Project Name: NanoWarriors
TechXplore 2007-2008, sponsored by the National Science & Technology Education Partnership (NSTEP).
This TechXplore project was completed by Bergen County Academies, Hackensack, NJ, with technical support from Jim Lowery of ITM- Instruments Technology, Machinery.
Cystic fibrosis is an escalating phenomenon with detrimental effects. A major part of this life shortening disease is the presence of excess mucus in the lungs. Currently, there is no cure and the only option for victims is periodically coughing up the build up of mucus. We propose packaging a chemical (possibly a gene since cystic fibrosis is a genetic disease) into an inhalable nanoparticle, which will eventually release the chemical into the lungs, reducing the mucus synthesis.
http://www.cff.org/AboutCF/Faqs/
Problem
Cystic fibrosis is a genetic disease that affects 30,000 Americans, with 1,000 new cases every year. Median age of survival is only 37 years, making it the top killer in genetic disorders. One of the worse symptoms of the disease is the clogging and inflammation of the lungs due to excess mucus. This problem causes major discomfort and pain to the patient, forcing them to cough up phlegm almost constantly. Cystic fibrosis is a life long plague with no cure. If this problem could be solved, thousands of people worldwide would benefit. As our mentor stated, “This is an excellent topic to pursue. An acquaintance of mine had Cystic Fibrosis and his difficulty breathing was always evident. Wouldn’t it be wonderful if something can be done to alleviate their suffering.” http://www3.nbnet.nb.ca/normap/cfstats.htm
http://www.medicalook.com/diseases_images/cystic_fibrosis.jpg
The cystic fibrosis gene is located on chromosome seven and in cystic fibrosis patients; a DNA mutation in this gene involves the production of a protein called (Cystic Fibrosis Transmembrane conductance Regulator), a part of the cell membrane in certain special epithelial (surface) cells that generate mucus. These special cells might line the airways of the nose and lungs or the stomach wall. One missing amino acid in the proteins calls for the majority of cystic fibrosis cases. The gene region has 230,000 DNA base pairs that spell out a series of 1,480 amino acids that curl up to make the CFTR protein. The little triangle in the diagram below shows the location of the three-base-pair deletion mutation.
http://www.science.ca/images/scientists/s1-tsui.jp
A normal gene makes CFTR that regulates the passage of chloride ions and hence the secretion of mucus in epithelial (surface) cells lining lungs. This is the corrected gene that we posses in our hands today. However, the major hindrance that has been experienced so far in administering this gene is an immune system rejection because of the chemical properties of the nanoparticles used to deliver the gene. Our team’s approach was to find a finite tactic to overcome such a hindrance.
Solution
Three Initial Ideas:
1) A microparticle that is inserted into the lungs (surgically) that can sense buildup of mucus and will disperse a chemical that will break down the mucus compounds. This microparticle would have sensing technology, capable of responding to stimuli.
2) A nanoparticle that can be inhaled (technology available) and that contains a fixing gene (which has already been discovered at Cornell) that will be delivered into the lungs. Our problem is battling the immune system in this case.
3) A box-type micro-machine that can suck up mucus and destroy it within the box.
Mentor Comments:
10/24/07
This is an excellent topic to pursue. An acquaintance of mine had Cystic Fibrosis and his difficulty breathing was always evident. Wouldn’t it be wonderful if something can be done to alleviate their suffering.
Since my background is in large mechanical devices Let me start by asking for some definitions. Microparticle (what size?, is it mechanical or chemical?), Nanoparticle (this sounds smaller than a Microparticle, is it mechanical or chemical?), and the phrase box-type. Is it just as it sounds, a small machine that has no real defined shape yet?
Narrowing the field – our first task is to look at the 3 proposals and decide which one has the least chance of success and eliminate it from further investigation.
If you have not already, Google search Cystic Fibrosis and see if there are any treatments available that you might be duplicating.
The box-type micro machine
Much progress has been made in recent years in the prototype manufacture of micromachines that are so small that a microscope is required to watch them work. They are mainly manufactured using the photo etch process developed for micro chips. How large is the mucus cells that the micro machine would have to suck up. It may be that the cell is so large that the micro machine would be rejected immediately. How large of an item can the body tolerate? Something the size of a golf ball would probable not be acceptable.
IDEAS
A Google search of Nano Machines comes up with a wealth of articles, maybe somewhere in there are the answers we are looking for.
Below is an excerpt from a web page on some nanotechnology that is being developed.
http://www.ed.ac.uk/news/050829nano.html
A key technological breakthrough led by the University of Edinburgh suggests that a futuristic world where people can move objects about “remotely” with laser pointers could be closer than we think. Chemists working on the nanoscale (80,000 times smaller than a hair's breadth) have managed to move a tiny droplet of liquid across a surface - and even up a slope - by transporting it along a layer of light-sensitive molecules.
Other, ridiculous ideas – many times in the design of a machine I toss out ridiculous ideas. Some of these get a good laugh while others lead to viable good ideas, here goes.
Put the patient on a turntable, (like a merry go round) with his head near the edge of the circle and his feet near the center. Spin the patient to force the mucus to the top of the lungs where it can be coughed out.
10/26/07
I received a brochure in the mail today called "The Materials For
Medical Devices Database". I went to their website (link below) and
they seem to have a free trial membership that you may be able to sign
up for. It looks like a good resource for the project. Let me know if
it works for you.
I was thinking yesterday about the mucous in the lungs and I wondered, if pressure, partial pressure of a gas, temperature, humidity or a combination of the four would help the process much like carbon black is used as a catalyst to make rubber tires stronger. For example in normal scuba diving we use compressed air which is made up of 21% oxygen and
79% nitrogen, the same as the air we breathe. We sometimes use a gas mixture of 32% Oxygen and 68% nitrogen (called enriched air NITROX) to change the partial pressure of oxygen which puts less nitrogen into the bloodstream thus reducing the risk of the bends upon returning to the
surface. By changing the percentage of one gas over another we achieve
a more desired result. Air pressure at sea level is 14.7psi as we
increase the pressure either by diving under water or by changing the
pressure in a hyperbaric chamber more or less gas is forced into
solution in the tissues and liquids of our bodies (mainly blood). When
the astronauts in the space shuttle are about to go on a extra vehicular
activity (space walk) they must breathe a combination of Oxygen and
Helium to purge their systems of nitrogen. In the space suit I believe
the pressure is 4 or 5 psi. At these pressures the nitrogen in their
blood while in the shuttle (14psi) is at equilibrium, in the suit(4psi)
would form bubbles like a soda pop when opened. So perhaps you can
explore the effects of Pressure, partial pressure of gases, temperature
and humidity on the mucous and the devices that you are developing to
fight the mucous.
http://asmcommunity.asminternational.org/portal/site/asm/
SilverAssist
As our mentor mentioned, the world is most definitely going nanoscale. This was the reason that the team eventually decided to reevaluate the solution of a micromachine or a box-like prototype that that has the capability to suck up mucus. Even micro- may be too large for the lungs to handle and the liklihood of an immune system rejection to occur is very high. Therefore, nano was the road to set about on. Upon starting our investigation on a nanoparticle that can be surgically inserted in the body, all team members automatically arrived to the conclusion that a surgery may eventually prove to be costly for patients. The chemical that the nanoparticle is supposed to disperse will eventually run out and repeated surgery involving the lungs may be fatal. Though we already had the corrected cystic fibrosis gene, its route of administration is still baffling many researchers. One in-school nanotechnology expert suggested that the team ponder over Exubera, which was the recent first FDA approved inhaled version of insulin. (http/::www.diabetesnet.com/diabetes_treatments/insulin_inhaled.php)
One alternative sight that it has fared well in the competition is into the lungs. Therefore, instead of the gene having to be surgically inserted, a simply inhalation with such a mechanism can safely deliver the gene into the lungs. However, there is a great likelihood that the gene by itself will trigger an immune system rejection as well. Therefore, designing the architecture of an outer layer or coating around the gene became absolutely vital. Upon much research, the team agreed upon the many properties of silver itself. Within the past year or so, silver has gained popularity as a safe, effective antimicrobial agent, and scientists are already looking into using nanochrystalline silver as a likely potential in the treatment for cystic fibrosis patients. Additionally, silver in the form of nanoparticles are sufficiently small to pass through the outer cell membranes of lung cells and enter the cells’ inner mechanisms. Coating the gene with a recognized antibiotic was an intial idea at first, but increasing doses lead to resistance and grave sideffects. Therefore, experimenting even with a minimal dose of antibiotic coating was out of question. Silver, on the other hand, runs a much less likelihood of resistance while providing minimal risks for side effects. Scientist at Leicester University have already built a machine that can produce such silver nanoparticles, which can be suspended in a liquid. In other words, it can be put into an Exubera-like aerosol and breathed into the lungs. What happens once the silver nanoparticles are produced? Well, these nanoparticles have already been used to create SilvaGard, a FDA approved silver nanoparticle antimicrobial coating. While AcryMed is using this silver nanotechnology breakthrough as protection against the formation of infection-causing biofilms or bacteria, our team has decided to employ this silver nanoparticle coating around the corrected cystic fibrosis gene. Upon its administration into the lungs via an inhaler, the silver nanoparticles have the ability to create tenacious bonds to any material, as tested, making it trouble-free to bond with the membranes of lung cells. (http://www.acrymed.com/medical.html)
Since the silver nanoparticles create a large surface area, their antimicrobial properties would tackle the cystic fibrosis infections within the surface of the lungs while the gene will be delivered to the cells. According to a study conducted at Oregon Health and Sciences University, such silver nanotechnology implements low toxicity levels because the nanoparticles were eventually removed through the feces, solid excretory product evacuated from the bowels. Moreover, the international nanotechnology business directory, Nanovip.com, labels such silver nanotechnology as well established, effective, and cost effective.
www.bcscience.com/.../ 0_quiz_insert_gene.jpg
Team Profile
NanoWarriors
Bergen County Technical Schools, Hackensack, NJ
High School Team
Evelyn Rios
The team members were able to improve teamwork and researching skills. They also learned about the field of nanotechnology and its application to everyday life. The team cultured an understanding about the cooperative parts of biology and technology, and how they can help lives. The team learned a lot and had fun!
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Team Roles:
Jessica K.: My strength is my ability to communicate between members of the group and the outside mentor. The role best suited for me is to compile and edit the information gathered by all of the members and relay the mentor’s messages.
Krizia A.: My strength is my ability to organize and design. The task best suited for me is leading the design process and coordinating the website.
Linda Z.: My strength is the ability to research in depth information on the topic and communicate with the inside mentor. The task best suited for me is gathering, verifying, and compiling the necessary information for the topic.
Bhumi P.: My strength is my ability to come up with new ideas and alternatives, as well as researching necessary information. The role best suited for me is compiling information and relaying it to the inside mentor. I am also responsible for the written report.
Mentors:
Jim Lowry was our assigned mentor who emailed us regularly with advice.
Dr. Robert Pergolizzi and Mrs. Donna Leonardi were our in-school mentor who provided us with information that helped us develop our idea.
Mrs. Rios was our project facilitator.
Thanks:
Our team would like to extend our sincere gratitude to Jim Lowry for his mentorship. Without his support and guidance, we would not have been able to develope our idea as fully as we have.
We would also like to thank Mrs. Rios for encouraging us and never giving up on our idea.
We would like to thank Dr. Robert Pergolizzi and Mrs. Donna Leonardi for their time and support.
Thank you TechXplore for this very educational opportunity and learning experience!
Feedback
NanoWarriors
“SilverAssist” is designed to be a solution to a problem faced by people with cystic fibrosis. The product particles would be inhaled and once delivered to the lungs, would deliver a gene against mucus production. The particles would be coated in silver.
- Have you ever heard of such a product in existence?
6% Yes 94%No
- Would you think our product would be successful as a good medical solution to patients with cystic fibrosis?
83%Yes 17%No
- Do you think this product is necessary and essential for patients with cystic fibrosis?
78%Yes 22%No
- Have you ever heard of nano technology?
94%Yes 6%No
- Have you ever heard of inhaling nano-particles into the body?
56%Yes 44%No
- Have you ever heard of Exubera?
33%Yes 67%No
- If you were a cystic fibrosis patient, would you participate in a clinical trial to test this product?
67%Yes 33%No
- Do you think this concept is realistic for future production?
78%Yes 33%No
- Do you think that this product would be in the average person’s price range?
44%Yes 56%No
- Do you think that this product will be endorsed by medical insurance companies to be available to the general population of cystic fibrosis patients?
72%Yes 28%No
Analysis:
Despite the fact that many have heard of the advantages of nanotechnology and the inhaling of nanoparticles, it is apparent from the survey results that not may have heard of employing silver nanoparticles as a method of gene delivery since it is a novel and effective research phenomena that has just hit the market. The population that we surveyed knew at least once victim of cystic fibrosis but could not think of an alternative solution in helping such people since there are no methods that have been clearly listed as the ultimate treatment. Therefore, seventy-eight percent of our survey population found the incorporation of nanotechnology and gene therapy as essential for such victims. Since nanotechnology and gene therapy are the forefronts in their respective fields and have fared well, many agreed that such a concept was realistic for future production. The majority of our survey population understood the potentials of such an advance for cystic fibrosis patients and stated that they would definitely participate in a clinical trial if they were diagnosed with cystic fibrosis themselves. Though fifty-six percent of our survey population considered that a patient him or herself will not be able to personally finance such a procedure, seventy-two percent agreed that insurance companies will most definitely endorse it.
Interactions with Mentor:
Describe your job, and how would it contribute to solving our problem?
My job involves designing mechanical machines and devices. The other aspect of my job is to oversee our design team to create commonality in our different projects. I use a Computer Aided Design Software (SolidWorks) which enables me to build the entire machine and perform some testing right on the computer. I create the drawings used by our machine shop to manufacture the parts and buy motors and pneumatic cylinders. The entire machine is assembled by our assembly team with my guidance. Our programming department creates the control program and brings the machine to life. Most of our machines are computer controlled with some type of robot inside. One or our devices is called the Perfusion Apparatus. This device is built into a Nikon Microscope for the purpose of injecting different medicines directly into cells for medical research. If you visit our website at www.itm-texas.com you will see what type of machines we build.
My job is well suited to contribute to this project because I have such a wide variety of companies and designs at my disposal.
What do you like best about your job?
The best thing I like about my job is the variety of projects that I get involved with. One day I am in a factory that builds engine control modules coming up with ideas for a mechanical assembly machine and the next day I might be at a giant bakery creating a way to slice cinnamon rolls so they fit into the package correctly.
What is your educational background?
I Graduated from High School and took 2 years of college courses in the engineering field, however, due to family pressures, I was unable to graduate. This has not stopped me from learning. I look for every opportunity to take in seminars and classes related to my field and have become a successful machine designer.
Thank you so much for helping us!! We look forward to further working with you!
Remember, If it was easy, everyone would be doing it.
Jim Lowery
Technologies Associated With Our Solution:
Biotechnology
A biotechnologist works with technology and biology to better the quality and usefulness of items ranging from everyday items, like disease-resistant yeast, to garments worn my astronauts used in space. Biotechnologists use instruments than can create and measure to finite proportions. A biotechnologist must graduate from college with a degree in biotechnology.
NanoTechnology
A nanotechnologist works at the atomic level to create products that can be used in fields ranging from chemistry to law to computer software – for example, stain resistant clothing. Because of this wide range of possibilities, a nanotechnologist needs to be very adept at math, and have a degree in a science or engineering field. Most have an advanced degree, such as a Masters or Doctorate.
Chemical Engineering
The third technological career involved in SilverAssit is chemical engineering, a career involved in converting raw materials and chemicals into more useful and valuble forms. For this career, an important sense of research and development is key, just like our team researched crucially on cystic fibrosis and silver nanoparticles and developed the idea of SilverAssist. A bachelors in chemistry or chemical engineering is deemed absolutely significant in this career. The biotechnology field has a need for chemical engineers, which may provide additional job growth for chemical engineers.
Link to resource
www.associatedcontent.com/article/ 63339/career_profile_nanotechnology.html
Presentation
These photos are from our class presentation of our project.
