Agilent Technologies, Inc.

Qualicon

Jay K Bass

John McEntee

Maryam Mobed-Miremadi

Tim J Lazaruk

Michael P Caren

Eric M Leproust

Roy H Kanemoto

Jacqueline M Tso

Peter G Webb

Kyle J Schleifer

Bill J Peck

Brent T Tolosko

Michelle M Maranowski

A method of fabricating an addressable array of biopolymer probes on a substrate according to a target array pattern using a deposition apparatus, and a deposition apparatus which can execute the method and computer program products for the apparatus. The deposition apparatus which, when operated according to a target drive pattern based on nominal operating parameters of the apparatus, provides the probes on the substrate in the target array pattern. The method includes examining at least one operating parameter for an error from a nominal value which error will result in use of the target drive pattern producing a discrepancy between the target array pattern and an actual array pattern deposited. When an error is detected deriving, based on the error, a corrected drive pattern different from the target drive pattern such that use of the corrected drive pattern results in a reduced discrepancy between the target and actual array patterns.

Methods of fabricating an addressable array of biopolymer probes

A method and system for economically packaging microarrays into sealed reaction chambers and storage vessels. A pocket strip is manufactured as a linear sequence of pockets, or wells, into which microarrays are positioned. A cover strip is then heat sealed to the upper surface of the pocket strip to create a linear sequence of sealed reaction chambers or storage vessels, each containing a microarray. Mechanical features or optical features are included along the length of the pocket strip to facilitate mechanical translation and positioning of microarrays embedded within the microarray strip. Septa are affixed to, or embedded within, the cover strip to provide resealable ports through which solutions can be introduced into, or extracted from, the reaction chambers. In an alternate embodiment, the microarrays are deposited directly onto the cover strip, eliminating the need for separate microarray substrates.

Automation-optimized microarray package

A method and system for economically packaging microarrays into sealed reaction chambers and storage vessels. A pocket strip is manufactured as a linear sequence of pockets, or wells, into which microarrays are positioned. A cover strip is then heat sealed to the upper surface of the pocket strip to create a linear sequence of sealed reaction chambers or storage vessels each containing a microarray. Mechanical features or optical features are included along the length of the pocket strip to facilitate mechanical translation and positioning of microarrays embedded within the microarray strip. Septa are affixed to, or embedded within, the cover strip to provide resealable ports through which solutions can be introduced into, or extracted from, the reaction chambers.

Methods, devices and apparatus are disclosed for carrying out multiple chemical reactions, such as in situ synthesis of polynucleotides, on a surface comprising an array of discrete sites. Molecules are deposited at a predetermined number of the discrete sites on the surface for reaction at the discrete sites. The surface is positioned relative to an outlet of a fluid ejection device, which is activated to dispense a small volume of a fluid through the outlet to the surface to provide uniform coating of a continuous region of the surface comprising a multiple of the discrete sites. The fluid is dispensed as uniform particles having a diameter such that the uniform particles form a sheet to coat the continuous region of the surface. In one embodiment of the present invention, liquid is dispensed as uniform particles through a fluid ejection device activated by means of ultrasonic energy. The invention has particular application to the in situ synthesis of polynucleotides in arrays on a surface.

Methods for applying small volumes of reagents

Methods are disclosed for synthesizing a plurality of compounds on the surface of supports. The synthesis comprises a series of cycles of steps in which reagents for conducting the synthesis are deposited on the surface of the support to form the chemical compounds. At least one physical parameter of the deposition varies between cycles The method comprises conducting the synthesis in at least two sets of cycles, arbitrarily designated as a first set and a second set. Each cycle comprises at least one step of depositing reagents on a surface by means of droplet dispensing elements that traverse the surface of the support. At least one, and desirably all, of the following deposition parameters are employed as indicated: The number of times of repetition for a step of depositing reagents in at least one cycle of the second set is less than the number of times of repetition for a corresponding step in at least one cycle of the first set. The rate of deposition in at least one cycle of the second set is slower than or equal to the rate of deposition in at least one cycle of the first set. The rate of traversal of the dispensing elements over the surface of the support in at least one cycle of the second set is greater than such rate of traversal in at least one cycle of the first set.

Manufacture of arrays with varying deposition parameters

A printhead fluid supply system for use in ink-jet or pulse-jet type printers is described. A manometer feature may be used as a pressure gauge to maintain desired pressure at a printhead. Additional features that may be used in the invention including a supply tubing setup configured to avoid introduction of air into a printhead. The system may be configured to allow for replenishing printing fluid supply while the system is running. This may be accomplished using a secondary fluid supply, to replenish a primary, pressure-compensated fluid reservoir. The system may be used in any sort of ink-jet or pulsejet printing system, such as those commonly used in document production or in more specialized applications such as microarray production.

Printhead fluid supply system

Arrays having multiple biopolymer features on a substrate, including elongated features which have a length/width ratio greater than 1.3 or more. Such arrays may be oriented in various directions and of shapes described, and fabricated using apparatus, methods, or computer program products of the invention.

Arrays with elongated features

A method, apparatus, and computer program product, for forming an addressable array of chemical moieties on a substrate. The method may include, for each of multiple locations on the substrate, depositing a reagent drop set during a cycle so as to attach a corresponding moiety for that location. This may be repeated as required, until the addressable array is formed. Test location are also formed by depositing drops from dispensers in a manner which can facilitate detection of dispenser errors.

Error detection in chemical array fabrication

Methods and apparatus are disclosed for synthesizing a purality of compounds such as biopolymers on the surface of supports. The synthesis comprises a plurality of steps in which reagents for conducting the synthesis are deposited o the surface of the support to form precursors of the chemical compounds and, ultimately, the chemical compounds themselves. An error in the deposition may occur in one or more of the plurality of steps. A reagent for forming the chemical compounds is deposited on the surface of the support. A determination is made as to whether an error occurred in the depositing of the reagent. If an error is detected, the support is treated to re-deposit at least some of those reagents that were not correctly deposited. In one approach the support is treated to stabilize precursors of the chemical compounds, the source of the error is corrected, and the reagent applied above is re-deposited on the surface.

Manufacture of arrays with reduced error impact

A method is provided for applying a fluid onto a surface of a solid substrate. The method employs a distribution member having an upper surface and a lower surface, and including a permeable portion having channels therethough. The distribution member is positioned such that the lower surface of the distribution member is in opposing relation to the surface of the substrate. Once the distribution member is in position, the fluid is dispensed onto the upper surface of the permeable portion of the distribution member such that the fluid penetrates the distribution member and is retained thereby. In addition, a distribution pressure differential is applied between the upper and lower surfaces without using mechanical means such as a squeegee so that a portion of the fluid passes through the channels of the permeable portion of the distribution member and onto the solid substrate surface. Other embodiments of the invention include an apparatus for carrying out the aforementioned method and a reagent application station for applying a plurality of reagents onto a surface of a solid substrate.

Apparatus for coating a substrate quickly and uniformly with a small volume of fluid

Apparatus and methods are disclosed for forming a reaction chamber having relatively small volumes. An apparatus comprises two elements and a mechanism for introducing a gas to form a movable aerodynamic seal between the elements. In this manner a chamber having a controllable interior environment is formed. One of the elements may have at least a portion of a device for dispensing reagents sealingly affixed therein. The other element may be adapted for introduction of a support into the interior of the chamber formed by the top and the bottom element. The apparatus may be used in methods for synthesizing biopolymers on a support.

Small volume chambers

Devices and methods are disclosed for synthesizing compounds on the surface of supports. The devices are flow devices, which include a housing comprising a housing chamber. The housing has an opening adapted for insertion of a support into the housing chamber. A sealing member is movably mounted in the housing chamber and adapted to engage the support to form a reagent chamber between a surface of the support and a surface of the sealing member. A mechanism is included for moving the sealing member within the housing chamber. The device has both an inlet and an outlet, which are both in fluid communication with the reagent chamber. In the methods of the invention a support is placed into a chamber of a device such as described above. The mechanism adapted to engage the support on a surface opposite the surface engaged by the sealing member is activated to urge the support toward the sealing member. The pressure-activated mechanism is activated to urge the support against the aforesaid mechanism and against an interior wall of the housing chamber to form the reagent chamber. A fluid reagent for conducting the reaction step is introduced into the reagent chamber by means of the inlet. Thereafter, the fluid reagent is removed from the reagent chamber. The pressure-activated mechanism is deactivated and the support is removed from the housing chamber. In this way the reagent chamber is formed and un-formed in situ.

Flow cell for chemical reactions

Apparatus and methods are disclosed for synthesizing a plurality of compounds on the surface of supports. Biopolymer features are attached to the surfaces of the supports. The synthesis generally comprises a plurality of steps. In the present invention at least two of the steps are performed by placing a support having a functionalized surface into a chamber of a flow cell and subjecting the surface to a step of the synthesis and placing the support into a chamber of another flow cell and subjecting the surface to another step of the synthesis. An apparatus generally comprises a plurality of flow cells and one or more fluid dispensing stations are mounted on the platform and are in fluid communication with one or more of the plurality of flow cells. A station for monomer addition to the surface of the support is mounted on the platform. The apparatus further comprises a mechanism for moving a support to and from the station for monomer addition and a flow cell and from one flow cell to another flow cell.

Methods for manufacturing arrays

A method, and apparatus and computer program products for executing the method. The method includes obtaining a set of multiple images of a target feature location on an array of multiple features, each image of the set representing the target feature location following deposition of a corresponding sub-set of multiple droplets for that feature. An overlay composite may be generated from the image set. The overlay composite may be used as a quality control tool, or in interrogating the array or processing results of the interrogation.

Growing community of inventors

Mountain View, CA, United States of America

Jay K Bass