Automated method and system for performing antiviral drug susceptibility and resistance testing

• US 6,351,690 B1
• Filed: 01/21/2000
• Issued: 02/26/2002
• Est. Priority Date: 01/21/2000
• Status: Expired due to Fees

• Current Assignee: Monogram Biosciences, Inc. (Laboratory Corporation Of America Holdings)
• Original Assignee: Virologic, Inc. (Laboratory Corporation Of America Holdings)
• Inventors: Lenz, Steven J.
• Primary Examiner(s): Cuchlinski, Jr., William A.
• Assistant Examiner(s): Marc, McDieunel, Marc, McDieunel
• Application Number:
  US09/489,221
• Time in Patent Office: 767 Days
• Field of Search: 700/245, 435/6, 435/320.1, 435/369, 435/463, 435/468, 435/91.41, 435/91.52, 435/477, 422/99, 422/100, 422/104, 536/23.5, 536/23.7
• US Class Current: 700/245
• CPC Class Codes: G01N 2035/00079 Evaporation covers for slides
• CPC Class Codes: G01N 2035/00752 bar codes
• CPC Class Codes: G01N 2035/0405 manipulating closing or opening means, e.g. stoppers, screw caps, lids or covers
• CPC Class Codes: G01N 2035/042 moved independently, e.g. by fork manipulator
• CPC Class Codes: G01N 2035/103 using disposable tips
• CPC Class Codes: G01N 35/0099 comprising robots or similar manipulators robots per se B25J
• CPC Class Codes: G01N 35/028 having reaction cells in the form of microtitration plates
• CPC Class Codes: G01N 35/109 with two horizontal degrees of freedom

Abstract

A system for performing antiviral drug susceptibility and resistance testing is automated using software and robotics. The system includes a transfection apparatus, an infection apparatus and a plate reading apparatus. One or more of the apparatuses may be automated.

Claims

1. A Transfection Apparatus in an automated system for performing antiviral drug susceptibility and resistance testing, comprising:

a robotic arm and a robotic arm controller which positions said robotic arm;

a system controller communicating with said robotic arm controller to control movement of said robotic arm, said system controller having a user interface for a user to design, schedule, optimize and monitor operation of said Transfection Apparatus; and

a liquid handler introducing a resistance test vector comprising a patient-derived segment and an indicator gene into a host cell, a host cell plate containing the host cell being moved by said robotic arm to and from said liquid handler under a control of said system controller.

2. An Infection Apparatus in an automated system for performing antiviral drug susceptibility and resistance testing, comprising:

a robotic arm and a robotic arm controller which positions said robotic arm;

a system controller communicating with said robotic arm controller to control movement of said robotic arm, said system controller having a user interface for a user to design, schedule, optimize and monitor operation of said Infection Apparatus; and

a pipettor harvesting viral supernatants from host cells in a packaging host cell plate, and introducing the viral supernatants into target host cells in a target host cell plate, the packaging host cell plate and target host cell plate being moved by said robotic arm to and from said pipettor under a control of said system controller.

3. A Plate Reading Apparatus in an automated system for performing antiviral drug susceptibility and resistance testing, comprising:

a robotic arm and a robotic arm controller which positions said robotic arm;

a system controller communicating with said robotic arm controller to control movement of said robotic arm, said system controller having a user interface for a user to design, schedule, optimize and monitor operation of said Plate Reading Apparatus;

a platewasher/dispenser for aspirating media from cells in a target host cell plate having a plurality of wells and adding a lysing reagent to at least one of said plurality of wells of the target host cell plate; and

a luminometer measuring expression of an indicator gene in the target host cells in the target host cell plate processed by said platewasher/dispenser,

wherein the target host cell plate is moved to and from said platewasher/dispenser and to and from said luminometer by said robotic arm under a control of said system controller.

4. An automated system for performing antiviral drug susceptibility and resistance testing, comprising:

a robotic arm and a robotic arm controller which positions said robotic arm;

a system controller communicating with said robotic arm controller to control movement of said robotic arm, said system controller having a user interface for a user to design, schedule, optimize and monitor operation of said system;

a Transfection Apparatus introducing a resistance test vector comprising a patient-derived segment and an indicator gene into a host cell in a host cell plate, under control of said system controller;

an Infection Apparatus harvesting viral supernatants from host cells in the host cell plate prepared by said Transfection Apparatus and introducing the viral supernatants into target host cells in a target host cell plate, under control of said system controller; and

a Plate Reading Apparatus having a luminometer that measures expression of an indicator gene in the target host cells in the target host cell plate prepared by said Infection Apparatus, under control of said system controller,

wherein the host cell plate and the target host cell plate are moved to, from and within said Transfection Apparatus, said Infection Apparatus and said Plate Reading Apparatus by said robotic arm under control of said system controller.

5. The automated system of claim 4 wherein antiviral drugs are added to the host cell plates by said Transfection Apparatus.

6. The automated system of claim 4 wherein said Transfection Apparatus includes a bar code scanner for scanning bar code labels applied to the host cell plates.

7. The automated system of claim 4 wherein said Transfection Apparatus processes samples according to a worklist.

8. The automated system of claim 4 wherein the host cell plates processed by said Transfection Apparatus include 96 well and/or 384 well type plates.

9. The automated system of claim 4 wherein antiviral drugs are added to the target host cell plates by said Infection Apparatus.

10. The automated system of claim 4 wherein the viral supernatants are harvested by said Infection Apparatus with filtration.

11. The automated system of claim 4 wherein the target host cell plates processed by said Infection Apparatus include 96 well and/or 384 well type plates.

12. The automated system of claim 4 wherein the target host cell plates are incubated for one minute after addition of the lyse reagent.

13. The automated system of claim 4 wherein the luciferase substrate is added by the luminometer.

14. The automated system of claim 4 wherein a plate lid is added and removed by a robot.

15. The automated system of claim 4 wherein bar code labels applied to the plates are used to track the plates through the system.

16. A transfection process in an automated system, which has a robotic arm, a system controller and a liquid handler, for performing antiviral drug susceptibility and resistance testing, comprising the steps of:

controlling said robotic arm to deliver a host cell plate containing a host cell to said liquid handler; and

sending a signal from said system controller to said liquid handler to control said liquid handler to introduce a resistance test vector comprising a patient-derived segment and an indicator gene into the host cell.

17. An infection process in an automated system, which has a robotic arm, a system controller and a pipettor, for performing antiviral drug susceptibility and resistance testing, comprising the steps of:

controlling said robotic arm to deliver a packaging host cell plate to said pipettor;

controlling said robotic arm to deliver a target host cell plate to said pipettor; and

sending a signal from said system controller to said pipettor to control said pipettor to harvest viral supernatants from host cells in the packaging host cell plate and to introduce the viral supernatants into target host cells in the target host cell plate.

18. A plate reading process in an automated system, which has a robotic arm, a system controller, a platewasher/dispenser and a luminometer, for performing antiviral drug susceptibility and resistance testing, comprising the steps of:

controlling said robotic arm to deliver a target host cell plate to said platewasher/dispenser;

sending a signal from said system controller to said platewasher/dispenser to control said platewasher/dispenser to aspirate media from cells in the target host cell plate and to add a lysing reagent to the wells of the target host cell plate;

controlling said robotic arm to deliver the target host cell plate processed by said platewasher/dispenser to said luminometer; and

sending a signal from said system controller to said luminometer to control said luminometer to measure expression of an indicator gene in the target host cells in the target host cell plate.