Optical detection system for the detection of organic molecules

Details Optical detection system for the detection of organic molecules Optical detection system for the detection of organic molecules

2000-01-18

2001-12-04

Borin, Michael (Department: 1631)

Chemical apparatus and process disinfecting, deodorizing, preser

Analyzer, structured indicator, or manipulative laboratory...

Means for analyzing liquid or solid sample

C422S068100, C422S082110, C422S082090, C422S082090, C436S006000, C436S094000, C436S149000

Reexamination Certificate

active

06325977

ABSTRACT:

FIELD OF THE INVENTION
The invention relates generally to the detection of organic molecules, and more particularly to the detection of organic molecules, such as DNA, utilizing an optical sensor array.
BACKGROUND
Organic molecules, such as DNA and RNA, can be analyzed utilizing genetic chips that include a matrix of test sites. A single genetic chip may include 1,000 to 500,000 individual test sites. The test sites are individually activated and responses are detected utilizing various activation and detection techniques. One technique for analyzing organic molecules involves combining the molecules with optically active receptors. The optically active receptors are then activated and light emitted from each test site is individually detected and quantified.
One known system for detecting light at a test site includes a charged coupled device (CCD) that is formed in close proximity to each test site. For example, an array of test sites can be formed over a CCD array such that each pixel of the CCD array corresponds to an individual test site. While this optical detection technique works well, there are disadvantages to utilizing CCD arrays.
Although CCD arrays have been widely utilized as image sensors, CCD arrays require specialized processes and equipment for fabrication. CCD arrays are also difficult to integrate with digital and analog circuitry that is designed around standard complementary metal oxide semiconductor (CMOS) technology. In addition, CCD arrays dissipate large amounts of power and may suffer from image smearing problems.
An alternative to a CCD array is active pixel sensor array. Active pixel sensor arrays can be fabricated utilizing CMOS technology and, therefore, can be easily integrated with digital and analog signal processing circuitry. Further, CMOS circuits dissipate smaller amounts of power compared to CCDs.
In view of the disadvantages of CCD arrays and the availability of active pixel sensors, what is needed is a system for optically detecting organic molecules that utilizes active pixel sensors.
SUMMARY OF THE INVENTION
The invention includes an integrated circuit, photosensors integrated with the integrated circuit, a passivation layer formed above the photosensors, and test sites formed on the passivation layer. The test sites may include test probes of organic material that are able to bind with target organic molecules. The combination of the test probes and target organic molecules can be activated such that light is given off from the test sites in proportion to the concentration of target molecules. Light given off from the test sites is detected by the photosensors that are present below the passivation layer. The photosensors generate electronic signals in proportion to the amount of light received from the test sites. The electronic signals are then transmitted from the photosensors to the integrated circuit for signal processing. Signal processing within the integrated circuit can enhance the quality of the electronic signals generated by the photosensors.
A first embodiment of an optical detection system includes an integrated circuit, an insulation layer, photodiodes, a transparent conductive layer, a passivation layer, and test sites.
The integrated circuit is electrically connected to the photodiodes and may include sensing circuits, signal processing circuits, or other circuits that support signal detection and readout. Techniques utilized to fabricate the integrated circuit may include CMOS, BiCMOS, or Bipolar.
The insulation layer separates the photodiodes from the integrated circuit. The insulation layer is patterned to provide contact holes (generally one per pixel) between the photodiodes and the integrated circuit.
The photodiodes, also referred to as active pixel sensors, generate electrical signals having amplitudes that are related to the intensity of the light that is received by the photodiodes. The photodiodes may include PIN, NIP, PN, or Schottky diodes.
The transparent conductive layer acts as the front electrode for the photodiodes. The transparent conductive layer is deposited as a continuous film and is a common electrode for all of the pixels.
The passivation layer is a transparent layer that provides an electrical barrier between the test sites and the transparent conductive layer. In an embodiment, the passivation layer is formed of silicon dioxide.
The test sites are preferably located directly above photodiodes such that each test site corresponds to a photodiode. That is, a test site and a photodiode are located in close proximity to each other and have a one to one correspondence.
The test probes include organic molecule receptors that are capable of binding to known molecular structures. The known molecular structures that bind to the receptors are referred to as targets. The targets may include biopolymers, such as polynucleotides, polypeptides, DNA, RNA, cells, or antibodies. The test probes are formed at the test sites utilizing techniques such as inkjet based writing, electrochemical based writing, and photolithography.
The targets, also referred to as the sample, are typically marked with tags that give off light when activated. For example, the tags may include compounds that fluoresce when activated. The targets are introduced to the test probes so that compatible test probes and targets can bind together. After the test probes and targets have bound together, the test sites are activated. Techniques for activating test sites in order to generate light include chemiluminescence, electroluminescence, and electrochemiluminescence. The particular activation technique is not critical to the invention and therefore is not described further. If an activated test site includes a tag bound to the test probe, then the test site generates light that is detected by the corresponding photodetector. The amount of light generated at each test site gives an indication of the presence and concentration of the target.
A method for forming a detection system includes fabricating an integrated circuit that includes photosensors. A passivation layer is deposited above the photosensors. Test sites are formed above the passivation layer. Additionally, test probes of organic material are bound to the passivation layer.
Preferably, test sites and photosensors are arranged in a manner that maximizes the collection efficiency of the light generated from each photosensor while minimizing interference from neighboring test sites. Because the test sites are located directly above the photosensors, there are no external optical paths between the test sites and the photosensors. The short optical paths between the test sites and the photosensors result in high light collection efficiency.
Other aspects and advantages of the present invention will become apparent from the following detailed description, taken in conjunction with the accompanying drawings, illustrating by way of example the principles of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1
shows an embodiment of an optical detection system that includes test sites and photodiodes that are formed above an integrated circuit, in accordance with the invention.
FIG. 2
shows an embodiment of an optical detection system that includes test sites and active pixel sensors that are formed above an integrated circuit, in accordance with the invention.
FIG. 3
shows an embodiment of an optical detection system that includes test sites and active pixel sensors that are formed above an integrated circuit, in accordance with the invention.
FIG. 4
shows an embodiment of an optical detection system that includes test sites formed above an integrated circuit that includes integrated photosensors, in accordance with the invention.
FIG. 5
is a process flow diagram of a method for forming a detection system that includes test sites formed above an integrated circuit that includes integrated photosensors, in accordance with the invention.


REFERENCES:
patent: 4926231 (1990-05-01), Hwang et al.
patent: 5846708 (1998-12-01), Hollis
patent: 5936261 (1999-08-01), Ma et al.
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