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Using state-of-the-art tissue engineering techniques and a 3D printer, researchers at Weill Cornell Medicine and Cornell Engineering have assembled a replica of an adult human ear that looks and feels natural.

The study, published online in Acta Biomaterialia recently, offers the promise of grafts with well-defined anatomy and the correct biomechanical properties for those who are born with a congenital malformation or who lose an ear later in life. 

Pictured is the intricate, left-ear plastic scaffold that was created on a 3D printer based on data from a person’s ear, anterior view, left, and posterior view, right. Image: Spector Lab.

"Ear reconstruction requires multiple surgeries and an incredible amount of artistry and finesse," said, Dr Jason Spector, chief of the Division of Plastic and Reconstructive Surgery at New York-Presbyterian/Weill Cornell Medical Center and a professor of surgery (plastic surgery) at Weill Cornell Medicine. 

"This new technology may eventually provide an option that feels real for thousands needing surgery to correct outer ear deformities."

Many surgeons build a replacement ear using cartilage removed from a child's ribs, an operation that can be painful and scarring.

And though the resulting graft can be crafted to resemble the recipient's other ear, it generally does not have the same flexibility.

Adding texture to structure

One way to produce a more natural replacement ear is to enlist the aid of chondrocytes, the cells that build cartilage.

In earlier studies, Dr Spector and his colleagues used animal-derived chondrocytes to seed a scaffold made of collagen, a key component of cartilage.

Though these grafts developed successfully at first, over time the well-defined topography of the ear – its familiar ridges, curves, and whorls – were lost.

"Because the cells tug on the woven matrix of proteins as they labour, the ear contracted and shrank by half," said Dr Spector.

To address this problem in this study, Dr Spector and his team used sterilised animal-derived cartilage treated to remove anything that could trigger immune rejection. 

This was loaded into intricate, ear-shaped plastic scaffolds that were created on a 3D printer based on data from a person's ear. 

The small pieces of cartilage act as internal reinforcements to induce new tissue formation within the scaffold.

Much like rebar, it strengthens the graft and prevents contraction.

Over the next three to six months, the structure developed into cartilage containing tissue that closely replicated the ear's anatomical features, including the helical rim, the 'anti-helix' rim-inside-the-rim and the central, conchal bowl.

"That's something that we had not achieved before," said Dr Spector.

To test the feel of the ear, biomechanical studies were performed in conjunction with Dr Spector's long time engineering collaborator Dr Larry Bonassar, the Daljit S and Elaine Sarkaria Professor in Biomedical Engineering at the Meinig School of Biomedical Engineering on Cornell's Ithaca campus.

This confirmed that the replicas had flexibility and elasticity similar to human ear cartilage.

However, the engineered material was not as strong as natural cartilage and could tear. 

To remedy this issue, Dr Spector plans to add chondrocytes to the mix, ideally ones derived from a small piece of cartilage removed from the recipient's other ear.

Those cells would lay down the elastic proteins that make ear cartilage so robust, producing a graft that would be biomechanically much more similar to the native ear, he said. 

 

Biomedical engineers produce grafts that replicate the human ear

Lee Calladine pricks his skin with a needle up to eight times a day to give himself an injection of insulin – the hormone that keeps his type 1 diabetes in check. 

Without insulin, his blood-sugar levels would become dangerously high and eventually fatal. 

 

Game changer

Calladine, aged 54, has been diabetic for 25 years and the insulin top-up routine is so familiar to him that he’s long past feeling squeamish about piercing his skin. Still, the practice is burdensome. 

"I have to rotate where I do my injections," says Calladine, who lives in Portsmouth and works as an event coordinator for the Diabetes Research & Wellness Foundation. "If you inject the same place too often, you damage the tissue and get a lump. And if you then inject into that lump, the insulin won’t get absorbed." 

While a cure for type 1 diabetes is the holy grail, another game changer for Calladine and millions of other people like him around the world would be the ability to deliver insulin without needles or syringes.

That is where Professor David Fernandez Rivas, a bioengineer at the University of Twente in the Netherlands, believes he can help.

Prof Fernandez Rivas leads a research project that received EU funding to develop a method to deposit liquids into skin and other soft materials using compression rather than needles.

The technique is known as BuBble Gun, which is also the name given to the five-year project that will run until the end of 2024. Prof Fernandez Rivas invented the BuBble Gun with his research team, which is now refining the technology in the hopes of turning it into a reality.

Speedy squeeze

While electronic pumps that release insulin into the body throughout the day do exist, they are imperfect and still require a cannula needle to be inserted at the connection point.

With BuBble Gun, a laser beam is directed at the fluid medicine in a glass cartridge, heating it until it boils and creates a bubble. This bubble grows until it squeezes the liquid at high velocity – 30 to 100 metres a second – out of its tube and, in the case of a medicine, into the skin. 

 
'The liquid effectively becomes the needle.' Prof David Fernandez Rivas, BuBble Gun

 

Rather than piercing the skin, the way a needle would, the drug is pushed between skin cells. This limits damage both to the skin and to the cells beneath it.

"The liquid effectively becomes the needle," says Prof Fernandez Rivas, who moved to the Netherlands from Cuba in 2007 with a first degree in nuclear engineering and has been working in bioengineering and green technology ever since.

This approach could be a relief not just for nine million people worldwide including Calladine who have type 1 diabetes but also for millions of others who have unrelated conditions that also require regular injections. 

Other potential beneficiaries are the 25% of people who are scared of needles and who can, as a result, avoid certain medical interventions including vaccination.

"Removing pain and fear from the injection process will have a big impact on a lot of people with needle phobia," says Prof Fernandez Rivas.

Tissue challenges 

Most injections penetrate the body until they reach muscle. These are regarded as the simplest injections to administer and the dose gradually diffuses out of the muscle into the body’s blood-circulation system. 

Many drugs, however, can do the job just as well – or perhaps better – when delivered into the more superficial layers of skin.

Prof Fernandez Rivas is confident that many vaccines, for instance, would work just as well when delivered between the layers of the skin. Currently, they tend to be injected into muscle. 

This means BuBble Gun has potential uses beyond insulin delivery.

A key technical challenge tackled by the research team relates to skin depth, which varies depending on age, gender, ethnicity and lifestyle. Smoking, for instance, makes the skin thinner. 

As a result, the 'gun' pressure needs to be adjusted to take these differences into consideration.

"You need the jet of fluid to penetrate the skin to just the right depth without splashback or seeping into nearby tissue or material, which would alter the dose unpredictably," says Prof Fernandez Rivas.

The researchers are still working on precisely controlling the drug jet as it enters soft tissue. 

Since 2018, they have been conducting laboratory experiments on materials that simulate skin as well as on real skin tissue. Tests on human tissue have been in progress since 2022. 

If all goes well, trials on healthy human volunteers will start later this year.

Planned prototype

The BuBle Gun team has created a startup company called FlowBeams. Through this, the researchers hope that a prototype of the gun will be ready to showcase to potential industry partners before 2025.

Prof Fernandez Rivas foresees a time eventually when diabetes patients will be able to use a modified version that incorporates the microjet technology into a skin patch. 

The patch would include a sensor that both tests blood-sugar levels on a continual basis and pushes insulin into the body as the need arises.

"Imagine how this would transform the life of an anxious parent who wakes up multiple times in the night to check their child with diabetes isn’t having a blood-sugar swing in their sleep," says Prof Fernandez Rivas.

Diabetes patients in line for needle-free insulin injections

More than 20 million Americans undergo colonoscopy screenings every year, and in many of those cases, doctors end up removing polyps that are 2cm or larger and require additional care. This procedure has greatly reduced the overall incidence of colon cancer, but not without complications, as patients may experience gastrointestinal bleeding both during and after the procedure. 

The researchers came up with a winning combination that includes a polymer called pluronic and also oxidised dextran. When sprayed, these materials instantly react with each other and with the lining of the gastrointestinal tract, forming a solid gel in less than five seconds. Image: Courtesy of the researchers.

In hopes of preventing those complications from occurring, researchers at MIT have developed a new gel, GastroShield, that can be sprayed onto the surgical sites through an endoscope. This gel forms a tough but flexible protective layer that serves as a shield for the damaged area. The material prevents delayed bleeding and reinforces the mechanical integrity of the tissue.

“Our tissue-responsive adhesive technology is engineered to interact with the tissue via complimentary covalent and ionic interactions as well as physical interactions to provide prolonged lesion protection over days to prevent complications following polyp removal, and other wounds at risk of bleeding across the gastrointestinal tract,” says Natalie Artzi, a principal research scientist in MIT’s Institute for Medical Engineering and Science, an associate professor of medicine at Harvard Medical School, and the senior author of the paper.

In an animal study, the researchers showed that the GastroShield application integrates seamlessly with current endoscopic procedures, and provides wound protection for three to seven days where it helps tissue to heal following surgery. Artzi and other members of the research team have started a company called BioDevek that now plans to further develop the material for use in humans.

Gonzalo Muñoz Taboada, CEO of BioDevek, and Daniel Dahis, lead scientist at BioDevek, are the lead authors of the study, which appeared recently in the journal Advanced Materials. Elazer Edelman, the Edward J Poitras Professor in Medical Engineering and Science at MIT and the director of IMES, and Pere Dosta, a former postdoc in Artzi’s lab, are also authors of the paper.

Adhesive gels

Routine colon cancer screenings often reveal small precancerous polyps, which can be removed before they become cancerous. This is usually done using an endoscope. If any bleeding occurs during the polyp removal, doctors can cauterise the wound to seal it, but this method creates a scar that may delay the healing, and result in additional complications.

Additionally, in some patients, bleeding doesn’t occur until a few days after the procedure. This can be dangerous and may require patients to return to the hospital for additional treatment. Other patients may develop small tears that lead the intestinal contents to leak into the abdomen, which can lead to severe infection and requires emergency care.

When tissue reinforcement is required, doctors often insert metal clips to hold tissue together, but these can’t be used with larger polyps and aren’t always effective. Efforts to develop a gel that could seal the surgical wounds have not been successful, mainly because the materials could not adhere to the surgical site for more than 24 hours.

The MIT team tested dozens of combinations of materials that they thought could have the right properties for this use. They wanted to find formulations that would display a low enough viscosity to be easily delivered and sprayed through a nozzle at the end of a catheter that fits inside commercial endoscopes.

Simultaneously, upon tissue contact, this formulation should instantly form a tough gel that adheres strongly to the tissue. They also wanted the gel to be flexible enough that it could withstand the forces generated by the peristaltic movements of the digestive tract and the food flowing by.

The researchers came up with a winning combination that includes a polymer called pluronic, which is a type of block copolymer that can self-assemble into spheres called micelles. The ends of these polymers contain multiple amine groups, which end up on the surface of the micelles.

The second component of the gel is oxidised dextran, a polysaccharide that can form strong but reversible bonds with the amine groups of the pluronic micelles.

When sprayed, these materials instantly react with each other and with the lining of the gastrointestinal tract, forming a solid gel in less than five seconds. The micelles that make up the gel are 'self-healing' and can absorb forces that they encounter from peristaltic movements and food moving along the digestive tract, by temporarily breaking apart and then reassembling.

“To obtain a material that adheres to the design criteria and can be delivered through existing colonoscopes, we screened through libraries of materials to understand how different parameters affect gelation, adhesion, retention, and compatibility,” says Artzi.

A protective layer

The gel can also withstand the low pH and enzymatic activity in the digestive tract, and protect tissue from that harsh environment while it heals itself, underscoring its potential for use in other gastrointestinal wounds at high risk of bleeding, such as  stomach ulcers, which affect more than four million Americans every year.

In tests in animals, the researchers found that every animal treated with the new gel showed rapid sealing, and there were no perforations, leakages, or bleeding in the week following the treatment. The material lasted for about five days, after which it was sloughed off along with the top layer of tissue as the surgical wounds healed.

The researchers also performed several biocompatibility studies and found that the gel did not cause any adverse effects.

“A key feature of this new technology is our aim to make it translational. GastroShield was designed to be stored in liquid form in a ready-to-use kit. Additionally, it doesn’t require any activation, light, or trigger solution to form the gel, aiming to make endoscopic use easy and fast,” says Muñoz, who is currently leading the translational effort for GastroShield.

BioDevek is now working on further developing the material for possible use in patients. In addition to its potential use in colonoscopies, this gel could also be useful for treating stomach ulcers and inflammatory conditions such as Crohn’s disease, or for delivering cancer drugs, says Artzi.

This sprayable gel could mean that minimally invasive surgeries are simpler and safer

Wellola, the digital health company, has announced the successful closure of a €2.2m funding round led by Elkstone with additional funding from Enterprise Ireland and Bay Advisory. The investment brings Wellola’s total funding to date to €4m and will accelerate market expansion to meet demand.

Founded in 2016 by Sonia Neary, chartered physiotherapist and CEO,, Wellola builds patient management solutions to deliver care in a rapidly changing environment. Built by clinicians, big healthcare organisations including Leeds Teaching Hospitals NHS Trust, the North East London Foundation Trust and Birmingham Community NHS Trust have already deployed Wellola’s Portasana® platform.

Reduce need for return appointments by 30%

Portasana® has enabled one NHS Trust department alone to reduce the need for return appointments by 30%, saving it about £325,000 a year. In a representative evaluation of more than 600 patients across the UK using education courses featured on the platform:

  • 95% Have a better understanding of their conditions;
  • 91% Feel more confident about managing their condition;
  • 88% Feel more confident about what to do if their condition gets worse;
  • 59% Have been to hospital less frequently.

“At Wellola, we are transforming healthcare delivery for both patients and health professionals through fully interoperable innovation. Digital interventions like ours can address health inequalities by being scalable, affordable, and accessible. This investment will enable us to further enhance our Portasana patient care and communication platform and also expand our footprint across the UK, ultimately empowering healthcare professionals to deliver more efficient, effective, and personalised care to their patients," said Sonia Neary, CEO at Wellola.

Wellola's expansion comes at a time of growing demand for digital health solutions, driven by the need for more accessible and patient-centric care delivery models. Hospital overcrowding, increased waiting times, and an over-extended infrastructure continues to plague healthcare systems across Europe.

Last year, Ireland reached a record high for hospital overcrowding while two in three doctors in the UK suffered moral distress. Wellola aims to change this by providing even more hospitals and community-based clinics with the digital communication tools needed to deliver healthcare outside of a hospital setting. 

Barry Brennan, ppartner at Elkstone, said: “Wellola is revolutionising how hospitals and clinics care for and communicate with their patients. As Ireland’s largest early-stage venture fund, we are always on the lookout for innovative Irish founders making an impact both at home and abroad. We are excited to support the team at Wellola as they continue to usher in a new era of healthcare in hospitals right across Ireland, the UK and Europe.”

Ruth McAvoy of Enterprise Ireland said: “Wellola has developed an international reputation for innovation and service delivery and Enterprise Ireland is proud to back this funding round which will see Sonia Neary and the Wellola team continue to expand in the UK and Europe.  Wellola’s technology brings benefits to both patients and healthcare systems and will play a critical role in the rapidly evolving healthcare sector.”

Wellola in €2.2m raising as it accelerates expansion to meet rising demand for digital healthcare programmes across UK and Ireland

Irish engineers are incredibly creative thinkers and innovators, but it's a big leap going from innovator to entrepreneur, and taking an idea you might have to market.

Today we hear from a prominent engineer with a fascinating career history, which took her from aeronautical engineering into the biomedical space. We'll be finding out how she looks at problems, overcomes obstacles, where she sees innovation and opportunity, and getting some great advice for any engineers who are thinking of launching their own business.

Our guest is CEO of Altratech and the Assistant Director of the Stokes Research Institute at University of Limerick, Dr. Tara Dalton.

THINGS WE SPOKE ABOUT

  • Transitioning through different disciplines of engineering
  • The benefits of working within interdisciplinary teams
  • Learning to ‘skate where the puck is’
  • Being aware of trends and spotting gaps in the market
  • Striving for progress over perfection and asking for help

 

GUEST DETAILS
Dr Tara Dalton, CEO of Altratech and Assistant Director of the Stokes Research Institute in the Department of Mechanical and Aeronautical Engineering at the University of Limerick.

Dr Dalton is a fellow of the Irish Academy of Engineers. She is one of the founders of Stokes Bio – a spin-out company that was sold to Life Technologies that developed high throughput microfluidic instruments for PCR. Her research interest is in the development of microfluidic devices for biological assays. She has graduated 20 PhD Students, published over 100 refereed papers and has over 50 granted patent and patent applications.

https://altratech.com/

https://ul.ie/research/dr-tara-dalton

 

MORE INFORMATION

Looking for ways to explore or advance a career in the field of engineering? Visit Engineers Ireland to learn more about the many programs and resources on offer. https://www.engineersireland.ie/  

 

Engineers Journal AMPLIFIED is produced by DustPod.io for Engineers Ireland.

 

QUOTES

In my mind, in engineering, you don't want to be at the cutting edge of absolute new science. You want to be just behind it, so you can help people with that science. - Tara Dalton

 

When you work with interdisciplinary team, and I work with medics, physicists, chemists or even with other entrepreneurs, it's just amazing, because I find that everybody wants to help you be better. Nobody, at least in my experience, gatekeeps their knowledge. - Tara Dalton

 

Skate where the puck is, right. It didn't matter that I had this great product, but to get venture capital funding, that was never going to happen, because it wasn't in that ecosystem at the time. So that was one really big learning lesson. - Tara Dalton

 

Ask for help. Everybody, ask for help. Go talk to people, go talk to Enterprise Ireland, go talk to lawyers, go talk to VCs. Don't go saying I want, want, want, just say, What should I do? How could you help me? You'd be surprised how many people will give you their time. - Tara Dalton

 

TRANSCRIPTION

For your convenience, we include an automated AI transcription

Dusty Rhodes  00:00

Right now on AMPLIFIED, we're about to find out how seemingly impossible things are eminently possible.

 

Tara Dalton  00:07

He never let perfection hinder progress. And so I just say, Okay, let's just make progress. I have to be consciously aware of thinking, Oh, God, we signed a contract to do something like what have we done? Knowing full well, that's going to be a really a hard ask.

 

Dusty Rhodes  00:26

Hello, my name is Dusty Rhodes and you're welcome to AMPLIFIED, the Engineers Journal podcast. I think we can agree that Irish engineers are incredibly creative thinkers and innovators. But it's a big leap going from innovator to entrepreneur, and taking an idea you might have to market. In this episode, we'll be hearing from a prominent engineer with a fascinating career history, which took her from aeronautical engineering into the biomedical space, we'll be finding out how she looks at problems, overcomes obstacles, where she sees innovation and opportunity, and getting some great advice for any engineers who are thinking of launching their own business. It's a pleasure to welcome the CEO of Altratech and the Assistant Director of the Stokes Research Institute at UL. Dr. Tara Dalton. Tara, how are you?

 

Tara Dalton  01:14

Hi, how are you? Hi, I'm good. Thank you so much.

 

Dusty Rhodes  01:18

Listen, welcome onto the podcast. I always start off by asking people what what made you want to be an engineer? How did you get into this game at all?

 

Tara Dalton  01:28

Um, actually, I think to be to be quite truthful, I think it was, it was my father. I had all sorts of different plans. And I, you know, I, I remember not really wanting to do honors maths at school. And my father sort of saying, you know, it opens up such a lot for you. So, you know, he like he worked at the University of Limerick. And he felt that that engineering was a really good combination of creativity and of maths, you know, because I always did like the sciences. I was interested in physics and chemistry, and biology. So I think, in some senses, there was serendipitous things, I suppose it was my dad really kind of pushed me to taking that on.

 

Dusty Rhodes  02:05

So when you went through school and university, you got into engineering then proper, and you started with aeronautical engineering. Tell me a bit more about that. So actually,

 

Tara Dalton  02:13

actually, I started with mechanical and then they launched aeronautical engineering when I was in third year. So at that time, it wasn't a discipline in itself, it was something you could specialize in, in third year, I think I was just so completely fascinated, because I think it goes against every instinct in our body that we can put that thing up in the sky. Every instinct and every single time I think about something that can't be done, I look at and say they they have an engine there that is going at, you know, 15,000 RPM, that's that's huge, up at 36,000 feet. Come on, like, Of course we can do it. So I think it for me, it's just, I think it's just fascinating and in almost a romantic way. And I still love it, you know, I changed because in some senses, there's a lot more I think innovation in biomedical engineering. You know, the aeronautical engineering is quite a regulated piece. So, you know, for me, it didn't allow that creativity and that innovation, so I changed biomedical engineering, but aeronautical engineering still has a huge, you know, soft spot, I said, I didn't know they're applying them, I'm gonna watch

 

Dusty Rhodes  03:23

this, there's a real passion there for you for aeronautical and flying, but you went from that then into biomedical why, why did you make the switch? Well,

 

Tara Dalton  03:33

he so I did, I did a postdoc in the University of Limerick. And at the time, again, you know, the government had this really amazing program, it was called the programs and advanced technology programs. And basically, what they encouraged you to do was as a postdoc, they encouraged you to work hugely with industry. And then they they supported that intervention. So they wanted to link university researchers with industry and we were fortunate, we had a great kind of Pac group. And we worked with Intel, we worked with you to Packard, we worked with, you know, Nokia at the time. And I just got this feed, I just, I loved it, you know, I love that idea that what you did had an impact, you know, even if it is in a in a large multinational or a small company, commensurate with that around the same time, the size foundation Arlindo setup, and at that time, they remit to fund two big things. So ICT at the time and bio, the and, you know, that was their decision. So I thought, okay, let's be real here. You know, if you want to go research, you want to, you know, you've you've to, you have to be like, you know, like Wayne Gretzky, you know, the great ice skater, he said, skate where the puck is going to be, you know, where the puck has been. He knows I mean, so, you know, you've got to look at the landscape and say, well, that's where the research money is going to be. If you think about at the time bio, the genome had just been sequenced. This was the biggest thing ever. There was a breakthrough for peace. See our reactions and everything. So when you looked at these like, okay, there's going to be so much scope for an engineer following breaking science, in my mind and engineering, you don't want to be at the cutting edge of absolute new science. But essentially, you just want to be just behind it. So you can help to, you know, help people with that science. So for me a deal, as I said, the genome has just been sequenced, I can see for the next 15 years, you know, there's going to be massive innovation in this space, which there was. So that's why I changed from Rob arrow mechanical to much more bio COVID. But it is really applying the same principles of any engineer just to a different class of problems. If you're

 

Dusty Rhodes  05:42

listening to you're talking about kind of biomedical, I mean, you're very passionate about it, but I kind of get the impression that you're more are you more passionate about the fact that you're doing something challenging, and something new, and something that's gonna help people rather than it being actually to do with aeronautical or biomedical?

 

Tara Dalton  06:00

Yeah, I think so as I said, the same principles are applied, you know, they think engineering principles are applied to everything. But I think in Biomedical Engineering, well, first of all, it's very interdisciplinary. So you get to learn from, you know, loads of people, and it's full of problems to be solved, which is great, you know, there's loads of things that we don't know, that we want to sell. And so for me, it's like, you know, it's like, it's like, a child in a sweet shop. It Oh, there's just so many interesting things to learn. And I love learning it, there's just so much. And the other thing is, when you work with interdisciplinary team, and I work with, you know, worked with medics, with physicists, or chemists with, you know, with entrepreneurs, with with finance people, it's just, it's just amazing, because I find that everybody wants to help you be better. Nobody, I, at least in my experience, kind of gatekeepers their knowledge. And I think in in, you know, when you're in that race, where you really want to try and solve a problem, I find that people don't take the knowledge because they want to find solutions. And so it's an extraordinary place to be. And also, I think, I'm not a person that some people I think, are really good. And you see people who kind of take a problem, and they dive into it. And deeper and deeper and deeper and deeper, I'm not that kind of person, I like to kind of spread out, you know what I mean? So look at, you know, applying this skill over here, over here from here, rather than doing kind of this classical, deep dive and understanding upon more. Absolutely, that's important as well, if that's just not me. So I think I think this type of problem solving, engineering suits me more than we'll say, a classic scientist, you know, where you're, you're really building on knowledge, and really getting a deep, deep understanding about that uncut of more. Okay, how do we solve a problem? So I think that's the difference between engineering Well, in my opinion, is difference between engineering and sort of deep science, if you like? Well,

 

Dusty Rhodes  08:00

I think that's what we do is, uh, you know, we look at problems and we go, Well, how can we fix this? Or how can we make it better? Now, a lot of people who will be working as engineers are within a company, and then they have all these thoughts and ideas. But sometimes, you know, things don't happen, because there's a boss upstairs, or the company doesn't want to go that way. You're different in that you kind of went, Well, I really want to do this. So I'm going to be an entrepreneur, and I'm going to start my own business, do you think that your engineering brain and the way that it works kind of helped you to stand on your own two feet and run your own business,

 

Tara Dalton  08:32

I think, on my experience, when I did the programs apart, so we ended up interacting with companies an awful lot. And I think that stood out to me. And also I just the idea that something that you created that somebody actually bought me, they paid money, I remember my my father in law saying to me that that money is a stored work, you know what I mean? And so, you know, this idea that somebody is going to pay for that. I thought, That's a brilliant idea. And I always wanted to do it, I always wanted to do it since I was like, since I was sort of 2627. And in a year, you know, whatever about a company in a university environment, you know, there's things are changing and have changed, but at that time, there is a lot of pressure put on publications, and this is what we do and the you know, it's to go and, and say, Okay, I'm going to I'm going to create a company. It's not necessary. Now, University of Limerick, I have to say we're brilliant. But you know, there are people who say, Okay, look at me, that isn't the job of an academic. But I think as an as an academic engineer, it is exactly my job, even if it's not to create enterprise to help enterprise and to work on on sort of, you know, engineering problems. So I always wanted to do that. And I think, you know, naivety is your friend in doing this, it really is because, you know, in some senses Ultratech is my second or was actually was actually technically it's my fourth company. You don't need one but That duck failed for very funny reasons. Oh, yeah, this is hilarious or silly like the first the first week, we had this amazing product, what went? Well, in my view, it was right, it was a fiber optic based system that actually was used to to turn on heaters to take ice off helicopter blades, you need to a wouldn't win helicopters and you know, obviously do ice forming on helicopter blades is really, really bad, depending on the type of ice anyway, it was a it was a piece of hardware. And for some reason I got picked to go to Boston. This is a this like 28 or something to pitch my idea in front of 100 requests, which would there would have been a lawyer firm, but with a lot of VC backing a lot of companies, there was a there was a lot of potential companies going to do that. So I remember sitting there and I had my little piece of hardware, it had my sheet with all this details on it. And I was listening to everybody present. And every single one of them was software companies, this was the.com thing. And they were to some of them were the most stupidest ideas you could ever imagine that but that wasn't the point. The point was, is they weren't getting funding these people were looking for 1.5 million 20. I learned straightaway, okay. Again, that was skate where the puck is, right. So it didn't matter, I had this great product, but to get venture capital funding, that was never going to happen, because it wasn't in that ecosystem at the time. So that was one really big learning lesson. And again, similarly, in the the second company that we did, you know, actually did work, but it wasn't again, it wasn't a high potential startup. So that was one of the reasons I changed to bio because you are basically in VCs, you know, they like to fund we're looking to fund you know, so you're thinking, Okay, I need to be in that in that area. Stokes bio was then the third company. And until we learn, okay, say okay, look, you know, this is what we're going to do, we're going to follow breaking science, we're going to use our own skills, I'm really careful about how we kind of positioned what what we did. And of course, you know, a lot of people said, we're engineers in, in in the biosciences, you haven't opened hell. And again, you just just ignore it, you know what I mean? And I think you ignore it, because you have so much fun doing it, it doesn't really matter. You know, what I mean, you're just really enjoying learning, and we'd love to PhD students, and, you know, we bring in collaborators, and, you know, to use that horrible word, but the journey, like was the you know, was, you know, that was as important as the exit and the final part of

 

Dusty Rhodes  12:33

it, but it is the journey, as you say, and what I love about what you're talking about, it's kind of like, you've given us two examples where you fell down, this isn't wrong with falling down, it's how you pick yourself up afterwards. Okay, so you fell down, once you fell down twice, you picked yourself up, once you picked yourself up twice, you went into the third one. Now, the third one was quite successful. And this is kind of you're very well known for Stokes was, you mentioned it, it's been a big part of your life, because they've kind of struggles commercial company and a university. And I don't understand how that works. So tell me about it.

 

Tara Dalton  13:06

Okay. So that, you know, yeah, so So, so myself and my co founder, Professor Mark Davies, so he was actually my PhD supervisor, and then, you know, we we kind of drifted apart, and then we came back together to, to do this. And again, the genome has been sequenced. And we're really fascinated with that. So we started a research group in the university. And you the advantage of starting your research in the university is, it's a very, it's a very gentle place to explore ideas, so that you're not giving away equity, if you make mistakes are, it's taking time that you know, for a long time, it wasn't, you know, the stuff we were doing wasn't working. And in an in a university environment, that's that can be tolerated a lot easier. And we had we had a number of PhD students, and interestingly, so actually, so we went to the SFI, even five times five times for funding and FBI wouldn't fund what we were doing, and that's okay, I get it, you know, we didn't have a history and what we were doing, and at the time, you know, reviewers would say, Look, you know, this isn't really that novel, etc. But engineering isn't supposed to be a hugely novel, it's supposed to take science and, and if you take, yeah, if you take a hero experiment that's done once you want to engineer it, so it's, you could do it 100 million times, you know, so that's kind of where we were coming at, and, and I can I get away as if i But anyway, I at that time, when I was like, Oh my God, you know, how are we going to get funding? What are we going to do now? Enterprise Ireland was, were really supportive of what we were doing, and they funded us. And I thought, okay, you know, what we'll do, we'll, we'll um, Bucha some publicity. So we did some publicity and and I contacted a publicist. And I said, Listen, you know, I think what we're doing is really kind of clever and interesting. Could you know, could we get some traction, just even on the Irish stage, not necessarily European or American. So It was caused and caught by the Irish Times, actually. And a VC saw it. And he approached us. And he said, When you spin this company out, can we be at the table, we'll give you 100,000 euros if we're at the table. And I said, look, let's forget that, let's just do it now. You know, I was so anxious. And you know, in some senses what I said we were a bit early. Probably. That's true. So the University of Limerick, and also, under the sea did a deal for our intellectual property, we did a deal for way to whole bunch of students. And we moved the company out of the university, I wanted it out to the university. So I wanted a real separation between what we did and do well, and what appealed to commercial aspect of what we were doing. And like the university, as I said, they were, they were amazing, they allowed me, myself and mark to remain as academics, okay, full time academics and to do the company. And that took a lot of creative thinking. And what we did is, they also, they assigned us our intellectual property, which means our intellectual property was owned by the company not licensed. And I know that that isn't done now. But it was such a really good thing for the company. It gave us huge freedoms later on and raising money and enjoying strategic relationships. So you know, I know that's not done nowadays. But it was it was great. So, so we ended up taking our PhD students into the company, thankfully, as they started to graduate. So we had this well, what's the word? I'm looking for conveyor belt of amazing, amazing people that we took into the company. And yeah, but you know, don't get me wrong. It was it was hard, because you know, we were new with this new what managing VCs knew what that relationships, they were raising money. And then finally, we got to strategic you know, for the the deal, the exit happened, and that was great. But it was it was tough, but fun. You know,

 

Dusty Rhodes  16:52

it's fascinating listening to you taking on this problem of having an idea and wanting to run a company to implement that idea, and the reasons why you did it. And it didn't work. The first time didn't work the second time, the third time it did work and to you, you had good partners and stuff like that. Eventually, you have to sell it, which is always you know, kind of heartbreaking. Did you make much?

 

Tara Dalton  17:11

Yeah, we did

 

17:14

it. Okay. So yeah, so we put a number on a Tyra Yeah, okay. Okay. Yeah.

 

Tara Dalton  17:19

So, so we ended up selling, so we raised about sort of maybe six, 7 million, and that we sold it for almost $50 million, which, which is a really nice return for everybody. Because if the company hadn't got had a really nice, simple cap table, it wasn't hugely diluted. So you know, it was good. It was good in that regard. So I think everybody did, did well.

 

Dusty Rhodes  17:40

Well, all I could do, I'm literally standing up and applauding. Good on you fair play, okay. Because it's brilliant. Because you follow that through and you worked on all of the problems and you had some success. Okay, as somebody that was great. And it was 2010, he sold us somewhere around Yeah,

 

Tara Dalton  17:55

then myself and Mark White to work for the company. The acquirers were like technologies that term proficient out. So we went, we took then a two year leave of absence to work with the integration of the technology into into which was, again, I got to work with a multinational for two years, which was really exciting. And that was still that was really different. And, you know, I teach my students, we do live, we do med devices, and we do like a Dragon's Den. So I teach them, you know, and one of the things this exact same thing you do with selling an idea to a VC, you'd sell an idea to your bosses in a multinational this is same thing, it's the same ideas. And so we, you know, we had that experience as well of kind of integrating the, what we were doing into, into a US multinational, which was, you know, which was, which was different, that's for certain.

 

Dusty Rhodes  18:46

So, as well as teaching and inspiring people in University of Limerick, still, you're also the CEO of ultra tech, as I mentioned in the intro, now, you're leading a team of over 20 engineers and scientists there to a layman like myself, can you describe what it is that you're working on?

 

Tara Dalton  19:01

Okay, so so I'll check it. I'm not a founder Valtryek there are two founders, one of the founders, I knew because he was founded, he founded his previous company, the same time we, I found his Stokes bio, and he was in the university as well. So and we were funded by the same venture capitalist, so we kind of knew each other. And then, you know, we kind of both he sold his company successfully, I thought line that we kind of got together. And he said he had this idea of, he's a silicon designers, electronics engineer. And he said, Oh, you know, could I do something with silicone in the bio space? And I was like, you know, it's really interesting. You say that, because there's been this huge explosion. So I know that that live technologies brought a secrecy company for silicone. I think they bought it for north of 600 million. Okay, so it was a huge acquisition. And there were some other companies that was nanopore, there was a few and I said, Juno's on the champ. I said, Yeah, you know, there's, there's an idea there. So he went away, and he kind of thought about it. And then no other venture capitalist said, you know, Tara, you know, you know Hold this space because, you know, I'd been in that kind of bio space, etc. And he said, You know what, you'll be on the board. And I was like, hey, yeah, absolutely. Because I'd been back in the university for a while I was doing some work on cancer stuff on stuff on heterogeneity of tumors. And I was like, Oh, I'm kind of feeling the itch again, now to do something outside of that. And so I said, Yeah, I'll be on the board. And then a week later, he goes, target you CEO. And I was like, Are you kidding me? I was like, oh, gosh, no, you know, and I said to my husband, I was like, Jeff, I said, Oh, God, this is Tony, you have to, you know, you have to like, so I was like, okay, okay. Okay, I'll do it. And so basically, what what it is that it's really compelling science. And it's so interdisciplinary, it's basically it's a methodology, or a product that can take that can detect any virus in a non clinical setting. Very importantly, it doesn't use an enzymatic step. So you would be aware, Okay, everybody, listen, he says, Beware of PCR, every, you know, if I was to tell everybody, there's like, three, four years ago, pre COVID, they look at me blankly, but now kind of people get it, right. So you know, what PCR is, you know, how the importance of it, and how, cuz it's such an accurate technique for detecting any virus from COVID, to flu to, you know, to HIV doesn't matter. But the trouble with PCR is, it's a technique that you can't really take outside the laboratory or the clinical setting. And so we've invented a way that can do that. And it uses a combination of, you know, really novel chemistry, biology, and micro fluidics, which is kind of white area, and silicon chip design. So it's really difficult. And it you know, it's been tough, you know, the technological development will just help. But if it wasn't taught me, it's not going to be worth it, right? Because you will say, well, then it is tough because it is so groundbreaking. And so it's going to change the world, in my view for for viral detection, in my view, but but it is, it is technically challenging.

 

Dusty Rhodes  22:06

You've mentioned several times, as you're always thinking about where the puck is going to be rather than where it is now. And when you talk about Ultra Tech, I mean, that was 20s, mid, mid 20, teens, whatever you were involved in that was it.

 

Tara Dalton  22:18

Yeah. Just prior to COVID. Exactly.

 

Dusty Rhodes  22:22

My point, right is because you got involved in this, and then COVID came along, and boom, your company is perfectly. Yeah,

 

Tara Dalton  22:28

it's so funny, because we wait a video we to do in 2000 2019, or just before COVID In November, we to do a presentation in Boston, and party me to make a video of what your technology does. And initially, we had on the video, this will this would be you know, suitable for pandemic management and etc. At that and Marty came up. The difficulty was we were our technology was too early for it. You know what I mean? Like, and when you get a crisis situation like that, what happens is, is you reposition old technology, because that's what you have to do, you don't really have the time to to invent something new. But what a crisis does is you reposition old technology. But then what it does is it makes people aware that oh my gosh, there's there's a need there, you know, there is a need for us to be able to, to manage pandemics in a much better way than obviously what we then what's happened. And there's going to be technologies that are going to enable that whether we get there whether we were in the race, I don't know. But we're definitely in with a chance.

 

Dusty Rhodes  23:33

I absolutely love how your brain works. Because seriously, because you think research development, innovation is very much key to you. You're kind of always thinking about the future. But you always seem to spot a gap in the market. And what I wanted to ask you is Do you even know in your own brain, how you are able to spot a gap in the market? What how do you weigh things up when you when you're looking at?

 

Tara Dalton  23:57

I think I think, first of all, I don't know whether I am or not, you know what I mean? I think that that remains to be seen. But anyway, I think it's because I generally, that's the broadness, this was not the deep dive person, like, you know, it's looking around you. So I've just gotten funding now for our next company, which after Ultratech and you know, and we were just doing the the early research now in the university, and it's on, it's on the immune system. It's on immunotherapies. And, you know, if I'm just asking you say, oh, yeah, okay, you get that because, you know, if you were to pick up the newspaper 10 years ago, you wouldn't read about immunotherapies you wouldn't think about it. Now we know we think about like the immune system, autoimmune diseases, allergies are our understanding about how we react to vaccines. immunotherapies for cancer, you know, that's exploded in the last 10 years. So again, we're going to need engineering behind that technology, you know, behind that science to support the growth in that area. So that's, you know, it's just it's just kind of watching and thinking that's new. Debrett's breaking signs really is where she wants to keep an eye on for me, that's what I keep an eye on. And then

 

Dusty Rhodes  25:04

when you see something that you think has potential, you look into it a little bit further. And then

 

Tara Dalton  25:10

you know, the the virus say, I mean, that's, that's kind of obvious if you though I mean, if you think about it, all the outbreaks that we've had no stars, you know, that you just know, and you know, it was going to happen. We knew it was going to happen. It was not a question of, of if it was, it was a question of weighty. Okay. I mean, you know, that's, that's 100% I mean, everything from the Spanish Flu guys, you know, it's just, it's just a matter of when, and we were lucky this time,

 

Dusty Rhodes  25:38

why are you so confident when you say that COVID Was it was a matter of when not if

 

Tara Dalton  25:43

it because there's been because others always outbreaks, there's always outbreaks, and all you need is the right conditions. So if you take something like, if you take a virus that is that, like kills people quickly, that is probably not going to spread much. It is something that spreads a lot, it's probably not going to. So all you need to do is just get that balance, right? Where a you know, spreads quickly, and it has a potentially devastating effect, that's going to happen again, of course it is, you know, and if you think about it, you know, how the world has changed global travel or interaction where something may have been contained. You know, I remember saying to somebody, you know, five years ago, I said, we will listen, somebody would use the word quarantine and in our lifetimes, and would hear the word quarantine again, you know, we were probably going up, did you ever hear the word quarantine in the 50s? You would have heard it hear when people had scarlet fever when people had people quarantined? Now, it's, it's, you know, obviously, we tried it, it's, you know, it's not really feasible. It's you know, so we need other ways of managing when these when these things happen. And it's got to be a combination of understanding and technology in my view. So

 

Dusty Rhodes  26:50

I think anybody in listening, I mean, I've my own ideas, my own radio broadcasting podcasting business about where it's going to be in 10 years time, there's engineers listening to it, and the guy, oh, my God, and she's right, because I know that in 10 years, time bump is going to be a problem, or this is going to happen again, or whatever it happens to be. If somebody is listening to you, they have a big, innovative idea in their head, but they just don't know how to move forward. What What would your advice to them be?

 

Tara Dalton  27:17

I think I think it depends where they are, you know, where they are in their we're in a physically working as well. And well, opportunities they have, you know, obviously, it's somebody's in a university there, you know, that's the that's the ecosystem, I understand. So I can, you know, very easily direct them. If somebody is in a multinational company, or somebody is not, I would have less understanding about how they would go about you know, about doing that. I think, regardless, ask for help. Everybody asked for help, go talk to people go talk to enterprise Ireland, go talk to lawyers, go talk to VCs, ask, and don't go say, I want one just say, What should I do? How could you help me? What can I do? And you'd be surprised? How many people will give you their time. And you'll be surprised at it? In my view? You know, we had we have top lawyers in Boston who did stuff for us pro bono, because they just think oh, yeah, this is really cool. We'll do that. And we'll be we'll make our money later on when they're successful. You know, there's a lot of people who will do that for you. So talk, go out there and share your idea.

 

Dusty Rhodes  28:31

I love the fact that I'm speaking to a lady who has sold a company for $50 million, and says that ask for help because it's what you did. And people were willing to step up. Isn't it amazing how Yeah, humankind

 

Tara Dalton  28:43

can even now no matter what you do, people come to me or I still go to meet with it. Okay, you know, I need help here are, I'm not sure. People who worked for me before and still do not work for me and outreach. I could work with me and Outotec and anybody, you start to build that community, and it's true, I will, I will call like, next PhD student or somebody I knows, crikey, I need help on that. Or they can call me and say, Tara, you know, to remember that you wouldn't give me an hour of your time. As like, yeah, of course you don't I mean, and I you know, I love it. So and people do love being asked for help.

 

Dusty Rhodes  29:16

That's brilliant advice, and I can't be overstated so much, how good that advice is and my own experience, I know that to be true. The other thing that I want to ask you about Tara is your approach to problem solving and again, thinking of an NGO saying I've got a brilliant idea and I want to go but it's too much oh my god, how do you know I have to get over this humongously big wall which I don't know how to get over how am I going to do it you're good problem solver what way do you break down that problem?

 

Tara Dalton  29:45

Well actually interesting. So I'm actually I'm a bit more the way you just like oh my god. Oh my god. Like John like that isn't They do jam via the site like dig, watch, scrape. Have you gotten into today? I was like, Yeah, I know. I know. I know. And it's like, and he would say, okay, you know, what can you do tomorrow? You know, stop borrowing Tobel it's got too much interest, you know what I mean? Just what can you do? And the person I worked Davies, who I worked with as well, he was really good. He never flapped he never let perfection get in hinder progress. And so I just say, Okay, let's just make progress. And and really, I had, but I, I have to be consciously aware of thinking, Oh, God, you know what I mean? What have we committed to? We signed the contract to do something like what have we done? Knowing full? Well, it that's going to be a really a hard ask, and then you think, Okay, nope, let's just, let's just put the head down. And don't think about it. You know what I mean? Literally just say, Okay, let's not have that hinder the small progresses, you don't have any so so yeah, but I would be more the way you described it, then I would be, you know, like auction, this is fine.

 

Dusty Rhodes  31:05

I've written down a sheet of paper here, never let perfection hinder progress. I'm gonna type that up. I'm gonna stick it on the wall. It's gonna stay there for six months.

 

Tara Dalton  31:13

Yeah, don't I mean, you know, to meet our, to our children, you know, children get on with it, you know what I mean? Rather than it will, because you can get this, if you see this huge problem, it's like, you just wrap it in the headlights, you just look at it and go and feel paralyzed. And then you just gotta go. Okay? No. And also, I think having people around you that you can see that too. There's a there's a guy I love listen to this. It's Simon Sinek. But he has his eight minute rule. And he says, like, you should have a team around you that, you know, for eight minutes, you could rant and that they're not instantly you know, sometimes you don't want somebody in solution space. You just want somebody to listen to you go like, Oh my god, oh my god, this is terrible. This is not going to work. What's going to happen that anatra and you give yourself eight minutes. That's it? And then it's over and over again. So So you know, I think I think you have to allow yourself that feeling and then say, Okay, push it away. Now, let's get let's let's get let's get on with it. You know, so, Tara,

 

Dusty Rhodes  32:13

I have to say like listening to you, and just chatting because I have a bit of an entrepreneurial spirit in me. And I have, I like to call myself a sound engineer. That's, that's that's how I get away with just presenting this particular thing. But like many engineers, I see problems and I want to fix them. And I want to make the world better. And I think you know, your success is amazing. And after listening to you for the last little while, you're now guarding my world. Okay? Well, this is it. Okay. That's what I wanted to ask you was, you know who people who are listening now who are inspired by you? What would you say to someone who's listening to us right now? Who does think you're an inspiration? Are you God? Are you a normal person?

 

Tara Dalton  32:56

I'm an engineer. I'm an engineer. Engineer. Those of us out there who do you know, who to all day see solve all these problems all the time? You know, and, and there's ones that artists zillion many, and I like, like Chad, when he was with this much better engineer than me, like, I'm always going to him with solving problems, you know, you know, Mark is much better. So yeah, you know, there's, I think I would say cheese your problem wisely. Often, in my mind of, for an engineer, they're often too focused on solutions, right, you solving problems. But if you want to, if you want to sort of have a impact, do that, choose your spend time choosing your problem, like, like when we were doing Stokes whale, like Mark and I spent two years in America watching what people were doing, and seeking out that landscape. So don't be afraid of taking time to figure that problem out. It'll be the solution. Anybody can do that, to be honest with you, like a lot of people if you give them a good problem, and you set the boundary conditions on that problem. And you say, okay, look, this is the kind of area that most most people weren't there salt can do that. I think that cleverness in my view, and is choosing the correct problem at the right time. That so that's what I would say, spend time doing that. And talking and socializing it and thinking of it and testing it, and arguing it. And that's why it's great to work with people because you get all that feedback. You know, it's like, if I say to you, look, I'm thinking of doing something there and you're like, why are silicones doing that? What's your angle are you know, I mean, don't be afraid to just let that argument be battered around a bit. And and it'll form much better outfits are sorry, I talk way too much apologies. Listen,

 

Dusty Rhodes  34:48

I can listen to you all day. Tara, I think what I was trying to get across was that what's inside of you and what's driven your success is inside all of us. It's an engineering in trait, and I just think listening to you and as I say, being inspired by what you're saying we can go off and we can just make our own lives a little bit better. So I just wanted to thank you very much for sharing with us today Dr. Tara Dalton, CEO of Altratech and Assistant Director of the Stokes Research Institute at UL Thank you.

 

Tara Dalton  35:17

Thank you so much. Appreciate it.

 

Dusty Rhodes  35:19

If you would like to find out more about Tara and some of the topics which we spoke about today you'll find notes and link details in the description area of this podcast right now. Also, if you enjoyed our podcast today do share with a friend in the business just tell them to search for engineers Ireland in their podcast player. Our podcast is produced by dustpod.io for Engineers Ireland. For advanced episodes, more information on engineering across Ireland or career development opportunities, there are libraries of information on our website at engineersireland.ie, until next time from myself Dusty Rhodes, as always, thank you for listening

From Engineer to Entrepreneur: Dr. Tara Dalton, CEO of Altratech

Many vaccines, including vaccines for hepatitis B and whooping cough, consist of fragments of viral or bacterial proteins. These vaccines often include other molecules called adjuvants, which help to boost the immune system’s response to the protein.

Most of these adjuvants consist of aluminium salts or other molecules that provoke a non-specific immune response. A team of MIT researchers has now shown that a type of nanoparticle called a metal organic framework (MOF) can also provoke a strong immune response, by activating the innate immune system – the body’s first line of defence against any pathogen – through cell proteins called toll-like receptors. 

MIT engineers designed a nanoparticle vaccine made from a metal organic framework called ZIF-8, which is coated with the SARS-CoV-2 receptor binding protein (blue) and an adjuvant called Gdq (green). Image: Courtesy of the researchers.

In a study of mice, the researchers showed that this MOF could successfully encapsulate and deliver part of the SARS-CoV-2 spike protein, while also acting as an adjuvant once the MOF is broken down inside cells.

While more work would be needed to adapt these particles for use as vaccines, the study demonstrates that this type of structure can be useful for generating a strong immune response, says the researchers.

“Understanding how the drug delivery vehicle can enhance an adjuvant immune response is something that could be very helpful in designing new vaccines,” says Ana Jaklenec, a principal investigator at MIT’s Koch Institute for Integrative Cancer Research and one of the senior authors of the study.

Robert Langer, an MIT Institute Professor and member of the Koch Institute, and Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center and a professor at Harvard Medical School, are also senior authors of the paper, which appeared recently in Science Advances. The paper’s lead author is former MIT postdoc and Ibn Khaldun Fellow Shahad Alsaiari.

Immune activation

In this study, the researchers focused on a MOF called ZIF-8, which consists of a lattice of tetrahedral units made up of a zinc ion attached to four molecules of imidazole, an organic compound. Previous work has shown that ZIF-8 can significantly boost immune responses, but it wasn’t known exactly how this particle activates the immune system.

To try to figure that out, the MIT team created an experimental vaccine consisting of the SARS-CoV-2 receptor-binding protein (RBD) embedded within ZIF-8 particles. These particles are between 100 and 200 nanometres in diameter, a size that allows them to get into the body’s lymph nodes directly or through immune cells such as macrophages.

Once the particles enter the cells, the MOFs are broken down, releasing the viral proteins. The researchers found that the imidazole components then activate toll-like receptors (TLRs), which help to stimulate the innate immune response.

“This process is analogous to establishing a covert operative team at the molecular level to transport essential elements of the Covid-19 virus to the body’s immune system, where they can activate specific immune responses to boost vaccine efficacy,” says Alsaiari.

RNA sequencing of cells from the lymph nodes showed that mice vaccinated with ZIF-8 particles carrying the viral protein strongly activated a TLR pathway known as TLR-7, which led to greater production of cytokines and other molecules involved in inflammation.

Mice vaccinated with these particles generated a much stronger response to the viral protein than mice that received the protein on its own.

“Not only are we delivering the protein in a more controlled way through a nanoparticle, but the compositional structure of this particle is also acting as an adjuvant,” says Jaklenec. “We were able to achieve very specific responses to the Covid protein, and with a dose-sparing effect compared to using the protein by itself to vaccinate.”

Vaccine access

While this study and others have demonstrated ZIF-8’s immunogenic ability, more work needs to be done to evaluate the particles’ safety and potential to be scaled up for large-scale manufacturing.

If ZIF-8 is not developed as a vaccine carrier, the findings from the study should help to guide researchers in developing similar nanoparticles that could be used to deliver subunit vaccines, says Jaklenec.

“Most subunit vaccines usually have two separate components: an antigen and an adjuvant,” says Jaklenec. “Designing new vaccines that utilise nanoparticles with specific chemical moieties which not only aid in antigen delivery but can also activate particular immune pathways have the potential to enhance vaccine potency.”

One advantage to developing a subunit vaccine for Covid-19 is that such vaccines are usually easier and cheaper to manufacture than mRNA vaccines, which could make it easier to distribute them around the world, the researchers say.

“Subunit vaccines have been around for a long time, and they tend to be cheaper to produce, so that opens up more access to vaccines, especially in times of pandemic,” says Jaklenec.

Biomedical engineers use new type of nanoparticle to make vaccines more powerful

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