Biochip detection system

• US 6,271,042 B1
• Filed: 08/26/1998
• Issued: 08/07/2001
• Est. Priority Date: 08/26/1998
• Status: Expired due to Fees

• Current Assignee: ProteinSimple (Bio-Techne Corporation)
• Original Assignee: Alpha Innotech Corporation (Bio-Techne Corporation)
• Inventors: Lee, James S., Chaudhry, Haseeb R., Watson, Robert Malcolm Jr.
• Primary Examiner(s): SNAY, JEFFREY R
• Application Number:
  US09/140,164
• Time in Patent Office: 1,077 Days
• Field of Search: 422/52, 422/82.07, 422/82.08, 436/172, 250/361.C, 250/458.1, 250/459.1
• US Class Current: 436/172
• CPC Class Codes: B01J 2219/00274 Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
• CPC Class Codes: G01N 2021/6419 Excitation at two or more wavelengths
• CPC Class Codes: G01N 2021/6441 with two or more labels
• CPC Class Codes: G01N 21/6452 Individual samples arranged in a regular 2D-array, e.g. multiwell plates

Abstract

A biochip detection system detects and locates samples that are labeled with multiple fluorescent tags and are located on a biochip. This biochip detection system includes a charge coupled device (CCD) sensor, a broad spectrum light source, a lens, a light source filter, and a sensor filter. The CCD sensor comprises two dimensional CCD arrays to simultaneously detect light waves from at least a substantial portion of the biochip. The broad spectrum light source is optically coupled to the CCD sensor and is configured to be utilized with a variety of different fluorescent tags which have differing excitation wavelengths.

Claims

1. An apparatus comprising:

a. a biochip configured for supporting an array of samples;

b. a sensor configured for detecting emitted light from the array of sample;

c. a single source board spectrum light source optically coupled to the sensor configured to illuminate the array of samples on the biochip with an excitation light having a first excitation wavelength and a second excitation wavelength;

d. a matched filter optically coupled between the array of samples and the single source board spectrum light source for selecting between the first excitation wavelength and the second excitation wavelength to pass therethrough and strike the array of samples; and

e. a matched filter optically coupled between the sample and the sensor for selecting between emitted light having a first emission wavelength and a second emission wavelength to pass therethrough and strike the sensor, the a first emission wavelength and a second emission wavelength resulting from the first excitation wavelength and the second excitation wavelength striking the array of samples, respectively.

2. The apparatus according to claim 1 wherein the sensor is a charge coupled device.

3. The apparatus according to claim 1 wherein the sensor is a two dimensional charge coupled device.

4. The apparatus according to claim 1, further comprising a lens optically coupled between the array of samples on a biochip and the sensor for focusing the emitted light.

5. The apparatus according to claim 4, wherein the lense has a focal length of approximately 25 millimeters and an f-stop value of 1:

0.85.

6. An apparatus comprising

a. a biochip configured to support a two-dimensional array of tag labeled samples;

b. a two dimensional CCD sensor for detecting emitted light from the tag labeled sample on the biochip; and

c. a lens optically coupled between the two dimensional CCD sensor and the biochip and configured to transmit the emitted light to the two dimensional CCD sensor wherein the lens has a focal length of approximately 25 millimeters and an f-stop value of 1;

0.85 and is configured to be within two inches of the tag labeled sample.

7. The apparatus according to claim 6, further comprising a sensor filter optically coupled between the two dimensional CCD sensor and the lens wherein the sensor filter is configured to only substantially allow light waves emitted from the two dimensional array of tag labeled samples on the biochip to reach the CCD sensor.

8. The apparatus according to claim 6, further comprising a light source to illuminate the two dimensional array of tag labeled samples on a biochip.

9. The apparatus according to claim 8, wherein the light source is a single source broad spectrum light source.

10. The apparatus according to claim 8, further comprising a light source filter configured to be optically coupled between the light source and the tag labeled sample on a biochip wherein the light source filter is configured to only substantially allow light waves having an excitation wavelength corresponding to the tag labeled samples to reach the two dimensional array of tag labeled samples on a biochip.

11. A system configured to detect and locate fluorescently labeled samples, the system comprising:

a. a biochip configured to hold the fluorescently labeled samples;

b. a light source configured to simultaneously illuminate all the fluorescently labeled samples on the biochip;

c. a two dimensional CCD sensor optically coupled to the light source and configured for concurrently detecting and locating emitted light from the fluorescently labeled samples on the biochip; and

d. a lens having a focal length of approximately 25 millimeters and an f-stop value of 1;

0.85 optically coupled between the light source and the two dimensional CCD sensor and configured to appropriately magnify the biochip onto the two dimensional CCD sensor.

12. A system configured to detect and locate a first set of samples labeled by a first fluorescent tag emitting a first emission wavelength and a second set of samples labeled by a second fluorescent tag emitting a second emission wavelength, the first and second set of samples, the system comprising:

a. a biochip for supporting the first and the second set of samples in a two dimensional array;

b. a light source configured to selectively illuminate all the flourescently labeled samples on the biochip at a first excitation wavelength and a second excitation wave length;

c. a two dimensional CCD sensor optically coupled to the light source and configured for concurrently detecting and locating the first emmision wavelength from the first set of samples and the second emmision wavelength from the second set of samples;

d. a lens optically coupled between the light source and the two dimensional CCD sensor and configured to transmit the first emmision wavelength and the second emmision wavelength to the two dimensional CCD sensor;

e. a first light source filter for selectively transmitting the first excitation wave wavelength to the to the first set of samples;

f. a first sensor filter selectively and optically coupled to the two dimensional CCD sensor and configured for substantially only transmitting the first emmision wavelength to the two dimensional CCD sensor;

g. a second light source filter for selectively transmitting the first excitation wave wavelength to the to the second set of samples; and

h. a second sensor filter selectively and optically coupled to the two dimensional CCD sensor and configured for substantially only transmitting the second emission wavelength to the two dimensional CCD sensor.

13. A method of detecting and locating a first sample labeled by a first fluorescent tag and a second sample labeled by a second fluorescent tag, the method comprising the following steps:

a. placing the first sample and the second sample on a biochip;

b. selectively exciting the first sample on the biochip by substantially directing only light having a first excitation wavelength for exciting the first fluorescent tag from a broad spectrum light source to the first sample;

c. selectively detecting the first sample during the step of exciting the first sample by substantially directing only light having a first emission wavelength emitted by and from the first sample to a two dimensional CCD sensor;

d. selectively exciting the second sample on the biochip by substantially directing only light having a second excitation wavelength for exciting the second fluorescent tag from the broad spectrum light source to the second sample; and

e. selectively detecting the second sample during the step of exciting the second sample by substantially directing only light having a second emission wavelength emitted by and from the second sample to the two dimensional CCD sensor.

14. A method of detecting and locating samples labeled with a fluorescent tag, the method comprising the following steps:

a. arranging the samples in an array on a biochip;

b. simultaneously illuminating the array of samples with a light source;

c. focusing an emitted light from the sample via a lens wherein the lens has a focal length of approximately 25 millimeters and an f-stop value of 1;

0.85 and is located at a distance that is less than 6.0 inches from the sample;

d. simultaneously detecting the emitted light from the samples labeled with the fluorescent tag via a CCD sensor.

15. The method according to claim 14, further comprising inserting a light source filter adjacent to the light source wherein the light source filter is configured to substantially block light waves that have wavelengths outside an excitation wavelength range of the fluorescent tag from reaching the array of samples on the biochip.

16. The method according to claim 14 further comprising inserting a sensor filter adjacent to the CCD sensor wherein the sensor filter is configured to substantially block light waves that have wavelengths outside an emission wavelength range of the fluorescent tag from reaching the CCD sensor.

17. The method according to claim 14 wherein the CCD sensor comprises a two dimensional array of charge coupled devices.