Systems for transiently dynamic flow cytometer analysis

Abstract

A flow cytometry apparatus and methods to process information incident to particles or cells entrained in a sheath fluid stream allowing assessment, differentiation, assignment, and separation of such particles or cells even at high rates of speed. A first signal processor individually or in combination with at least one additional signal processor for applying compensation transformation on data from a signal. Compensation transformation can involve complex operations on data from at least one signal to compensate for one or numerous operating parameters. Compensated parameters can be returned to the first signal processor for provide information upon which to define and differentiate particles from one another.

Description

[0001] This application is a continuation of U.S. application Ser. No. 10 / 111,026 filed Apr. 18, 2002, which was the United States National Stage of International Application No. PCT / US00 / 41372 filed Oct. 20, 2000, which claims the benefit of U.S. Provisional Application 60 / 160,719, filed Oct. 21, 1999, each hereby incorporated by reference.[0002] This application makes reference to a Computer Program Listing Appendix submitted on two compact discs (which includes one duplicate copy), having the file name, “computerprogram.doc” containing 48 KB, all of which is hereby incorporated by reference herein. The compact discs were created on Mar. 30, 2006. I. TECHNICAL FIELD [0003] Specifically, flow cytometry apparatus and methods to process information incident to particles or cells entrained in a sheath fluid stream allowing assessment, differentiation, assignment, and separation of such particles or cells even at high rates of speed. II. BACKGROUND [0004] Flow cytometry is a field whic...

AI Technical Summary

Benefits of technology

The present invention is a flow cytometer with DSP technology that solves problems associated with high-speed serial occurrences, multiple parameter analysis, and detection of defects in products or services. The invention can convert original signals incident to the environment, instrument, or fluid stream into digital signals and apply compensation transformations to provide compensated parameters. It can also allocate, align, or coordinate data generated from the original signals and perform complex operations on the signals. The invention can save the original signal in a memory element or memory storage element without altering its quality or quantity. The invention provides software to implement various applications on DSP technology.

Problems solved by technology

Unfortunately, variation in equipment operation, sheath fluid stream dynamics, or observed particle characteristics still exists and are exacerbated by increasing the speed at which entrained substances are carried in the jet.

Some of the practical problems which have also been recognized is the fact that only a limited amount of space and time exists within which to conduct sensing and analysis.

As can be understood, a substantial problem can be that the data generated from an occurrence must be sensed and reacted upon in an extremely short period of time.

The challenge for this unique flow cytometry situation is that original or raw signal data can be sub-optimal and even unusable.

This processing can be complex and can require more processing speed and power than is available not just with typical commercial systems, but even with today's highest-speed computer systems.

Further, as the desire for higher processing frequencies is pursued, problems can be compounded.

To some degree, these expectations have been so prevalent that quality control, good manufacturing practices, regulatory approval, and other concerns have been set aside, diminished, or even compromised.

Another significant problem associated with conventional analysis and compensation of variables in flow cytometry can be the preservation of original signal data from an occurrence incident to the fluid stream prior to subsequent processing steps.

It may not have been possible to preserve or store original signal data until now due to the short amount of time in which to analyze or compensate the original signal.

Yet another problem with conventional analysis may be the inability to process high speed serial occurrences, to compensate multiple parameters, to perform complex operations, to provide transformation compensation of original data, or to apply compensated parameters.

Conventional analysis can be limited by the amount of information that can be processed and returned in between serial events which can occur at a rates of at least 10,000 per second.

Conventional flow cytometer signal processors, often because they are analog, are not capable of dealing with large amounts of signal information, cannot perform operations on low quality signal information, cannot practically accomplish complex transformation operations (such as those which use algebraic expressions or structure), or they perform only reflexive feed back operations rather than serial or multi-variant analysis followed by subsequent parameter compensation.

In part, conventional infrastructure may not deal with how the streams of information are allocated, aligned, and coordinated.

As such, it can become increasingly difficult to synchronize various aspects of flow cytometer operation as the number of feed back loops increases.

Moreover, these feed back loops may be completely uncoupled.

A third aspect of this inability may be lack of symmetry reduction in the application of transformed data.

The lack of symmetry reduction or the inability to apply symmetry reduction to analysis terms may increase execution time.

As mentioned above, there has been a long felt but unsatisfied need for apparatus and methods which permit complex signal transformation, and use of compensated parameters resulting from complex signal transformation, real time analysis using compensated parameters, or storage of original signal data generated incident to the fluid stream, instrument variance, or environmental variance.

This may have been the result of the fact that those skilled in the art did not truly appreciate the nature of the problem or it may have been the result of the fact that those skilled in the art were misled by some of the presumptions and assumptions with respect to the type of systems which could be considered.

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