Thursday, December 30, 2010

Commercial Circulating Tumor Cell CTC technology platforms



For a comprehensive review on the various CTC technologies and the clinical significance of CTCs, please refer to our review paper downloadable here

Company
Website
Technology
Veridex Cellsearch systemhttp://www.veridex.com/cellsearch/Products.aspxEpCAM coated beads based positive selectio using magnetic beads followed by stainign and image analysis
http://clincancerres.aacrjournals.org/content/10/20/6897.short
http://youtu.be/Sg8-LNR4cIA
Biocept Laboratorieshttp://www.biocept.com/Biocept's microfluidic channel is coated with Streptavidin . CTCs are captured using an antibody cocktail, which includes EpCAM, that is added to cells prior to capture. 
http://bmf.aip.org/resource/1/biomgb/v5/i3/p034119_s1?isAuthorized=no
Onqityhttp://www.on-q-ity.com/EpCAM coated microposts arranged in a geometric pattern to creat a size gradient. end result is a compbination of EpCAM and size enrichment
http://www.on-q-ity.com/science/
*Update: I received information from an ex-employee that they have run out of funding and closing operations as of Jan 2013
official: http://bit.ly/13z6ESz
Screencell http://www.screencell.com/size-based filtration 6.5 um and 5.5 um porous membranes for fixed and unfixed cells respectively
http://ar.iiarjournals.org/content/31/2/427.short
Apocell http://www.apocell.com/ dielectrophoretic flow field fractionation. uses electrical property differentiation between normal blood cells and tumor cells
http://bmf.aip.org/resource/1/biomgb/v6/i2/p024133_s1?ver=pdfcov
Parsortixhttp://www.angleplc.com/ uses size and deformability using a wier-type step filter
http://vimeo.com/40643776
Clearbridge Biomedics http://www.clearbridgebiomedics.com/lateral traps to capture tumor cells based on size and deformability
http://vimeo.com/30298239
http://link.springer.com/article/10.1007%2Fs10544-009-9305-9
Creatv Microtech http://www.creatvmicrotech.com/ctc.htmlprecision manufactured size-filter
http://www.creatvmicrotech.com/Documents/AACR_CTC_poster.pdf
Epic Biosciences http://epicsciences.com/PBMCs are layered on glass slide and imaaged using a high definition scanner
http://iopscience.iop.org/1478-3975/9/1/010301
Adnagen http://www.adnagen.com/hosting_i24/daten/combination of antibodies on magnetic beads to enrich cells followed by nested PCR
http://www.adnagen.com/hosting_i24/daten/HTML_Dateien/e_technology_references.htm
Genetx ariol http://www.genetix.com/en/home/index.htmlautomated imaging
Grenier Bio one -oncoquick http://www.greinerbioone.com/en/row/articles/catalogue/article-groups/283_11/ficoll gradient tube with filter to keep the separated fractions from intermizing.
Miltenyi Biotech http://www.miltenyibiotec.com/en/NN_1038_Automated_Cell_Separation.aspxEpCAM magnetic bead based selection
http://clincancerres.aacrjournals.org/content/early/2011/04/28/1078-0432.CCR-10-0498.full.pdf
FAST http://www.parc.com/event/744/detection-and-characterization-of-circulating-tumor-cells.htmlLaser scanning of all blood cells

Ikonisys http://www.ikonisys.com/?q=node/2automated imaging platform combined with size-based isolation
http://www.youtube.com/watch?v=XSUg9LJ7_IU
EPISPOT http://www.lorentzcenter.nl/lc/web/2011/442/abstracts.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/22527495
Silicon Biosystems http://www.siliconbiousa.com/electronic chip to further purify coarsely enriched CTCs
Celula

Celltrafix(http://celltraffix.com/content/blogcategory/15/34/ http://link.springer.com/article/10.1007%2Fs10549-011-1603-2?LI=true
Cynvenio Biosystemshttp://cynvenio.com/high throughput microfluidic sheath flow isolation technology by ferrofluid with cell staining plus downstream DNA analysis via next generation sequencing and/or quantitative allele-specific PCR (Q-PCR) 
http://www.cynvenio.com/storage/technical-library/AACR2012Poster.pdf
Advanced Cell diagnosticshttp://www.acdbio.com/multi-fluorescent RNA in situ hybridisation (ISH)-based CTC detection system named CTCscopeTM
Fluxion Biosystemshttp://www.fluxionbio.com/products/isoflux-circulating-tumor-cell-system/default.aspx 

EpCAM based positive selection
http://youtu.be/QaqULssda98
Sysmex http://www.sysmex.co.jp/en/news/press/2009/090121.html
Synergex corporation http://www.synergxcorp.com/pacs.htm
Vitatexhttp://www.vitatex.com/default.asp?f=on
Bioview http://www.bioview.co.il/HTMLs/Home.aspxAutomated imagining and FISH. isolaiton is performed using ScreenCell's paltform
Aviva Bioscienceshttp://avivabio.com/products/selectionfilter.phpcombination of size-based RBC depletion and WBC depletion
http://pubs.rsc.org/en/Content/ArticleLanding/2010/LC/b922301k
Denovo scienceshttp://www.denovosciences.com/stealth mode
Biofluidicahttp://www.biofluidica.com/EpCAM coated chip to capture followed by release of cells and electrical counting
http://pubs.acs.org/doi/abs/10.1021/ja8015022
Rarecellshttp://www.rarecells.com/size-based enrichment with track-etched polycarbonate membrane
http://www.rarecells.com/iset-publication.html
Maintrachttp://www.maintrac.com /Cells from EDTA-blood were subjected to erythrocyte lysis, isolated by centrifugation, and incubated with a fluorescence-labeled antibody against. EpCAM. The numbers of vital cells were counted via fluorescence microscopy
http://www.laborpachmann.de/pdf/NuklearmedizinWinkens_nu5241208.pdf
Fluidigmhttp://www.fluidigm.com/single cell analysis platform
http://www.fluidigm.com/publications.html 
Precelleonhttp://www.precelleon.com/magnetic cell enrichment
http://www.precelleon.com/files/yang_liying.pdf
TelomeScanhttp://www.oncolys.com/en/index.htmlTelomeScan system does not use EpCAM enrichment. TelomeScan is viral diagnostic reagent to detect viable CTCs including lung cancer. Currently Oncolys BioPharma Inc. in Tokyo is conducting various feasibility studies to detect viable CTCs from 7.5 mL blood and differenciate EMT-CTC and CSC.
http://www.jci.org/articles/view/38609/files/pdf
Cytotrackwww.cytotrack.comCytoTrack detects CTCs without enrichment (such as EpCAM) and without bias on size (such as filtration). CytoTrack has a capacity to scan 100 million cells in just one minute. CytoTrack is commercial available. Please see video on our website.
http://www.cytotrack.com/video.html
ODOSA
(One-Drop, One-Step Assay for Circulating Tumor Cell Detection)
http://bit.ly/XvFumj


The invention is a cell-specific, intracellularly-activated, one step assay for the detection of circulating tumor cells (CTC) in a single drop of blood. The invention is based on cell-specific aptamers linked to fluorophores and quenchers. Lysosomal degradation leads to release of quenching and switches on a strong fluorescent signal in CTCs.





Most promising CTC technologies (from opinion poll conducted by World CTC-Berlin 2013)


image source: http://worldctc-berlin.com/uploads/ffiles/2013/03/145979.pdf



CellSearch (FDA-approved, sFDA (china)-approved, CE-marked)
Company info: 
Veridex, LLC, a Johnson & Johnson Company was founded in 2004 to market the only FDA–approved CTC test.
http://www.veridex.com/
https://www.cellsearchctc.com/sites/default/files/docs/cellsearch-brochure.pdfDescription:
The CellSearch® system consists of the CellTracks Autoprep to immnomagnetically enrich cells expressing EpCAM from 7.5 ml of blood and fluorescently label enriched cells with DAPI, CD45-APC and CK-PE. After which the cells are re-suspended in the cartridge, which is then placed in the CellTracks Magnest which is subsequently placed on the CellTracks Analyzer II. The Analyzer system acquires images using a 10 X NA 0.45 objective with filters for DAPI, PE and APC. The computer generated images are reviewed to confirm CTCs as nucleated DAPI+ cells, lacking CD45 and expressing CK-PE. 



ON-Q-ITY 
Company info: 
On-Q-ity of Waltham, Massachusetts, is commercializing a microchip developed in the lab of Mehmet Toner at Massachusetts General Hospital and Harvard University. On-Q-ity, which stands for “Oncology + Quality + Clarity: On-Q-ity” is an innovative diagnostic company focused on novel technique for circulating tumor cell (CTC) capture and characterization
http://www.on-q-ity.com/
Description:
On-Q-ity employs technology which uses a geometrically enhanced microfluidic immunocapture approach. The OnQChip™ dual capture microfluidic chips capture CTCs by both size and affinity. Chips are manufactured by hot embossing procedure which produces an open chamber containing ~100,000 posts from a plastic slide. The OnQChip™ derivatized with a antiEpCAM, capture cells and filters the blood. Captured cells on the chip were then fixed, permeabilized, and stained with a pan-cytokeratin PE MAb, an anti-CD45 Alexa647 Ab, and DAPI for fluorescent visualization under 5x magnifications using the OnQScan™ fluorescent microscope system. 

AdnaGen 
Company info: Adnagen was acquired by Alere.

http://www.adnagen.com/

Description:
AdnaGen's proprietary 'combination-of-combinations-principle' allows the reliable and very sensitive detection of CTCs. In their approach cancer cells are first enriched in vitro from cancer patient’s blood samples (EDTA or AdnaCollect) using magnetic bead conjugated antibodies. The labeled cells are extracted by a magnetic particle concentrator (AdnaMag and AdnaMag-S) and are subsequently lysed. The cell lysate is used to get mRNA for further analysis. The isolated mRNA is transcribed into cDNA that can be amplified in a following multiplex-PCR. The multiplex PCR detection step analyses the tumor associated gene expression of a variety of relevant tumor markers to make sure that the selected cells are cancer cells. Tests are offered as reagent sets for the detection of cancer cells in human blood. 

BIOCEPT 
Company info: 
Biocept Inc of San Diego, California, in May received a patent for its microfluidic device to isolate circulating tumor cells from body fluids.
www.biocept.com

Description:
 The company's technology captures rare cells in a microfluidic device, which can be used for a variety of different tests. Their unique technology (CEETM-cell enrichment and extraction) and family of laboratory tests (OncoCEETM) offer high value oncology tests. This cell enrichment technology exploits the placement of posts and flow rates through mathematical modeling to enhance isolation and capture of extremely rare cells within a microfluidic channel. By using the CEETM attachment chemistry, the CTCs are captured, immobilized and heated to temperatures for denaturation and hybridization of direct labeled DNA FISH probes to targeted sequences. The cells can also be retrieved through high shear from within the microchannel and concentrated for Taqman real-time PCR assessment of single gene mutations or deletions.

BioCep
Company info: 
BioCep, an Israeli medical device research company, has developed a Cell Enrichment Process (CEP) system for cell separation from various clinical sources
http://www.biocep.com/

Description:
BioCep utilizes the magnetic, closed circuit, generated "virtual mesh" with immunomagnetic marked cells for target cell separation without any surface contact with the targeted cells. Also it uses continuous, linear separation areas created by use of tubing as both transport and separation vessels. Tests have shown that the CEP renders 96-99% pure cells with recovery of 80-99% and viability of 99% in 5-15 min for 109 cells. BioCep is currently developing applications in non-invasive prenatal testing and stem cell separation, based on its advanced technology. The company will market its CEP system as research use only device and will provide consumable kits to its customers.

Fluxion 
Company info: 
Fluxion, founded in 2005 in South San Francisco area, developed IsoFlux Rare Cells Access System for CTCs detection. 
www. fluxionbio.com

Description:
      Benchtop instrument and microfluidic chip for CTC isolation using flow focusing to achieve high efficiency cell separation. Immunomagnetic beads support user-defined capture criteria using one or more capture antibodies (e.g. not limited to EpCAM). Enriched CTC samples are optimized for downstream molecular workflows (qPCR, NGS, FISH, etc.) by providing low elution volume (<20uL), high CTC capture, and minimal background cells.
                                                           
STEMCELL Technologies Inc
Company info: 
 STEMCELL Technologies Inc is a privately-owned biotechnology company that develops speciality cell culture media and cell separation products primarily. STEMCELL grew out of the Media Preparation Service (originally created in 1981) of the Terry Fox Laboratory for Hematology/Oncology Research at the British Columbia Cancer Agency. In 1993, the Media Preparation Service was spun off as STEMCELL Technologies Inc.
Description:
 STEMCELL Technologies offers a wide range of optimized cell separation products for the isolation of cancer cells with their cell separation platforms (high purity and recovery), RosetteSep®, EasySep®, and RoboSep®. They are based on surface antigen immunochemistry based cell separation. They also have column based immunomagnetic negative selection of human epithelial tumor cells StemSep® which is a semi-automated mesofluidic system for epithelial tumor cell isolation.
                                                                                               
BioFluidica Microtechnologies
Company info: 
 BioFluidica Microtechnologies LLC, formed in 2007 develops and commercializes medical diagnostics, pathogen detection, and personalized medicine.
www.biofluidica.com

Description:
 Their CTC detection technology was developed at Louisiana State University. BioFluidica's CTC detection system consists of a portable instrument that works in conjunction with a disposable test-specific polymer cartridge the size of a standard microscope slide. The cartridge has a nano-engineered, high-aspect ratio capture bed. Monoclonal antibodies or aptamers, specific for antigenic integral membrane proteins (EpCAM and/or others) expressed by the target cells, are immobilized on the surfaces of this capture bed. Once the entire sample has been processed, the fluidic channels are rinsed to assure high purity of the subsequent elution of the target cells.  Then the target cells are released from the capture surface and swept through a highly specific, single-cell conductivity sensor, where they are counted and then collected. This counting method eliminates the need for cell labeling and expensive optical detection. Because these cells are intact and viable, they are then available for molecular and/or other analyses. The instrument housing for BioFluidica's CTC detection system contains all the equipment, sample and bulk chemicals needed to process the sample in the polymer cartridge. Typically, the instrumentation include micropumps, a sample container, bulk reagent containers, electronics for the electrical conductivity sensor, and a data acquisition card that can be connected to a USB port. The instrument housing is approximately 1 cubic foot in size, and lightweight. Their applications are focused on CTC detection and molecular diagnostics.

Cynvenio biosystems 
Company info: 
www.cynvenio.com

Description:
Cynvenio biosystems is developing an automated and integrated system that includes upstream CTCs isolation by using combination of microfluidics sheath flow technology and magnetic separation, and the downstream DNA analysis by using quantitative allele-specific PCR (Q-PCR) method. The sample is collected by using special kit supplied by the company and then delivered to the Cynvenio lab for entire process, including CTC isolation and enumeration, and molecular analysis. In the future, the company is targeting to provide an automated instrument, which offers CTC recovery and three staining processes on-chip, including DAPI, CD45-, Cytokeratin, for imaging analysis along with downstream PCR molecular analysis.
             
Miltenyi Biotech 
Company info: 
http://www.miltenyibiotec.com/

Assay principle:
Miltenyi Biotech has developed a technology called MACS® Technology for cell isolation. MACS® Technology offers various separation strategies, which provide the  basis for the isolation of almost any cell type from any species and various sample materials. In their system desired cells in a single-cell suspension are magnetically labeled with MACS® MicroBeads. The sample is then applied to a MACS column placed in a MACS separator to separate the cellsThe unlabeled cells pass through while the magnetically labeled cells are retained within the column. The flow-through can be collected as the unlabeled cell fraction. After a short washing step, the column is removed from the separator, and the magnetically labeled cells are eluted from the column. In this method separation column plays an important part. MACS Columns contain a matrix composed of ferromagnetic spheres covered with a cell-friendly coating. When placed on a magnetic separator, the spheres amplify the magnetic field by 10,000-fold, thus inducing a high gradient within the column. This is crucial for isolation of cells which are only minimally labeled, leaving enough epitopes free for concurrent antibody staining. The space between the spheres is several times larger than primary and most cultured cells. This allows the cells to freely flow through the column. Magnetically labeled cells are held in suspension within the column and do not actually “bind” the column matrix. This suspension minimizes stress on the cells and allows for efficient sterile washing by avoiding cell aggregation. Their system can also be used to isolate a particular target cell type in an unlabeled, i.e., untouched form by magnetically labeling the non-target cells and depletion. During separation, the unlabeled target cell type is collected in the flow-through fraction.


Synergex corporation
Company info: 
Sysmex Corp of Japan is working with privately held Oncolys BioPharma to develop a technology using a virus that copies itself and emits fluorescent light in tumor cells. Synergx Corporation, a wholly-owned subsidiary of Morphogenesis, Inc., is an emerging cell therapy company which began operations in 1996.

Description:
 They utilize synergy of two cutting-edge technologies, one which detects and isolates circulating tumor cells and the other which takes the tumor cells and transforms them into a potent immunological therapy to create an unprecedented approach to the management of malignant conditions. For cell separation they have developed a unique cell separation system, called Polymer-Antibody Cell Separation (PACS™). The system uses cell-specific antibodies with a special polymer that has no affinity for the stem cells themselves, thus eliminating the non-specific collection of unwanted cells which is a common problem and limitation of existing cell separation devices. The unique nature of the polymer also allows the PACS™ method to separate multiple cell types in one operation. With the hardware/software components of the PACS™ device completed, the prototype cell separation cartridge is expected to go to design freeze and beta testing at multiple sites later this year.

CellSievo 
Company info: 
(http://www.biospectrumasia.com/biospectrum/influencers/1536/cancer-diagnostics-device-kick-starts-cellsievo)

Description:
CellSievo is a Singapore-based start-up set up in 2011 to commercialize a non-invasive cancer diagnostics device for personalized cancer management. SureCELL developed by CellSievo is a micro-fabricated silicon microsieve device, which utilize CTCs in human blood as a biomarker and isolates them from patients' whole blood and report its quantity. Isolated cells can be easily eluted out for further molecular analysis. System is based on size based separation of CTCs where device allows blood cells to freely flow through it, while restraining and capturing the targeted cancer cells on the micro sieve surface. Captured cells are stained with fluorescence dyes, which automatically get identified under a microscope with a companion image processing program.

Aviva biosciences 
Company info: 
http://avivabio.com/products/selectionfilter.php

Description:
Aviva bioscience founded in 1999 is currently developing innovative rare cell enrichment technologies, particularly focused on circulating tumor cells (CTC). Their system includes a micro fabricated and nano-fabricated channel to separate cells. Device utilize features that reduces the hydrodynamic pressure experienced by the cells during separation, isolation and concentration process and therefore reduce the likelihood of cell lyses or other damage to the cells. 

Clearbridge BioMedics 
Company info: 
www.clearbridgebiomedics.com

Description:
Clearbridge BioMedics is a spin-off from National University of Singapore (NUS) that specializes in novel platforms with applications in oncology research and diagnostics. The ClearCellTM System comprises patent-pending CTChips® which are microfluidic biochips able to effectively detect and isolate wholly-intact CTCs from small quantities of patient blood samples. The CTChips® contains thousands of crescent shaped microstructures that can isolate CTCs without antibody or magnetic beads. By fluid dynamics, the cells are trapped on the microstructures and reversal of microfluidic flow allows cell retrieval for further molecular analysis. The ClearCellTM system aims to be the next generation non-invasive “liquid biopsy” approach for cancer screening, diagnosis, staging, personalized medication and treatment monitoring. The isolation efficiency of their system is at least 80 % with breast and colon cancer cells.
                                                      
Screen cell 
Company info: 
www.screencell.com

Description:
ScreenCell was founded in 2006 for creating technologies that allow CTCs to become potential end points in future oncology therapeutic arsenals by filtering out healthy live tumor cells. Such live tumor cells are enabled for molecular biology, cell culture and enumeration & cytomorphology evaluation. ScreenCell® filtration device is a small compact and low-cost non-invasive technology for isolating CTCs from whole blood. They provide a full range access to phenotypical, genotypical and functional characterization of CTCs and Circulating Tumor Microemboli (CTMs). Their isolation technology avoids any bias introduced by antibodies and generating false negatives paving way for direct and simple access to molecular biology

Creatv Microtech 
Company info: 
www.creatvmicrotech.com

Description:
Creatv Microtech is a privately-held company founded in 1996. Their business is based on high-aspect ratio microfabrication and ultra-sensitive bio detection. Highly efficient isolation of CTCs from peripheral blood is rapidly achieved through the novel precision microfilter called CellSieveTM. These microfilters have uniform 8 µm diameter pores in a polymer with approximately 90,000 pores imprinted on a 9 mm diameter area in a standard 13 mm filter format. The filtration efficiency using CellSieveTM  were efficient and reproducible with 98 % ± 2 % for fixed and 85 % ± 2 % for unfixed MCF-7 cells wherein contamination of blood cells on the microfilter is on an average of 1000 cells per sample and zero for red blood cells.

Silicon biosystem 
Company info: 
http://www.siliconbiosystems.com/silicon_website.page

Description:
Silicon Biosystems has developed a chip called DEP Array based on their proprietary lab-on-a-chip technology platform designed to individually identify, manipulate and sort specific cells within a heterogeneous population. The base of DEP Array™ is a microelectronic active silicon substrate embedding control circuitry for addressing each individual dielectrophoretic (DEP) cage. In their approach, the electric field is generated by a silicon chip directly interfaced to a micro-chamber containing living or non-living particles in liquid suspension . The micro-chamber is confined between the chip surface and a conductive transparent lid spaced tens of microns apart. The chip surface implements a two dimensional array of micro-locations, each consisting of a surface electrode, embedded sensors and logic. The electrodes induce suitably closed nDEP cages in the spatial region above selected micro-sites, within which single particles may be trapped and levitated individually. Further, the step by step, DEP potential cages can be moved around the device plane concurrently and independently, thus grabbing and dragging single cells and/or micro-beads to or from any micro-chamber location. The device embeds more than 300,000 20μm x 20μm electrodes, which can be used to create up to 76,800 DEP cages in a tiny volume of about 11 μl. Due to the small size of the electrodes in the chip, DEP cage sizes can be set to accommodate one single cell, thus enabling individual manipulation of a large number of cells. In their system samples including 1 to 100,000 cells in suspension can be managed on a single microelectronic chip, which ensures independent motion control for each cell by means of powerful dedicated software. Cells have been found to maintain viability with completely intact DNA and unmodified proliferation capability. The unprecedented flexibility and selectivity afforded by this device represent a breakthrough in biological research and analysis. This DEP Array technology has been fully developed and is now commercially available. 

ApoCell
Company info: 
www.apocell.com
company news
http://bionews-tx.com/news/2013/05/16/apocell-delivers-first-apostream-prototypes-to-national-cancer-institute/

Description:
   ApoCell was founded in 2004 to commercialize biomarker technologies for the effective monitoring of cancer drugs by measuring biomarker expression patterns in tumor biopsy specimens. ApoCell’s ApoStreamTM technology, deploys the inherent difference of circulating tumor cells and other rare circulating cells from peripheral blood mononuclear cells (PBMCs) in morphology and dielectric properties within a microchannel flow field to isolate CTCs using dielectrophoresis field flow fractionation (DEP-FFF)  


Celltrafix 
Company info: 
http://celltraffix.com/

Description:
CellTraffix has developed platform technologies for the selection and manipulation of a broad range of target cells, including CTC, found in the bloodstream for modification, collection, or elimination. Unlike existing products based on antibodies or other molecular tools their system manipulates target cells by mimicking the mechanisms of cell trafficking employed by the body itself. The core platform technology involves a flow-mediated adhesion system, built on a biocompatible device substrate. Their system utilizes a class of molecules called selectins for adhering and rolling target cells either in vitro (in benchtop research kits or clinical diagnostics) or in vivo (in implantable devices), replicating the cellular trafficking mechanisms of the human body.  Once target cells adhere and begin rolling, they can either be purified or removed, or therapeutically modified using a secondary set of signaling molecules on the device surface. CellTraffix is engaging in commercial discussions with selected parties with an intend to pursue both co-development and/or joint-licensing relationships for therapeutic applications.


Sysmex 
Company info: 
http://www.sysmex.co.jp

Description:
Sysmex Corporation has developed a sensitive technology for detecting living tumor cells freely suspended in blood using a virus that replicates and emits fluorescence in tumor cells. In 2010 they have started full-scale research jointly with the National Cancer Center Hospital (Location: Chuo-ku, Tokyo, Japan) to verify clinical usefulness of a technology. In their research work, they detected CTC in breast cancer patients by using the telomerase-specific replication-selective adenovirus OBP-401 which once transferred replicate in telomerase expressing cells and emit fluorescence. In their 50 metastatic patients study 21 patients (42%) were identified as positive with the OBP-401 assay and 27 patients (54%) with the Cell Search assay.

Epic Biosciences
Company info: 
Epic Sciences of San Diego, California, is a start-up founded in mid-2008 by members of Peter Kuhn's lab at the Scripps Research Institute. The company has licensed technology being developed by the lab, which has some big-name partners, including Microsoft, Pfizer and Novartis.
http://epicsciences.com/default.aspx

Description:
Dr Kuhn and diagnostic pathologist Kelly Bethel has recently unveiled what Dr Kuhn calls a “next-generation technology” for detecting and analyzing CTCs in patients’ blood samples. Their approach involves spreading a layer of all nucleated cells found in a blood sample onto a glass surface, and adding fluorescent antibodies to cytokeratin, an essential component of CTCs. The technology then uses a digital microscope and an image-processing algorithm to scan the slide for clumps of aberrant fluorescence. The process requires high-performance computing to help analyze and manage the data, and high-definition imaging to help cellular pathologists identify and analyze any of those fluorescent clumps that signify circulating tumor cells.
                   
RareCells 
Company info: 
www.rarecells.com
video: http://vimeo.com/63360066

Description:
RareCells Inc. was founded in July 2012 to commercialize the patented isolation technology by Size of Epithelial/Throphoblastic Tumor cells (ISET) to isolate Circulating Rare Cells in blood, ISET provides the high sensitivity platform for the isolation of CTCs from whole blood treated within 4 h of collection. After which the isolated CTCs can be characterized by immunolabelling, FISH, Tunel and molecular RNA and DNA analyses etc. This technology enables the search for gene mutation in CTCs as identified by the cytopathological analysis (ex: K-ras, HER2 etc.) for theranostics.

           
Vitatex Inc 
Company info: 
Vitatex of Stony Brook, New York, an affiliate of Stony Brook University and the Research Foundation of the State University of New York, claims its blood test for circulating tumor cells is 10 times more sensitive than current tests.
http://www.vitatex.comhttp://www.vitatex.com/

Description:
Vitatex Inc is a Biotech Company focusing on research and commercialization of rare cell enrichment and diagnostics product. Their products fall among Vita-Cap™ and Vita-Assay™ categories. Vita-Cap™ are modified blood collection tubes (6ml tube format) that use proprietary cell adhesion matrices (CAM) to capture, and preserve viable rare circulating cells in a single step from blood or tissue fluids. Vitatex claim that Vita-Cap™ enriches rare cells in 1-ml of blood to 1-10% purity of a specific rare cells compared to background blood cells. Vita-Assay™ (16-well slide format) is a cell culture plate that also uses CAM to capture and preserve viable rare circulating cells after removal of red blood cells from blood or bone marrow. Vita-Assay™ is useful when further culturing of the rare cells is required.  Both products enable molecular characterization of the enriched cells using analytic tools. They have 3 application platforms namely Cell Separation Technologies for cancer diagnostics, Cell Separation Technologies for anti-cancer drug discovery and Cell Separation Technologies for discovery research.

Oncoquick 
Company info: 
www.greinerbioone.com
Description:
Oncoquick® is a product developed by Greiner Bio-one for CTCs enrichment purpose. It is a density gradient based separation approach. A porous barrier was placed within the 50 mL tube that contains 15 to 30 mL whole blood sample.  After centrifugation of sample, the layer of CTC and platelets can be separated from the leukocytes and erythrocytes.  The average recovery rate is 72% when the average repeatability is 83% with average detection limit of 1.46 CTCs per 20 mL whole blood sample. 
Apart from the above mentioned technologies, Celula has developed a mvs360 cell sorter chip for separating rare cells.Chip enable >90% purity with recovery from upto 500000 cells in 50 µl solution in 5 to 60 min time. Parsortix CTC separation device from ANGEL’s, targets for CTC recovery in relation to lung, pancreatic and colo-rectal cancers.

Epispot:
Company info: 

Description:
In order to overcome the drawback of distinguishing viable from apoptotic cells by both immunocytochemistry and RT-PCR, a new technique has been emerged offering the most significant discrimination for DTC/CTC analyses. This technique was designated EPISPOT (for epithelial immunospot) and is based on the secretion or active release of specific marker proteins using an adaptation of the enzyme-linked immunospot (ELISPOT) technology. The EPISPOT assay offers the advantages that only viable tumor cells will be detected and that protein secretion can be detected at an individual cell level.


Advanced cell Diagnostics
Company info: 
Advanced Cell Diagnostics, Hayward, California, is adapting its RNAscope technology -- a system that looks for small bits of genetic material -- to search for cancer cells circulating in the blood. The company recently won a three-year, $3 million grant from National Cancer Institute.

Description:
Instead of enriching CTCs in patient’s blood by either CTCs size or surface epithelial markers verification, California-based ACD developed a multi-fluorescent RNA in situ hybridisation (ISH)-based CTC detection system named CTCscopeTM. By employing this technology, they are not only able to perform CTCs counting, but also the molecular profiling and viability checking of the CTCs.  ACD filed more than 8 patents along with technologies in-licensed from Affymetrix.  Both companies are in partnership in order to deliver the CTCScope system by year 2013.  

Natural Nano Inc.:
Company info: 
NaturalNano Inc of Rochester, New York, wants to use its nanotube technology to help capture of circulating tumor cells in the blood. A recent Cornell University study found coating the surface of a capture device with nanotubes helped cancer cells stick better.

Description:



Onco Vista
Company info: 
OncoVista Innovative Therapies Inc of San Antonio, Texas, which owns a majority interest in German-based diagnostic company AdnaGen AG, is developing a test that detects slight changes in different cancer biomarkers found on circulating tumor cells.

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Precelleon
Company info: 
Filtini
Company info: 
Filtini, located in Menlo Park, CA, provided a CTCs size-based isolation platform by using specialized microfilter membrane made by Parylene. The technologies will be applicable to different cancer patients, including prostate cancer, breast cancer, colon cancer and pancreas cancer. 

Description:
Filtini uses microfabricated pores on parylene membranes for cell isolation.

Denovo Sciences
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Cellula

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Ariol:

Company info: 
 http://www.genetix.com/en/home/index.html
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Bioview:
Company info: 
http://www.bioview.co.il/HTMLs/Home.aspx
Description: 
Bioview develops automated microscopy solutions for FISH. The microscope is paired up with a size filter for upstream isolation of tumor cells. Bioview has a partnership with screencell.


Ikonisys:
Company info: 
http://www.ikonisys.com/

Description:
Ikonisys develops automated microscopy solutions for cytometry. The microscope is paired up with a size filter for upstream isolation of tumor cells

Canopus Biosciences:
Company info: