Battelle Memorial Institute

Other

Brigham Young University

Ryan T Kelly

Richard Dale Smith

Keqi Tang

Jason S Page

Ying Zhu

Adam T Woolley

Melissa Draper Fisk

Kristin E Burnum-Johnson

Ronald J Moore

Xuefei Sun

Paul D Piehowski

Provided herein are methods and systems for biochemical analysis, including compositions and methods for processing and analysis of small cell populations and biological samples (e.g., a robotically controlled chip-based nanodroplet platform). In particular aspects, the methods described herein can reduce total processing volumes from conventional volumes to nanoliter volumes within a single reactor vessel (e.g., within a single droplet reactor) while minimizing losses, such as due to sample evaporation.

Nanoscale biochemical sample preparation and analysis

Provided herein are methods and systems for proteome analysis that are at least partially automated and/or performed robotically. In some aspects, the methods and systems described herein can rapidly and efficiently provide protein identification of each of the proteins from a proteome, or a complement of proteins, obtained from extremely small amounts of biological samples. The identified proteins can be imaged quantitatively over a spatial region. Automation and robotics facilitates the throughput of the methods and systems, which enables protein imaging and/or rapid proteome analysis.

Methods and systems of proteome analysis and imaging

Microchip capillary electrophoresis (CE) utilizing a sample injector based on a mechanical valve rather than electrokinetic injection can provide improved sample injections, enhanced capabilities, and can eliminate the need for changing the electric field in the separation channel to induce sample injection. In one instance CE electrodes continuously apply an electric field for CE separation along a separation channel. A sample channel is connected to the separation channel at an intersection and has a sample pressure that is greater than that which is present in the separation channel near the intersection. The sample channel does not have electrodes that apply voltages for electrokinetic injection. A sample injector in the sample channel or at the intersection comprises a mechanical valve to control sample injection from the sample channel to the separation channel.

Microchip capillary electrophoresis absent electrokinetic injection

Systems and methods that provide up to complete transmission of ions between coupled stages with low effective ion losses. An 'interfaceless' electrospray ionization system is further described that operates an electrospray at a reduced pressure such that standard electrospray sample solutions can be directly sprayed into an electrodynamic ion funnel which provides ion focusing and transmission of ions into a mass analyzer. Furthermore, chambers maintained at different pressures can allow for more optimal operating conditions for an electrospray emitter and an ion guide.

Low pressure electrospray ionization system and process for effective transmission of ions

A microchip with capillaries and method for making same is described. A sacrificial material fills microchannels formed in a polymeric substrate, the filled microchannels are covered by a top cover to form filed capillaries, and the sacrificial material is removed to form the microcapillaries. The sacrificial material fills the microchannels as a liquid whereupon it becomes solid in the microchannels, and is liquefied after the top cover is applied and affixed to remove the sacrificial material. The top cover may be solvent sealed on the substrate and of the same or different material as the substrate. The top cover may also be an in situ applied semipermeable membrane.

Phase-changing sacrificial materials for manufacture of high-performance polymeric capillary microchips

A transfer structure for droplet-based microfluidic analysis is characterized by a first conduit containing a first stream having at least one immiscible droplet of aqueous material and a second conduit containing a second stream comprising an aqueous fluid. The interface between the first conduit and the second conduit can define a plurality of apertures, wherein the apertures are sized to prevent exchange of the first and second streams between conduits while allowing lossless transfer of droplets from the first conduit to the second conduit through contact between the first and second streams.

Lossless droplet transfer of droplet-based microfluidic analysis

Electrospray ionization emitter arrays, as well as methods for forming electrosprays, are described. The arrays are characterized by a radial configuration of three or more nano-electrospray ionization emitters without an extractor electrode. The methods are characterized by distributing fluid flow of the liquid sample among three or more nano-electrospray ionization emitters, forming an electrospray at outlets of the emitters without utilizing an extractor electrode, and directing the electrosprays into an entrance to a mass spectrometry device. Each of the nano-electrospray ionization emitters can have a discrete channel for fluid flow. The nano-electrospray ionization emitters are circularly arranged such that each is shielded substantially equally from an electrospray-inducing electric field.

Radial arrays of nano-electrospray ionization emitters and methods of forming electrosprays

A system and method are disclosed that provide up to complete transmission of ions between coupled stages with low effective ion losses. A novel 'interfaceless' electrospray ionization system is further described that operates the electrospray at a reduced pressure such that standard electrospray sample solutions can be directly sprayed into an electrodynamic ion funnel which provides ion focusing and transmission of ions into a mass analyzer.

Methods of forming electrospray ionization emitter tips are disclosed herein. In one embodiment, an end portion of a capillary tube can be immersed into an etchant, wherein the etchant forms a concave meniscus on the outer surface of the capillary. Variable etching rates in the meniscus can cause an external taper to form. While etching the outer surface of the capillary wall, a fluid can be flowed through the interior of the capillary tube. Etching continues until the immersed portion of the capillary tube is completely etched away.

Growing community of inventors

West Richland, WA, United States of America

Ryan T Kelly