Chemistry: molecular biology and microbiology – Apparatus – Including measuring or testing
Reexamination Certificate
2001-04-05
2004-07-06
Ponnaluri, Padmashri (Department: 1639)
Chemistry: molecular biology and microbiology
Apparatus
Including measuring or testing
C435S287100, C435S287200, C435S006120, C435S007920, C435S007930, C436S164000, C436S172000
Reexamination Certificate
active
06759235
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention generally provides devices, compositions of matter, kits, systems and methods for detecting and identifying a plurality of signals from within a signal area. In a particular embodiment, the invention provides systems and methods for detecting and identifying a plurality of spectral barcodes from throughout a sensing area, especially for identifying and/or tracking inventories of elements, for high-throughput assay systems, and the like. The invention will often use labels which emit identifiable spectra that include a number of discreet signals having measurable wavelengths and/or intensities.
Tracking the locations and/or identities of a large number of items can be challenging in many settings. Barcode technology in general, and the Universal Product Code in particular, has provided huge benefits for tracking a variety of objects. Barcode technologies often use a linear array of elements printed either directly on an object or on labels which may be affixed to the object. These barcode elements often comprise bars and spaces, with the bars having varying widths to represent strings of binary ones, and the spaces between the bars having varying widths to represent strings of binary zeros.
Barcodes can be detected optically using devices such as scanning laser beams or handheld wands. Similar barcode schemes can be implemented in magnetic media. The scanning systems often electro-optically decode the label to determine multiple alphanumerical characters that are intended to be descriptive of (or otherwise identify) the article or its character. These barcodes are often presented in digital form as an input to a data processing system, for example, for use in point-of-sale processing, inventory control, and the like.
Barcode techniques such as the Universal Product Code have gained wide acceptance, and a variety of higher density alternatives have been proposed. Unfortunately, these standard barcodes are often unsuitable for labeling many “libraries” or groupings of elements. For example, small items such as jewelry or minute electrical components may lack sufficient surface area for convenient attachment of the barcode. Similarly, emerging technologies such as combinatorial chemistry, genomics research, microfluidics, micromachines, and other nanoscale technologies do not appear well-suited for supporting known, relatively large-scale barcode labels. In these and other developing fields, it is often desirable to make use of large numbers of fluids, and identifying and tracking the movements of such fluids using existing barcodes is particularly problematic. While a few chemical encoding systems for chemicals and fluids have been proposed, reliable and accurate labeling of large numbers of small and/or fluid elements remains a challenge.
Small scale and fluid labeling capabilities have recently advanced radically with the suggested application of semiconductor nanocrystals (also known as Quantum Dot™ particles), as detailed in U.S. patent application Ser. No. 09/397,432, the full disclosure of which is incorporated herein by reference. Semiconductor nanocrystals are microscopic particles having size-dependent optical and/or electrical properties. As the band gap energy of such semiconductor nanocrystals vary with a size, coating and/or material of the crystal, populations of these crystals can be produced having a variety of spectral emission characteristics. Furthermore, the intensity of the emission of a particular wavelength can be varied, thereby enabling the use of a variety of encoding schemes. A spectral label defined by a combination of semiconductor nanocrystals having differing emission signals can be identified from the characteristics of the spectrum emitted by the label when the semiconductor nanocrystals are energized.
While semiconductor nanocrystal-based spectral labeling schemes represent a significant advancement for tracking and identifying many elements of interest, still further improvements would be desirable. In general, it would be beneficial to provide improved techniques for sensing or reading these new spectral labels. It would be particularly beneficial to provide improved techniques for applying these labeling and tracking technologies to high-throughput assay systems now being developed.
Multiplexed assay formats would be highly desirable for improved throughput capability, and to match the demands that combinatorial chemistry is putting on established discovery and validation systems for pharmaceuticals. For example, simultaneous elucidation of complex protein patterns may allow detection of rare events or conditions, such as cancer. In addition, the ever-expanding repertoire of genomic information would benefit from very efficient, parallel and inexpensive assay formats. Desirable multiplexed assay characteristics include ease of use, reliability of results, a high-throughput format, and extremely fast and inexpensive assay development and execution.
A number of known assay formats may be employed for high-throughput testing. Each of these formats has limitations, however. By far the most dominant high-throughput technique is based on the separation of different assays into different regions of space. The 96-well plate format is the workhorse in this arena.
In 96-well plate assays, the individual wells (which are isolated from each other by walls) are often charged with different components, and the assay is performed and then the assay result in each well measured. The information about which assay is being run is carried with the well number, or the position on the plate, and the result at the given position determines which assays are positive. These assays can be based on chemiluminescence, scintillation, fluorescence, scattering, or absorbance/colorimetric measurements, and the details of the detection scheme depend on the reaction being assayed.
Multi-well assays have been reduced in size to enhance throughput, for example, to accommodate 384 or 1536 wells per plate. Unfortunately, the fluid delivery and evaporation of the assay solution at this scale are significantly more confounding to the assays. High-throughput formats based on multi-well arraying often rely on complex robotics and fluid dispensing systems to function optimally. The dispensing of the appropriate solutions to the appropriate bins on the plate poses a challenge from both an efficiency and a contamination standpoint, and pains must be taken to optimize the fluidics for both properties. Furthermore, the throughput is ultimately limited by the number of wells that one can put adjacent on a plate, and the volume of each well. Arbitrarily small wells have arbitrarily small volumes, resulting in a signal that scales with the volume, shrinking proportionally with the cube of the radius. The spatial isolation of each well, and thereby each assay, has been much more common than running multiple assays in a single well. Such single-well multiplexing techniques are not widely used, due in large part to the difficulty in “demultiplexing” or resolving the results of the different assays in a single well.
For even higher throughput genomic and genetic analysis techniques, positional array technology has been shrunk to microscopic scales, often using high-density oligonucleotide arrays. Over a 1-cm square of glass, tens to hundreds of thousands of different nucleotides can be written in, for example, 25-&mgr;m spots, which are well resolved from each other. On this planar test structure or “chip,” which is emblazoned with an alignment grid, a particular spot's x,y position determines which oligonucleotide is present at that spot. Typically fluorescently-labeled amplified DNA is added to the array, hybridized and is then detected using fluorescence-based techniques. Although this is a very powerful technique for assaying a large number of genetic markers simultaneously, the cost is still very high, and the flexibility of this assay is extremely limited.
Once a chip is made with particular DNA sequences at particular locations, they
Empedocles Stephen A.
Watson Andrew R.
Barrish, Esq. Mark D.
Ponnaluri Padmashri
Quantum Dot Corporation
Townsend & Townsend & Crew LLP
Tran My-Chau T.
LandOfFree
Two-dimensional spectral imaging system does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Two-dimensional spectral imaging system, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Two-dimensional spectral imaging system will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3242561