Researcher, Department of Solid State Physics, Lund University

elke.hebisch@ftf.lth.se received funding from seedling project grants through NanoLund; for research research, my mentor christelle.prinz@ftf.lth.se received funding from ERC-CoG grant NanoPokers (662206); Sweden Strategic Research Foundation (funded by ITM17), Swedish Research Council, Craford Foundation and NanoLund. It is also worth mentioning that one of our co-authors (Martin Hjort) is the CTO of Navan Technologies, Inc., a startup company that commercializes nanopipettes.

Lund University provides funding as a member of The Conversation UK.

Over the years, scientists have put together a series of amazing microscopic markers, as long as they need to mark and observe different parts of the cell, they can place them inside the cell. This marker is used in a wide range of research, including cancer research.

However, it is far from easy to sneak these markers into cells through membranes that protect cells from harmful substances. Injecting the marker can cause excessive cracks in the cell membrane to be fatal to the cell. In addition, once they are smuggled inside, many of the markers are actually toxic-either they are attacked by the cell or they cause the cell to die.

In the search for non-toxic marks, scientists discovered nano-diamonds: the same as those dazzling engagement rings, but one million times smaller. Nanodiamonds are excellent reporter molecules in cells, but they have not yet appeared in scientists' toolkits, because putting them in cells without damaging the cell membrane has proven too difficult.

Under the leadership of Christelle Prinz, my mentor from NanoLund at Lund University, our team created a new method that can sneak nanodiamonds into cells without causing damage or stimulating cells to attack them. Our new technology will help scientists study the properties of living cells at the molecular level, but it may also become a versatile new tool that helps us learn more about cell diseases such as cancer and Alzheimer's.

Our body is made up of approximately 40 trillion cells, ranging in size from 1 to 100 microns. Some of these cells sometimes get sick-causing cancer in various tissues, or neurological diseases such as Alzheimer's in brain cells. By monitoring diseased cells, researchers can learn more about the origin and development of these diseases.

Read more: Cancer growth in the body may originate from a single cell-target it to revolutionize treatment

Microscopes can look inside cells, but they cannot distinguish diseased cells from healthy cells. For more detailed monitoring, researchers label cells with biomarkers, which can learn more about what is happening inside the cell.

Existing biomarkers, such as organic dyes and fluorescent proteins, can expose some conditions in cells for researchers to study. But these markers usually kill cells, which limits their usefulness in long-term cell research. On the other hand, nanodiamonds do not kill cells-which is why they are now used by researchers in cell science.

Nanodiamonds are either produced by detonating synthetic diamonds, or produced from the powder left over from the grinding of natural diamonds. Despite their luxurious connotations, for researchers like us, purchasing them is actually relatively cheap—the cost is about the same as existing biomarkers.

Crucially, nanodiamonds are biocompatible: when they are placed in living tissue, they are completely harmless and non-toxic. This means that they can hide in our cells. Once inside, the nanodiamond emits light inside the cell-sending information back to the researcher in the form of fluorescence, the wavelength of which changes according to the pH or temperature inside the cell.

Putting nanodiamonds into cells is not easy. Cell membranes have evolved an impressive protective device that can shut out unwanted invaders. In order for nanodiamonds to sneak in, we either want cells to voluntarily invite them to enter-this is a very slow and inefficient process-otherwise we must force them to enter through the cell membrane.

Microinjection using a microneedle has been used to deliver markers such as nanodiamonds to the cell membrane without causing fatal damage to the cells, but this is an arduous method and usually unsuccessful.

Even after successful infiltration, nanodiamonds are still at risk of being swallowed by cell lysosomes, which are a bit like the bodyguard of cells. Biomarkers captured and confined in lysosomes are of little use to researchers trying to observe whole cells.

We have developed a new method that can sneak a large amount of nanodiamonds into cells, basically undetectable by lysosomes, and will not damage the cells themselves. Our method combines a very mild electric field with a so-called "nanopipette", which allows cell membranes to open easily, just like a pipette, but very small on the nanoscale.

In our study, we used cells from lung cancer patients. We place these cells on thousands of nanopipettes, equivalent to a tiny nail bed. Under these nanopipettes is our nanodiamond, in a slightly conductive solution.

When we applied low-voltage electrical pulses to the nanopipettes, small openings appeared in the cell membrane. At the tip of each nanopipette, a pathway was created for the nanodiamonds to enter the cell.

The electrical pulse forces the conductive solution up through the straw, dragging the nanodiamonds through the tiny gaps in the cell membrane. When we stop the pulse, the small opening in the cell membrane closes behind the smuggled nanodiamond cargo.

Our new technology is about 300 times faster than simply growing cells in a nanodiamond solution and waiting for some of them to naturally enter the cells. It also reduces the retention of nanodiamonds in the lysosome, so that most of the transported nanodiamonds remain free and move inside the cell: successful infiltration.

Since nanodiamonds can report the temperature or acidity of different parts of cells over time, we hope that our nanodiamond infiltration technology can help identify and track cancer cells or brain cells related to Alzheimer's disease. Moreover, if we can find a way to pair nanodiamonds with certain chemicals, we can also find more elaborate ways to monitor the conditions within the basic building blocks of our bodies.

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