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  • Coleman Murray

Extremely Rare and Incredibly Difficult: Challenges and solutions to isolating rare cell types

When I was eight years old, my dad would take me to a river near our house to go gold panning. I remember piling the black silt from the river bottom into our pan and watched as he gently washed out the fine grains, leaving the heavier objects at the bottom. At first glance I thought were going to be rich as the pan was glittering with freshly filtered “gold.” Unfortunately, most of it was iron pyrite more commonly known as fool’s gold which we had to pick out individually with tweezers. After a long and laborious day, we ended up with just a few milligrams of gold.

In a way, this is the experience that many biomedical researchers have when they need to isolate rare types of cells (<1%) from a blood or tissue sample which happens quite often during development of new diagnostic or therapeutic platforms. For example, researchers developing allergy and autoimmune therapies need to capture rare antigen specific cellswhich contain key information needed to treat the disorders. In the field of cancer research, clinical scientists need to isolate rare cancer stem cells to better combat metastasis and target specific tumor attributes.

While this might seem like a classic needle in a haystack problem, I would argue that it is much more challenging. Cells are living things that adapt quickly to their environment. Therefore, there is a delicate balance in isolating rare cells rapidly and gently to keep them viable for downstream processing. Imagine trying to pan for gold that slowly starts to turn into iron pyrite the minute you take it out of the river. That is a more accurate description of the challenge for clinical researchers trying to pick out rare cells.


Challenges of a multi-step and multi-site process to enrich rare cells

Generally, rare cell separation is performed using a two-step process: a bulk filtration to reduce the background followed by a precision filtration step to get a highly purified sample. Similar to the gold panning example, the pan is used to filter out most of the unwanted silt followed by a precise but slower filtration process to pick out the gold which, for cells is usually done using a combination of magnetic and laser-based separation techniques.

The challenge is that this process is time consuming and expensive, making it difficult to scale for the quick experiment turnaround needed to move research from the lab bench into the clinic. For rare cells, the magnetic step will capture the target cells along with a lot of unwanted background cells, just like the gold and fool’s gold at the bottom of the pan. Although you can try run the process multiple times, you’ll probably lose most of your target cells. To further purify the sample a laser-based technique called flow cytometry is used which is precise but time consuming and expensive. As I mentioned in my previous article, researchers generally perform the bulk magnetic cell separations in their own lab then transport their sample to an on-campus core facility to perform the precision flow cytometry sorting. This core facility format is necessary because the flow cytometry machines are usually too expensive for an individual lab to purchase and maintain. Here, practical limitations can greatly impede the R&D process as researchers compete for space and time on the shared tools and pay a hefty hourly rate. In some cases, the flow cytometry cannot even be performed because the process requires several thousand cells to operate which is a problem is the cells are too rare.


Ferrologix Rare Cell Separation: Next Generation Magnetic Sorting

My company, Ferrologix Inc, is trying to address these challenges with a new approach to magnetic cell separation. Using a specialized magnetic nanotechnology developed at UCLA, we have created a chip that can perform very precise magnetic separations essentially condensing the bulk and precision cell filtration steps into one chip. In side by side comparisons to standard magnetic separations our system was able to recover rare cells (0.01%) with a 95% purity compared to a 2% purity with the traditional approach. Our vision is to provide clinical researchers with an affordable tool that will allow them to get the rare cells they need quickly, in order to accelerate their experimental workflows and get their research from the lab bench to the clinic.


Ferrologix Rare Cell Separator:

  •  Purify rare cells, 1%-0.01% of total cell population, with >95% purity

  • Total assay time < 1 hour

  • High cell viability

  • Affordable option that can be deployed for individual researchers

Interested in a Demo?

We are currently performing a pilot study with the Ferrologix Rare Cell Separation platform. If you are interested in demoing a system, please feel free to connect and message me via LinkedIn or email at cmurray@ferrologix.com.


Resources and Journal Publications

1.      http://www.ferrologix.com/

2.      https://www.ncbi.nlm.nih.gov/pubmed/26890496

3.      https://www.ncbi.nlm.nih.gov/pubmed/29281498

4.      https://onlinelibrary.wiley.com/doi/full/10.1002/adfm.201703106

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