Tag Archives: pancreatic cancer

Attomolar cancer detection: measuring microRNAs in blood

Leave a reply

The latest research does not lead to a magical disease detector where nanoscale sensors swim through the body continuously monitoring our health and alerting us should something untoward occur (see this Oct. 28, 2014 article on RT.com for more about Google X’s development plans for it and this Nov. 11, 2015 news item on Nanowerk for a measured response from a researcher in the field).

Now onto some real research, a Nov. 17, 2015 news item on ScienceDaily announces an ultrasensitive (attoscale) sensor employing gold nanoparticles for detecting cancer,

A simple, ultrasensitive microRNA sensor developed and tested by researchers from the schools of science and medicine at Indiana University-Purdue University Indianapolis and the Indiana University Melvin and Bren Simon Cancer Center holds promise for the design of new diagnostic strategies and, potentially, for the prognosis and treatment of pancreatic and other cancers.

A Nov. 17, 2015 Indiana University-Purdue University Indianapolis news release on EurekAlert, which originated the news item, provides more detail about research that seems to have focused largely on pancreatic cancer detection (Note: Links have been removed),

In a study published in the Nov. [2015] issue of ACS Nano, a peer-reviewed journal of the American Chemical Society focusing on nanoscience and nanotechnology research, the IUPUI researchers describe their design of the novel, low-cost, nanotechnology-enabled reusable sensor. They also report on the promising results of tests of the sensor’s ability to identify pancreatic cancer or indicate the existence of a benign condition by quantifying changes in levels of microRNA signatures linked to pancreatic cancer. MicroRNAs are small molecules of RNA that regulate how larger RNA molecules lead to protein expression. As such, microRNAs are very important in biology and disease states.

“We used the fundamental concepts of nanotechnology to design the sensor to detect and quantify biomolecules at very low concentrations,” said Rajesh Sardar, Ph.D., who developed the sensor.

“We have designed an ultrasensitive technique so that we can see minute changes in microRNA concentrations in a patient’s blood and confirm the presence of pancreatic cancer.” Sardar is an assistant professor of chemistry and chemical biology in the School of Science at IUPUI and leads an interdisciplinary research program focusing on the intersection of analytical chemistry and the nanoscience of metallic nanoparticles.

“If we can establish that there is cancer in the pancreas because the sensor detects high levels of microRNA-10b or one of the other microRNAs associated with that specific cancer, we may be able to treat it sooner,” said Murray Korc, M.D., the Myles Brand Professor of Cancer Research at the IU School of Medicine and a researcher at the IU Simon Cancer Center. Korc, worked with Sardar to improve the sensor’s capabilities and led the testing of the sensor and its clinical uses as well as advancing the understanding of pancreatic cancer biology.

“That’s especially significant for pancreatic cancer, because for many patients it is symptom-free for years or even a decade or more, by which time it has spread to other organs, when surgical removal is no longer possible and therapeutic options are limited,” said Korc. “For example, diagnosis of pancreatic cancer at an early stage of the disease followed by surgical removal is associated with a 40 percent five-year survival. Diagnosis of metastatic pancreatic cancer, by contrast, is associated with life expectancy that is often only a year or less.

“The beauty of the sensor designed by Dr. Sardar is its ability to accurately detect mild increases in microRNA levels, which could allow for early cancer diagnosis,” Korc added.

Over the past decade, studies have shown that microRNAs play important roles in cancer and other diseases, such as diabetes and cardiovascular disorders. The new IUPUI nanotechnology-based sensor can detect changes in any of these microRNAs.

The sensor is a small glass chip that contains triangular-shaped gold nanoparticles called ‘nanoprisms.’ After dipping it in a sample of blood or another body fluid, the scientist measures the change in the nanoprism’s optical property to determine the levels of specific microRNAs.

For anyone concerned about the cost associated with creating sensors based on gold, about patents, or about current techniques for monitoring microRNAs, there’s more from the news release (Note: A link has been removed),

“Using gold nanoprisms may sound expensive, but it isn’t because these particles are so very tiny,” Sardar said. “It’s a rather cheap technique because it uses nanotechnology and needs very little gold. $250 worth of gold makes 4,000 sensors. Four thousand sensors allow you to do at least 4,000 tests. The low cost makes this technique ideal for use anywhere, including in low-resource environments in this country and around the world.”

Indiana University Research and Technology Corporation has filed a patent application on Sardar’s and Korc’s groundbreaking nanotechnology-enabled sensor. The researchers’ ultimate goal is to design ultrasensitive and extremely selective low-cost point-of-care diagnostics enabling individual therapeutic approaches to diseases.

Currently, polymerase chain reaction technology is used to determine microRNA signatures, which requires extraction of the microRNA from blood or other biological fluid and reverse transcription or amplification of the microRNA. PCR provides relative values. By contrast, the process developed at IUPUI is simpler, quantitative, more sensitive and highly specific even when two different microRNAs vary in a single position. The study demonstrated that the IUPUI nanotechnology-enabled sensor is as good as if not better than the most advanced PCR in detection and quantification of microRNA.

Here’s a link to and a citation for the paper,

Label-Free Nanoplasmonic-Based Short Noncoding RNA Sensing at Attomolar Concentrations Allows for Quantitative and Highly Specific Assay of MicroRNA-10b in Biological Fluids and Circulating Exosomes by Gayatri K. Joshi, Samantha Deitz-McElyea, Thakshila Liyanage, Katie Lawrence, Sonali Mali, Rajesh Sardar*, and Murray Korc. ACS Nano, Article ASAP DOI: 10.1021/acsnano.5b04527 Publication Date (Web): October 7, 2015

Copyright © 2015 American Chemical Society

This is an open access paper.

The researchers have provided this illustration of gold nanoprisms,

Caption: Indiana University-Purdue University Indianapolis researchers have developed a novel, low-cost, nanotechnology-enabled reusable sensor for which a patent application has been filed. Credit: Department of Chemistry and Chemical Biology, School of Science, Indiana University-Purdue University Indianapolis

Caption: Indiana University-Purdue University Indianapolis researchers have developed a novel, low-cost, nanotechnology-enabled reusable sensor for which a patent application has been filed. Credit: Department of Chemistry and Chemical Biology, School of Science, Indiana University-Purdue University Indianapolis

15-year-old Jake Andraka and his nanotechnology-enabled test for pancreatic cancer

1 Reply

We’re led to believe that good ideas can come from anyone, anywhere, at any time and that they will be recognized as such. Every once in a while it’s nice to see evidence that there’s some truth to that notion. Jake Andraka, 15 years old, has invented a test for pancreatic cancer that seems to be mostly accurate and is cheap making it far superior to any other such test currently available. (H/T Foresight Institute, Mar.6.13 posting)

The Jan. 29, 2013 article by Damien Gayle for the UK’s Daily Mail highlights these points and goes on to describe Jake’s accomplishments at more length (there are are also videos embedded in the article),

  • Jack Andraka’s new test detects pancreatic cancer earlier than any other
  • Deadly disease currently kills 19 out of 20 within five years
  • He claims his invention could raise survival rates to ‘close to 100 per cent’

… Jack’s invention, for which he was last month awarded the grand prize of $75,000 in scholarship funds at the 2012 Intel Science Fair, means that patients now have a simple method to detect pancreatic cancer before it becomes invasive.

His novel patent-pending sensor has proved to be 28 times faster, 28 times less expensive, and over 100 times more sensitive than current tests.[emphasis mine]

…

The test works in a similar way to diabetic testing strips, with his paper strips using only a drop of blood to determine whether patients carry the mesothelin biomarker.

It is said to be over 90 per cent accurate, practically instant – and costs only 3 cents.

And what’s more, his simple test can also be used to detect ovarian and lung cancer, and it could be easily altered to detect the biomarkers of a range of other conditions.

‘What’s so cool about that is its applicability to other diseases…for example other forms of cancer, tuberculosis, HIV, environmental contaminants like E Coli, salmonella,’ Jack told Take Part.

Andraka is also profiled in a December 2012 article by Abigail Tucker for the Smithsonian Institution. It reads more like a profile for a fan magazine (in parts) than one might expect from the Smithsonian but all that’s mixed in with some science and a discussion about product availability,

It’s first period digital arts class, and the assignment is to make Photoshop monsters. Sophomore Jack Andraka considers crossing a velociraptor with a Brazilian wandering spider, while another boy grafts butterfly wings onto a rhinoceros. Meanwhile, the teacher lectures on the deranged genius of Doctor Moreau and Frankenstein, “a man who created something he didn’t take responsibility for.”

“You don’t have to do this, Jack!” somebody in back shouts.

The silver glint of a retainer: Andraka grins. Since he won the $75,000 grand prize at this past spring’s Intel International Science and Engineering Fair, one of the few freshman ever to do so, he’s become a North County High School celebrity to rival any soccer star or homecoming queen.

…

That’s exactly what Andraka may have invented: A small dipstick probe that uses just a sixth of a drop of blood appears to be much more accurate than existing approaches and takes five minutes to complete. It’s still preliminary, but drug companies are interested, and word is spreading. “I’ve gotten these Facebook messages asking, ‘Can I have the test?’” Andraka says. “I am heartbroken to say no.” [emphasis mine]

According to the Jan. 27, 2013 article by Andri Antoniades for Take Part, Andraka has been talking to companies such as LabCorp and QuestDiagnostics,

He has big plans to turn the medical community on its ear by mass marketing his work, making it widely available. He says, “Essentially what I’m envisioning here is that this could be on your shelf at your Walgreens, your Kmart. Let’s say you suspect you have a condition…you buy the test for that. And you can see immediately if you have it. Instead of your doctor being the doctor, you’re the doctor.” The teenager reports that he’s already in talks with major corporations like LabCorp and QuestDiagnostics to bring his kits to store shelves “as soon as possible,” though how long that may actually take isn’t yet known.

John Nosta’s interview with Andraka, which highlights some of the difficulties associated with science research, was published in a Feb. 1, 2013 posting on Forbes.com,

–Was your discovery easy?  Did the innovation come in a flash…then the details worked out?

I like to read a lot of journals and articles about different topics and then lie on the couch or take a walk and just let all the information settle. Then all of a sudden I can get an idea and connect some dots. Then it’s back to reading so I can fill in missing pieces. With this sensor I had put in a lot of time learning about nanoparticles for my previous research on the effects of bulk and nano metal oxides on marine and freshwater organisms. I felt that single walled carbon nano tubes were like the super heroes of material science and I wanted to work with them some more. Then when I was reading a paper about them in biology class, the teacher was explaining about antibodies. All of a sudden I made a connection and wondered what would happen if I dispersed single wall carbon nanotubes with an antibody to a protein over-expressed in pancreatic cancer. Then of course there was a lot of reading, learning and planning in front of me!

… It seemed so easy so I stalked the internet and found the names and professional emails of lots of professors in my area who were working on pancreatic cancer. Then I just figured I’d sit back and wait for the acceptances to roll in! Week after week I’d receive endless rejections. The most helpful one was actually from a researcher who took the time to point out every flaw and reason why my project was impossible. I began to despair!

… Finally, after 199 rejections, I received one email from Dr Maitra at Johns Hopkins School of Medicine. He invited me to come for a meeting. My mom drove me there and dropped me off. It was pretty exhilarating yet scary to walk in to the interview! Luckily I was really prepared and even had the cost and catalog numbers of the material I needed. He said it was like reading a grant proposal. I still had a great deal of basic lab routine to learn and I appreciate the time and patience of both Dr Maitra [Anirban Maitra] and Dr Chenna [V. Chenna], the post- doc who supported me.

There’s a brief description of Andraka’s test in an article (published June 16, 2012 online) by Devin Powell for Science News, 181 (12),

Searching for a better detector for mesothelin, Andraka coated paper with tiny tubes of atom-thick carbon. Antibodies stuck to the carbon nanotubes can grab the telltale protein and spread the tubes apart. The carbon’s resistance to the flow of electricity drops measurably as more protein attaches. Tests of the paper using blood samples from 100 people with cancer at different stages of the disease identified the presence of cancer every time, Andraka reported.

It’s quite a story on any number of levels. It’s not just Andraka’s age. There’s the simplicity of the idea, the difficulty of getting anyone to pay attention (199 rejections, that number seems suspiciously poetic), and what was undoubtedly a lot of painstaking, boring, hard work. Finally, the reference to a patent seems very much in the tenor of the times. I wish Andraka good luck with his work and I hope the test is available soon.