VivaDX
You walk into the living room, your slack pings and while checking the post you bump the candle on the table, which causes the couch to burst into flames. What is the first thing you do?
You shout for everyone to evacuate the building! And call 911!
Your first priority is communicating this problem with others.
Now let’s shrink the scenario down to the cellular level. A cell is hanging out expressing genes and suddenly detects some impending crisis (ex. a cancer cell). Like you in the fire, the cell will also communicate this problem using its own language — biomarkers. These biomarkers flow all around your body through the bloodstream, hoping that someone, anyone, will hear their warning and come save them, but do we listen?
Nope.
Because our current healthcare system is symptoms-based, we only realize that something is wrong when we physically feel something wrong, and often, that’s too late.
Cancer is one of the leading causes of death across the world. This issue is that 30–50% of cancer deaths could be prevented had they been detected early (before symptoms appear) and key risk factors controlled. Similarly, 47% of sudden cardiac deaths occur outside the hospital, meaning that patients don’t recognize early warning signs. One of the main reasons these diseases are so deadly is because we can’t detect them in time.
Like how no two individuals are the same, no two diseases are the same either. Certain blood cancers only respond to a certain skin cancer medication. For some people, sushi is more dangerous than ice cream. Understanding biomarkers is crucial for personalized healthcare and ultimately, this will lead to a much more efficient system.
Opportunity: The need for live-cell communication to Detect Disease
Live Cell Communication
Three leaders in biological engineering gather at Synbiobeta: the largest synthetic biology conference. These leaders are Jim Collins (Professor of Bioengineering at MIT), Aoife Brennan (CEO of Synlogic), and Jason Kelly (CEO of Ginkgo Bioworks).
While exchanging ideas about the future of biotechnology, Jim says “We’re lacking real-time feedback tools that allow us to see what is happening inside living cells. Such a tool could replace flow cytometry, greatly increase the speed of the design-build-test cycle, and enable us to design genetic circuits with more predictability.”
Diseases
Dave Asprey, biohacker and CEO of Bulletproof labs shares his research about the deadliest diseases. He calls them the four killers: cancer, heart disease, Alzheimer’s disease, and diabetes. Being a longevity supporter, Dave sees these diseases as problems that increase millions of people’s chance of dying.
Despite being so common and having so many researchers working on these problems, we’re still lacking fundamental understanding about these diseases, especially in vivo and in real-time.
If we could get nano-scale or even micro-scale insights into patients… how they’re reacting to drugs, how their metabolome is evolving, or if we could do that non-invasively, and interpret the results with Artificial Intelligence… we could be 10 steps closer to ‘killing these killers’.
Current approaches to monitoring cells
One method is reductionist, isolating and culturing cells in vitro so that specific signals can be carefully tested with chemicals and cellular responses can be measured.
Another more holistic method involves measuring cellular signaling in vivo by applying specific chemical agents that block or activate receptors in a tissue region. The response is measured via an electrode that relays the activity of ion currents or via fluid sampling of the activated area. For both approaches, measuring the small cellular entities is indeed a challenge.
Other approaches include:
- Use sophisticated time-lapse microscopy to track labeled molecules that travel between subcellular compartments.’
- Mass spectrometry techniques that permit measurements of picomolar amounts, enabling the tracking of intracellular second messenger molecules that are crucial in the regulation of signals in the intracellular environment.
- Gold nanoparticles are widely used in immunohistochemistry to identify protein-protein interaction. However, the multiple simultaneous detection capabilities of this technique are fairly limited.
The science behind our solution
Introducing the world’s first cell computer interface (or CCIs). CCIs are nanobots that flow through your bloodstream and constantly communicate cellular information to an external computer, represented by the name vivaDX, meaning the pill of life. Our CCIs will be taken in pill form to diffuse into the bloodstream and detect for specific biomarkers that indicate disease. If an abnormal concentration of these biomarkers is detected, a signal will be sent to a wristband which will amplify it to the wearer’s phone, alerting them to schedule an appointment with their doctor for a more comprehensive diagnosis and plan forward.
Nanobot anatomy
- Aptamer
- Chromium
- Silica base
- Silica dioxide
- Carbon nanotubes
- PEG
A typical biosensor configuration has a three-element system: a bioreceptor that is responsible for the selectivity of the device (e.g., enzymes, antibodies, lipid), a transducer that translates the physical or chemical change by recognizing the analyte, and a signal-processing unit (signal output).
The shape is most often spherical, but cylindrical, plate-like and other shapes are possible. The size and size distribution might be important in some cases, for example, if penetration through a pore structure of a cellular membrane is required.
Electrochemical biosensors
In order to create this interface between the organic and the inorganic, we need to work with a biochemical biosensor. These have been in existence for quite a while. The difference, of course, is bringing them to the nano-scale, and to do that, we will use aptamers.
Aptamers are oligonucleotide (DNA) or peptide (protein) molecules that bind to a specific target molecule through various non-covalent interactions. Now, those who are into biology may be wondering how aptamers are better than antibodies. Well, aptamers offer molecular recognition properties that the rivals can’t. They are really versatile and selective due to their tendency to form helices and single-stranded loops.
High-level, aptamers are like locks with a very specific shape. Our bodies contain different types of keys, but only one type can open our specific aptamer. When it does, that means we’ve detected a disease biomarker.
What happens next after the CCI pill detects? The whole point of biomarkers and biosensors is having a quantitative analysis of disease. Thankfully, electrochemical reactions (like the ones we’re doing) usually provide an electronic signal directly, avoiding the requirement of expensive equipment. The science behind this is the redox properties of the reported molecules, which are detected by a biosensor component called a transducer.
Talking about components, other parts of this electrochemical sensor are:
- Bioreceptor: binds to the *analyte selectively
- Interface: where the chemical signal is measured. In this case, we will use electrodes. Materials like platinum, gold, carbon (graphite), and silicon compounds are commonly used, depending on the analyte
- Transducer: turns the signal into an electronic signal and amplifies it
- Software: converts the electronic signal into a physical parameter that can meaningfully be interpreted
- User interface: present the data to the user
*Analyte: substance whose chemical constituents are being identified and measured
Materials
Making an artificial object that is going into your body can be difficult, especially one as small as a nanobot. Fortunately, there are many safe options for your body. To create the best diagnosis device, the CCI is made from a silica and carboxyl base, encoated in PEG.
The base of the nanobot is one of the most important parts because it needs to be small enough to navigate through your bloodstream, well also being strong enough to transport technology. Previously, the use of silica has been controversial when making nanobots for medical use, because silica can leach into the body and cause harmful side effects. Recently, scientists have discovered new coatings for silica, such as PEG, that help contain silica and prevent it from leaching into your body.
Carboxyl is a type of active group that helps float the nanobot and make biosensing possible. Right now, most nanotechnology is not hydrophilic, which means that it can not easily biosense because of its separation from the blood or body material. By using Carboxylic acid as part of our nanobot, we can allow for the biosensing technology to become incorporated into the bloodstream, allowing for easier and more accurate diagnoses.
As I mentioned before, PEG is a helpful coating for nanotechnology. Besides increasing the silica to prevent leaching, PEG also works to prevent immune rejection. When encasing nanotechnology, PEG creates a semi-permeable membrane that allows for protein molecules to bind to it, well as preventing cytotoxicity (from silica) to escape, which essentially makes it invisible to the immune system. Because of this, cheaper materials can be used to make effective biosensors without harming the body!
What are we sensing?
There are hundreds of different diseases, all with different signs and symptoms, so how do we create a technology that works to diagnose the majority of them? The answer…biomarkers! Biomarkers are different chemicals or proteins specific to a disease. For example, a biomarker for kidney disease is a protein called BTP.
With our nanobots, our goal is to diagnose diseases in the early stage or before they happen, so that you can get the best and most effective treatment. To do this, the nanobot will be monitoring any changes in chemicals or proteins in your bloodstream. All you have to do is take a pill, and then the technology will enter your body and start looking for the biomarkers.
Specifically, we are not only looking for biomarkers for diseases but also changes in chemical and protein amounts in your bloodstream. Many diseases, even if they don’t have specific biomarkers, can be diagnosed by changes in your body, and our goal is to do that minimally-invasively! No more expensive, unnecessary blood tests!
How do we diagnose?
Once the nanobot is in your bloodstream, it is time to look for those diseases! To help identify specific diseases, the nanobot will look for biomarkers in your bloodstream, which are chemicals that appear when you get a certain disease like cancer. For example, if you have Carcinoid cancer, there will be tiny pieces of cancer cells floating in the bloodstream that the nanobot could recognize.
So how does the nanobot recognize these biomarkers? At the front of the nanobot, there are tiny pieces of DNA called aptamers. Aptamers are pieces of DNA that are really good at recognizing different proteins in chemicals, such as the biomarkers we are looking for! The aptamer will be programmed to detect certain biomarkers, and then once they find them they will activate a logic gate inside of the nanobot.
A logic gate is a function that takes an input to do output. For example, flipping the light switch turns on the light bulb. The input, in this case, will be the detection of the biomarkers from the aptamer. This will trigger the nanobot to make a diagnosis, and then send the information to a computer.
Communication with computer
After the chemical signal gets converted into an electrical signal, it will be detected by a wristband which will amplify and digitize the signal. It will then convert the signal into radio waves to send to the user’s phone through Bluetooth.
How can you use it?
So now that you know about how the pill works, how would you use it? The first step is taking the pill! Twice a year, all you have to do is take a tiny pill. Once you do this, then you just wait! The pill that you just took will enter your body and navigate its way to the bloodstream.
Once the pill is in the bloodstream, it is going to look for the biomarkers. If/when the biomarkers are detected in your body, the aptamer will send a chemical signal to the nanobot, which will then be transformed into an electrical signal. The electrical signal will be picked by your phone and send your results to an app, where you can look at them or send them to a doctor.
You’re probably thinking this sounds great, but how much is it going to cost me. Well, guess what… it is only going to cost $50!! That is 29% less than you would have to pay for a normal blood test. And, not only is it cheap, but it is also basically painless because of how small it is. Introducing viviaDX, the cheaper, painless way to get accurate diagnoses quickly!
Want to learn more? Check us out at our website: http://vivadx.org/
