Aviva Biosciences Corporation

Mingxian Huang

Lei Wu

Xiaobo Wang

Junquan Xu

Jing Cheng

Guoliang Tao

George T Walker

Jia Xu

Douglas T Yamanishi

Paul G Hujsak

Joe Ouyang

David M Rothwarf

Sara F Snyder

Ping Lin

Charina Schmitigal

Guo Liang Tao

Antonio Guia

Litian Liu

Weiping Yang

Depu Chen

Wei Shao

Baoquan Sun

Julian Yuan

Elizabeth Kwok

Charina Yap

Zhaohuai Yang

Jing Tsinghua University Cheng

The present invention recognizes that diagnosis and prognosis of many conditions can depend on the enrichment of rare cells, especially tumor cells, from a complex fluid sample such as a blood sample. In particular, the present invention is directed to methods and compositions for detecting a non-hematopoietic cell, e.g., a non-hematopoietic tumor cell, in a blood sample via, inter alia, removing red blood cells (RBCs) from a blood sample using a non-centrifugation procedure, removing white blood cells (WBCs) from said blood sample to enrich a non-hematopoietic cell, if any, from said blood sample; and assessing the presence, absence and/or amount of said enriched non-hematopoietic cell.

Methods and compositions for detecting non-hematopoietic cells from a blood sample

The present invention includes methods of enriching rare cells, such as cancer cells, from biological samples, such as blood samples. The methods include performing at least one debulking step on a blood sample and selectively removing at least one type undesirable component from the blood sample to obtain a blood sample that is enriched in a rare cell of interest. In some embodiments magnetic beads coupled to specific binding members are used to selectively removed components.

Methods and compositions for separating rare cells from fluid samples

The present invention includes biochips for the measurement of cellular ion channels and methods of use and manufacture. The biochips of the present invention have enhanced sealing capabilities provided in part by chemically modifying the surface of the biochip surface or substrate or by exposure to an ionized gas. The present invention also includes novel cartridges for biochips.

High-density ion transport measurement biochip devices and methods

The present invention recognizes that the determination of an ion transport function or property using direct detection methods, such as patch-clamps, whole cell recording or single channel recording, are preferable to methods that utilize indirect detection methods, such as FRET based detection system. The present invention provides biochips and methods of use that allow for the direct analysis of ion transport functions or properties using microfabricated structures that can allow for automated detection of one or more ion transport functions or properties. These biochips and methods of use thereof are particularly appropriate for automating the detection of ion transport functions or properties, particularly for screening purposes.

Biochips including ion transport detecting structures and methods of use

This invention relates generally to the field of moiety or molecule isolation, detection and manipulation and library synthesis. In particular, the invention provides a microdevice, which microdevice comprises: a) a magnetizable substance; and b) a photorecognizable coding pattern, wherein said microdevice has a preferential axis of magnetization. Systems and methods for isolating, detecting and manipulating moieties and synthesizing libraries using the microdevices are also provided.

Microdevices having a preferential axis of magnetization and uses thereof

This invention relates generally to the field of moiety or molecule isolation, detection and manipulation and library synthesis. In particular, the invention provides a bead, which bead comprises: a) a magnetizable substance; and b) an electrically conductive substance or an optical labeling substance. Methods and kits for isolating, detecting and manipulating moieties and synthesizing libraries using the beads are also provided.

Composite beads comprising magnetizable substance and electro-conductive substance

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.

Methods, compositions, and automated systems for separating rare cells from fluid samples

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. A first aspect of the present invention is a microfabricated filter for filtering a fluid sample. A microfabricated filter of the present invention comprises at least one tapered pore, and preferably comprises at least two tapered pores whose variation in size is 20% or less. The present invention also includes a method of enriching rare cells of a fluid sample using a microfabricated filter of the present invention. Another aspect of the invention is solutions for the selective sedimentation of red blood cells (RBCs) from a blood sample comprising a red blood cell aggregating agent and at least one specific binding member that selectively binds RBCs. Solutions of the present invention include a combined solution for rare cell enrichment that comprise RBC aggregating agents, at least one specific binding member that selectively binds RBCs, and at least one additional specific binding member for the removal of undesirable sample components other than RBCs. The invention also includes methods of using selective RBC sedimentation solutions and combined 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 comprises or engages one or more microfabricated filters of the present invention; automated means for directing fluid flow through the one or more filtration chambers of the automated system, and means for collecting enriched rare cells. The present invention also includes methods of using an automated system for separating rare cells from a fluid sample. Preferred fluid samples are effusion, blood, 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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San Diego, CA, United States of America

Mingxian Huang