April 17, 2025 | Researchers at The University of Texas at El Paso (UTEP) are developing a point-of-care device for diagnosing colorectal cancer which, like blood glucose devices, uses electrochemical sensors. The microchip electrode features an immunosensor that detects disease biomarkers in a drop of blood, opening the possibility of an accessible, inexpensive test for the nation’s second leading cause of cancer-related deaths, says Carlos Cabrera, Ph.D., professor and chair of the department of chemistry in whose lab the method was devised.
If the system can be validated as a reliable strategy for the early detection of colorectal cancer in human serum samples, it could save an untold number of lives as well as spare patients unnecessary worry and costly, potentially harmful, medical interventions, says Sourav Roy, Ph.D., associate professor of biological sciences at UTEP. His lab has been identifying over-expressed proteins in colon cancer tissues at different stages.
On the publishing front, the screening approach was initially used for the detection of colon cancer secreted protein-2 (CCSP-2), a well-recognized biomarker of the disease (ACS Measurement Science Au, DOI: 10.1021/acsmeasuresciau.4c00073).
But researchers are now focused on using the device for the detection of two other proteins—cell cycle-related protein cyclin B1 (CCNB-1) and minichromosome maintenance protein 10 (MCM-10)—which are overexpressed in people with colorectal cancer and are detectable at early stages of the disease, Roy says. These biomarkers are each to be identified and quantified, along with CCSP-2, in a pair of immunosensors being developed in the Cabrera lab.
The latest paper represents the doctoral research of Ruma Paul, working under the guidance of Cabrera and Roy. She designed the electrochemical biosensor for colorectal cancer diagnosis, which could be miniaturized and mass-produced for use at home or in a doctor’s office. The next plan for this device would be detecting two biomarkers simultaneously, including CCSP-2 since it is highly correlated with colorectal cancer, says Paul. The addition of the second biomarker is to aid in the prognosis, or likely course, of the disease.
The motivation for the project is that colorectal cancer is often diagnosed at later stages (III and IV) because the disease doesn’t cause noticeable symptoms in early stages (I and II) when it is highly treatable, Paul says. Younger adults often don't undergo routine screening but, concerningly, they are increasingly being diagnosed with advanced stage disease.
Colonoscopies are also unpopular and underutilized, and carry some risks, while noninvasive alternatives such as stool and DNA tests have varying levels of specificity, says Paul. Blood-based tests involving a simple blood draw hold the most promise for early detection and improved outcomes, especially where healthcare resources are in short supply, but the currently available options yield false positives that limit their clinical utility.
The collaboration between the Cabrera and Roy labs began after they met at a meeting two years ago and learned of their common interest in working on improved diagnostics for colorectal cancer. While Cabrera was developing immunosensors, Roy was looking at differentially expressed genes between Hispanics and non-Hispanic whites in different stages of the disease.
In an earlier, “entirely computational” study published in the International Journal of Environmental Research and Public Health (DOI: 10.3390/ijerph18115525), Roy and his colleagues identified 24 genes differentially expressed in colorectal cancer. Subsequently, the genes were screened for transcript-level expression in six different colorectal cancer cell lines and complementary DNA arrays revealed at which disease stages the genes were differentially regulated.
From there, Roy says, immunohistochemical staining of tissue microarrays helped the team identify the overexpressed proteins and their differential expression in Hispanics versus non-Hispanic whites. The analyzed tissue samples came primarily from Spain and Russia, respectively, supplemented by a moderate number of local samples.
For the first joint project with the Cabrera lab, the focus was on CCSP-2 whose presence in colon cancer cells is much higher than in normal colon cells, even though there are wide variations between samples and each stage, notes Roy.
Those differences are being considered with the biosensors Paul is now developing, which couple CCSP-2 with the CCNB-1 or MCM-10 sensor. False-positives are a potential problem with existing noninvasive tests, Roy says, including the popular at-home cancer screening test Cologuard that detects both blood and DNA in the stool. Most large polyps also go undetected by Cologuard, and fecal immunochemical tests perform particularly poorly in this respect.
The difficulty in coming up with a more accurate test is directly related to the biology of the colon, he explains. Cancers appearing on the ascending, transverse, descending, or sigmoid colon can be quite different. Right-sided colon cancers (in cecum, ascending colon, hepatic flexure, or transverse colon), for example, can potentially be more advanced and aggressive at diagnosis, while left-sided cancers may have a better response to certain treatments.
Genetic mutations, including those affecting the KRAS and BRAF genes, also have an impact on prognosis and treatment response in colon cancer. It’s important to remember that cancer is not a single disease and that its location and aggressiveness are among multiple factors influencing its likely course, says Roy. This is also why the treatment may not be similar for everyone.
The latest study used a commercial gold electrode chip (BASi), which the team plans also to use in future work, says Paul. The immunosensor works on the gold surface of the chip where antibodies are immobilized and bind to target antigens, creating a specific electrochemical signal that can be efficiently detected.
The goal here is to create a cost-effective, clinic-ready immunosensor device for capturing the biochemical reactions indicative of cancer. The most famous electrochemical sensor on the market currently is the one for measuring glucose, says Cabrera.
From the early days, researchers in his lab have imagined a similar type of test strip for antigens associated with colon cancer that would also be available for purchase at local retail pharmacies. But it’s going to take perhaps a decade or more, as it did for glucose sensors.
Cabrera says he and his team have been collaborating with a company in Puerto Rico on ways to speed up the measurement process, which is enabled in glucose sensors by an algorithm that does all the calculations for test strip users. Getting a read from the microchip electrode currently requires the expertise of the two UTEP labs.
Patents need to be had, and a startup company developed, to get the funding necessary to move the device toward clinical use, says Cabrera. The required steps for regulatory approval include validation studies of the electrochemical technique in samples from multiple patient communities that are available, but not inexpensively, from various repositories.
Another blood-based colorectal cancer test, called Shield (Guardant Health), was approved by the U.S. Food and Drug Administration just last year. It detects DNA mutations and epigenetic alterations and is intended for adults 45 years or older at average risk of developing colorectal cancer and need to undergo screening.
In addition to missing cases among younger people, Sheild catches only 83% of colorectal cancers in the targeted population and has a 10% false-positive rate. The work underway with the new electrochemical immunosensor aims to detect biomarkers specific to colon cancer “with high sensitivity and specificity, at early stages, and potentially in younger individuals,” says Paul.
“By targeting protein biomarkers associated with early-stage colon cancer and using a label-free, low-cost detection approach,” she says, the device holds promise in “improving diagnostic accuracy and making screening more accessible and scalable across diverse healthcare settings.”