Transcript for:
Overview of Surface Plasmon Resonance Applications

There will be reflection. If we keep increasing the angles, what will we see? We will see the total internal reflection. This is the basic thing. If we put another metal film on the surface, there will be another chemical.

Because on the surface of the atmosphere, we have a lot of energy, right? We have three electrons. And the light itself is actually an energy, right? It's an electromagnetic wave.

So, with the introduction of the light, the reduction of the electron magnetic fields, the free electrons, they will oscillate. When this oscillation wavelengths match with the wavelength through the surface of the magnet, there will be the resonance. And from this equation, we can see here, it is related to the angle. At a certain angle, you will see when the resonance is learned.

how the reflected light will be absorbed by the electron scales. So we will see a very sharp heap. here as we see this is the right one we have a deep this is called sprd or spr angle so as it's angle all the energies are on the surface of the of the gold film or the silver film so it will give us a very high sensitive surface so among all these uh concepts i just mentioned there are two there are two uh two words i want to use one is which is actually when the total is trapped at the surface of the metal.

And that one is the evanescent wave. And also another concept is the surface emphasmus, which is activated electrons on the surface. So this is a very important concept involved in the SPR examination.

So with this... With this process, you can see here is a video. It may give you a better description of this process.

You see there is an evanescent energy wave. So when it occurs, there will be a change in the reflection intensities. So this is SPR.

And SPR, the reason we want to work with SPR is basically it's really sensitive to boundary conditions. All the refractive index change, all the electron change properties can give us signals. And also it's a very universal signal, so we don't need any labeling. We can do the real-time label-free detection. And with this real-time detection, we can not only detect the constitution of the analysis, we can also monitor genetics.

It is especially important for some drug screenings because when we are ranking we want to know how fast the drug can advance and how long it can stay with the target and we have to evaluate the efficacy of the drug. And also, it's actually a very good technology to be combined with other methods, like the electrodes and so on. So when we combine the bioreceptor elements, we can we can obtain both various specific and also various synthetic techniques for the data. Since SPR is one of my work, so I will go directly to some of my work here. So my basic work here and my research, my research actually we're trying to build label-free techniques and also some optical instrumentation.

We are trying to solve the clinical issues. So there are two different directions here. So first one we are trying to solve the precision, we are trying to screen the targeted drugs and target as cell surface receptors. So another action we are working on is the anti-microbial resistance.

We are trying to build a peer-to-peer instrument to enable the So I direct the AST deck. We are going to reduce the current very long period of sustainability time to about two to three hours. So today I will first focus on the osmotic imaging interactions.

So you can see here what we do to improve this technology is we switch, we like replace the photo character with the system cameras. So when we change it with the camera we will see what we can see resolve spatial information. We can see some local changes as you can see from these two videos.

So we can enable high throughput and also we can see into the subspecial locations of single cells how the molecular reaction, how the binding occurs. And furthermore, we are trying to Further improve our spatial resolution in both x and y and y and replace the prism with a high numerical vector of objectives which can allow us to give a high angle translation. So with this setup we can resolve very small here as we show here we can resolve like this hundred. less than less than uh silicon particles which is actually already smaller than the reflection limit this is because this is very sensitive so the very small particles are resolved also also with the imaging of single cells we can obtain not only the shape of itself we can see the 3d structures we will know which part is more closer to the surface which part is away from the surface so it will give us another view of the cell what the optical like the red field microspeed cannot be right also also because SPR is very sensitive to both the charges and the effects so we integrate the electrical detection together as with this one the capability of our measures. We can use the transmitted image to show the morphology of the signals.

And use SPR to show the dynamic molecular interactions. And for the impedance ones, see how the cell is intact, how it's already broken with the chemical impedance signals here. So with this method, we have already achieved single molecule imaging.

We can do single protein interactions, and also we can see single cells, like signal transaction. We already see the action potential in the neuron cells, how it transmits, how it propagates along the single axis. And today I will use one typical...

applications we have been using with SPR macrosystems, which is the molecular is the connection of the cell surface. Why we are very particularly interested in this process? Because the receptor of the cell surface is very important. It is a start. of a lot of self-recognition and the community.

Also, more importantly, it is a target of the current drugs. So you can see from here, it's already been established. more than 60% of the protein is in the membrane proteins. But currently, we are trying to develop, we are trying to screen and track it as this receptor.

What we have to do is we have to... express the targets on the cell, then we have to isolate and purify, which is a very laborious process. And also sometimes when we get the membrane out, it will lose its function, lose its structure. So there is a very specific need to develop a very native method.

by trying to capture the native reaction on the cell surface. Yeah this is another summary of the motivation, the significance, why we are doing molecular interaction on the cell surface. We want to understand cellular reaction, the signal And also we want to be one of the drugs, right? So the current challenge is that it's really hard for the marrow, because it's very hard to prove as they are in this surface. And apparently, the membrane protein is called drug-borne drugs.

So a lot of studies have been focused on evaluating the methods to improve that. So what we have done is we just combined the cell culture with our SPR imaging systems. So you can see from here, we can see the blood field, we see the morphology of the cells, and then also we can see how the cells interact with the certain system. When we introduce the drug-based on the surface, we will see the real-time banding and both the temporal responses and the spatial distribution.

So currently, we're trying to establish this method with a very typical receptor, which is encoded in the DNA, which has been demonstrated in related ways with the development of cancer cells. So we use another cell, which is the A4V3-1 cell. They are over-expressive with the HF-R receptor.

So we're trying to screen antibody drug which can block this target, which will stop the ever-growing, the keep growing of the cells. Stop the growing. the cancer element. So you can see from our signals, we can see very obvious binding signals here, which indicate the antibody drug really binds to a target, it binds.

And also from the binding curve, we can get the kinetics, which is associated with it. It tells us how fast the drug reacts with it and also we can associate with rate constant. It tells us how long it can stay.

So with these two values it is very easy to rank. So with this method we collaborate with pharmaceutical companies by trying to provide some data and some values for their screening. And also based on the connections between the drug molecules, we see very diverse binding kinetics. So we thought it should be related with some mechanisms.

So you can see from here, we test the binding kinetics between the resistant cells and some sensitive cells. Because in the clinical, when we use this structural down, some patients will stop responding to the drug. That means it's involuntary resistance to the drugs. but the mechanism is not very clear. From our results, you can see for the resistant patients, the drug seems to bend and drop.

It's very fast. We call it non-small-small banding. It's very likely because the banding has been blocked by other molecules.

So with our results of the banding, we can hypothesize the resistant mechanism. So there may be two different ways of resistance binding. One is called the high passing hypothesis.

So if the binding curve is still very beautiful binding, but the patient is not responding to the therapy, it means it goes through the high passing hypothesis. The DNA rather is not signaling ways to activate the growth of the cells. But if the binding is likely to be successful, If the band is pulled very fast and then drops out, it causes another alternative pathogenesis.

It means the banding protein is dropped. So that's why we use our genetics to screen the drug, also to explain why the patient is resistant to certain drugs. And also, as we mentioned, here is a mass sensitivity.

So we can trust the response, the signal response to the mass density we obtained. So what we can do is we can quantify the We can quantify the receptor expression levels in a single step. This is very important because we know EGFR is a cancer biomarker, right?

If we can quantify the ecostatic expression levels, we can use it to evaluate the status of the disease. And also we can use it to evaluate whether the treatment is working or not. So cancer also provides us a good way for tumor cell resection. So based on this context, we developed another evaluation. we are trying to modify, to profile the glycoproteins on the single cells.

Because glycans are very important. From this one we can see it's a no-bulb mice in 2023. They are given to the scientists. find the clear chemistry to labeling the glycans on surfaces. Because glycans are very diverse and very hard. So what we can do is we are trying to solve this problem not with labeling but with specific specific applications.

We can quantify the very real-time planning terms and to recognize. and recognize different classes. So based on this proposal, we already achieved the capture of multiple classes with a little bit less molecules. We use lectins here. So we quantify the glycans.

And we can see for the tumor cells. We test the normal cells, and the pre-cancer cells, and the tumor cells, and the tumor cells, and the metastasis tumor cells. observe very different kinds of glycan expression. So with this measure, give us another choice, maybe not the best method, but another choice, and use less targets, use less groups, and without labeling, we can map the distribution of this on the cell surface, and for the cancer cell detection, and for the cancer status.

Okay, so another application we are trying to see how the cancer development will affect cell and surface interactions. So what we do is we're trying to quantify the real-time process of surface and substrate information. But also we are trying to measure the movement and the repromotions when the cell attaches which is related to the linkers which is related to the cells from this from this cartoon here, we have to know it's not like they are lying down on the surface. They are actually have a lot of linkers. They tether the cells in the surface.

And the number of the number of and the and the like the strings that spring constant of the linker is related to how much the cell is tethered. So what we can quantify is we can quantify the tether numbers. we quantify the tethered strength. With this method, what we observe is that with the primed tumor cells, sometimes it attaches itself to the surface more closely and faster. For the metastatic tumor cells, it's very hard for them to attach to the surface.

And also, it's very loose. I didn't show the videos here, but you can imagine it's like a from the surface and move a lot. So it's a very weak ending with metastasis and mitous and dandruff tumors. So with this method, we can do the study of the tumor.

progression, progression, distribution, right? So this is another application we are trying to do. So this slide, this is the video.

So it's similar, it's still the surface and the cell. You can see when we give another external stimulation, antigenic stimulation, you can see very, very fast responding of the cells. You can observe like holes over there.

It's actually some part of the cell's wave on the surface. So our method is that we can really see a different view of the cell, how it interacts with the surface or with other molecules. With this kind of information, it's very hard to be achieved with traditional optical imaging systems.

Okay? Oh okay, so this one is very interesting. Just because of time limit, I'm just going to quickly introduce it. This is, we are trying to use our microscopy to imaging the intracellular agonist.

This agonist is a metacondriac. This is how metacondriac is moving along the cytoskeleton. Yeah, this is actually the... very interesting.

It tells us that all the organelles inside the cells are not being virally rendered. All traffic is through the ankylactam. So this is another work we have been working on. A little bit summary. I cannot go through all the examples here.

So basically with very high sensitivity of our SPR imaging and macroscopic systems, can see all the local interactions of the cells, including the extracellular interactions, also the intracellular macromandibular. So we also have done some functional images. We're trying to resolve the single action potentials along the neurons. The image left here is the cortex primary neurons. We can see the structure of neurons.

yeah i forgot to put a video here actually we can see how the action potential is trafficking or propagation allows access it's also very interesting if you guys want to know more you can check with the papers they have we have papers for completion on this one okay Okay, this one is actually another, I will give you a summary of another work that I have been working on. It's actually the direct antibacterial accessibility testing. Like I mentioned, we are trying to solve the threat of the resistant process. So we We build a very sensitive single cell density spectra. You can see here all those blinking ones are single bacterial cells.

Like the blinking stars are cyanide. So the basic principle is that we are trying to build a black field image. We remove the background densities of the light.

Then we can see the single... With this method, we can allow for the identification of single-parent bacteria with raw blood samples. We also tried the urine samples.

What we have achieved is that it can cause a susceptibility test within two to three hours, which has been over three days. So this is another work that we are recently doing. this manuscript has already been in the revision right now.

I think that's basically what I want to cover about some of my work. And the next I'm going to go to is Professor Liu's research. So Professor Liu is mainly working on the global systems.

So the problem he's trying to solve is continuous monitoring of the signals. And the measures we're trying to use is electrical Because the easy method is more easy for us to make it small, so it's more compatible with the wearable system. I can see the motivation.

Okay, the motivation why we want to do the monitoring, why we want to do the wearable devices. Basically, because in the current medical care, what we determine is happening. It's just one point right on the triangle. So it provides a very limited.

Sometimes it gives us maybe false positive or false negative. Due to this problem, so we have solutions. We have a but we can achieve multiple ones. Still, it's very hard for the patient to follow the detection all the time. and also give us very limited prediction data for the diagnosis.

A better solution we are trying to achieve is a wearable disease analysis. We want to get the continuous monitoring and also the real-time to predict the disease propagation. So this is basically the motivation for this study.

And currently we have a lot of smart phones, smart screens, right? We are trying to monitor the body temperature, oxygen, and the pulse. But when we come to the chemical sensors, there are very limited products here. But...

people are trying to propose. We have to propose if we have a biomechanical sensing smartwatch, that would be very meaningful because it can help us monitor all the metabolites inside our bodies from the saliva, urine, it can give us a very comprehensive information. So this is a fundamental production of the wearable devices.

And due to this, I'm limited. I will just go from here. So what Professor Liu is trying to solve is actually, we want to carry down the battery.

The battery is very bulky and you need to recharge it frequently. So it's not very optimal solution for wearable DLF6. So one solution we use is Arm4D, which is a near-field NFC DLF6.

We all know we use NFC to purchase, right? We use NFC to communicate with our cell phones. Based on this cell phone business, we develop a lot of cell phone So this example is a pressure-free and wireless electrical system for the slide. They can continuously monitor the glucose and also the ions.

This is to show how the real-time you can see when you are when you are doing some exercise there's white there's white you'll be monitored only to see how the eyes all the eyes is is is it's producing or using And also, apart from the ions, based on the immunosensory disease, they also achieve the detection of the which is very important for the evaluation of the stress levels. This is so very obvious in the morning and in the evening, even in the cortisol levels. Also, apart from the monitoring, we are also trying to close this loop from monitoring to treatment.

So, what we did is we developed a study of dressing. With this dressing, we can monitor the vitals. temperature, pH, and also the urea. We are trying to describe the infectious bacteria.

And if it's new in the infectious condition, we will use it. use the electrical release of the drug. You can see the drug molecules can be released as necessary. So with this measure, we can not just monitor the drug.

This is a paper we published on AFM. And another very recent version we are trying to do is we are trying to get rid of the cell phone power. We are trying to work on the cell powered systems. Cell powered technology is called. We are trying to harvest the body heat.

So with the body heat, we can transform the heat into the electrical signals and use it to preserve our sensors. So with this method, we have achieved real-time tracking and monitoring of a variety of indicators, including the heart rate, and the blood pressure, and the blood pressure. the ions and also the blasts.

So it gives us another way of our management. This is the way to integrate the gas sensors. This is some other applications.

by using this wearable device to monitor the food, the environment monitoring, and also for the breast monitoring. Okay? I said the...

I may have started it. Okay. So, do you guys have any questions?

Thank you, Prof. Zhang for the presentation. Now we will proceed to the Q&A session. Any student who would like to ask a question can type in the chat box or unmute yourself. Any questions? It's very hard to communicate like this.

You guys can hide or ask anything. You guys want to ask questions, you can go to the front using the laptop microphone or using your guys'not in one. I think like, how do you buy a pencil sharpener?

You don't think you can get it? Go ask around. This person is a professor. He's very young, he's less than 33 years old. Go meet him.

Go ask around. Can you open it here? You open the question. ah we have a question from here Sorry, I cannot.

Maybe typing? Yeah, his question is about the EGFR receptor. Sorry, the EGFR receptor what? Yeah, what's the meaning of that?

Oh, what's the meaning? Oh, okay. The epidermal growth factor receptors.

It can react with the growth factor. Does that make sense? So when the growth factor will react to the receptor on the cell surface, it will stimulate the cell to continuously grow and to become a cancer cell. So that's why it's oncogenesis and a lot of cancer cells over-express with this receptor.

Does that make sense? Yes, this already answered his question.