Category Archives: BioEngineering

March 8, 2017 The MucoJet could one day make vaccine delivery needless. Credit: Stephen McNally/UC Berkeley

Patients could one day self-administer vaccines using a needleless, pill-sized technology that jet-releases a stream of vaccine inside the mouth, according to a proof-of-concept study conducted at UC Berkeley.

The study did not test vaccine delivery in people, but demonstrated that the technology, called MucoJet, is capable of delivering vaccine-sized molecules to immune cells in the mouths of animals. The technology is a step toward improved oral vaccine delivery, which holds the promise of building immunity in the mouth's buccal region of cells, where many infections enter the body. When patients hold the MucoJet against the inside of their cheek, the device releases a jet stream that directly targets the buccal region. This region is rich in immune cells but underutilized in immunology because of the challenge of efficiently penetrating the thick mucosal layer in this part of the oral cavity with existing technologies, such as the oral spray often used for influenza vaccination.

In laboratory and animal experiments, the research team showed that the MucoJet can deliver a high-pressure stream of liquid and immune system-triggering molecules that penetrate the mucosal layer to stimulate an immune response in the buccal region. The jet is pressurized, but not uncomfortably so, and would remove the sting of needles.

"The jet is similar in pressure to a water pick that dentists use," said Kiana Aran, who developed the technology while a postdoctoral scholar at Berkeley in the labs of Dorian Liepmann, a professor of mechanical and bioengineering, and Niren Murthy, a professor of bioengineering. Aran is now an assistant professor at the Keck Graduate Institute of Claremont University.

The portable technology, designed to be self-administered, stores vaccines in powder form and could one day enable vaccine delivery to remote locations, but years of further study are needed before the device would be commercially available.

The study will be published March 8 in the journal Science Translational Medicine and is available for download on EurekAlert!.

MucoJet is a 15-by-7-milimeter cylindrical, two-compartment plastic device. The solid components were 3D-printed from an inexpensive biocompatible and water-resistant plastic resin. The exterior compartment holds 250 mililiters of water. The interior compartment is composed of two reservoirs separated by a porous plastic membrane and a movable piston. One interior compartment is a vaccine reservoir, containing a 100-ml chamber of vaccine solution with a piston at one end and a sealed 200-micrometer (m) diameter delivery nozzle at the other end. The other interior compartment is the propellant reservoir, which contains a dry chemical propellant (citric acid and sodium bicarbonate) and is separated from the vaccine reservoir at one end by the built-in porous membrane and movable piston and is sealed at the other end from the exterior compartment with a dissolvable membrane

To administer the MucoJet, a patient clicks together the interior and exterior compartments. The membrane dissolves, water contacts the chemical propellant and the ensuing chemical reaction generates carbon dioxide gas. The gas increases the pressure in the propellant chamber, causing the piston to move. The free-moving piston ensures uniform movement of the ejected drug and blocks the exit of fizz from the carbon dioxide through the nozzle. When the pressure in the propellant chamber is high enough, the force on the piston breaks the nozzle seal of the vaccine reservoir. The vaccine solution is then ejected from the MucoJet nozzle, penetrates the mucosal layer of the buccal tissue, and delivers the vaccine to underlying vaccine targets, called antigen-presenting cells.

To test the MucoJet's delivery system, researchers designed a laboratory experiment in plastic dishes using mucosal layers and buccal tissues from pigs. They tested the MucoJet's ability to deliver ovalbumim, an immune stimulating protein, across the mucosal layer. The experiments showed an eightfold increase in the delivery of ovalbumin over the course of three hours compared to a control experiment of administering ovalbumim with a dropper (similar to how oral vaccines, such as for the flu, are administered today).

The researchers then tested different pressures of the vaccine jet and found that increasing the MucoJet output pressure increased the ovalbumin delivery to the tissue, indicating that the delivery efficiency improves with increased pressure.

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"The pressure is very focused, the diameter of the jet is very small, so that's how it penetrates the mucosal layer," Aran said.

The researchers then tested the MucoJet's ability to deliver ovalbumim to buccal tissue in rabbits. The MucoJet delivery resulted in a sevenfold increase in the delivery of ovalbumin compared to control experiments with droppers. Animals treated with ovalbumin by MucoJet had key antibodies in their blood that were three orders of magnitude higher than in the blood from rabbits treated with ovalbumin by a dropper.

The study did not compare the MucoJet to vaccine delivery with a needle, but data suggests that the MucoJet can trigger an immune response that is as good or better than delivery with a needle, especially for mucosal pathogens.

The next step in MucoJet's development is to test the delivery of a real vaccine in larger animals. The researchers hope the MucoJet can be available in five to 10 years. They also hope to engineer a version of the MucoJet that can be swallowed and then release vaccines internally.

The researchers are considering other shapes, sizes and designs to simplify vaccine administration procedures and increase patient compliance, especially for children. For example, the MucoJet could be fabricated into a lollipop.

"Imagine if we could put the Mucojet in a lollipop and have kids hold it in their cheek," Aran said. "They wouldn't have to go to a clinic to get a vaccine."

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Patients could one day self-administer vaccines using a needleless, pill-sized technology that jet-releases a stream of vaccine inside the mouth, according to a proof-of-concept study conducted at UC Berkeley.

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Oral delivery system could make vaccination needle-free - Medical Xpress

This sky-diving, squash-playing, thrill-seeking student is gearing up for her next great adventurein biomedical engineering research and discovery.

Why did you decide to concentrate in biomedical engineering?

As a child, I always had a love of math and science, and I liked to use my hands to create thingsI shunned Barbie dolls for building blocks. I was already a math and science nerd, but what appealed to me about bioengineering specifically is the breadth and diversity of research options, from organs on a chip to medical device design, and everything in between. The research that is happening right nowlike trying to grow a human heart outside the bodyis so cutting-edge and exciting.

Tell us about some of the bioengineering research youve had the opportunity to conduct at SEAS.

During my sophomore year, I began working in David Mooneys lab on developing the TheraCardium, which is a cardiac device for stem cell delivery to the heart for patients who have suffered a heart attack. The device supports regrowth of the damaged tissue and helps to prevent scarring of the dead heart muscle, in an effort to help prevent future cardiac events.

Mendez works on a biomedical research project in the Mooney lab. (Photo by Eliza Grinnell/SEAS Communications.)

Why was that research experience beneficial for you?

By working on that project, I experienced many different types of research, from preclinical studies in animals, to tissue engineering, to the materials science involved in building the device, to various soft robotic manufacturing techniques. I had the opportunity to work with many new technologies that I hadnt been exposed to in the classroom.

What is the topic of your senior thesis project?

Drawing on my work on the TheraCardium, I am designing a soft robotic drug delivery system. The device involves a hydrogel adhered to a soft robotic balloon that could be placed on the surface of the heart to directly delivery therapy to the muscle. Inflation of the balloon stretches the mesh size of the hydrogel, enabling delivery of the drug encapsulated within the hydrogel. By controlling the balloon inflation, we can achieve radio control, or the ability for on-and-off delivery. The device could also incorporate multiple balloons, delivering different drugs to separate areas of the heart.

In addition to your academic and research success, youve also served as co-captain of the Harvard Womens Squash team. How did you get involved with that sport?

I started playing squash competitively when I was 8 years old. The neighborhood where I grew up had one of the best junior squash programs in the country. I was inspired by my older sister, Haley, who is a great squash player. She was recruited to play squash at Harvard. When it came time for me to apply to college, the coach told me he had used all his recruiting spots, but if I could get into Harvard, I could play, too. It all worked out, and Ive been on the team for the past four years. There is a big mental aspect to squash. Your tactics and shot selection become critically important at the college level, since all the players are very technically proficient.

Are you and your older sister squash rivals?

Were a very competitive family. When we play board games, it gets so competitive it is almost scary. Haley has always been better than I was on the squash court, but we still play all the time. We are definitely competitive academically, as well, and while I love squash, I feel like my true passion lies in academics.

When playing squash at the college level, tactics and shot selection become incredibly important, Mendez said. (Photo by Eliza Grinnell/SEAS Communications.)

Do you think academics will play a role in your future plans?

Definitely. I am planning to apply for Ph.D. programs in bioengineering, and Harvard is my first choice. Ive been really excited about the research Ive been able to do as an undergraduate, and I want to continue contributing to science and advancing the field. The projects Ive been working on are just so cool, and I want to keep my research momentum going.

How do you feel that SEAS has prepared you for your future?

Beyond learning the technical skillslike how to code and use machinesbeing able to work closely with my peers on teams has given me a lot of confidence. As an engineer, you need to be able to communicate ideas effectively to people who may not be engineers. Collaboration is key within engineering, with each team member contributing an important piece to the puzzle. I have also been humbled, and learned when to ask for help, when to seek out peers, and when to work collaboratively in groups as opposed to attempting to do everything myself.

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Student profile: Keegan Mendez - Harvard School of Engineering and Applied Sciences

Cal State Fullerton faculty and students are presenting research on such subjects as bioengineering, broadcast journalism, free speech and communication styles at conferences and programs across the country. Among those delivering posters, papers and talks:

A research project conducted by Ashley Le-Pham while an undergraduate at Cal State Fullerton is among research projects that have been accepted for presentation at the April Posters on the Hill event in Washington, D.C. The program, established by the Council on Undergraduate Research, is an opportunity for select students from across the country to present their work before legislative leaders, federal agency program officers and the press.

Le-Pham 16 (B.S. biochemistry) will deliver Starch Bioengineering An Attempt to Combat Global Food Insecurity. Her faculty mentor was Christopher Meyer, professor of chemistry and biochemistry.

Brent Foster, associate professor of communications and interim director of undergraduate studies and general education, will present his paper Broadcast Armageddon: My Mom Just Posted a Youtube Video, at the annual convention of the Broadcast Education Association in April. The presentation discusses YouTube as a platform for media creators and encourages broadcast faculty members to become unconventional in their teaching, curriculum and course creation.

Also presenting at the BEA convention in Las Vegas are:

Jason Shepard, chair and associate professor of communications, was a presenter at the Free Speech and Open Inquiry on Campus conference at Chapman University Saturday, Feb. 25. Shepard discussed how to involve students in free speech advocacy on college campuses.

Human communication studies majors Joseph Fontana and Joseph Leung presented their research study, Does Your Coach Affect You? An Exploration of the Influences of Coaches Communication Styles on Team Sports Players at the Western States Communication Associations 2017 Undergraduate Scholars Research Conference in Salt Lake City. The two seniors conducted the research under the guidance of Tara Suwinyattichaiporn, assistant professor of human comminication studies, while enrolled in Suwinyattichaiporns Quantitative Research Methods course.

Link:
Exploring Bioengineering and Communication Faculty and Students Present, Discuss Research - CSUF News

Bioengineers at the University of California San Diego have developed a new tool to identify interactions between RNA and DNA molecules. The tool, called MARGI (Mapping RNA Genome Interactions), is the first technology that's capable of providing a full account of all the RNA molecules that interact with a segment of DNA, as well as the locations of all these interactions -- in just a single experiment.

RNA molecules can attach to particular DNA sequences to help control how much protein these particular genes produce within a given time, and within a given cell. And by knowing what genes produce these regulatory RNAs, researchers can start to identify new functions and instructions encoded in the genome.

"Most of the human genome sequence is now known, but we still don't know what most of these sequences mean," said Sheng Zhong, bioengineering professor at the UC San Diego Jacobs School of Engineering and the study's lead author. "To better understand the functions of the genome, it would be useful to have the entire catalog of all the RNA molecules that interact with DNA, and what sequences they interact with. We've developed a tool that can give us that information."

Zhong and his team published their findings in the February issue of Current Biology.

Existing methods to study RNA-DNA interactions are only capable of analyzing one RNA molecule at a time, making it impossible to analyze an entire set of RNA-DNA interactions involving hundreds of RNA molecules.

"It could take years to analyze all these interactions," said Tri Nguyen, a bioengineering Ph.D. student at UC San Diego and a co-first author of the study.

Using MARGI, an entire set of RNA-DNA interactions could be analyzed in a single experiment that takes one to two weeks.

The MARGI technique starts out with a mixture containing DNA that's been cut into short pieces and RNA. In this mixture, a subset of RNA molecules are interacting with particular DNA pieces. A specially designed linker is then added to connect the interacting RNA-DNA pairs. Linked RNA-DNA pairs are selectively fished out, then converted into chimeric sequences that can all be read at once using high-throughput sequencing.

Zhong and his team tested the method's accuracy by seeing if it produced false positive results. First, the researchers mixed RNA and DNA from both fruit fly and human cells, creating both "true" RNA-DNA pairs, meaning they're either fully human or fully fruit fly, and "false" RNA-DNA pairs, meaning they're half human and half fruit fly -- these are the ones that shouldn't be detected. The team then screened the entire mixture using MARGI. The method detected a large set of true RNA-DNA interactions, but it also detected approximately 2 percent of the false ones.

"This method is not perfect, but it's an important step toward creating a full functional annotation of the genome," said co-first author Bharat Sridhar, a visiting bioengineering researcher in Zhong's group.

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Decoding the Genome's Cryptic Language - Bioscience Technology

Big news in biotech: Scientists created what appeared to be a mouse embryo using stem cells. From the Telegraph story:

Artificial human life could soon be grown from scratch in the lab, after scientists successfully created a mammal embryo using only stem cells.

Cambridge University mixed two kinds of mouse stem cells and placed them on a 3D scaffold. After four days of growth in a tank of chemicals designed to mimic conditions inside the womb, the cells formed the structure of a living mouse embryo.

The breakthrough has been described as a masterpiece in bioengineering, which could eventually allow scientists to grow artificial human embryos in the lab without the need for a sperm or an egg.

First, this wouldnt be from scratch, as if they scientists brewed DNA from raw chemicals. It involved existing cells.

Second, we already know that mammalian life can be created without egg and sperm, for example, as in cloning, of which this is a variant technique that fuses different cells into a new organism.

Third, IF they ever create a human organism in this way, it would not be an artificial life but a real and fully human being thatshould be treated as such in ethics and in law.

More here:
Bioengineered Human Life Would Not Be Artificial - National Review

Almost every woman in engineering Ive talked to knows the pressure of having to prove herself.

She knows what its like to be meticulously perfect in her calculations, and to accept that regardless of her intelligence, her work will be checked again by someone who doesnt trust her.She knows that at the end of the day, mistakes hold more weight than they should.

I say almost every woman because I am one of the few that has rarely experienced this. Im lucky. Im an anomaly.

Bioengineering at Santa Clara University has a relatively large percentage of female students, compared to the other engineering disciplines. Im not intimately familiar with gender tensions in the classroom because there arent any in the classes I take, and I rarely feel the need to prove that I am better than the men I work with.

My mentors dont expect me to make mistakes, and are genuinely surprised when I do. Im not pressured to be perfect, but at the same time, the expectations for the work I do are just as high as anyone elses. The psychological effects of this are subtle, but theyve shaped how I perceive my own abilities, goals, and expectations.

Because Im held to an equal standard, I believe that I am equal. For that reason, I have my mentors to thank for my experiences as a woman in engineering. I realize that theyve given me what they didnt have, and I owe them much of who I am today.

It wasnt that easy for my mentors, and for many women today. My mentors have had to fight expectations to get where they are, and to defy the underlying notion that women just arent as smart and thats why they dont hold as many positions in engineering.

However, its not an IQ problem. Its an expectation that women just cant compete at the same level. This expectation is subtle, and its ingrained whether we realize it or not.

Its unintentional, intangible, and ever-present. Yet its effects are far reaching; being constantly undervalued and coddled teaches young girls that its okay to strive for less than the best, and to settle for goals that theyve been told are more realistic than the ones they would like to reach.

The women that inspire me hold me to a higher standard, and expect me to reach for whats unreachable. In doing so, they gave me the confidence to pursue engineering and taught me that I need to do the same forthe next generation.

We cant treat little girls differently from the boys that radiate confidence because its hard to be confident when youre expected to under perform. Instead, expect them to set impossible goals, and dont wait on the sidelines for them to fail. Expect them to compete at the same level, and be disappointed when they dont.

If we change our expectations, I guarantee you the next generation will meet them.

Shiyin Lim, a sophomore at Santa Clara University majoring in bioengineering, is part of Blue Marble Space Institute of Sciences Young Scientist Program focusing on research in space biosciences. She wrote this for The Mercury News.

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Opinion: Set high expectations of women engineers and they'll meet them - The Mercury News