A Goal in MiNDS

A team of researchers from MIT have taken the first steps towards the development of a needle that can deliver drugs to specific parts of the brain (1) – potentially reducing the off-target effects that come with drugs used to treat neurodegenerative conditions. The researchers tested the device – which they call MiNDS – in mice and a rhesus macaque monkey. The results showed that the device could deliver drugs selectively to small deep-brain structures in a controlled manner.

Positron emission tomography imaging showed localized drug delivery with a volume of ~1-mm^3. “This is essential, given that many key neural circuit nodes have such small volumes,” says Canan Dagdeviren, assistant professor at MIT and lead author of the study.

Dagdeviren took her inspiration from an unusual source: Turkish coffee – specifically the fine porcelain cups and plates that are served on a tray in Dagdeviren’s home country.

The miniaturized neural drug delivery system has multiple tiny components, including two fluidic channels connected to wireless micropumps for delivering nanoliters of drugs on demand, and an electrode to record neural activity for potential feedback control. “These components are all thinner than a hair fiber and can’t be handled with bare hands,” says Dagdeviren.

Much like a Turkish coffee tray provides stability to the tiny, fine-featured coffee cups and plates, Dagdeviren microfabricated a polymer tray on a plannar silicon substrate in 2D to support the delicate components. “While the mechanical stability is provided by the polymer tray, I used microfabrication tricks to lift-off the entire device platform from the planar, rigid substrate and encase it in a round, flexible stainless steel needle,” she says.

The result is a 3D platform able to reach deep brain structures without the need of an extraneous guide tube to implant in the brain. MiNDS has a diameter of 200 µm – slightly thicker than a hair fiber – and can be scaled: for small animals the team used a small MiNDS with a length of 1 cm, whereas for non-human primates they used a 10 cm one.

Although previous studies have reported on devices with various sizes, down to 70 µm and infusion volumes as small as 10 nl, Dagdeviren says they suffer from diffusion and leakage problems. “Our infusion micropumps can be refilled, even while implanted, via a septum that can be penetrated using a 31-gauge needle,” she says. “Our experimental findings show no infusion past the programmed end of pumping with the micropumps, indicating that there is negligible passive leakage of fluid out of the drug infusion channels.”

Dagdeviren envisages additional uses for the device beyond the brain. “Another potential use of MiNDS could be for targeted delivery of chemotherapeutics to tumors in the body,” she says. “Such a technique would provide delivery of higher doses without the associated systemic toxicity.” She also believes MiNDS could be used to deliver growth factors and stem cells to regions of significant cellular necrosis. “For neurological and cardiovascular diseases, combining growth factor therapy with electrical stimuli might help regenerate electroactive cells. The customizable features of MiNDS could open new routes to deliver not only light but also chemicals and electricity to other organs with pinpoint spatiotemporal resolution,” says Dagdeviren.