High throughput capture of circulating tumor cells using an integrated microfluidic system

ScienceDirect.com - Biosensors and Bioelectronics - High throughput capture of circulating tumor cells using an integrated microfluidic system


"we achieved an enrichment factor of 1500X, and a high processing throughput of 9.6 mL/min with
90% capture yield and more than 50% capture purity at cell concentration 102 cells/mL"

I believe this is the highest reported throughput with 90% capture efficiency. Impressive!

The principle used in isolation is a combination of Deterministic lateral displacement (DLD) and EpCAM-based capture.

Most of you know about EpCAM based capture on microposts. Below is a video on how DLD works



some related prior art:

Isolation of rare circulating tumour cells in cancer patients by microchip technology

Isolation of circulating tumor cells using a microvortex-generating herringbone-chip

A focus review on affinity-based, dielectrophoresis and hydrophoresis

Microfluidic devices for the isolation of circulating rare cells: a focus on affinity-based, dielectrophoresis and hydrophoresis - Hyun - ELECTROPHORESIS - Wiley Online Library

Wow, its review season, quite a number of reviews already in 2013
Focus of review: Microfluidic- affinity-based (antibody-antigen), dielectrophoresis and Hydrophoresis- (aka inertial microfluidics)

some perspectives expressed by the authors

"Several isolation methodologies based on affinity-based positive enrichment using epitopes
expressed on the cell surface have been developed. However, all circulating rare cells do not express the same specific antigens, as they are heterogeneous by nature. Although it is controversial whether positive or negative enrichment is more efficient, it is clear that the latter is more advantageous than the former because the target cells can be captured in intact form. Novel approaches for negative enrichment (affinity-based methods using antibodies to isolate hematologic cells or non-affinity-based methods such as dielectrophoresis and hydrophoresis) should be developed, because a negative enrichment microfluidic chip enables the simultaneous isolation of various types of circulating rare cells, such as circulating endothelial cells (CECs), cancer stem cells (CSCs), circulating progenitor cells (CPCs), and circulating tumor cells (CTCs), including nucleated red blood cells (nRBCs). The number of intact and heterogeneous circulating rare cells collected continuously by such a device will provide researchers with many opportunities to investigate the molecular nature of these rare cells."

Enrichment, Detection and Clinical Significance of Circulating Tumor Cell - Lab on a Chip (RSC Publishing)

Enrichment, Detection and Clinical Significance of Circulating Tumor Cell - Lab on a Chip (RSC Publishing)

Comprehensive review on CTC technologies and clinical significance

direct download link

CTC user survey results 2013

Here is a survey conducted by World CTC organization to gather feedback on the top priorities of CTC community in 2013 and beyond

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

Key questions covered in the survey

How highly would you rate the priority of CTCs in your organisation?

What do you think is the biggest challenge in current CTC research?

What is your current research priority?

In your opinion, what needs to be done to validate the use of CTCs in the clinic?

What do you think is the timeline for CTCs to become an important part of the clinical decision
making process?

What do you think is stopping you from making CTCs your top priority?

Which companies/technologies do you think hold the most promise for improving our ability to study and measure CTCs?


Highlights:

• 74.3% of respondents in the survey highlighted CTCs as either a "very high" or "high priority" for their organisation 
• When questioned what was the biggest challenges faced in this field the top challenge was identified as “Current technology is neither sensitive or specific enough” (33%) with the second biggest challenge being that “There is no agreed golden standard for technology” (25.5%) 
• A resounding 48.8% thought that to validate CTCs in the clinic there needs to be “more clinical trials validating CTCs as a diagnostic/prognostic prospective”

Thanks to world CTC for conducting the survey and publishing the results. 
please view full report here
http://worldctc-berlin.com/uploads/ffiles/2013/03/145979.pdf

Circulating Tumor DNA Detects Metastatic Breast Cancer

Circulating Tumor DNA Detects Metastatic Breast Cancer (original link)

link with my annotations is here
https://diigo.com/0xl25

link for NJEM paper is http://www.nejm.org/doi/full/10.1056/NEJMoa1213261

The battle between cell-free DNA versus cells was won by cf DNA in non-invasive prenatal diagnostics (at least for now)

It will be interesting to watch this unfold for cancer

Complex tumor genomes inferred from single circulating tumor cells by array-CGH and next-generation sequencing

Complex tumor genomes inferred from single circulating tumor cells by array-CGH and next-generation sequencing