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'''CellSqueeze''' 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.<ref>[http://sqzbiotech.com/technology/ How It Works]. SQZ Biotech. Retrieved on 2014-05-18.</ref><ref name=":0">{{Cite journal|last=Sharei|first=Armon|last2=Zoldan|first2=Janet|last3=Adamo|first3=Andrea|last4=Sim|first4=Woo Young|last5=Cho|first5=Nahyun|last6=Jackson|first6=Emily|last7=Mao|first7=Shirley|last8=Schneider|first8=Sabine|last9=Han|first9=Min-Joon|date=2013-02-05|title=A vector-free microfluidic platform for intracellular delivery|url=http://www.pnas.org/content/110/6/2082|journal=Proceedings of the National Academy of Sciences|language=en|volume=110|issue=6|pages=2082–2087|doi=10.1073/pnas.1218705110|issn=0027-8424|pmc=PMC3568376|pmid=23341631}}</ref> It is an alternative method to [[electroporation]] or [[cell-penetrating peptides]]. It is a gentler version of a [[French press]], that only temporarily disrupts cells, rather than completely bursting them.<ref name=":1">{{Cite journal|last=Meacham|first=J. Mark|last2=Durvasula|first2=Kiranmai|last3=Degertekin|first3=F. Levent|last4=Fedorov|first4=Andrei G.|date=2013-06-27|title=Physical Methods for Intracellular Delivery|url=http://journals.sagepub.com/doi/10.1177/2211068213494388|journal=Journal of Laboratory Automation|language=en|volume=19|issue=1|pages=1–18|doi=10.1177/2211068213494388|pmc=PMC4449156|pmid=23813915}}</ref>
{{Advert|date=May 2016}}

'''CellSqueeze''' is 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.<ref>[http://sqzbiotech.com/technology/ How It Works]. SQZ Biotech. Retrieved on 2014-05-18.</ref>

When used for the delivery of [[transcription factors]], the device produced a marked improvement in colony formation compared with other methods like [[electroporation]] and [[cell-penetrating peptides]]. The method is a high-throughput, vector-free microfluidic platform for [[intracellular]] delivery of a wide range of materials, including carbon nanotubes, proteins and siRNA. The technique has been used for over 20 cell types, including embryonic stem cells and naïve immune cells.<ref>{{cite web|url=http://www.the-scientist.com/?articles.view/articleNo/36099/title/Narrow-Straits/|title=Narrow Straits - The Scientist Magazine®|publisher=}}</ref> Cells can be ''sqeezed'' 'at a rate of about one million per second, which makes this method quite fast and easy compared to other methods like electroporation and cell-penetrating peptide use. An added benefit is that when the cells undergo the squeezing procedure, they show no changes in the genes they express and no other long-term effects. On the other hand, when a jolt of electricity (through electroporation) is applied to the cells to make them more permeable to deliver DNA and RNA, more than 7,000 genes are affected. This less invasive approach makes CellSqueeze preferable in some studies that require the gene expression and genes to be controlled at all times.<ref>{{cite web|url=http://news.mit.edu/2016/cell-squeezing-enhances-protein-imaging-0201/|title=Cell squeezing enhances protein imaging|publisher=MIT News Office|author=Anne Trafton|date=2 February 2016}}</ref>


== Method ==
== Method ==


The microfluidics platform is a device 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 times its original size and it is at this time that the forced rapid change in cell shape temporarily creates holes in the membrane, without damaging or killing the cell.
The cell-disrupting change in pressure is achieved by passing cells through a narrow opening in a [[Microfluidics|microfluidic device]]. The device is made up of channels etched into a [[Wafer (electronics)|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 times 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.<ref>[http://www.rdmag.com/news/2013/07/researchers-put-squeeze-cells-deliver Researchers put squeeze on cells to deliver]. Rdmag.com (2013-07-22). Retrieved on 2014-05-18.</ref>
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.<ref>[http://www.rdmag.com/news/2013/07/researchers-put-squeeze-cells-deliver Researchers put squeeze on cells to deliver]. Rdmag.com (2013-07-22). Retrieved on 2014-05-18.</ref> The throughput is approximately one million per second. Mechanical disruption methods can cause fewer gene expression changes than electrical or chemical methods.<ref name=":1" /> This can be preferable in studies that require the gene expression to be controlled at all times.<ref>{{cite web|url=http://news.mit.edu/2016/cell-squeezing-enhances-protein-imaging-0201/|title=Cell squeezing enhances protein imaging|date=2 February 2016|publisher=MIT News Office|author=Anne Trafton}}</ref>


== Applications ==
== 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.<ref>{{cite web|url=http://www.the-scientist.com/?articles.view/articleNo/36099/title/Narrow-Straits/|title=Narrow Straits - The Scientist Magazine®|publisher=}}</ref> Initial applications focused on immune cells, for example delivering:
Applications have focused on immune cells, delivering:


* Anti-HIV siRNAs for blocking HIV infection in CD4+ T cells<ref>{{cite journal |author1=Armon Sharei |author2=Radiana Trifonova |author3=Siddharth Jhunjhunwala |author4=George C. Hartoularos |author5=Alexandra T. Eyerman |author6=Abigail Lytton-Jean |author7=Mathieu Angin |author8=Siddhartha Sharma |author9=Roberta Poceviciute |author10=Shirley Mao |author11=Megan Heimann |author12=Sophia Liu |author13=Tanya Talkar |author14=Omar F. Khan |author15=Marylyn Addo |author16=Ulrich H. von Andrian |author17=Daniel G. Anderson |author18=Robert Langer |author19=Judy Lieberman |author20=Klavs F. Jensen | title = A vector-free microfluidic platform for intracellular delivery | journal = PLoS ONE | date = 2015| doi = 10.1371/journal.pone.0118803 | pmid=25875117 | volume=10 | pages=e0118803 | pmc=4395260}}</ref>
* Anti-HIV siRNAs for blocking HIV infection in CD4+ T cells.<ref>{{Cite journal|last=Sharei|first=Armon|last2=Trifonova|first2=Radiana|last3=Jhunjhunwala|first3=Siddharth|last4=Hartoularos|first4=George C.|last5=Eyerman|first5=Alexandra T.|last6=Lytton-Jean|first6=Abigail|last7=Angin|first7=Mathieu|last8=Sharma|first8=Siddhartha|last9=Poceviciute|first9=Roberta|date=2015-04-13|title=Ex Vivo Cytosolic Delivery of Functional Macromolecules to Immune Cells|url=http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0118803|journal=PLOS ONE|volume=10|issue=4|pages=e0118803|doi=10.1371/journal.pone.0118803|issn=1932-6203|pmc=PMC4395260|pmid=25875117}}</ref>
* Whole protein antigen and enabling [[MHC class I]] processing/presentation in polyclonal [[B cells]], facilitating B cell-based vaccine approaches.<ref>{{cite journal |author1=Gregory Lee Szeto |author2=Debra Van Egeren |author3=Hermoon Worku |author4=Armon Sharei |author5=Brian Alejandro |author6=Clara Park |author7=Kirubel Frew |author8=Mavis Brefo |author9=Shirley Mao |author10=Megan Heimann |author11=Robert Langer |author12=Klavs Jensen |author13=Darrell J Irvine | title = Microfluidic squeezing for intracellular antigen loading in polyclonal B-cells as cellular vaccines | journal = Sci. Rep. | date = 2015 | doi = 10.1038/srep10276 | pmid=25999171 | volume=5 | pages=10276 | URL = http://www.nature.com/srep/2015/150515/srep10276/full/srep10276.html | pmc=4441198}}</ref>
* Whole protein antigen and enabling [[MHC class I]] processing/presentation in polyclonal [[B cells]], facilitating B cell-based vaccine approaches.<ref>{{cite journal |author1=Gregory Lee Szeto |author2=Debra Van Egeren |author3=Hermoon Worku |author4=Armon Sharei |author5=Brian Alejandro |author6=Clara Park |author7=Kirubel Frew |author8=Mavis Brefo |author9=Shirley Mao |author10=Megan Heimann |author11=Robert Langer |author12=Klavs Jensen |author13=Darrell J Irvine | title = Microfluidic squeezing for intracellular antigen loading in polyclonal B-cells as cellular vaccines | journal = Sci. Rep. | date = 2015 | doi = 10.1038/srep10276 | pmid=25999171 | volume=5 | pages=10276 | URL = http://www.nature.com/srep/2015/150515/srep10276/full/srep10276.html | pmc=4441198}}</ref>


== Commercialization ==
== Commercialization ==


The process was originally developed by Armon Sharei, in the lab of [[Robert S. Langer|Langer]] and Jensen at [[Massachusetts Institute of Technology]].<ref>{{cite journal |author1=Armon Sharei |author2=Janet Zoldan |author3=Andrea Adamo |author4=Woo Young Sim |author5=Nahyun Cho |author6=Emily Jackson |author7=Shirley Mao |author8=Sabine Schneider |author9=Min-Joon Han |author10=Abigail Lytton-Jean |author11=Pamela A. Basto |author12=Siddharth Jhunjhunwala |author13=Jungmin Lee |author14=Daniel A. Heller |author15=Jeon Woong Kang |author16=George C. Hartoularos |author17=Kwang-Soo Kim |author18=Daniel G. Anderson |author19=Robert Langer |author20=Klavs F. Jensen | title = A vector-free microfluidic platform for intracellular delivery | journal = PNAS | date = 2013 | doi = 10.1073/pnas.1218705110 | pmid=23341631 | pmc=3568376 | volume=110 | pages=2082–7}}</ref> In 2014 Sharei founded SQZ Biotech<ref>{{Cite web|url=http://sqzbiotech.com/|title=Home|website=SQZ Biotech|access-date=2016-06-11}}</ref> to demonstrate the technology. That year, SQZ Biotech won the $100,000 grand prize in the annual startup competition sponsored by Boston-based accelerator MassChallenge.<ref>{{cite web|url=http://www.reuters.com/article/2014/10/30/ma-sqz-biotech-idUSnBw305865a+100+BSW20141030 |title=Archived copy |accessdate=March 6, 2015 |deadurl=yes |archiveurl=https://web.archive.org/web/20150402225745/http://www.reuters.com/article/2014/10/30/ma-sqz-biotech-idUSnBw305865a+100+BSW20141030 |archivedate=April 2, 2015 }}</ref>
The process was originally developed in 2013 by Armon Sharei, in the lab of [[Robert S. Langer|Langer]] and Jensen at [[Massachusetts Institute of Technology]].<ref name=":0" /> In 2014 Sharei founded SQZ Biotech to demonstrate the technology.<ref>{{Cite web|url=http://sqzbiotech.com/|title=Home|website=SQZ Biotech|access-date=2016-06-11}}</ref> That year, SQZ Biotech won the $100,000 grand prize in the annual startup competition sponsored by Boston-based accelerator MassChallenge.<ref>{{cite web|url=http://www.reuters.com/article/2014/10/30/ma-sqz-biotech-idUSnBw305865a+100+BSW20141030 |title=Archived copy |accessdate=March 6, 2015 |deadurl=yes |archiveurl=https://web.archive.org/web/20150402225745/http://www.reuters.com/article/2014/10/30/ma-sqz-biotech-idUSnBw305865a+100+BSW20141030 |archivedate=April 2, 2015 }}</ref>


[[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). This was the largest total prize awarded to a single company in the accelerator’s history. Named one of ''Ten World Changing Ideas'' by [[Scientific American]], the CellSqueeze platform enables scientists to manipulate cells with unprecedented simplicity ushering in new discoveries.<ref>{{cite web|url=http://www.scientificamerican.com/article/how-to-hijack-a-cell/ |title=How to Hijack A Cell |first= Ryan |last=Bradley |date= December 1, 2014}}</ref>
[[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). This was the largest total prize awarded to a single company in the accelerator’s history. Named one of ''Ten World Changing Ideas'' by [[Scientific American]], the CellSqueeze platform enables scientists to manipulate cells with unprecedented simplicity ushering in new discoveries.<ref>{{cite web|url=http://www.scientificamerican.com/article/how-to-hijack-a-cell/ |title=How to Hijack A Cell |first= Ryan |last=Bradley |date= December 1, 2014}}</ref>

Revision as of 12:25, 9 June 2017

CellSqueeze 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. It is a gentler version of a French press, that only 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 times 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, in the lab of Langer and Jensen at Massachusetts Institute of Technology.[2] In 2014 Sharei founded SQZ Biotech to demonstrate the technology.[9] That year, SQZ Biotech 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—worth more than $200,000—to support the use of CellSqueeze on the International Space Station (ISS). This was the largest total prize awarded to a single company in the accelerator’s history. Named one of Ten World Changing Ideas by Scientific American, the CellSqueeze platform enables scientists to manipulate cells with unprecedented simplicity ushering in new discoveries.[11]

See also

References

  1. ^ How It Works. SQZ Biotech. Retrieved on 2014-05-18.
  2. ^ a b Sharei, Armon; Zoldan, Janet; Adamo, Andrea; Sim, Woo Young; Cho, Nahyun; Jackson, Emily; Mao, Shirley; Schneider, Sabine; Han, Min-Joon (2013-02-05). "A vector-free microfluidic platform for intracellular delivery". Proceedings of the National Academy of Sciences. 110 (6): 2082–2087. doi:10.1073/pnas.1218705110. ISSN 0027-8424. PMC 3568376. PMID 23341631.{{cite journal}}: CS1 maint: PMC format (link)
  3. ^ a b Meacham, J. Mark; Durvasula, Kiranmai; Degertekin, F. Levent; Fedorov, Andrei G. (2013-06-27). "Physical Methods for Intracellular Delivery". Journal of Laboratory Automation. 19 (1): 1–18. doi:10.1177/2211068213494388. PMC 4449156. PMID 23813915.{{cite journal}}: CS1 maint: PMC format (link)
  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. ^ Sharei, Armon; Trifonova, Radiana; Jhunjhunwala, Siddharth; Hartoularos, George C.; Eyerman, Alexandra T.; Lytton-Jean, Abigail; Angin, Mathieu; Sharma, Siddhartha; Poceviciute, Roberta (2015-04-13). "Ex Vivo Cytosolic Delivery of Functional Macromolecules to Immune Cells". PLOS ONE. 10 (4): e0118803. doi:10.1371/journal.pone.0118803. ISSN 1932-6203. PMC 4395260. PMID 25875117.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  8. ^ 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; 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. 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. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)CS1 maint: archived copy as title (link)
  11. ^ Bradley, Ryan (December 1, 2014). "How to Hijack A Cell".
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