The principle of our approach is pretty simple and the fabrication techniques that we use are fairly straightforward. It’s all relative, but compared to some of the other experiments with which I’ve been involved, these were easy experiments to pull off. I think that the real challenges will come in the future.
Prof Dr Madhavi Krishnan
Researchers from the University of Zurich (UZH) have developed a new method of measuring the electrical charges of individual nanoparticles. The ability to determine the charges of different nanoparticles could find applications within fields such as pharmacology, where a particle’s electrical charge enables it to pass through cell membranes, thus allowing it to transport drugs to their destination.
The nanoscientists created thousands of round energy holes with weak electrostatic charges in between two small glass plates. By ‘enticing’ particles into electrostatic traps and observing their subsequent movements, the team succeeded in determining the electrical charges of individual nanoparticles. A particle that possesses a small electrical charge makes large circular movements when in its trap, whereas those which are highly charged make smaller movements.
I spoke to Professor Dr Madhavi Krishnan from UZH’s Institute of Physical Chemistry to find out more about her work. I began by asking Professor Krishnan about how this method improves upon those previously used to calculate the electrical charges of nanoparticles.
"We have performed direct measurements," she replied. "We are talking about nanoparticles in a solution, which is of course different from the method used by Robert A Millikan 100 years ago. In a solution, things get complicated because it can become very difficult to measure charge directly. Previously, researchers have measured something known as zeta potential. Whilst this approach offers a very approximate measurement method, there has been a dearth of techniques capable of doing any better.
"Historically, people have been interested in trapping objects so that they can be studied. A couple of years ago, we developed our electrostatic method of trapping objects. To date, we have used this method to capture nanoparticles, but in theory, it could even be used to trap single proteins. The physics of the trap allows us to discern things about the objects themselves. Not only can we study complicated things like dynamics, but we can also measure other physical parameters of objects such as size and charge. The existing methods are basically bulk methods. Not only are their measurements principally limited, but they only provide an average for a whole number of particles.
"People have tried to make measurements at the single particle level and they have had some success, but these are still approximate results. Previously, it has not been possible to observe a single particle over a period of hours because without a trap, it is lost. Now that we have a trap, we can see how an object behaves in isolation and this tells us about the particle itself; its size and its charge."
Cross-section through two chip-sized glass plates in which a nanoparticle is trapped in an energy hole (or 'potential well' to use the scientific term). The coloured fields show the different charges in the electrostatic field. The red zone signifies a very low charge, while the blue edges have a strong charge.
Professor Krishnan explained that the experiments so far conducted have gone fairly smoothly. In developing their method, the team has worked with fairly ‘user-friendly’ objects. However, as Dr Krishnan explains, new materials could pose new challenges.
"The principle of our approach is pretty simple and the fabrication techniques that we have used are fairly straightforward," she said. "It’s all relative, but compared to some of the other experiments with which I’ve been involved, these were easy experiments to pull off. I think that the real challenges will come in the future.
"When working with gold particles and other robust objects, you don’t tend to encounter many problems. The challenges come when we start working with sticky objects like proteins. Such objects will want to stick to walls. This is a well-known hurdle for scientists working within our field. However, we hope to be able to get around such problems by using lipid coatings. Reducing the scale of our operations might also prove challenging. Right now, we are working at a scale of around 200nm, but we intend to go down to 20nm. That could pose a whole host of new challenges."
The electrical charges of nanoparticles contained within industrially manufactured solutions help to prevent such fluids from becoming ‘lumpy’. Moreover, within the field of medicine, nanoparticles transport drugs to their intended destinations. Electrical charge plays an important role in allowing nanoparticles to pass through tissue and cell membranes during the performance of such tasks, so the ability to accurately measure the charges of individual particles could find significant applications within this area.
"In terms of medical delivery, transportation methodologies have to make physical changes in order to release drugs," Professor Krishnan explained. "In such cases, surface chemistry tends to be extremely important. Alternatively, you might want to determine how many copies of a particular protein are contained within the membrane of a vesicle from a cell. There are a range of possible applications for this research and I think that our method will provide very high resolution diagnostic tools from a medical standpoint."
I concluded our conversation by asking Professor Krishnan about the research that she and her colleagues had planned for the future.
"We would like to be able to trap single proteins," she replied. "From the standpoint of trapping biologically interesting matter, I think that this is the Holy Grail; the ability to trap a single protein in a solution. I would like to achieve this feat using our method. The race is on to trap a single protein but as I said, proteins tend to stick to walls. There are also other problems that you don’t tend to encounter when working on the 100nm scale. The physics becomes a little different as the scale reduces. There are already techniques that might allow us to overcome these sorts of challenges. Every one of these problems has been overcome in a modular fashion, but they haven’t been put together. We must combine all of these facets to make a trap that will work for a single protein. That is going to be the challenge."