Ensemble-decision aliquot ranking

Abstract

Provided herein, among other aspects, are methods and apparatuses for ranking aliquots from a suspension containing bioparticles. In certain embodiments, the bioparticles may be cells, organelles, proteins, DNAs, debris of biological origin, microbeads coated with biological compounds, or viral particles. As such, the methods and apparatuses provided herein may be used to quantify rare cells such as circulating cancer cells, fetal cells and other rare cells present in bodily fluids for disease diagnosis, prognosis, or treatment.

Description

CROSS-REFERENCES TO RELATED APPLICATIONS[0001]The present application claims the benefit of U.S. Provisional Application No. 61 / 168,892 filed Apr. 13, 2009, expressly incorporated herein by reference in its entirety for all purposes.STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT[0002]NOT APPLICABLEREFERENCE TO A “SEQUENCE LISTING,” A TABLE, OR A COMPUTER PROGRAM LISTING APPENDIX SUBMITTED ON A COMPACT DISK[0003]NOT APPLICABLEBACKGROUND OF THE INVENTION[0004]Body fluids are complex suspensions of biological particles in liquid. Blood, for example, includes plasma and cells (red blood cells, white blood cells, platelets) and the cells occupy about 55% of blood. Plasma is mostly water and it transfers proteins, ions, vitamins, enzymes, hormones, and other chemicals to cells in the body.[0005]Red blood cells are about 6 to 8 μm in size and serve to provide oxygen to cells. White blood cells are about 10 to 13 μm in diameter and they defend th...

AI Technical Summary

Benefits of technology

The present invention provides methods and apparatuses for quickly scanning a large volume of fluid to detect and quantitate desired bioparticles by ranking aliquots. This approach, called Ensemble-Decision Aliquot Ranking (eDAR), is particularly useful for detecting rare cells in biofluids. The invention can provide a diagnosis or prognosis for a condition associated with the presence of a rare particle in a biological fluid by detecting the rare particle in an aliquot of the fluid sample, assigning a value to the aliquot based on the presence or absence of the rare particle, and providing a diagnosis or prognosis to the subject based on the assigned value. The invention also includes a device for detecting a rare particle in a fluid sample with a detector, a mechanism for directing the flow of the fluid sample, and a computer capable of assigning a value to the fluid sample based on the presence, absence, identity, composition, or quantity of rare particles in the sample.

Problems solved by technology

Using conventional techniques, such as automatic digital microscopy (ADM) scanning at a typical speed of 800 cells / second, would require 18 hours to complete a sample that size, rendering it monetarily and temporally impractical for clinical use.

However, flow cytometry requires that the cells are organized linearly in a row and detect each cell singularly because simultaneous detection of two cells cannot be interpreted correctly using existing technology.

As such, flow cytometry is not suitable for detecting or recovering rare cells.

Detecting cells one at a time (serially) and making a decision on the trajectory of every cell is too time-consuming when analyzing a large number of cells.

For rare cell, often 7-15 mL of blood is required to collect a statistically significant number of rare cells; using a flow cytometer to recover rare cells is an impractical consumption of clinical resources and can translate to a very high testing cost.

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