Docket #: S07-132
MagSweeper: high purity capture of circulating tumor cells and other rare cells
An interdisciplinary team of Stanford researchers have developed MagSweeper, a patented robotic liquid biopsy device that efficiently isolates and purifies live CTCs (circulating tumor cells) from blood while removing 100% of contaminating blood cells. Downstream analysis of these cells can then be used to characterize the gene expression of metastases without an invasive biopsy. This device captures CTCs or other rare cells from a liquid sample using magnetic rods covered with removable plastic sleeves. These sleeves enable multiple capture and release cycles thereby assuring high purity and capture efficiency. For example, CTCs in patient blood samples (approximately 0-10 CTCs per 7.5cc tube) can be isolated with about 100% purity and 60% capture efficiency. In addition to capturing CTCs, MagSweeper could be used to isolate fetal stem cells or immune cells from fluid or tissue suspension samples.
Stage of Research
The inventors have demonstrated the utility of MagSweeper for isolating live CTCs from patient blood samples using the cancer-specific EpCAM protein as a biomarker. In that study, downstream analysis revealed the genetic diversity of CTCs.
Applications
- Rare cell capture - magnetic isolation of live cells with end-user applications such as:
- liquid biopsy of CTCs from blood samples
- fetal stem cell capture from cord blood
- immune cell isolation from blood or tissue
Advantages
- Efficient capture - MagSweeper has approximately 60% capture efficiency for CTC cells (0-10 cells per 7.5cc tube)
- High purity:
- approximately 100% pure target cells without blood cell contamination
- number and stringency of washes can be controlled to ensure complete clearance of contamination
- Live cells - captured cells are viable with intact RNA for downstream expression studies
Publications
- Deng G, Krishnakumar S, Powell AA, Zhang H, Mindrinos MN, Telli ML, Davis RW, Jeffrey SS. Single cell mutational analysis of PIK3CA in circulating tumor cells and metastases in breast cancer reveals heterogeneity, discordance, and mutation persistence in cultured disseminated tumor cells from bone marrow. BMC Cancer. 2014 Jun 19;14:456.
- Cann GM, Gulzar ZG, Cooper S, Li R, Luo S, Tat M, Stuart S, Schroth G, Srinivas S, Ronaghi M, Brooks JD, Talasaz AH. mRNA-Seq of single prostate cancer circulating tumor cells reveals recapitulation of gene expression and pathways found in prostate cancer. PLoS One. 2012;7(11):e49144.
- Powell AA, Talasaz AH, Zhang H, Coram MA, Reddy A, Deng G, Telli ML, Advani RH, Carlson RW, Mollick JA, Sheth S, Kurian AW, Ford JM, Stockdale FE, Quake SR, Pease RF, Mindrinos MN, Bhanot G, Dairkee SH, Davis RW, Jeffrey SS. Single cell profiling of circulating tumor cells: transcriptional heterogeneity and diversity from breast cancer cell lines. PLoS One. 2012;7(5):e33788.
- Ameri K, Luong R, Zhang H, Powell AA, Montgomery KD, Espinosa I, Bouley DM, Harris AL, Jeffrey SS. Circulating tumour cells demonstrate an altered response to hypoxia and an aggressive phenotype. Br J Cancer. 2010 Feb 2;102(3):561-9.
- Talasaz, A. H., Powell, A. A., Huber, D. E., Berbee, J. G., Roh, K. H., Yu, W., ... & Jeffrey, S. S. (2009). Isolating highly enriched populations of circulating epithelial cells and other rare cells from blood using a magnetic sweeper device. Proceedings of the National Academy of Sciences, 106(10), 3970-3975.
- Surprising genetic diversity found in cells shed by tumors, Inside Stanford Medicine, May 21, 2012.
External Publications Using MagSweeper
FROM HARVARD/MIT/BROAD/DANA-FARBER
Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer. Lohr JG, Adalsteinsson VA, Cibulskis K, Choudhury AD, Rosenberg M, Cruz-Gordillo P, Francis JM, Zhang CZ, Shalek AK, Satija R, Trombetta JJ, Lu D, Tallapragada N, Tahirova N, Kim S, Blumenstiel B, Sougnez C, Lowe A, Wong B, Auclair D, Van Allen EM, Nakabayashi M, Lis RT, Lee GS, Li T, Chabot MS, Ly A, Taplin ME, Clancy TE, Loda M, Regev A, Meyerson M, Hahn WC, Kantoff PW, Golub TR, Getz G, Boehm JS, Love JC. Nat Biotechnol. 2014 May;32(5):479-84. doi: 10.1038/nbt.2892. Epub 2014 Apr 20. PMID: 24752078
FROM LUDWIG INSTITUTE FOR CANCER RESEARCH AND KAROLINSKA INSTITUTE, Stockholm, Sweden
Full-length mRNA-Seq from single-cell levels of RNA and individual circulating tumor cells. Ramsköld D, Luo S, Wang YC, Li R, Deng Q, Faridani OR, Daniels GA, Khrebtukova I, Loring JF, Laurent LC, Schroth GP, Sandberg R.
Nat Biotechnol. 2012 Aug;30(8):777-82. PMID: 22820318
FROM SAMSUNG MEDICAL CENTER, SUNGKYUNKWAN UNIVERSITY SCHOOL OF MEDICINE, SEOUL, SOUTH KOREA
Transcriptome analysis of CD133-positive stem cells and prognostic value of survivin in colorectal cancer. Kim ST, Sohn I, DO IG, Jang J, Kim SH, Jung IH, Park JO, Park YS, Talasaz A, Lee J, Kim HC. Cancer Genomics Proteomics. 2014 Sep-Oct;11(5):259-66. PMID: 25331798
TECHNICAL NOTE FROM SILICON BIOSYSTEMS - MAGSWEEPER AND DEP ARRAY
http://cdn2.hubspot.net/hub/304284/file-315922036-pdf/Doc/Isolation_of_Tumor_Cells_after_Immunomagnetic_Enri.pdf?t=1462530328123
Patents
- Published Application: 20090220979
- Published Application: WO2009076560
- Published Application: 20120045828
- Issued: 8,071,395 (USA)
- Issued: 9,267,943 (USA)
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