CellSqueeze

Cell Squeeze® is the commercial name for a method for deforming a cell as it passes through a small opening, disrupting the cell membrane and allowing material to be inserted into the cell.[1][2] It is an alternative method to electroporation or cell-penetrating peptides and operates similarly to a french cell press that temporarily disrupts cells, rather than completely bursting them.[3]

Method

The cell-disrupting change in pressure is achieved by passing cells through a narrow opening in a microfluidic device. The device is made up of channels etched into a wafer through which cells initially flow freely. As they move through the device, the channel width gradually narrows. The cell's flexible membrane allows it to change shape and become thinner and longer, allowing it to squeeze through. As the cell becomes more and more narrow, it shrinks in width by about 30 to 80 percent[2] its original size and the forced rapid change in cell shape temporarily creates holes in the membrane, without damaging or killing the cell.

While the cell membrane is disrupted, target molecules that pass by can enter the cell through the holes in the membrane. As the cell returns to its normal shape, the holes in the membrane close. Virtually any type of molecule can be delivered into any type of cell.[4] The throughput is approximately one million per second. Mechanical disruption methods can cause fewer gene expression changes than electrical or chemical methods.[3] This can be preferable in studies that require the gene expression to be controlled at all times.[5]

Applications

Like other cell permeablisation techniques, it enables intracellular delivery materials, such as proteins, siRNA, or carbon nanotubes. The technique has been used for over 20 cell types, including embryonic stem cells and naïve immune cells.[6] Initial applications focused on immune cells, for example delivering:

  • Anti-HIV siRNAs for blocking HIV infection in CD4+ T cells.[7]
  • Whole protein antigen and enabling MHC class I processing/presentation in polyclonal B cells, facilitating B cell-based vaccine approaches.[8]

Commercialization

The process was originally developed in 2013 by Armon Sharei and Andrea Adamo, in the lab of Langer and Jensen at Massachusetts Institute of Technology.[2] In 2014 Sharei founded SQZBiotech® to demonstrate the technology.[9] That year, SQZBiotech® won the $100,000 grand prize in the annual startup competition sponsored by Boston-based accelerator MassChallenge.[10]

Boeing and the Center for the Advancement of Science in Space CASIS awarded the company the CASIS-Boeing Prize for Technology in Space to support the use of Cell Squeeze® on the International Space Station (ISS).[11]

See also

References
  1. How It Works Archived 2014-03-10 at the Wayback Machine. SQZBiotech®. Retrieved on 2014-05-18.
  2. Jensen, Klavs F.; Langer, Robert; Anderson, Daniel G.; Kim, Kwang-Soo; Hartoularos, George C.; Kang, Jeon Woong; Heller, Daniel A.; Lee, Jungmin; Jhunjhunwala, Siddharth; Basto, Pamela A.; Lytton-Jean, Abigail; Han, Min-Joon; Schneider, Sabine; Mao, Shirley; Jackson, Emily; Cho, Nahyun; Sim, Woo Young; Adamo, Andrea; Zoldan, Janet; Sharei, Armon (5 February 2013). "A vector-free microfluidic platform for intracellular delivery". Proceedings of the National Academy of Sciences. 110 (6): 2082–2087. doi:10.1073/pnas.1218705110. PMC 3568376. PMID 23341631.
  3. Meacham, J. Mark; Durvasula, Kiranmai; Degertekin, F. Levent; Fedorov, Andrei G. (February 2014). "Physical Methods for Intracellular Delivery". Journal of Laboratory Automation. 19 (1): 1–18. doi:10.1177/2211068213494388. PMC 4449156. PMID 23813915.
  4. Researchers put squeeze on cells to deliver. Rdmag.com (2013-07-22). Retrieved on 2014-05-18.
  5. Anne Trafton (2 February 2016). "Cell squeezing enhances protein imaging". MIT News Office.
  6. "Narrow Straits - The Scientist Magazine®".
  7. Jensen, Klavs F.; Lieberman, Judy; Langer, Robert; Anderson, Daniel G.; Andrian, Ulrich H. von; Addo, Marylyn; Khan, Omar F.; Talkar, Tanya; Liu, Sophia; Heimann, Megan; Mao, Shirley; Poceviciute, Roberta; Sharma, Siddhartha; Angin, Mathieu; Lytton-Jean, Abigail; Eyerman, Alexandra T.; Hartoularos, George C.; Jhunjhunwala, Siddharth; Trifonova, Radiana; Sharei, Armon (13 April 2015). "Ex Vivo Cytosolic Delivery of Functional Macromolecules to Immune Cells". PLOS ONE. 10 (4): e0118803. doi:10.1371/journal.pone.0118803. PMC 4395260. PMID 25875117.
  8. Irvine, Darrell J.; Jensen, Klavs; Langer, Robert; Heimann, Megan; Mao, Shirley; Brefo, Mavis; Frew, Kirubel; Park, Clara; Alejandro, Brian; Sharei, Armon; Worku, Hermoon; Egeren, Debra Van; Szeto, Gregory Lee (22 May 2015). "Microfluidic squeezing for intracellular antigen loading in polyclonal B-cells as cellular vaccines". Scientific Reports. 5: 10276. doi:10.1038/srep10276. PMC 4441198. PMID 25999171.
  9. "Home". SQZ Biotech. Retrieved 2016-06-11.
  10. "Archived copy". Archived from the original on April 2, 2015. Retrieved March 6, 2015.CS1 maint: archived copy as title (link)
  11. "Partner to Award Entrepreneurial Research Through MassChallenge". Retrieved 2018-06-12.
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