Device and method for extracting target objects from a sample

Inventors

Molho, Joshua I. • Stearns, Daniel G. • Chen, I-Jane • Tran, Danh • Rice, Bradley W. • Wheeler, Tobias Daniel • Dukhovny, Alexander V.

Assignees

Caliper Life Sciences Inc

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Publication Number

US-9297784-B2

Patent

Publication Date

2016-03-29

Expiration Date


Abstract

The invention provides devices, systems, and methods for extracting target objects from a sample. In the method, a stream of sample containing a plurality of target and non-target objects is directed by first and second streams of buffer through a sample inlet channel into a fluid junction and through the fluid junction into a sample waste channel. In response to detecting a target object within the stream of sample, an actuator is energized to close a normally open valve, resulting in a transient burst of cross-flow into the fluid junction that briefly diverts the flow of sample within the fluid junction and results in an aliquot of sample being directed into an aliquot delivery channel. The combination of the valve and the actuator acts as a self-limiting pulse generator.

Core Innovation

The invention relates to a microfluidic device for extracting target objects from a sample. An aliquotting segment includes a sample inlet channel, a first buffer inlet channel, a sample waste channel, and an aliquot delivery channel fluidly coupled at a fluid junction, together with a second buffer inlet channel and a normally open valve operably coupled to the second buffer inlet channel.

The normally open valve and the fluid junction are used to create aliquotting functionality in the microfluidic device. A trapping segment is provided in fluid communication with the aliquotting segment, including a trapping chamber, a plurality of trapping structures disposed in the trapping chamber, a collection channel, and a waste channel in fluid communication with the trapping chamber. This arrangement supports extraction by capturing target objects in the trapping chamber and routing collected material via the collection channel and waste via the waste channel.

In embodiments, the trapping chamber includes an external wall having a material penetrable by an externally generated electric field extending into the chamber, and the external wall can be anisotropically conducting. Trapping structures can be hydrophobic, and the trapping chamber can include a passage enabling trapped objects to be manipulated through the passage.

The normally open valve can be defined by a valve structure spanning the width of the second buffer inlet channel, with deformable material covering the channel except at the valve structure area so fluid can flow over the valve structure. The invention further relates to optically transparent trapping-chamber wall materials and electrode positioning constraints using an external electrode not bonded to the device, with an electric field extending into the chamber for manipulating trapped objects.

Claims Coverage

The independent claim defines one microfluidic device architecture for extracting target objects using an aliquotting segment coupled at a fluid junction to a trapping segment, with inventive focus on a normally open valve coupled to a second buffer inlet and a trapping chamber with a plurality of trapping structures plus collection and waste channels. Dependent claims refine the trapping chamber wall properties for external-field penetration, trapping-structure material properties, an optional manipulation passage, and a specific normally-open valve structural implementation.

Junction-coupled aliquotting segment with normally open valve and trapping segment

A microfluidic device having an aliquotting segment with a sample inlet channel, a first buffer inlet channel, a sample waste channel, and an aliquot delivery channel fluidly coupled at a fluid junction, the aliquotting segment further including a second buffer inlet channel and a normally open valve operably coupled to the second buffer inlet channel, and a trapping segment in fluid communication with the aliquotting segment, the trapping segment comprising a trapping chamber with a plurality of trapping structures, a collection channel, and a waste channel in fluid communication with the trapping chamber.

Penetrable external wall for externally generated electric field

A trapping chamber comprising an external wall made of a material penetrable by an externally generated electric field that extends into the chamber.

Anisotropically conducting trapping-chamber external wall

The trapping chamber includes an external wall formed of an anisotropically conducting material.

Normally open valve spanning width with deformable coverage except at valve structure

The normally open valve is a valve structure spanning the width of a second buffer inlet channel, with deformable material covering the second buffer inlet channel except at the valve structure area so fluid can flow over the valve structure.

Hydrophobic trapping structures

Trapping structures are made from a hydrophobic material.

Passage enabling manipulation of trapped objects

A passage in the trapping chamber allows trapped objects to be manipulated through the passage.

Across the independent claim and key dependent refinements, the inventive coverage centers on a microfluidic device architecture that couples a junction-based aliquotting segment to a trapping segment having a trapping chamber with a plurality of trapping structures and collection/waste channels. Further refinements specify an electric-field-penetrable and optionally anisotropically conducting trapping-chamber wall, hydrophobic trapping structures, and a passage for manipulating trapped objects, together with a normally open valve structure spanning the second buffer inlet width.

Stated Advantages

Documented Applications

No documented applications found

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