Qiagen Sciences, LLC

Intelligent Bio-systems, Inc.

Qiagen Waltham, Inc.

Phillip Alan Veatch

Steven Jeffrey Gordon

David Ray Stoops

Jerzy Olejnik

The invention provides methods and compositions, including, without limitation, algorithms, computer readable media, computer programs, apparatus, and systems for determining the identity of nucleic acids in nucleotide sequences using, for example, data obtained from sequencing by synthesis methods. The methods of the invention include correcting one or more phenomena that are encountered during nucleotide sequencing, such as using sequencing by synthesis methods. These phenomena include, without limitation, sequence lead, sequence lag, spectral crosstalk, and noise resulting from variations in illumination and/or filter responses.

Sample preparation

A DNA flow cell processing method including positioning the flow cell on a stage at a predetermined location relative to a camera, illuminating the flow cell from a side with a first light source to reflect light off the DNA fragment bead locations, obtaining a first image of the flow cell and identifying a first reference pattern of bead locations in the first image, moving at least one of the flow cell and the stage relative to the camera, attempting to reposition the stage at the predetermined location, obtaining a second image of the flow cell, identifying the first reference pattern in the second image, and evaluating a first offset, relative to the camera, between the first reference pattern in the first image and the first reference pattern in the second image.

Flow cell alignment methods and systems

Methods and compositions for base calling nucleic acids

Imagers and alignment methods for use by imagers imaging deoxyribonucleic acid (DNA) fragments on a flow cell are disclosed. The imagers capture intensity values at DNA fragment bead locations in tiles with each tile having a reference location in the flow cell. Flow cells may be aligned by obtaining a dark field image of each tile during a first imaging session, identifying dark field constellations of bead locations within two separate tiles during the first imaging session, identifying corresponding constellations during a second imaging session, altering the reference location of at least one tile during the second imaging session to correct for a linear offset in the corresponding constellations, and applying at least one correction factor for reading out intensity values from the imager for the bead locations in the flow cell to correct for an angular offset determined from offsets in the corresponding constellations.

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Arlington, MA, United States of America

Phillip Alan Veatch