CellSqueeze

CellSqueeze is a high-throughput, vector-free microfluidic platform for intracellular delivery developed by Dr. Armon Sharei, at the Massachusetts Institute of Technology in the labs of Prof. Robert S. Langer and Prof. Klavs Jensen.[1] CellSqueeze mechanically deforms cells as they pass through a constriction smaller than the cell diameter.[2] The resulting controlled application of compression and shear forces results in the formation of transient holes that enable diffusion of material from the surrounding buffer into the cells. It eliminates the possibility of toxicity or off-target effects as it does not rely on exogenous materials or electrical fields.

It is a generalized approach for getting molecules of all shapes and sizes into any type of cell.[3] The method has demonstrated the ability to deliver a range of material, such as carbon nanotubes, proteins, and siRNA, to over 20 cell types, including embryonic stem cells and naïve immune cells. When used for the delivery of transcription factors, the microfluidic devices produced a 10-100 fold improvement in colony formation relative to electroporation and cell-penetrating peptides respectively.

The device, a microfluidic delivery platform, is made up of channels etched into a silicon wafer through which cells initially can flow freely. However, as the cells move through the device—like an inner tube along a water slide—the channel width narrows until a cell finds itself in a tight spot—forced to fit through a space that is narrower than the cell. The supple cell membrane allows the cell to squeeze through the constriction. However, the forced, rapid change in cell shape creates temporary holes in the cell membrane, without permanently damaging or killing the cell.

While the cell membrane is temporarily disrupted, the molecules to be delivered pass through the holes in the membrane and enter the cell. As the cell rebounds to its normal shape, the holes in the membrane close; the cell is loaded successfully. Virtually any type of molecule can be delivered into large numbers of any type of cell.[4] Recent applications of the platform have focused on immune cells: 1) delivery of anti-HIV siRNAs for blocking HIV infection in CD4+ T cells[5] and 2) delivering whole protein antigen and enabling MHC class I processing/presentation in polyclonal B cells, facilitating B cell-based vaccine approaches.[6]

SQZ Biotech, exclusive license holder of the CellSqueeze technology, won the $100,000 grand prize in the annual startup competition sponsored by Boston-based accelerator MassChallenge.[7] Additionally, Boeing. and the Center for the Advancement of Science in Space (CASIS) awarded the company the CASIS-Boeing Prize for Technology in Space—worth more than $200,000—to support the use of CellSqueeze on the International Space Station (ISS), which totaled to the largest total prize awarded to a single start-up company in the accelerator’s five year history. Recently named one of Ten World Changing Ideas by Scientific American, the CellSqueeze platform enables scientists to manipulate cells with unprecedented simplicity, ushering in new approaches to cell-based therapies.[8]

See also

References

  1. ↑ Armon Sharei, Janet Zoldan, Andrea Adamo, Woo Young Sim, Nahyun Cho, Emily Jackson, Shirley Mao, Sabine Schneider, Min-Joon Han, Abigail Lytton-Jean, Pamela A. Basto, Siddharth Jhunjhunwala, Jungmin Lee, Daniel A. Heller, Jeon Woong Kang, George C. Hartoularos, Kwang-Soo Kim, Daniel G. Anderson, Robert Langer, and Klavs F. Jensen (2013). "A vector-free microfluidic platform for intracellular delivery". PNAS 110: 2082–7. doi:10.1073/pnas.1218705110. PMC 3568376. PMID 23341631.
  2. ↑ How It Works. SQZ Biotech. Retrieved on 2014-05-18.
  3. ↑ http://www.the-scientist.com/?articles.view/articleNo/36099/title/Narrow-Straits/
  4. ↑ Researchers put squeeze on cells to deliver. Rdmag.com (2013-07-22). Retrieved on 2014-05-18.
  5. ↑ Armon Sharei, Radiana Trifonova, Siddharth Jhunjhunwala, George C. Hartoularos, Alexandra T. Eyerman, Abigail Lytton-Jean, Mathieu Angin, Siddhartha Sharma, Roberta Poceviciute, Shirley Mao, Megan Heimann, Sophia Liu, Tanya Talkar, Omar F. Khan, Marylyn Addo, Ulrich H. von Andrian, Daniel G. Anderson, Robert Langer, Judy Lieberman, and Klavs F. Jensen (2015). "A vector-free microfluidic platform for intracellular delivery". PLoS ONE 10: e0118803. doi:10.1371/journal.pone.0118803. PMID 25875117.
  6. ↑ Gregory Lee Szeto, Debra Van Egeren, Hermoon Worku, Armon Sharei, Brian Alejandro, Clara Park, Kirubel Frew, Mavis Brefo, Shirley Mao, Megan Heimann, Robert Langer, Klavs Jensen and Darrell J Irvine (2015). "Microfluidic squeezing for intracellular antigen loading in polyclonal B-cells as cellular vaccines". Sci. Rep. 5: 10276. doi:10.1038/srep10276. PMID 25999171.
  7. ↑ http://www.reuters.com/article/2014/10/30/ma-sqz-biotech-idUSnBw305865a+100+BSW20141030
  8. ↑ http://www.scientificamerican.com/article/how-to-hijack-a-cell/
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