Flow cell based motion system calibration and control methods

Patent metadata

Field	Value
Publication number	US-2024100518-A1
Application number	US-202318474589-A
Country	US
Kind code	A1
Filing date	Sep 26, 2023
Priority date	Sep 26, 2022
Publication date	Mar 28, 2024
Grant date	—

Abstract

The presently described techniques relate generally to providing motion feedback (e.g., motion system calibration and/or sample alignment) in the context of an imaging system (such as a time delay and integration (TDI) based imaging system). The architecture and techniques discussed may achieve nanoscale control and calibration of a movement feedback system without a high-resolution encoder subsystem or, in the alternative embodiments, with a lower resolution (and correspondingly less expensive) encoder subsystem than might otherwise be employed. By way of example, certain embodiments described herein relate to ascertaining or calibrating linear motion of a sample holder surface using nanoscale features (e.g., sample sites or nanowells or lithographically patterned features) provided on a surface of the sample holder.

First claim

1 . A patterned flow cell, comprising:
a substrate; a plurality of sample sites in a non-fiducial region of the substrate, wherein the plurality of sample sites is arranged in a periodic pattern; and a plurality of sample site-based fiducials formed on the substrate in a scanning direction, wherein the sample site-based fiducials comprise an arrangement of sample sites and blank regions formed linearly in a first dimension associated with a scan direction of the patterned flow cell.

2 . The patterned flow cell of claim 1 , wherein the periodic pattern comprises a hexagonal or a rectilinear pattern.

3 . The patterned flow cell of claim 1 , wherein the blank regions correspond to locations in the periodic pattern where a sample site should be located but is not or where empty sample sites are located.

4 . The patterned flow cell of claim 1 , wherein a plot of brightness versus position along the scan direction for the sample site-based fiducials corresponds to a sinusoidal waveform.

5 . The patterned flow cell of claim 1 , wherein the sample site-based fiducials comprise, within a column of pixels, a plurality of alternating sample sites and blank regions.

6 . The patterned flow cell of claim 5 , wherein the sample site-based fiducials comprise pairs of sample sites and one or more blank regions disposed between the pair of sample sites within the column.

7 . The patterned flow cell of claim 1 , wherein the sample site-based fiducials comprise, within a column of pixels, a pattern of sample sites having a first value of a geometric parameter, sample sites having a second value of the geometric parameter, and one or more blank regions.

8 . The patterned flow cell of claim 7 , wherein the geometric parameter comprises one or both of diameter or depth.

9 . The patterned flow cell of claim 7 , wherein the sample site-based fiducials comprise a first pair of sample sites having a first diameter, a second pair of sample sites having a second diameter less than the first diameter and positioned between the first pair of sample sites within the column, and the one or more blank region positioned between the second pair of sample sites within the column.

10 . The patterned flow cell of claim 1 , wherein the sample site-based fiducials comprise a multi-column fiducial, wherein each column of the multi-column fiducial comprises a pattern of sample sites having a first value of a geometric parameter, sample sites having a second value of the geometric parameter, and one or more blank regions.

11 . The patterned flow cell of claim 10 , wherein each column of the multi-column fiducial comprises a first pair of sample sites having a first diameter, a second pair of sample sites having a second diameter less than the first diameter and positioned between the first pair of sample sites within the respective column, and the one or more blank region positioned between the second pair of sample sites within the respective column.

12 . A patterned flow cell, comprising:
a substrate; a plurality of sample sites in a non-fiducial region of the substrate, wherein the plurality of sample sites is arranged in a periodic pattern; and a plurality of fiducials provided on the substrate in a first dimension associated with a scan direction of the patterned flow cell, wherein each fiducial comprises a plurality of features that are separated by one or more blank regions, wherein each feature is contiguous across one or more columns of the periodic pattern.

13 . The patterned flow cell of claim 12 , wherein each feature comprises a reflective feature formed on or in the patterned flow cell.

14 . The patterned flow cell of claim 12 , where each feature comprises a fluorescent feature formed on or in the patterned flow cell.

15 . The patterned flow cell of claim 14 , wherein each feature fluoresces at different wavelengths than the sample sites.

16 . The patterned flow cell of claim 12 , wherein each fiducial comprises a pair of bar-shaped features each formed lengthwise in a second dimension perpendicular to the first dimension and corresponding to a cross-sample direction perpendicular to the scanning direction associated with the patterned flow cell.

17 . The patterned flow cell of claim 16 , wherein a respective blank region is present between each pair of bar-shaped features of each respective fiducial.

18 . A sequencing instrument, comprising:
a sample stage configured to support a flow cell; an objective lens, a photodetector, and a light source configured to operate in combination to image the flow cell when present on the sample stage; and a controller configured to perform operations comprising:
advancing the flow cell when undergoing an imaging operation along a linear scan path;
imaging a patterned surface of the sample container as it is advanced along the linear scan path, wherein the patterned surface comprises:
a plurality of sample sites arranged in a periodic pattern, wherein a subset of the sample sites are sample site-based fiducials comprising an arrangement of sample sites and blank regions formed linearly in a first dimension associated with a scan direction of the patterned flow cell;

determining a current feature pattern of the flow cell based on the sample-site based fiducials;
comparing the current feature pattern with an expected feature pattern; and
adjusting one or both of a location of the sample stage or a speed at which the sample stage is moved based upon the comparison of the current feature pattern with the expected feature pattern.

19 . The sequencing instrument of claim 18 , wherein comparing the current feature pattern with the expected feature pattern comprises evaluating a sinusoidal waveform derived from the sample site-based fiducials.

20 . The sequencing instrument of claim 18 , wherein the controller is further configured to perform operations comprising:
determining at least a rate of motion of the flow cell in the scan direction based on a sinusoidal signal derived based on the sample site-based fiducials.

Assignees

• Illumina Inc

Inventors

• Hage Matthew
• Earney John
• Holst Gregory
• Majette Mark

Classifications

• B01L3/502715 Primary

  characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces · CPC title

• B01L2300/0654

  Lenses; Optical fibres · CPC title

• B01L2300/0893

  having a very large number of wells, microfabricated wells · CPC title

• B01L2300/0896

  Nanoscaled · CPC title

• B01L9/527

  for microfluidic devices, e.g. used for lab-on-a-chip · CPC title