NEW YORK (360Dx) – Researchers at the New Jersey Institute of Technology are developing a microfluidic biochip that if successful could result in diagnosing ailments ranging from infectious diseases to cancers in about 1 minute, they said.
The technology is still in its very early stages, and it may be years before it becomes commercially available, if it all. But if proven successful, Eon Soo Lee — an assistant professor of mechanical and industrial engineering at NJIT, who is leading the work developing the biochip — envisions an iteration of the technology being sold in pharmacies that could be used with portable existing testing platforms.
Lee and Ph.D. candidate Bharath Babu Nunna co-invented the technology, and last month the New Jersey Health Foundation awarded them and their colleagues a $50,000 Innovation Grant to further develop their work.
Their device is based on electrical sensing mechanisms to detect biomarkers from blood. That approach, according to Lee, confers several advantages over optical-based biochips including greater accuracy and speed. Also, by leveraging nanofabrication technology, "we can harness the IT technology, or chip manufacturing technology, on a very small scale," and enable multiple biomarkers to be detected simultaneously, Lee said in an interview.
Lee and his colleagues described their work in a study published in July in Sensors & Transducers, in which they tested their biochip for the early detection of ovarian cancer by incorporating six biomarkers that have been associated with ovarian cancer onto their chip — CA-125; human epididymis protein 4; alpha-fetoprotein receptor; prostasin; apolipoprotein A-1; and transthyretin.
Surface-treated microchannels were built into the chip to control the self-driven flow of a blood sample, while a capacitance-sensing mechanism was incorporated into the chip to detect biological interactions, such as antigen-antibody complex formation. To enhance the detection of multiple antigens using multiple antibodies in different channels, the researchers also designed the biochip to enable multichannel distribution from a single inlet of the blood sample.
Multiple gold nano interdigitated electrodes (IDE) were incorporated into different sections of the microchannel to detect the biological interactions with the enhanced signal and to increase sensitivity, while gold nano IDEs were connected to individual contact pads to monitor each IDE signal individually, the researchers wrote. Meanwhile, attaching each IDE with a different cancer antibody increased the signal of the corresponding antigen-antibody complex formation, allowing individual concentrations of the specific antigens in the blood sample to be detected.
By detecting changes in electrical properties, including voltage, current, impedance, and capacitance, the biochip could detect biomolecular reactions and interactions. In the case of ovarian cancer, the "antigen-antibody complex results in the change of the dielectric properties of the medium, and thus causes the change in the capacitance of the nano circuit," resulting eventually in the detection of the cancer, the researchers wrote. "Thus, the POC biochip can detect ovarian cancer existence and its severity by detecting the cancer antigens' existence and its composition in the blood sample."
Lee said that a major feature of the biochip is that the sample separation step is done inside the chip. The result is that total analysis time takes about 1 minute.
He and his associates noted that the technology could have particular use for detecting ovarian cancer at the very earliest stages. In their paper, they said that current methods can detect only 15 percent of the disease in early stages. "Most of the ovarian cancer [cases] are detected at the later stage [when] it's too late to treat," Lee said.
They are continuing their efforts to increase the technology's sensitivity, and are preparing a study for potential publication. While Lee declined to share any data, he said that the biochip can detect blood-based biomarkers at the pico-level concentration.
Ovarian cancer is a starting point for the technology, Lee said, but the biochip could be used for detecting other cancers and other diseases, as long as the biomarkers for them exist.
"We are not developing the biomarker. We only use any well-developed biomarkers, [US Food and Drug Administration]-approved biomarkers," he said.
While the biomarkers used in the July study were protein biomarkers, Lee said his team is testing the chip's performance with other biomarker types. Early results have demonstrated that the technology also works with miRNA biomarkers, he added.
When fully developed, the biochip could be used not only to diagnose disease, but also to monitor patients and how they respond to different therapies, according to Lee. Aside from different biomarkers, the workflow would be identical.
Lee has his eye on the point-of-care market, such as a physician's office, for the technology. Longer term, he sees it being used by patients who would purchase the chip at a drug store, place it on a portable testing device, and then self-test for a wide range of diseases.
However, one researcher said that even if the device works as the NJIT researchers hope, it will be a long haul getting it to the POC setting.
"I don't think we're ready for point of care at this time," said K. Stephen Suh, the director of the Genomics and Biomarkers Program at the John Theurer Cancer Center at Hackensack Meridian Health. He also is listed as an inventor on the patent application for the technology. NJIT and Hackensack University Medical Center have jointly filed for the patent.
Along with regulatory approval, getting clinicians, patients, and insurers to adopt the technology will take time, Suh added. For example, if a doctor were to tell a patient that he/she has a choice of paying $100 out of pocket for a point-of-care test, or pay nothing for a test conducted at a reference lab, it's likely they would choose to have the test done at the lab, he said, adding that even in a clinical setting, barriers to adoption aren't insignificant.
"The clinic already knows how to diagnose that particular disease," he said. "We have a pathologist, we have molecular pathologists, we have doctors, we have a whole setup that the clinic has been developing for decades. We know how to diagnose that disease, and that procedure is approved by the FDA and approved for reimbursement.
"If you bring some diagnostic device … to the clinic, we could use it as long as the reimbursement side decides to pay for it. But without it, the clinic could [still] do the diagnosis [accurately]. We don't need all those things next to us for our diagnosis," Suh noted.
Diagnostic tests based on microfluidics and nanofluidics "will eventually come into the clinic and eventually replace traditional technologies," he continued. "How fast is it going to come? It all depends on the reimbursement side."
In the near term, the focus is on getting a lab prototype for the biochip and preparing to run clinical samples on the chip, followed by pursuit of FDA clearance for the technology. Lee said that he expects those steps to happen in about two years, and about a year after that, manufacturing of the biochip could commence.
In the meantime, he said that he's received inquiries about the technology from industry, though he declined to provide details.
"At this point, we are more interested in starting up this technology, instead of licensing the technology to the outside," he said. "I'm a little more focused on our own effort and with current available resources and current available collaboration partners. That's enough at this point."