Microfluidic selection of library elements

Patent metadata

Field	Value
Publication number	US-9879360-B2
Application number	US-14327208-A
Country	US
Kind code	B2
Filing date	Jun 20, 2008
Priority date	Jun 20, 2008
Publication date	Jan 30, 2018
Grant date	Jan 30, 2018

Abstract

Disclosed herein is a microfluidic device comprising a chip; a flow channel being disposed in the chip; the flow channel being in communication with an entry port and an exit port; the flow channel being operative to permit the flow of a library from the entry port to the exit port; a substrate; the substrate being disposed upon the chip; the substrate being operative to act as an upper wall for the flow channels; and a plurality of receptors; the plurality of receptors being disposed on the substrate; the plurality of receptors being operative to interact with an element from the library.

First claim

What is claimed is:

1. A non-electrophoretic microfluidic device comprising:
a chip;
an entry port, an exit port and a plurality of microfluidic flow channels disposed in said chip, said entry port being in communication with a loading pad also disposed in said chip;
said loading pad being in fluid communication with said entry port;
said plurality of microfluidic flow channels forming a linear path being in fluid communication with said entry port and said exit port, said plurality of microfluidic flow channels operative to permit the flow of a library selected from the group consisting of bacteriophages and viruses from said entry port to said exit port, and said microfluidic flow channels being in communication with one another at a junction;
said microfluidic flow channels being closed systems and said fluid flow within being laminar;
said exit port, disposed in said chip, has an opening on a face of said chip that is opposed to a face upon which said flow channels are disposed;
said exit port also has a lip disposed thereon in fluid communication with a pump;
said pump, in the absence of an electric field, is positioned in said microfluidic device and is adapted to transport a solution via said loading pad through said entry port into said flow channel and out said exit port at said lip;
a metal layer, disposed, in contact with said chip, said metal layer said loading pad, said entry port, said flow channel and said exit port, all contact said library;
a passivation layer disposed upon said metal layer;
said plurality of flow channels in said microfluidic network comprising a first flow channel, a second flow channel and a third flow channel respectively, each of said respective flow channels being controlled by valves;
said second flow channel and said third flow channel being in fluid communication with and located downstream of said first flow channel;
said second flow channel and said third flow channel being branches of said first flow channel, said branches being formed at a first junction;
said flow through said first flow channel, said second flow channel and said third flow channel being controlled by a first valve, a second valve and a third valve respectively, said valves disposed either on or off said chip;
an elastomeric substrate disposed on said chip to prevent leakage, said substrate operative to act as an upper wall for said plurality of flow channels, and being operative to seal said flow channel, said entry port and said exit port;
a first receptor and a second receptor disposed on said substrate that are also disposed on said chip;
said first receptor is disposed on said first flow channel, and said second receptor is disposed on said second flow channel;
said first receptor forming an element-receptor complex after exposure to a first solution to binding elements in said library, said first junction being the source of all non-binding elements on said library solution that is diverted to said third flow channel, said non-binding elements not interacting with said second receptor;
said first receptor and said second receptor being selected from the group consisting of an enzyme, a peptide, a protein, an inorganic particle, a cell, a glycan, a viral particle, an antibody, an antigen or a combination comprising at least one of the foregoing receptors any of which can have a ligand-receptor type of interaction with proteins or peptides displayed by bacteriophages;
said bacteriophages adapted to bind said first and second receptors in a flow channel;
wherein said first junction is configured to direct non-binding elements of said library with respect to said first receptor to said third flow channel, and to direct eluted elements bound to said first receptor to said second flow channel, thereby facilitating what results in a mode of screening that determines library elements that bind to both said first receptors and said second receptors.

2. The microfluidic device of claim 1 , wherein the receptors comprise an enzyme, a peptide, a protein, an inorganic particle, a cell, a glycan, a viral particle, a polymer, an antibody, an antigen, or a combination comprising at least one of the foregoing receptors.

3. A non-electrophoretic microfluidic device comprising:
a chip;
an entry port, an exit port and five microfluidic flow channels disposed in said chip, said entry port being in communication with a loading pad also disposed in said chip;
said microfluidic five flow channels operative to permit the flow of a library selected from the group consisting of bacteriophages and viruses from said entry port to said exit port,
said microfluidic five flow channels being in serial communication at a junction;
said five microfluidic flow channels being closed systems and said fluid flow within being laminar;
said five microfluidic flow channels being in fluid communication with said entry port and said exit port, said five flow channels operative to permit the flow of said library from said entry port to said exit port;
said exit port disposed in said chip, creates an opening on a face of said chip that is opposed to a face upon which said five flow channels are disposed;
said exit port also having a lip disposed thereon in fluid communication with a pump;
said pump, positioned in said microfluidic device, in the absence of an electric field, is adapted to transport a solution via said loading pad through said entry port into said five flow channels and out saw exit port at said up;

a metal layer contacting structures disposed in said chip, said disposed structures being in contact with said library, said disposed structures consisting of said metal layer, said loading pad, said entry port, said flow channel and said exit port;
a passivation layer disposed upon said metal layer;
said five flow channels comprising a first flow channel, a second flow channel, a third flow channel, a fourth flow channel and a fifth flow channel respectively;
said five flow channels being in fluid communication with said entry port and said exit port, said plurality of flow channels operative to permit the flow of said library from said entry port to said exit port;
said first flow channel, said third flow channel and said fourth flow channel being in fluid communication with one another being joined at a first junction;
said second flow channel, said third flow channel, said fourth flow channel and said fifth flow channel are each downstream of said first flow channel;
said second flow channel, said third flow channel and said fifth flow channel are in fluid communication with one another and meet at a second junction;
an elastomeric substrate disposed upon said chip to prevent leakage, said substrate being operative to act as an upper wall for said plurality of flow channels, and being operative to seal said flow channel, said entry port and said exit port;
a first receptor and a second receptor are each disposed on said chip and are patterned at their respective surfaces;
said first receptor is disposed on said first flow channel, and said second receptor is disposed on said fifth flow channel;
said first receptor and said second receptor being selected from the group consisting of an enzyme, a peptide, a protein, an inorganic particle, a cell, a glycan, a viral particle, an antibody, an antigen or a combination comprising at least one of the foregoing receptors any of which can have a ligand-receptor type of interaction with proteins or peptides displayed by bacteriophages;
said bacteriophages adapted to bind said first and said second receptors in a flow channel;
said second flow channel, said third flow channel and said fourth flow channel are devoid of receptors;
said microfluidic device forming a first element-receptor complex resulting from a first fraction of library elements from said first flow channel

Assignees

• Delamarche Emmanuel
• Lovchik Robert
• Solis Daniel J
• IBM

Inventors

• Delamarche Emmanuel
• Lovchik Robert
• Solis Daniel J

Classifications

• C40B60/12

  for screening libraries · CPC title

• B01L2300/087

  Multiple sequential chambers · CPC title

• C40B30/04 Primary

  by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding · CPC title

• G01N33/54366

  Apparatus specially adapted for solid-phase testing · CPC title

• B01L2300/0864

  comprising only one inlet and multiple receiving wells, e.g. for separation, splitting · CPC title