Methods, compositions, and automated systems for separating rare cells from fluid samples
First Claim
1. An automated system for enriching rare cells of a fluid sample, comprising:
- a) automated fluid volume sensing means for sensing the volume of at least one sample or a portion thereof provided in at least one tube or vessel, said automated fluid volume sensing means comprising at least one collated light source and at least one light-sensor;
b) at least one filtration chamber that comprises or engages at least one microfabricated filter comprising one or more tapered pores;
c) at least one power supply or signal source or control circuit for automated control and powering of fluid flow through said at least one filtration chamber; and
d) means for collecting enriched rare cells.
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Accused Products
Abstract
The present invention recognizes that diagnosis and prognosis of many conditions can depend on the enrichment of rare cells from a complex fluid sample. In particular, the enrichment of fetal cells from maternal samples, such as maternal blood samples, can greatly aid in the detection of fetal abnormalities or a variety of genetic conditions. In addition, the present invention recognizes that the enrichment of rare malignant cells from patient samples, can aid in diagnosis, prognosis, and development of therapeutic modalities for patients. The invention includes microfabricated filters for filtering fluid samples and methods of enriching rare cells of fluid samples using microfabricated filters of the present invention. The invention also includes solutions for the selective sedimentation of red blood cells (RBCs) from a blood sample and methods of using selective RBC sedimentation solutions for enriching rare cells of a fluid sample. Yet another aspect of the invention is an automated system for processing a fluid sample that includes: at least one filtration chamber that includes a microfabricated filter; automated means for directing fluid flow through at least one filtration chamber of the automated system, and means for collecting enriched rare cells. The present invention also includes methods of using automated systems for separating rare cells from fluid samples. Preferred fluid samples are blood, effusion, or urine samples, and rare cells that can be enriched from such sample include nucleated red blood cells and cancer cells.
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Citations
66 Claims
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1. An automated system for enriching rare cells of a fluid sample, comprising:
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a) automated fluid volume sensing means for sensing the volume of at least one sample or a portion thereof provided in at least one tube or vessel, said automated fluid volume sensing means comprising at least one collated light source and at least one light-sensor; b) at least one filtration chamber that comprises or engages at least one microfabricated filter comprising one or more tapered pores; c) at least one power supply or signal source or control circuit for automated control and powering of fluid flow through said at least one filtration chamber; and d) means for collecting enriched rare cells. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 45)
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23. A filtration unit, comprising:
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a filtration chamber, wherein said filtration chamber comprises an antechamber and a post-filtration subchamber separated by one microfabricated filter comprising one or more tapered pores;
wherein said antechamber comprises an inlet and wherein said post-filtration subchamber comprises an outlet and at least one side port;a frame comprising; a loading reservoir; at least one sample loading valve that can provide fluid communication between said loading reservoir and said filtration chamber; at least one waste port that can reversibly engage said post-filtration subchamber via said outlet; and at least one port for collecting enriched rare cells that can reversibly engage said antechamber via said inlet. - View Dependent Claims (24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55)
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56. An automated fluid volume sensing system for determining the level of a sample or a portion of a sample, comprising:
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at least one bar in an essentially horizontal orientation, that is positioned or can be positioned proximal to a rack or sample holder, wherein said bar comprises; a light source on one end of said bar and a light sensor on another end of said bar, wherein the vertical level of the bar corresponds to the vertical level of the light source; wherein when a sample is in said rack or sample holder, said light source is positioned on one side of said sample, and said light sensor is positioned on the opposite side of said sample; further wherein said bar can move in a vertical direction, to allow said light source and said light sensor to scan a sample held in said rack or sample holder. - View Dependent Claims (57, 58, 59)
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60. An automated fluid volume sensing!fluid volume uptake system for determining a volume of a sample supernatant in a sample tube or vessel and removing said volume of a sample supernatant from said sample tube or vessel, comprising:
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at least one bar in an essentially horizontal orientation, that is positioned or can be positioned proximal to a rack or sample holder, wherein said bar comprises; a light source on one end of said bar and a light sensor on another end of said bar, wherein the vertical level of the bar corresponds to the vertical level of the light source; wherein when a sample is in said rack or sample holder, said light source is positioned on one side of said sample, and said light sensor is positioned on the opposite side of said sample; further wherein said bar can move in a vertical direction, to allow said light source and said light sensor to scan a sample held in said rack or sample holder; a collection tip, wherein said collection tip is comprises a conduit for the uptake and dispensing of fluid, further wherein said collection tip can move in a horizontal plane, to position itself over a tube in said rack or holder, and can move in a vertical plane, to reach the level of the bar or a level within said sample tube. - View Dependent Claims (61, 62, 63, 64, 65, 66)
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Specification