AC waveforms biasing for bead manipulating chucks

• US 6,475,351 B2
• Filed: 01/30/2001
• Issued: 11/05/2002
• Est. Priority Date: 06/10/1998
• Status: Expired due to Fees

• Current Assignee: Delsys Pharmaceutical Corporation (Perrigo Company PLC)
• Original Assignee: Delsys Pharmaceutical Corporation (Perrigo Company PLC)
• Inventors: Desai, Nitin Vithalbhai, Rosati, Dominic Stephen, Puliniak, Eugene Samuel, Singh, Bawa, Sun, Hoi Cheong
• Primary Examiner(s): Mayekar, Kishor
• Application Number:
  US09/772,536
• Publication Number:
  US 20020015275A1
• Time in Patent Office: 644 Days
• Field of Search: 204/164, 422/186.04, 427/2.14, 118/624, 118/DIG.2, 361/234, 279/128
• US Class Current: 204/164
• 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 2219/00468 by manipulation of individual beads
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: G01N 2035/00574 Means for distributing beads
• CPC Class Codes: H02N 13/00 Clutches or holding devices using electrostatic attraction, e.g. using Johnson-Rahbek effect
• CPC Class Codes: Y10S 118/02 Bead coater
• CPC Class Codes: Y10T 279/23 with magnetic or electrostatic means

Abstract

AC waveforms biasing of bead transporter chucks and their accumulated charge sensing circuits tailored for low resistivity substrates and beads where if traditional DC quasi-static biasing potentials were used, the bead attraction potentials of the chuck would undergo rapid RC decay and cause the bead transporter chuck to stop working. Methods for selecting AC waveforms are given, including those that maximize the time average of the bead attraction potential at the bead collection zone of the bead contact surface.

Claims

1. A method for adhering charged grains to a bead collection zone on a bead contact surface comprising:

(1) adhering a substrate to an electrostatic chuck, with the substrate arrayed over a grain-attracting electrode of the electrostatic chuck so that a surface of the substrate defines the bead contact surface;

(2) applying an AC waveform potential to the grain-attracting electrode to create a grain attracting field, wherein the AC waveform potential comprises a grain-attracting potential pulse followed by a recovery period adapted to allow an effective grain attraction potential at the bead collection zone on activation of a subsequent grain-attracting potential pulse; and

(3) attracting and retaining grains to the bead collection zone.

2. The method of claim 1, wherein the AC waveform potential has frequency of 100 Hz or less and the recovery period is at least 0.1 times substrate resistivity (in Ω

-cm) times 10<sup>−

9</sup> mS.

3. The method of claim 2, wherein grains are attracted to apply at least 300 μ

g/4 mm of grains to bead collection zone.

4. The method of claim 2, wherein the recovery period is at least 1.25 times substrate resistivity (in Ω

-cm) times 10<sup>−

9</sup> mS.

5. The method of claim 4, wherein grains are attracted to apply at least 300 μ

g/4 mm of grains to bead collection zone.

6. The method of claim 1, further comprising:

(4) applying a bias to the electrostatic chuck to create a force favoring release of the attracted grains, and releasing the grains onto another surface or surfaces.

7. The method of claim 6, wherein the other surfaces are found on a microtiter plate.

8. A method for adhering charged grains to a bead collection zone on a bead contact surface comprising:

(1) adhering a substrate with a resistivity below 10 ¹¹ Ω

-cm to an electrostatic chuck, with the substrate arrayed over a grain-attracting electrode of the electrostatic chuck so that a surface of the substrate defines the bead contact surface;

(2) applying an AC waveform potential to the grain-attracting electrode to create a grain attracting field, wherein the AC waveform potential comprises a grain-attracting potential at the bead collection zone on activation of a subsequent grain-attracting potential pulse,

wherein the AC waveform potential corresponds to applied voltages and time periods effective so that the voltage at the bead collection zone resulting from the grain-attracting potentials following a grain-attracting potential is at least 10% of an initial voltage at the bead collection zone, or

the AC waveform potential corresponds to applied voltages and time periods effective so that the integrated voltage at the bead collection zone integrated over the pulse period during which a grain-attracting voltage is applied voltage at the bead collection zone is at leat 20% of an initial integrated voltage; and

(3) attracting and retaining a grain to the bead collection zone.

9. The method of claim 8, additionally comprising:

(4) providing an accumulated charge sensing circuit for the bead transporter chuck having a charge sensing electrode for monitoring accumulated charge on a bead collection zone of the bead contact surface, comprising

(a) an AC bias source,

(b) a sensing capacitor electrically connected between the charge collector electrode and the AC bias source, and

(c) an electrometer electrically connected between the AC bias source and coupling capacitor to measure the potential the sensing capacitor;

(5) terminating the application of the AC waveform potential when the charge sensing circuit indicates that sufficient grains have been accumulated at the bed collection zone, or, where there are multiple bead collection zones and two or more charge sensing circuits, adjusting AC waveform potentials so that grain accumulation at various bead collection zones is adjusted.

10. The method of claim 8, wherein grains are attracted to apply at least 300 μ

g/4 mm of grains to bead collection zone.

11. The method of claim 8, wherein the AC waveform potential is configured such that the grain attraction potential at the bead collection zone is greater, on average, than the obtained with a time-averaged DC potential corresponding to the AC waveform potential.

12. The method of claim 8, comprising fabricating dosage forms by:

providing an edible substrate as the substrate; and

operating the electrostatic chuck pursuant to steps (1) through (3) to deposit measured amounts of powder, comprising a pharmaceutically active substance, on spatially resolved regions of the edible substrate.

13. The method of claim 8, wherein the recovery period is at least 1.0 times substrate resistivity (in Ω

-cm) times 10<sup>−

9</sup> mS.

14. The method of claim 8, wherein the recovery period is at least 1.25 times substrate resistivity (in Ω

-cm) times 10 <sup>−

9</sup> mS.

15. The method of claim 8, further comprising:

(6) applying a bias to the electrostatic chuck to create a force favoring release of the attracted grains, and releasing the grains onto another substrate.

16. The method of claim 15, wherein the other surfaces are found on a microtiter plate.

17. An electrostatic chuck for attracting charged grains to a bead collection zone on a bead contact surface comprising:

a bead electrode for selectivity establishing a grain attracting field to the bead collection zone, the bead electrode shaped and configured in such a manner so that when an AC waveform potential is applied thereto, the grains are influenced by it and guided to selective retention by the bead electrode to the bead collection zone; and

an electronic driver programmed to deliver the AC waveform potential configured to provide a repeated effective grain attraction potential at the bead collection zone, wherein the AC waveform potential comprises a grain-attracting potential pulse followed by a recovery period wherein

(a) the AC waveform potential corresponds to applied voltages and time periods effective so that the voltage at the bead collection zone resulting from the grain-attracting potentials following a grain-attracting potential (other than an initial grain-attracting potential) is at least 10% of an initial voltage at the bead collection zone, or

(c) the AC waveform potential corresponds to applied voltages and time periods effective so that the integrated voltage at the bead collection zone integrated over the pulse period (other than an initial pulse period) during which a grain-attracting voltage is applied voltage at the bead collection zone is at least 20% of an initial integrated voltage.

18. The electrostatic chuck of claim 17, wherein the electronic driver is programmed to deliver the AC waveform potential configured such that the grain attraction potential on the bead collection zone is greater, on average, than that obtained when applying a time-averaged DC potential corresponding to the AC waveform potential.

19. The electrostatic chuck of claim 17, wherein

(a) the AC waveform potential corresponds to applied voltages and time periods effective so that the voltage at the bead collection zone resulting from the grain-attracting potentials following a grain-attracting potential (other than an initial grain-attracting potential) is at least 10% of an initial voltage at the bead collection zone.

20. The electrostatic chuck of claim 17, wherein

(b) the AC waveform potential corresponds to applied voltages and time periods effective so that the integrated voltage at the bead collection zone integrated over the pulse period (other than an initial pulse period) during which a grain-attracting voltage is applied voltage at the bead collection zone is at least 20% of an initial integrated voltage.