Readout method for molecular biological electronically addressable arrays

• US 6,251,685 B1
• Filed: 02/18/1999
• Issued: 06/26/2001
• Est. Priority Date: 02/18/1999
• Status: Expired due to Fees

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Dorsel, Andreas Nikolaus, Gordon, Gary B., Kronick, Mel N.
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): GAKH, YELENA G
• Application Number:
  US09/252,208
• Time in Patent Office: 859 Days
• Field of Search: 422/68.1, 422/52, 422/82.05, 422/82.07, 422/82.11, 422/91, 422/107, 422/108, 422/186.15, 422/186.16, 422/99, 422/102, 436/172, 436/159, 436/180, 436/46
• US Class Current: 436/172
• CPC Class Codes: B01J 2219/00608 DNA chips
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00617 by chemical means
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00628 Ionic
• CPC Class Codes: B01J 2219/00635 by reactive plasma treatment
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00653 the compounds being bound to electrodes embedded in or on the solid supports
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: G01N 21/66 electrically excited, e.g. electroluminescence
• CPC Class Codes: G01N 21/76 Chemiluminescence; Bioluminescence
• CPC Class Codes: Y10T 436/112499 with sample on test slide
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

A method for reading out data from microlocations of a microelectronic array involves activating multiple microlocations in parallel and simultaneously detecting the responses from the activated microlocations to determine concentrations of molecular biological material at each microlocation. In a preferred embodiment, the microelectronic array includes electronically addressable electrodes at each microlocation which can be individually activated via a control system. An electrochemiluminescent detection technique is used to detect the presence and determine the concentration of bound molecular biological material that is located at each microlocation. Electrochemiluminescent material is utilized because it gives off light when excited by an applied electrical field. With an addressable microelectronic array, electrical fields can be applied to various combinations of microlocations simultaneously to allow readout of several microlocations in parallel. This is in contrast to the laser-based readout approach which applies activation energy to one microlocation at a time by impacting each microlocation with a single laser system. Reading out multiple microlocations simultaneously in accordance with the invention can produce significant time savings in large arrays.

Claims

1. A method for reading data from microlocations of a microelectronic array comprising steps of:

providing said microelectronic array having a plurality of individually activatable microlocations, each microlocation having molecular biological material thereon;

selecting a biological detection technique by which optical energy is generated in response to applying activation energy to a microlocation at which molecular biological material resides, with a specific characteristic of the generated optical energy being related to a specific characteristic of said molecular biological material;

simultaneously activating a plurality of microlocations such that each activated microlocation is surrounded by a plurality of inactive microlocations, said plurality of microlocations being activated to generate optical energy at each activated microlocation having molecular biological material, said optical energy being indicative of said specific attribute of molecular biological material at each microlocation, said surrounding inactive microlocations serving to reduce optical interference between said plurality of activated microlocations;

simultaneously detecting said optical energy generated at each said activated microlocation; and

quantifying said specific attribute for said molecular biological material residing at each of said activated microlocations based upon said detected optical energy at each said activated microlocation.

2. The method of claim 1 wherein said selected biological detection technique utilizes electrochemiluminescence to generate said optical energy, said specific characteristic of said generated optical energy being intensity and said specific characteristic being a concentration of said molecular biological material.

3. The method of claim 2 wherein said step of activating includes a step of simultaneously applying a voltage to a plurality of electrodes having an arrangement that corresponds with an arrangement of said plurality of microlocations.

4. The method of claim 1 wherein said step of activating includes a step of activating microlocations at the intersections of every M^th column and every N^th row, where M and N are integers greater than 1.

8. The method of claim 4 further including a step of changing said activated columns and rows such that previously inactive microlocations are activated.

5. A method for reading out data from electronically addressable microlocations of a microelectronic array comprising the steps of:

providing said microelectronic array having a plurality of individually activatable microlocations, each microlocation having molecular biological material thereon;

utilizing electrochemiluminescence to generate optical energy in response to electrical energy applied to a plurality of discrete microlocations to detect molecular biological material at said discrete microlocations;

simultaneously activating a plurality of microlocations of said microelectronic array such that each activated microlocation is surrounded by a plurality of inactive microlocations, said plurality of microlocations being activated in order to generate optical energy at each activated microlocation, where the optical energy is related to a concentration of molecular biological material at each activated microlocation;

simultaneously detecting generated optical energy from each activated microlocation with a multi-dimension resolving detector; and

determining a concentration of molecular biological material at each activated microlocation, where said determined concentration is related to said detected optical energy at respective microlocations.

6. The method of claim 5 wherein said step of simultaneously activating a plurality of microlocations includes a step of simultaneously activating microlocations at the intersections of every M^th column of microlocations and every N^th row of microlocations in said microelectronic array, where M and N are integers greater than 1.

7. The method of claim 6 wherein said step of simultaneously activating includes a step of utilizing on-chip address decoders to simultaneously activate said plurality of microlocations.

9. A method for reading data from microlocations of a microelectronic array comprising steps of:

providing said microelectronic array having a plurality of individually activatable microlocations, each microlocation having molecular biological material thereon;

selecting a biological detection technique by which optical energy is generated in response to applying activation energy to a microlocation at which molecular biological material resides, with a specific characteristic of the generated optical energy being related to a specific characteristic of said molecular biological material;

activating a plurality of columns of microlocations simultaneously to generate optical energy at each microlocation having molecular biological material, each of said activated columns being separated by at least one column of inactive microlocations, said optical energy being indicative of said specific attribute of molecular biological material at each microlocation;

simultaneously detecting said optical energy generated at each said activated microlocation; and

quantifying said specific attribute for said molecular biological material residing at each of said activated microlocations based upon said detected optical energy at each said activated microlocation.

10. The method of claim 9 wherein said step of activating includes activating every M^th column of microlocations, where M is an integer that is greater than 1.

11. The method of claim 10 wherein M is equal to 2, such that every other column of microlocations is activated in parallel.

12. The method of claim 10 further including a step of changing said activated columns by one column, such that previously inactive columns of microlocations are activated.

13. A method for reading data from microlocations of a microelectronic array comprising steps of:

providing said microelectronic array having a plurality of individually activatable microlocations, each microlocation having molecular biological material thereon;

selecting a biological detection technique by which optical energy is generated in response to applying activation energy to a microlocation at which molecular biological material resides, with a specific characteristic of the generated optical energy being related to a specific characteristic of said molecular biological material;

activating a plurality of rows of microlocations simultaneously to generate optical energy at each microlocation having molecular biological material, each of said activated rows being separated by at least one row of inactive microlocations, said optical energy being indicative of said specific attribute of molecular biological material at each microlocation, N being an integer that is greater than 1;

simultaneously detecting said optical energy generated at each said activated microlocation; and

quantifying said specific attribute for said molecular biological material residing at each of said activated microlocations based upon said detected optical energy at each said activated microlocation.

14. The method of claim 13 wherein said step of activating includes activating every N^th row of microlocations, where N is an integer greater than 1.

15. The method of claim 14 wherein N is equal to 2, such that every other row of microlocations is activated in parallel.

16. The method of claim 14 further including a step of changing said activated rows by one row, such that previously inactive rows of microlocations are activated.

17. A method for reading data from microlocations of a microelectronic array comprising steps of:

providing said microelectronic array having a plurality of individually activatable microlocations, each microlocation having molecular biological material thereon;

selecting a biological detection technique by which optical energy is generated in response to applying activation energy to a microlocation at which molecular biological material resides, with a specific characteristic of the generated optical energy being related to a specific characteristic of said molecular biological material;

simultaneously activating microlocations at the intersections of every M^th column and every N^th row to generate optical energy at each microlocation having molecular biological material, said optical energy being indicative of said specific attribute of molecular biological material at each microlocation, M and N being integers greater than 1;

simultaneously detecting said optical energy generated at each said activated microlocation; and

quantifying said specific attribute for said molecular biological material residing at each of said activated microlocations based upon said detected optical energy at each said activated microlocation.

18. The method of claim 17 further including a step of changing said activated columns and rows such that previously inactive microlocations are activated.

19. A method for reading out data from electronically addressable microlocations of a microelectronic array comprising the steps of:

utilizing electrochemiluminescence to generate optical energy in response to electrical energy applied at a discrete microlocation to detect molecular biological material at said discrete microlocation;

simultaneously activating microlocations at the intersections of every M^th column of microlocations and every N^th row of microlocations in said microelectronic array in order to generate optical energy at each activated microlocation, where the optical energy is related to a concentration of molecular biological material at each activated microlocation, M and N being integers greater than 1;

simultaneously detecting generated optical energy from each activated microlocation with a multi-dimension resolving detector; and

determining a concentration of molecular biological material at each activated microlocation, where said determined concentration is related to said detected optical energy at respective microlocations.