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Jul 23rd, 2013
Putting the squeeze on cells to deliver
Imagine being able to redirect powerful immune cells to fight cancer.
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Fig 1: The cell membrane is disrupted.
Fig 1: The cell membrane is disrupted.

How about reprogramming a diabetic’s skin cell into a cell that could manufacture the insulin their pancreas no longer produces? Could we dial down the production of fat cells in obese adolescents? These are major health problems and medical challenges that may be more achievable with a new fundamental technology that gets vital control molecules into cells faster, safer, and more effectively.NIBIB-funded engineers at the Massachusetts Institute of Technology (MIT) have developed a rapid and highly efficient system for transferring large molecules, nanoparticles, and other agents into living cells, providing new avenues for disease research and treatment. Cells carrying these “transferred molecules”– the intended therapy - can be used in many ways, including therapeutic and diagnostic interventions in patients and experimental therapies in animal models of disease. The technique offers a powerful tool for probing how cells and their molecular components work by studying how transferred molecules affect a cell’s behavior and functions.The system uses controlled mechanical force (relatively gentle squeezing) that is non-toxic to cells, unlike other methods that use viruses, chemicals or electric shock, which can kill cells and damage the transferred molecules. In addition, the new device is “high throughput,” which means it works rapidly, treating a remarkable 20,000-100,000 cells per second.The speedy transfer of therapeutic molecules into cells with minimal cell damage and death allows millions of cells to be treated in a very short period of time. This is important because usually, large numbers of treated cells are needed to achieve diagnostic and therapeutic effects.The system was developed through a collaboration between the laboratories of Robert Langer and Klavs Jensen, both at MIT. The work is published in the February 5 edition of the Proceedings of the National Academies of Science ("A vector-free microfluidic platform for intracellular delivery").

Fig 1: The cell membrane is disrupted when the cells (blue dots) are forced through constrictions in the channels of the microchip.

How it works
The device, known as a microfluidic delivery platform, is made up of channels etched into a silicon microchip 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.

Read more: http://www.nanowerk.com/news2/newsid=31469.php#ixzz2ZqxWdQ4K

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