Xcella Biosciences, Inc.

Leland Stanford Junior University

Bob Chen

Jennifer R Cochran

Spencer Caleb Alford

Thomas Michael Baer

Ivan Krastev Dimov

James Robert Swartz

Arturo M Escajeda

Jennifer Lynn Lahti

Cheuk Lun Leung

Arvind Kannan

Sungwon Lim

Ming X Tan

Bertrand Howyen Lui

Lateral loading methods of use in high-throughput methods for screening large populations of variant proteins are provided. The methods utilize a flow cell encompassing large-scale arrays of microcapillaries, where each microcapillary comprises a solution containing a variant protein, an immobilized target molecule, and a reporter element. Immobilized target molecules may include any molecule of interest, including proteins, nucleic acids, carbohydrates, and other biomolecules.

Lateral loading of microcapillary arrays

Multi-stage sample-recovery systems, including automated 2-stage and 3-stage sample-recovery systems, are provided. Such systems enable the rapid screening and recovery of samples, including viable cell-based samples, from high-throughput screening systems, including systems utilizing large-scale arrays of microcapillaries. In specific screening systems, each microcapillary comprises a solution containing a variant protein, an immobilized target molecule, and a reporter element. Immobilized target molecules may include any molecule of interest, including proteins, nucleic acids, carbohydrates, and other biomolecules. The association of a variant protein with a molecular target is assessed by measuring a signal from the reporter element. The contents of microcapillaries identified in the assays as containing variant proteins of interest can be identified and recovered using the multi-stage systems disclosed herein.

Multi-stage sample recovery system

High-throughput methods for screening large populations of variant proteins are provided. The methods utilize large-scale arrays of microcapillaries, where each microcapillary comprises a solution containing a variant protein, an immobilized target molecule, and a reporter element. Immobilized target molecules may include any molecule of interest, including proteins, nucleic acids, carbohydrates, and other biomolecules. The association of a variant protein with a molecular target is assessed by measuring a signal from the reporter element. The contents of microcapillaries identified in the assays as containing variant proteins of interest can be isolated, and cells expressing the variant proteins of interest can be characterized. Also provided are systems for performing the disclosed screening methods.

Methods and systems for screening using microcapillary arrays

Microcavity arrays and methods for quantitative biochemical and biophysical analysis of populations of biological variants. Examples include high-throughput analysis of cells and protein products use a range of fluorescent assays, including binding-affinity measurement and time-resolved enzyme assays. Laser-based extraction of microcavity contents.

Micro-screening apparatus, process, and products

Compositions that are EGF polypeptides that possess improved biological activity as compared to the biological activity exhibited by wild-type EGF are provided. Also provided are methods for the preparation of these mutants, methods for the use of these mutants, methods for rationally designing new polypeptide mutants, and methods for screening mutants polypeptides to identify novel EGF mutants with desirable biological activities.

Mutant epidermal growth factor polypeptides with improved biological activity and methods of their making and use

Growing community of inventors

East Palo Alto, CA, United States of America

Bob Chen