Methods for placing, accepting, and filling orders for products and services

• US 9,464,320 B2
• Filed: 04/27/2012
• Issued: 10/11/2016
• Est. Priority Date: 01/25/2002
• Status: Active Grant

• Current Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Original Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Inventors: Xu, Lily, Smith, Leila G., Koehler, Ryan T., Livak, Kenneth J., Stevens, Junko, De La Vega, Francisco M., Rhodes, Michael, Bellon, Laurent R., Williams, Julie, Madden, Dawn, Gilbert, Dennis A., Wang, Yu N., Spier, Eugene G., You, Xiaoqing, Heil, Jeremy, Glanowski, Stephen, Winn-Deen, Emily S., McMullen, Ivy
• Primary Examiner(s): Brusca, John S
• Application Number:
  US13/458,879
• Publication Number:
  US 20120303472A1
• Time in Patent Office: 1,628 Days
• US Class Current: 1/1
• CPC Class Codes: B01L 2300/021 Identification, e.g. bar codes
• CPC Class Codes: B01L 3/545 for laboratory containers
• CPC Class Codes: B01L 3/5453 for test tubes
• CPC Class Codes: C12Q 1/6858 Allele-specific amplification
• CPC Class Codes: C12Q 2547/101 by confinement to a single tube/container
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: G01N 35/00663 of consumables
• CPC Class Codes: G06Q 30/0621 Item configuration or customization
• CPC Class Codes: G06Q 30/0633 Lists, e.g. purchase orders, compilation or processing
• CPC Class Codes: G06Q 30/0641 Shopping interfaces
• CPC Class Codes: G06Q 50/22 Social work or social welfare, e.g. community support activities or counselling services
• CPC Class Codes: G16B 25/00 ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
• CPC Class Codes: G16B 25/10 Gene or protein expression profiling; Expression-ratio estimation or normalisation
• CPC Class Codes: G16B 30/00 ICT specially adapted for sequence analysis involving nucleotides or amino acids
• CPC Class Codes: G16B 30/10 Sequence alignment; Homology search
• CPC Class Codes: G16B 30/20 Sequence assembly
• CPC Class Codes: G16B 35/00 ICT specially adapted for in silico combinatorial libraries of nucleic acids, proteins or peptides
• CPC Class Codes: G16B 35/20 Screening of libraries
• CPC Class Codes: G16B 45/00 ICT specially adapted for bioinformatics-related data visualisation, e.g. displaying of maps or networks
• CPC Class Codes: G16B 50/00 ICT programming tools or database systems specially adapted for bioinformatics
• CPC Class Codes: G16B 50/10 : Ontologies; Annotations
• CPC Class Codes: G16C 20/60 : In silico combinatorial chemistry
• CPC Class Codes: G16H 10/40 : for data related to laboratory analysis, e.g. patient specimen analysis

Abstract

Methods and systems for ordering assays which detect SNPs or gene expression are provided. The methods use PCR and RT-PCR procedures. Collections of stock assays are assembled using pre- and post-manufacturing quality control procedures and made available to consumers via the Internet. In addition, custom assays are prepared upon order from the consumer and these assays are also prepared using pre- and post-manufacturing quality control procedures. The assays are then delivered to the consumer.

Claims

1. A method for providing assays to a consumer, comprising:

providing a web-based user interface configured to receive an order for one or more assays designed for one or more nucleic acid targets;

manufacturing or causing to be manufactured one or more assays designed for said one or more nucleic acid targets, including performing pre-processing selection, designing probes and/or primers directed to one or more sequence regions of said one or more nucleic acid targets, and performing an in silico quality control operation, wherein said performing pre-processing selection comprises identifying sequence regions for the one or more nucleic acid targets that do not contain any single nucleotide polymorphisms and also do not contain any repeat sequences;

validating said manufactured one or more assays, including performing a quality control testing for one or more components of said manufactured one or more assays, the quality control testing being based on a measured synthesis yield; and

delivering or causing to be delivered to the consumer at least one assay including at least two designed primers in response to the order for said one or more assays from the consumer.

2. A method in accordance with claim 1, wherein identifying sequence regions for the one or more nucleic acid targets comprises utilizing at least one method selected from the group consisting of masking single nucleotide polymorphisms and repeat sequences in at least one expressed transcript or portion thereof to avoid designing probes and/or primers thereon, mapping the at least one expressed transcript or portion thereof against at least two genomic databases to identify discrepancies to avoid designing probes and/or primers thereon, and combinations thereof.

3. A method in accordance with claim 1, wherein identifying sequence regions for the one or more nucleic acid targets comprises masking dinucleotide repeats and masking repeat sequences selected from the group consisting of di nucleotide repeats, tri-nucleotide repeats, Alu restriction site repeats, long interspersed nuclear elements, and short interspersed elements, wherein such masked repeat sequences are avoided when designing the probes and/or primers.

4. A method in accordance with claim 1, wherein said probes and/or primers are designed to conform with T_m and GC content specifications and one or more specifications selected from the group consisting of buffer and salt conditions, oligonucleotide concentration in assay, low secondary structure of oligonucleotide, amplicon size, and low incidence of primer-dimer formation.

5. A method in accordance with claim 4, wherein said probes and/or primers are designed to conform with one or more specifications selected from the group consisting of amplicon size and low incidence of primer-dimer formation.

6. A method in accordance with claim 1, wherein said performing the in silico quality control operation comprises determining quality of designed probes and/or primers utilizing genome BLAST scoring and one or more scoring methods selected from the group consisting of transcript BLAST scoring, scoring size of intron across which a probe spans for multiexon genes, and combinations thereof.

7. A method in accordance with claim 1, wherein the probes and/or primers are designed based on one or more pre-selected scoring criteria comprising one or more of assigning high transcript BLAST scoring for matching to self and no other transcript, assigning high genome BLAST scoring for matching to self and no other genome region, and assigning high scoring for intron size greater than 10 kilobases.

8. A method in accordance with claim 1, wherein designing probes and/or primers directed to one or more sequence regions of said one or more nucleic acid targets further comprises avoiding the inclusion of regions of discrepancy between at least two genomic databases in probe and/or primer sequences.

9. A method in accordance with claim 1, wherein identifying sequence regions for the one or more nucleic acid targets comprises utilizing at least identifying exon-exon boundaries for expressed transcripts of multi-exon genes in order to design probes and/or primers thereon.

10. A method in accordance with claim 1, wherein the quality control testing based on a measured synthesis yield comprises ensuring that each designed probe and/or primer in the manufactured one or more assays has a synthesis yield of 60% (w/w) or greater expressed as the weight of the desired probe and/or primer to the total weight of the synthesized product multiplied by 100.

11. The method of claim 1, wherein the quality control testing based on a measured synthesis yield comprises ensuring that each designed probe and/or primer in the manufactured one or more assays has a synthesis yield of 80% (w/w) or greater expressed as the weight of the desired probe and/or primer to the total weight of the synthesized product multiplied by 100.

12. A method for providing assays to a consumer, comprising:

providing a web-based user interface configured to receive an order for one or more custom and/or stock assays for one or more nucleic acid targets;

manufacturing or causing to be manufactured one or more custom and/or stock assays for said one or more nucleic acid targets, including performing pre-processing selection, designing a probe and primers directed to one or more sequence regions of said one or more nucleic acid targets, and performing an in silico quality control operation;

validating said manufactured one or more custom and/or stock assays, including performing a quality control testing for one or more components of said manufactured one or more custom and/or stock assays based on a measured synthesis yield and a quality control testing for one or more components of said manufactured one or more custom and/or stock assays based on a measured mass indicative of sequence accuracy; and

delivering or causing to be delivered to the consumer at least one custom and/or stock assay including at least the designed probe and primers in response to the order for said one or more custom and/or stock assays from the consumer, wherein said probe and primers are designed in accordance with one or more criteria comprising at least avoiding inclusion of both single nucleotide polymorphisms and repeat sequences in probe and/or primer sequences.

13. A method in accordance with claim 12, wherein the one or more criteria further comprise-avoiding inclusion of regions of discrepancy between at least two genomic databases in probe and primers sequences.

14. The method of claim 12, wherein the quality control testing based on a measured synthesis yield comprises ensuring that a designed probe and/or primer in the manufactured one or more custom and/or stock assays has a synthesis yield of 60% (w/w) or greater expressed as the weight of the desired probe and/or primer to the total weight of the synthesized product multiplied by 100, and wherein the quality control testing based on a measured mass indicative of sequence accuracy comprises ensuring that the measured mass of a designed probe and/or primer in the manufactured one or more custom and/or stock assays is not more than about 20% greater or lesser than a calculated mass of the designed probe and/or primer.

15. The method of claim 12, wherein the quality control testing based on a measured synthesis yield comprises ensuring that a designed probe and/or primer in the manufactured one or more custom and/or stock assays has a synthesis yield of 80% (w/w) or greater expressed as the weight of the desired probe and/or primer to the total weight of the synthesized product multiplied by 100, and wherein the quality control testing based on a measured mass indicative of sequence accuracy comprises ensuring that the measured mass of a designed probe and/or primer in the manufactured one or more custom and/or stock assays is not more than about 10% greater or lesser than a calculated mass of the designed probe and/or primer.

16. A method for validating assays to be provided to a consumer, comprising:

providing a web-based user interface configured to receive an order for one or more assays designed for one or more nucleic acid targets;

manufacturing or causing to be manufactured one or more assays designed for said one or more nucleic acid targets, including performing pre-processing selection, designing probes and/or primers directed to one or more sequence regions of said one or more nucleic acid targets, and performing an in silico quality control operation, wherein said performing pre-processing selection comprises identifying sequence regions for the one or more nucleic acid targets that do not contain any single nucleotide polymorphisms and also do not contain any repeat sequences; and

validating said manufactured one or more assays, including performing a quality control testing for one or more components of said manufactured one or more assays, the quality control testing being based on a measured synthesis yield.

17. The method of claim 16, further comprising manufacturing at least one SNP assay and performing functional testing of the manufactured at least one SNP assay by performing PCR reactions against from about 10 to about 20 genomic DNA samples.

18. The method of claim 16, wherein the web-based user interface is further configured to receive an order for at least one gene expression assay from a group of at least 10,000 gene expression assays.

19. The method of claim 18, further comprising manufacturing at least one gene expression assay and performing functional testing of the manufactured at least one gene expression assay by performing PCR against at least 10 human cDNA samples with a transcript detection threshold of less than 35 PCR cycles.