Array fabrication with drop detection

• US 6,998,230 B1
• Filed: 04/26/2000
• Issued: 02/14/2006
• Est. Priority Date: 04/26/2000
• Status: Expired due to Fees

• Current Assignee: Agilent Technologies Europe BV (Agilent Technologies, Inc.)
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Caren, Michael P., Tella, Richard P., Schleifer, Kyle J., Fisher, William D., Schantz, Christopher A., Webb, Peter G.
• Primary Examiner(s): FORMAN, BETTY J
• Application Number:
  US09/558,532
• Time in Patent Office: 2,120 Days
• Field of Search: 347/19, 347/163, 347/6, 435/6, 435/287.2, 435/283.1, 422/58, 422/100, 422/68.1, 346/1.1
• US Class Current: 435/287.2
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00547 Bar codes
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00639 the compounds being trapped in or bound to a porous medium
• CPC Class Codes: B01J 2219/00657 One-dimensional arrays
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00662 Two-dimensional arrays within two-dimensional arrays
• CPC Class Codes: B01J 2219/00664 Three-dimensional arrays
• CPC Class Codes: B01J 2219/00675 In-situ synthesis on the substrate
• CPC Class Codes: B01J 2219/00677 Ex-situ synthesis followed by deposition on the substrate
• CPC Class Codes: B01J 2219/00689 using computers
• CPC Class Codes: B01J 2219/00691 using robots
• CPC Class Codes: B01J 2219/00693 Means for quality control
• CPC Class Codes: B01J 2219/00695 : Synthesis control routines, e.g. using computer programs
• CPC Class Codes: B01J 2219/00722 : Nucleotides
• CPC Class Codes: B01J 2219/00725 : Peptides
• CPC Class Codes: B01J 2219/00729 : Peptide nucleic acids [PNA]
• CPC Class Codes: B01L 3/0268 : using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
• CPC Class Codes: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites

Abstract

A drop deposition apparatus, and a method and computer program products using the drop deposition apparatus, for fabricating at least one addressable array of biopolymers on a substrate. The drop deposition apparatus has a drop dispenser unit and a sensing element. The method comprises includes for each of multiple addresses, dispensing droplets carrying the biopolymers or biopolymer precursors from a drop dispenser unit onto the sensing element, and onto the substrate so as to fabricate the array. Electrical signals resulting from dispensed droplets striking the sensing element are detected. A performance characteristic of the deposition apparatus is evaluated based on the detected signals.

Claims

1. A method A method of fabricating at least one addressable array of biopolymers with multiple features on a substrate using a drop deposition apparatus having a drop dispenser unit and a sensing element, comprising:

(a) for each of multiple addresses, dispensing droplets carrying the biopolymers or biopolymer precursors from a drop dispenser unit onto the sensing element, and onto the substrate so as to fabricate the array;

(b) detecting electrical signals resulting from dispensed droplets striking the sensing element;

(c) evaluating a performance characteristic of the deposition apparatus based on the detected signals

wherein the sensing element optionally comprises the substrate;

additionally comprising;

when after the dispensing of some droplets onto the substrate an error is detected in which an evaluated performance characteristic is outside a predetermined tolerance, then the source of the error is corrected prior to dispensing of other of the droplets onto that same substrate or the deposition apparatus is operated so as to compensate for the error during dispensing of other of the droplets onto that same substrate.

2. A method according to claim 1 wherein the error is detected after the dispensing of some of the droplets for an array, and the source of the error is corrected prior to dispensing of other of the droplets for the same array or the deposition apparatus is operated so as to compensate for the error during dispensing of other of the droplets for the same array.

3. A method according to claim 1 wherein:

multiple arrays are fabricated on the same substrate; and

wherein the error is detected after the dispensing of droplets for at least one of the arrays on the same substrate, and the source of the error is corrected prior to dispensing of droplets for other of the arrays on the same substrate or the deposition apparatus is operated so as to compensate for the error during dispensing of droplets for the same array or other of the arrays on the same substrate.

4. A method according to claim 1 wherein the dispenser unit comprises a pulse jet which ejects a droplet in response to a signal and which can de-prime, and the error is corrected by re-priming the pulse jet.

5. A method of fabricating at least one addressable array of biopolymers with multiple features on a substrate using a drop deposition apparatus having a drop dispenser unit and a sensing element, comprising:

(a) for each of multiple addresses, dispensing droplets carrying the biopolymers or biopolymer precursors from a drop dispenser unit onto the sensing element, and onto the substrate so as to fabricate the array;

(b) detecting electrical signals resulting from dispensed droplets striking the sensing element;

(c) evaluating a performance characteristic of the deposition apparatus based on the detected signals;

wherein the sensing element optionally comprises the substrate;

additionally comprising changing biopolymers or biopolymer precursors in the dispenser unit to different biopolymers or biopolymer precursors, wherein the detection and evaluation are performed after the changing and before a dispensing of any droplets for an array.

6. A method of fabricating at least one addressable array of biopolymers with multiple features on a substrate using a drop deposition apparatus having a drop dispenser unit and a sensing element, comprising:

(a) for each of multiple addresses, dispensing droplets carrying the biopolymers or biopolymer precursors from a drop dispenser unit onto the sensing element, and onto the substrate so as to fabricate the array;

(b) detecting electrical signals resulting from dispensed droplets striking the sensing element;

(c) evaluating a performance characteristic of the deposition apparatus based on the detected signals;

wherein the sensing element optionally comprises the substrate;

additionally comprising when an error is detected in which an evaluated performance characteristic is outside a predetermined tolerance, identifying one or more features on the array which are defective as a result of the error.

7. A method according to claim 6 additionally comprising communicating an identity of the identified defective features to a remote location or saving such information onto a storage medium.

8. A method of fabricating at least one addressable array of biopolymers with multiple features on a substrate using a drop deposition apparatus having a drop dispenser unit and a sensing element, comprising:

(a) for each of multiple addresses, dispensing droplets carrying the biopolymers or biopolymer precursors from a drop dispenser unit onto the sensing element, and onto the substrate so as to fabricate the array;

(b) detecting electrical signals resulting from dispensed droplets striking the sensing element;

(c) evaluating a performance characteristic of the deposition apparatus based on the detected signals

wherein the sensing element optionally comprises the substrate;

and wherein;

the dispenser unit is repeatedly scanned across the substrate while dispensing droplets so as to fabricate the array;

the sensing element is struck by droplets so as to generate electrical signals when the dispenser unit passes beyond the array being fabricated on multiple scans during fabrication of the array.

9. A method according to claim 8 wherein the sensing element is struck by droplets so as to generate electrical signals when the dispenser unit passes beyond the array being fabricated on each of multiple scans during fabrication of the array.

10. A method of fabricating at least one addressable array of biopolymers with multiple features on a substrate using a drop deposition apparatus having a drop dispenser unit and a sensing element, comprising:

(a) for each of multiple addresses, dispensing droplets carrying the biopolymers or biopolymer precursors from a drop dispenser unit onto the sensing element, and onto the substrate so as to fabricate the array;

(b) detecting electrical signals resulting from dispensed droplets striking the sensing element;

(c) evaluating a performance characteristic of the deposition apparatus based on the detected signals

wherein the sensing element optionally comprises the substrate;

and wherein the evaluated performance characteristic is the velocity of droplets dispensed from the drop dispenser unit;

the method additionally comprising dispensing multiple droplets from the dispenser unit at each of at least two different distances from the sensor, and wherein droplet velocity is evaluated based on the phase difference between the detected signal from multiple droplets at each distance.

11. An apparatus for fabricating at least one addressable array of biopolymers on a substrate, comprising:

(a) a drop dispensing unit which can deposit droplets carrying the biopolymers or biopolymer precursors onto different addresses on the substrate so as to fabricate the array;

(b) a sensing element and amplifier to detect electrical signals resulting from dispensed droplets striking the sensing element;

(c) a processor which;

causes the drop dispensing unit to dispense droplets toward the sensing element after the dispensing of some droplets onto the substrate and evaluates a performance characteristic of the dispensing unit based on the resulting detected signals; and

when an error is detected in which an evaluated performance characteristic is outside a predetermined tolerance then the processor, prior to causing the drop dispenser to dispense droplets onto that same substrate, activates an operator alert or operates the apparatus so as to correct for the error before, or compensate for the error during, dispensing of other of the droplets onto that same substrate.

12. An apparatus according to claim 11 wherein:

the processor causes the drop dispensing unit to dispense droplets toward the sensing element after dispensing of some droplets for an array; and

when the error is detected the processor activates the operator alert or operates the apparatus so as to correct for the error before, or compensate for the error during, dispensing of the other droplets for that same array.

13. An apparatus according to claim 11 wherein;

the processor causes the drop dispensing unit to dispense droplets so as to form multiple arrays on the same substrate, and to dispense droplets toward the sensing element after dispensing some of the droplets for the arrays on the same substrate;

when the error is detected the processor operates the apparatus so as to correct for the error before, or compensate for the error during, dispensing of the other droplets for other of the arrays on the same substrate.

14. An apparatus for fabricating at least one addressable array of biopolymers with multiple features on a substrate, comprising:

(a) a drop dispensing unit which can deposit droplets carrying the biopolymers or biopolymer precursors onto different addresses on the substrate so as to fabricate the array;

(b) a sensing element and amplifier to detect electrical signals resulting from dispensed droplets striking the sensing element;

(c) a processor which;

causes the drop dispensing unit to dispense droplets toward the sensing element after the dispensing of some droplets onto the substrate and evaluates a performance characteristic of the apparatus based on the resulting detected signals; and

when an error is detected in which an evaluated performance characteristic is outside a predetermined tolerance, identifies one or more features on the array which are defective as a result of the error.

15. An apparatus according to claim 14 wherein the processor additionally communicates an identity of the identified defective features to a remote location or saves such information onto a storage medium.

16. An apparatus for fabricating at least one addressable array of biopolymers on a substrate, comprising:

(a) a drop dispensing unit which can deposit droplets carrying the biopolymers or biopolymer precursors onto different addresses on the mounted substrate so as to fabricate the array;

(b) a sensing element and amplifier to detect electrical signals resulting from dispensed droplets striking the sensing element;

(c) a processor which causes the drop dispensing unit to dispense droplets toward the sensing element and which evaluates a performance characteristic of the apparatus based on the resulting detected signals, wherein the evaluated performance characteristic is the velocity or placement of droplets;

wherein the processor causes the dispenser unit to dispense multiple droplets at each of at least two different distances from the sensor, and wherein droplet velocity is evaluated based on the phase difference between the detected signal from multiple droplets at each distance.

17. A computer program product comprising a computer readable storage medium carrying computer readable program code, for use with an apparatus for fabricating an array of features which apparatus includes a drop deposition unit and a sensing element, the program code when loaded into the computer performing the steps of:

(a) for each of multiple addresses, dispensing droplets carrying the biopolymers or biopolymer precursors from a drop dispensing unit onto the substrate, so as to fabricate the array;

(b) detecting electrical signals resulting from dispensed droplets striking a sensing element during step (a);

(c) evaluating a performance characteristic of the apparatus based on the detected signals; and

(d) when an error is detected in which an evaluated performance characteristic is outside a predetermined tolerance then, prior to causing the drop dispenser to dispense droplets onto that same substrate, activating an operator alert or operating the apparatus so as to correct for the error before, or compensate for the error during, dispensing of other of the droplets onto that same substrate.

18. A computer program product comprising a computer readable storage medium carrying computer readable program code, for use with an apparatus for fabricating an array of features which apparatus includes a drop deposition unit and a sensing element, the program code when loaded into the computer performing the steps of:

(a) for each of multiple addresses, dispensing droplets carrying the biopolymers or biopolymer precursors from a drop dispensing unit onto the substrate, so as to fabricate the array;

(b) dispensing droplets toward the sensing element after the dispensing of some droplets onto the substrate;

(b) detecting electrical signals resulting from dispensed droplets striking a sensing element during step (b);

(c) evaluating a performance characteristic of the apparatus based on the detected signals; and

(d) when an error is detected in which an evaluated performance characteristic is outside a predetermined tolerance, identifying one or more features on the array which are defective as a result of the error.