Figure 1. Schematic of the sensor structure and cell-sensor interface.
Tech Briefs: What got you started on this project?

Professor Jun Yao: I was trained during my postdoc time to work with silicon nanowire. It’s amazing — it’s a tiny sensor that can listen to, for example, cells in the body. And the beauty is a silicon nanowire is so tiny that when it listens to or measures cell properties, it doesn’t introduce any kind of harm to the cell itself. Human cells are really tiny — we cannot see them using our bare eyes. A silicon nanowire is 1000 times smaller in diameter than that of a human cell. So, that's why we designed it as a probe that can detect in real time what's happening in a cell body.

Tech Briefs: How does it do both electrical sensing and mechanical sensing?

Yao: Imagine that a silicon nanowire is a cable. If there is a certain kind of electrical activity happening nearby, that electrical activity can affect current in the cable to induce a sensing signal.

Tech Briefs: Is that through magnetic induction?

Yao: It's similar but different. I’m using this as an analogy. It causes a field effect so it's actually through the electrical field.

Tech Briefs: So, it's more like capacitive coupling?
Figure 2. SEM (scanning electron microscope) image of a suspended nanowire.

Yao: Correct. The silicon nanowire is a semiconductor so if there's any kind of electrical activity happening nearby, it produces an electric field. That field can affect the conduction in the silicon nanowire, which will then change the current passing through it as the sensing signal.

So now, how about the mechanical sensing? Imagine that the silicon nanowire is free-standing like a suspended cable. Let's imagine there's a wind current: it's going to drag the cable — this is similar. When the cell in the body moves, it drags the silicon nanowire. That causes a so-called piezoresistive effect, which is a common effect with any kind of material. If you apply a mechanical force, it causes a tiny deformation in its shape. Imagine if we pull a rope, its cross section is slightly reduced. That can change the conductance, leading to the change of the current as the sensing signal.

So, we have two processes that can induce conductance change in the silicon nanowire at the same time. One is through the electrical field effect, and the other is through the mechanical piezoresistive effect. You can imagine that if we place the nanowire close to the cell body, it can listen to the electrical activity and simultaneously probe its mechanical activity.

Tech Briefs: How do you distinguish one effect from the other?

Yao: That's a great question. We know that the biological signals fall in different so-called frequency domains. We can tell which is which because their frequencies are different.

Tech Briefs: Could you tell me something about cells? I mean in what way are cells both mechanical and electrical? And what's the significance of those two different cell functions?

Yao: Most cells have both electrical and mechanical activity, especially cardiac cells. Our heart is constantly beating and that comes from cell movement. That cell movement is triggered by an electrical signal. The human heart is just like an electrical pump. The electrical signal propagates over the entire heart. And that signal triggers the mechanical contraction.

This is of course, organ-level activity. But the organ activity originates from cell level activity. At the cell level, the so-called electrical signal is the action potential. The action potential passes from one cell to the next, causing each to contract. That means that the mechanical and electrical signals in a cell are coordinated.

If something is wrong, let's say you have certain kind of heart disease, for example, arrythmia, which means that the heartbeat is irregular — that could cause big trouble. That is because the coupling between the electrical and mechanical responses at the single cell level is not healthy.

Tech Briefs: Could you explain what an action potential is.

Yao: An action potential is like an electric pulse, it is an electrical signal from one cell to the next, which causes that cell to have mechanical motion. It's like a trigger — for example in any kind of mechanical gear, we use an electrical signal to get something started.

Tech Briefs: How could the ability to make these measurements be helpful?

Yao: When we try to diagnose a disease mechanism, there could be lots of reasons for it. We want to know as much as possible about the details so that we can find out what is really going on.

The heart system involves these correlated processes — the electrical signal and the mechanical signal. If we can know both together, we can have much richer information, to have a better idea about what could be the reason, the mechanism, underlying a diseased heart.

Previously, it's been very hard for us to detect those signals simultaneously. Usually, you can only detect one signal at a time — either electrical or the mechanical — you wouldn’t be able to see how they are correlated. And that is missing part of the rich information.

In principle, you can do that by plugging in two types of sensors at the same cell. But you can imagine how difficult that would be. For one thing, their detection mechanisms would be different. Second, that kind of signal recording is not easy. And third, if you place two sensors in the same cell, you introduce further perturbations, it will put stress on the cell.

Tech Briefs: Would you say that knowing this information on the cellular level will help you make correlations between cell level and macro level heart issues that could not be done without this?

Yao: Yes. Lots of those are markers for disease phenotypes, so we wanted to know the details of the cell in order to better understand disease.

Tech Briefs: So, what stage are you at now — how have you experimented on cells?

Yao: This is a new technology; we have already filed for a patent on it. I think it has commercial value because these days, people are interested in biochips. But people are concerned about placing chips, in the human body.

So, the safer way is that we work on human cells outside the living human body to do the study. For example, although we take medicines for curing disease, they can have adverse side-effects.

So, we need to do drug-effect studies — how are we going to do that since we don’t want to use a living human being? A simple way is that we can look at human cells outside of the body and add the drug we are studying to see its effects.

Now, how can we know whether the drugs are going to do something harmful. We need to listen to what’s going on in the cell. This type of tiny sensor can tell you if the drug is going to affect the cell’s electrical or mechanical activity.

That's one thing we can see at this stage, with what we call an in vitro study, (outside of a living body). This kind of sensor can enable a system model. But in the long run, we also hope that, because these things are so tiny, we can easily make these kinds of sensors on a very flexible substrate. Maybe they will be able to be implanted into a living body so it can detect in real time what’s happening. But I think that's a bit far away because it involves lots of safety regulations, although I think this will eventually be accepted.

Tech Briefs: How do you pick up the signals?

Yao: Since the sensor is tiny, the change in current level, is in nanoamperes (10-9 amperes).

So, what we need is a so-called current amplifier to amplify the signal and then we can use a computerized recording system to record it. That's standard for many kinds of electrical sensing recordings.

Tech Briefs: Can you attach wires to it if you are doing an in vivo (inside a living body), study?

Yao: It's possible, but it depends on your actual needs. Sometimes, if it's for an animal model, the animal can still be compliant, which means you probably don't need wireless. You can use a wire tethered to the animal in a confined space, which will still enable necessary reading and study. But, for example, if you wanted the animal to be in an environment that is much freer, we would probably need to consider wireless communication. And that actually is possible, because nowadays wireless communication protocols are pretty mature. So, you could have a device on the animal’s body that serves as a wireless communication station and that can deliver a signal to a remote terminal.

Tech Briefs: What do you see as the timeline for the ability to use this for in vivo investigations?

Yao: I don't think it's going to be far away — it really depends, for one thing, on whether we have the resources. Also, whether we can identify a particular biomedical problem for which this sensor can immediately provide information that was not previously accessible.

In fact, I was reached out to by a colleague from our school who has been studying the effects of jet lag on the cardiac system. Of course, that study is on a living system — but it could be done on an animal and not necessarily directly on a human body. He said they could do probing from outside the body, using available imaging systems, but those have very low resolution. If he could somehow look into a living animal’s body and then receive that kind of information at much higher resolution, he could observe much more subtle effects caused by jet lag.

I’m not always the one who can identify an application; it's most often people who are working in the biomedical field. When they are made aware of our device, they could think of a way of applying it to a particular problem. So, at this point I'm waiting for other people to come by and say “Hey, we’ve got this problem and it looks like this is kind of a cool technology, can we just try it out?”

Tech Briefs: Yeah, that’s exciting. I believe that’s the way much scientific progress takes place — with people talking to each other, coming together saying: “I have a problem” and “I have a solution.”

Yao: I am an electrical engineer, so my passion or interest is to develop these kinds of tools. But I don’t necessarily know much about concrete, or logical, or mathematical problems. So, I take pride that I can help a colleague in their research, someone who might come by and say, “hey, this is usable to us” — I take pride in that. I like to see myself as having a supportive role — to say “what do you need? — “we can probably come up with a tool for you.”