A new paper diagnostic test for cancer? That is what engineers at the Massachusetts Institute of Technology (MIT) have developed—a simple, low-cost, noninvasive paper test that can improve diagnosis rates and hasten treatment.1 The test, which essentially works like a pregnancy test, may have the potential to determine if a patient has cancer—within minutes.
Developed by Sangeeta Bhatia, MD, PhD, director of the laboratory for multiscale regenerative technologies at MIT, the technology is based on nanoparticles that interact with proteases (proteins, known to be overexpressed in numerous tumors, that can cleave peptide bonds), which can release hundreds of biomarkers that can be detected in the patient’s urine. Bhatia’s group designed nanoparticles conjugated to ligand-encoded reporters through protease-sensitive peptide substrates. The ligand on the nanoparticles is targeted to reach the disease site, be it solid tumors or blood clots or other sites, where upregulated proteases cleave the peptide substrates and release the reporters that are excreted in the urine. The urine can be tested either by a paper lateral flow assay or a sandwich enzyme-linked immunosorbent assay.2 This diagnostic platform, claim the authors, can be applied in any disease setting without expensive equipment or trained medical personnel, and may allow low-cost diagnosis of disease at the point of care in resource-limited settings.
The novel aspect of Bhatia’s work is designing the exogenous nanoparticle biomarkers; companion point-of-care (POC) diagnostic paper strips were originally invented through a collaborative effort between researchers at Harvard University and the University of Sao Paulo. Driven by the need to develop easy-to-use diagnostics in the developing world, based on the World Health Organization’s ASSURED (affordable, sensitive, specific, user-friendly, rapid and robust, equipment free, and deliverable to end-users) criteria, the microfluidic paper-based analytical devices (mPADs) were developed as a new class of POC diagnostic.3 Urinalysis assays using mPADs proved that the platform was ideal for ASSURED diagnostics.
Diagnostics For All (DFA), a company based in Cambridge, Massachusetts, has licensed out this patterned paper technology that was developed by the Harvard research group, with the aim of developing POC diagnostics for the developing world.4 Currently, the company is working on the following diagnostic tests:
• Liver function tests (to monitor patients on antiretroviral therapies)
• Rapid immunity assessment (to monitor efficacy of vaccination against tetanus and measles; funded by the Bill and Melinda Gates Foundation)
• Child nutrition monitoring (funded by the Bill and Melinda Gates Foundation)
• Nucleic acid detection to diagnose Brucella abortus
When contacted by e-mail, DFA informed Evidence-Based Oncology that it is not currently developing any oncology diagnostic test.
Although Bhatia’s PNAS paper describes using the platform to detect colorectal cancer and thrombosis, diseases associated with an abundance of active proteases, the applications are enormous. These studies were conducted in a mouse model; in order to guide the results to the next level and study patient populations, Bhatia aims to develop a business plan for a startup based on a Technological Innovation grant that the group received to commercialize the technology and conduct clinical trials.1 The research group is also working on developing an implantable nanoparticle formulation that could aid long-term monitoring.
The engineering of low-cost and rapid assays to detect cancer has been on the rise. Mechanical engineers at the University of Washington, working in collaboration with a pathologist in the school of medicine, have developed a device that can help diagnose pancreatic cancer earlier and faster by avoiding the time-consuming manual labor associated with processing biopsy tissue samples. The microfluidic gadget (simply a modified petri dish with Teflon tubes) uses fluid transport to perform the basic steps of processing a biopsy sample. This device is expected to automate and streamline the manual process that a pathologist follows to help diagnose a biopsy sample. Another advantage is that this technology would allow for 3-dimensional imaging, unlike the current technique followed by pathologists which only allows 2-dimensional imaging, providing a much more detailed and complete view of the tumor.5
VOC Diagnostics, a start-up company that is the brainchild of business school students at the University of Louisville, Kentucky, is developing a lung cancer diagnostic test that has the easiest sample collection technique: the patient simply breathes into a bag. The air from the sealed bag is then released over a diagnostic microchip called VitaLung, also developed at the University of Louisville, which then detects volatile organic compounds in a person’s breath. The results from the patient sample are then compared against the molecular profile (biomarkers) of lung cancer to make a diagnosis. VOC Diagnostics initiated efficacy trials at the beginning of 2013, and early results showed 90% accuracy.6
The American Lung Association recommends an annual low-dose computed tomography (LDCT) screen in individuals with a high risk for the disease, such as current or former smokers.7 Although beneficial in high-risk individuals, an exhaustive review published in the Journal of the American Medical Association evaluating the effect of LDCT on lung cancer mortality screening concluded that the screen could potentially be harmful, as it cannot distinguish between benign and cancerous tumors. Therefore, additional imaging to confirm potentially benign nodules increases the patient’s exposure to radiation, while surgeries undertaken to excise benign nodules can result in complications.8 Considering these complications, VitaLung is safer and was definitely found to be accurate based on preliminary results.
1. Trafton A. A paper diagnostic for cancer. Massachusetts Institute of Technology website. http://web.mit.edu/newsoffice/2014/a-paper-diagnostic-for-cancer-0224.html. Published February 24,
2014. Accessed March 28, 2013.
2. Warren AD, Kwong GA, Wood DK, Lin KY, Bhatia SN. Point-of-care diagnostics for noncommunicable diseases using synthetic urinary biomarkers and paper microfluidics. PNAS. 2014;111(10):3671-3676.
3. Martinez AW, Phillips ST, Whitesides GM, Carrilho E. Diagnostics for the developing world: microfluidic paper-based analytical devices. Anal Chem. 2010;82:3-10.
4. Diagnostics For All website. http://www.dfa.org/projects/projects-overview.php. Accessed March 31, 2014.
5. Ma M. Credit card-sized device could analyze biopsy, help diagnose pancreatic cancer in minutes. University of Washington website. http://www.washington.edu/news/2014/02/06/creditcard-sized-device-could-analyze-biopsy-help-diagnose-pancreatic-cancer-in-minutes/. Published February 6, 2014. Accessed March 31, 2014.
6. Combs V. Biomarker test could make screening for lung cancer cheap and easy. Medcity News website. http://medcitynews.com/2013/02/biomarker-test-could-make-screening-for lungcancer-cheap-and-easy/. Published February 27, 2013. Accessed April 1, 2014.
7. New lung cancer screening assessment tool. American Lung Association website. http://www.lung.org/about-us/our-impact/top-stories/newlung-cancer-screening.html. Published October 30,
2013. Accessed April 1, 2014.
8. Bach PB, Mirkin JN, Oliver TK, et al. Benefits and harms of CT screening for lung cancer: a systematic review. JAMA. 2012;307(22):2418-2429.
The currently prevalent tests for cancer diagnosis, including computed tomography, magnetic resonance imaging, and positron-emission tomography, require not just specialized instruments, but also highly trained staff to conduct the examination and then to interpret the reports. The entire process is therefore time consuming as well as expensive. Innovative ideas being developed by academicians in partnership with venture capitalists or the pharmaceutical industry could simplify the process and also prove economical.