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Publication Number
US-9951375-B2
Publication Date
2018-04-24
Expiration Date
Abstract
Methods, devices and systems for handling sample liquids, encapsulating liquids and magnetic particles are disclosed.
Core Innovation
The invention describes continuous-flow capillary/conduit biomolecule isolation in which a sample liquid containing magnetic particles is handled together with an encapsulating liquid that is immiscible with the sample liquid. The sample liquid is surrounded by the encapsulating liquid and is located at a predetermined trapping site within the conduit while magnetic particles are immobilized at the trapping site by applying a magnetic field at the trapping site. The conduit is heated at the trapping site to heat the immobilized magnetic particles.
After heating, an elution liquid is flowed in the conduit so that the elution liquid is surrounded by the encapsulating liquid, the sample liquid is flowed away from the trapping site, and the elution liquid is flowed to the trapping site and surrounds the immobilized magnetic particles. The immobilized magnetic particles thereby remain at the trapping site while the sample liquid is displaced by the elution liquid, enabling handling of target biomolecules associated with the magnetic particles.
The documented implementations further describe handling multiple immiscible sample liquids by flowing a first sample liquid to a trapping site, immobilizing magnetic particles, heating the immobilized particles, flowing the first sample liquid away while the particles remain immobilized, and then flowing a second immiscible sample liquid so it surrounds the immobilized magnetic particles. Additional described sequences include heating the trapping site, optional freeing of target biomolecules by surrounding the magnetic particles with an elution liquid, and optionally mobilizing the magnetic particles by deactivating the magnetic field to enable cleaning and decontamination of the conduit for reuse.
Claims Coverage
The patent includes three independent claims. Across these claims, the inventive coverage centers on immiscible encapsulating/sample flow in a conduit with a predetermined trapping site, magnetic-field immobilization of magnetic particles at the trapping site, thermal processing at the trapping site, and elution using an elution liquid that surrounds the immobilized magnetic particles.
Immiscible encapsulation flow with trapping-site magnetic immobilization and elution
Flowing an encapsulating liquid in a conduit; flowing a sample liquid so it is surrounded by the encapsulating liquid and located at a predetermined trapping site within the conduit; immobilizing magnetic particles at the trapping site by applying a magnetic field at the trapping site; heating the conduit at the trapping site to heat the immobilized magnetic particles; and flowing an elution liquid so it is surrounded by the encapsulating liquid, causes the sample liquid to be flowed away from the trapping site, and is flowed to the trapping site and surrounds the immobilized magnetic particles.
Trapping-site heating with sequential immiscible sample-liquid handling and re-encapsulation around immobilized particles
Flowing an encapsulating liquid in a conduit; flowing a first sample liquid so it is surrounded by the encapsulating liquid and located at a predetermined trapping site within the conduit; immobilizing magnetic particles at the trapping site by applying a magnetic field at the trapping site; heating the conduit at the trapping site to heat the immobilized magnetic particles; flowing the first sample liquid away from the trapping site while the magnetic particles remain immobilized; and flowing a second sample liquid so it is surrounded by the encapsulating liquid and surrounds the immobilized magnetic particles.
Controller-driven conduit system with trapping site, selective magnetic activation, heating, and encapsulated elution
Providing a liquid handling system comprising a conduit having a predetermined trapping site; a pump configured to apply positive pressure, negative pressure, or no external pressure; a magnetic field source configured to apply a magnetic field at the trapping site when activated and substantially no magnetic field when not activated; a heating element configured to apply heat to the conduit at the trapping site; and a controller operably attached to the pump and the magnetic field source, programmed to activate the pump to flow an encapsulating liquid, activate the pump to flow a sample liquid containing magnetic particles so the sample liquid is surrounded by the encapsulating liquid and located at the trapping site, activate the magnetic field source to immobilize the magnetic particles at the trapping site, activate the heating element to heat the immobilized magnetic particles, and activate the pump to flow an elution liquid so the elution liquid is surrounded by the encapsulating liquid, flows the sample liquid away from the trapping site, and is flowed to the trapping site and surrounds the magnetic particles.
Overall, the independent claims collectively cover a method and corresponding system for handling immiscible encapsulating/sample liquids in a conduit with a predetermined trapping site, immobilizing magnetic particles using a selectively activated magnetic field, heating at the trapping site, and performing elution by flowing an elution liquid that surrounds the immobilized magnetic particles.
Stated Advantages
Not explicitly described in patent.
Documented Applications
NGS library cleanup.
Size selection.
Nucleic acid purification.
Protein/cell enrichment.
Synthetic nucleic acid assembly.
Viral RNA VLP detection.
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