digital RT-LAMP. The overall arrangement is presented as minimizing contamination and enabling multiple reactions across stacked layers with intermediate capture regions.

Claims Coverage

The document provides one independent claim defining a multilayer sample preparation device with a membrane matrix intermediate layer and relative movement among the sample, wash/elute chambers, and membrane matrix. Inventive features across the independent claim focus on the layered chamber architecture and the ability to connect components by relative movement.

Multilayer sample preparation with membrane-matrix intermediate layer

A sample preparation device comprising a first layer having a plurality of first chambers including a sample chamber, a washing chamber with a washing buffer, and an eluting chamber with an elution buffer; a second layer having one or more second chambers; and an intermediate layer disposed between the first and second layers, where the intermediate layer comprises a membrane matrix.

Component connectivity by relative movement

At least one of the plurality of first chambers, at least one of the one or more second chambers, and the membrane matrix are able to be connected by relative movement.

Independent claim 1 is directed to a layered sample preparation device that integrates a membrane-matrix intermediate layer between a first layer (sample, washing, eluting chambers) and a second layer (one or more chambers), where the membrane matrix and chamber regions can be connected by relative movement.

Stated Advantages

Minimizing contamination.

Autonomous operation/pumping and slipping for sample preparation and preservation.

Enabling preservation through rapid drying and reversible vapor contact.

Supporting quantified volume control using cavity volume V1 and open system volume V0.

Enabling concentration via controlled evaporation, including complete drying or partial drying with selective recovery.

Providing recovery and analysis data for nucleic acids, including HIV RNA recovery efficiency and storage stability.

Enables liquid or dry sample preservation at room temperature, including dry-chip configurations compatible with stabilization matrices and membrane-matrix integration.

Supports sample recovery/rehydration and downstream sample preparation workflows using membrane-matrix capture and filtration/capture regions.

Provides compatibility with nucleic acid analysis workflows including qPCR and digital RT-LAMP.

Supports sample concentration by evaporation.

Documented Applications

Gel electrophoresis comparing RNA recovered from SlipChip devices.

qPCR and digital RT-LAMP data for HIV RNA recovery efficiency and storage stability.

Whole blood volume quantification calibration using volume ratio calibration.

Preservation of RNA using RNAstable® with compatibility for downstream nucleic acid analysis.

Nucleic acid extraction using integrated membranes including systems described as ChargeSwitch® and QIAamp-like filters.

Downstream nucleic acid amplification workflows including qPCR and digital RT-LAMP.

Sample preparation workflows including plasma separation and WBC enrichment described as using plasma separation membrane and related capture/enrichment materials.

Sample treatment including filtration/capture using membrane matrix regions and recovery/rehydration in dry and liquid states.

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