Reading chemical arrays

Abstract

Methods of using an addressable array of biopolymers which has been exposed to a sample, and apparatus and computer program products for use of the arrays. In one embodiment the method includes detecting signals from the exposed array to obtain a signal image of the array. The array signal image is saved in a memory. Based on the detected signals, a shape of each region in one or more sets of multiple regions on the array signal image is established. A definition of the shapes of the established regions of each set is saved in a memory. Each region of each set is processed according to a corresponding routine for that set.

Description

FIELD OF THE INVENTION [0001] This invention relates to arrays, particularly biopolymer arrays (such polynucleotide arrays, and particularly DNA arrays) which are useful in diagnostic, screening, gene expression analysis, and other applications. BACKGROUND OF THE INVENTION [0002] Arrays of biopolymers, such as arrays of peptides or polynucleotides (such as DNA or RNA), are known and are used, for example, as diagnostic or screening tools. Such arrays include regions (sometimes referenced as features or spots) of usually different sequence biopolymers arranged in a predetermined configuration on a substrate. The arrays, when exposed to a sample, will exhibit a pattern of binding which is indicative of the presence and / or concentration of one or more components of the sample, such as an antigen in the case of a peptide array or a polynucleotide of particular sequence in the case of a polynucleotide array. The binding pattern can be detected by reading the array, for example, by observ...

AI Technical Summary

Benefits of technology

[0009] In another aspect, the method may include retrieving the saved shapes of the established regions from the memory and displaying images of them. This retrieval may particularly be performed prior to retrieving from the memory the majority (that is, greater than 50%, and optionally greater than 60% or 80%) or any of other processed data for each region of each set of the retrieved shapes, which data was processed according to a corresponding routine for that set. Optionally, the array signal image may also be retrieved and the retrieved region shapes and array signal images displayed as overlaid images. In one embodiment, each displayed region may be linked to processed data for that region. This may be accomplished using a graphical user interface in which an individual viewing the displayed region may retrieve saved data (such as the processed results for the corresponding region) simply by selecting any desired region of interest (for example, by pointing and clicking on any region of interest). The method may further optionally include altering a result obtained from the processing of a region based on the displayed shapes of the established regions, for example in response to an alteration of the shape of the displayed region by a user. The present invention further provides a method in which a sub-set of a set of processed data from an addressable array of biopolymers which was exposed to a sample, is retrieved from a memory (such as a non-volatile memory). Optionally, the retrieved data may be reviewed and additional processed data of the set retrieved from the non-volatile memory based on the results of the review. The sub-set retrieved may, for example, be from regions of any one or more sets of regions-as discussed herein. For example, an operator (or a suitably programmed processor) may review an initially retrieved sub-set (such as shapes of regions of one or more sets) on a display and, if such data appears questionable (that is, some part or all of it appears to be outside predetermined limits), may then retrieve further data to confirm or dismiss an error (such as in the data or the exposed array). Such a method can, for example, be operated to facilitate rapid review of processed data from multiple different arrays, by allowing the operator to initially review for each only a predetermined sub-set expected to most likely reveal an error. If no error is detected during a sub-set review for an array, review of further processed data for the same array may be avoided thereby saving time during a review of the data for the multiple arrays while still retaining a relatively high level of confidence that an error for that array is unlikely.

[0012] The present invention further provides an apparatus for using an addressable array of biopolymers on a substrate which array has been exposed to a sample. The apparatus may include a processor, and optionally may also include a detector to detect signals from the exposed array to obtain a signal image of the array and also optionally a memory. The processor is capable of executing any steps of a method of the present invention (other than detecting the actual signals from the array, which is performed by the detector). For example, the processor may save the array signal image in the memory and establish, based on the detected signals, a shape of each region in one or more sets of multiple regions on the array signal image. The processor may further save the definition of the shapes of the established regions of each set in a memory, and process each region of each set according to a corresponding routine for that set. It will be appreciated that the detected signals from the array may have been previously detected and saved and thus, an apparatus of the present invention need not necessarily include a detector and the processor need not necessarily perform the signal image saving.

[0014] One or more of the various aspects of the present invention may provide one or more of the following, or other, useful benefits. For example, region shape definitions for one or more arrays can be quickly reviewed to facilitate detection of a potential problem in the application of an automatic feature extraction routine to a particular array in a large batch of automatically extracted arrays.

Problems solved by technology

In array fabrication, the quantities of DNA available for the array are usually very small and expensive.

During array fabrication however, the resulting fabricated array may not have an actual layout which is precisely the same as a target layout.

For example, some features actually deposited may have errors in position, dimensions, or presence (and may not be present at all due to intermittent errors in the drop deposition apparatus).

Incorrectly designating regions as features or otherwise incorrectly calculating a total signal value for a feature in a determination of results from the exposed array, can read to serious errors in result interpretation.

However, with thousands of features on each array, such a manual procedure is very slow, and does not lend itself to reproducible results.

For example, a routine which establishes a feature boundary based only on regions of highest signal strength, may fail to recognize a region where features have been smeared due to a scratch or other contact with the array.

The present invention further recognizes that while this can be reproduced by running the same feature extraction program on the raw signal data acquired during array reading such a method is computationally intensive and therefore time consuming.

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