Biomarker Detection of Whole Blood

Blood is filtered and transferred to nanosensors on a chip, which can detect and measure cancer biomarkers. Credit: Mark Reed/Yale University

A team led by Yale University researchers has used nanosensors to measure cancer biomarkers in whole blood for the first time. They used nanowire sensors to detect and measure concentrations of two specific biomarkers: one for prostate cancer and the other for breast cancer.

To overcome the challenge of whole blood detection, the researchers developed a novel device that acts as a filter, catching the biomarkers—in this case, antigens specific to prostate and breast cancer—on a chip while washing away the rest of the blood. Creating a buildup of the antigens on the chip allows for detection down to extremely small concentrations, on the order of picograms per milliliter, with 10 percent accuracy. This is the equivalent of being able to detect the concentration of a single grain of salt dissolved in a large swimming pool.

Until now, detection methods have only been able to determine whether or not a certain biomarker is present in the blood at sufficiently high concentrations for the detection equipment to give reliable estimates of its presence. “This new method is much more precise in reading out concentrations, and is much less dependent on the individual operator’s interpretation,” Fahmy said.

The new device could also be used to test for a wide range of biomarkers at the same time, from ovarian cancer to cardiovascular disease, Reed said. “The advantage of this technology is that it takes the same effort to make a million devices as it does to make just one. We’ve brought the power of modern microelectronics to cancer detection.”

Nature Nanotechnology: Label-free biomarker detection from whole blood

Label-free nanosensors can detect disease markers to provide point-of-care diagnosis that is low-cost, rapid, specific and sensitive. However, detecting these biomarkers in physiological fluid samples is difficult because of problems such as biofouling and non-specific binding, and the resulting need to use purified buffers greatly reduces the clinical relevance of these sensors. Here, we overcome this limitation by using distinct components within the sensor to perform purification and detection. A microfluidic purification chip simultaneously captures multiple biomarkers from blood samples and releases them, after washing, into purified buffer for sensing by a silicon nanoribbon detector. This two-stage approach isolates the detector from the complex environment of whole blood, and reduces its minimum required sensitivity by effectively pre-concentrating the biomarkers. We show specific and quantitative detection of two model cancer antigens from a 10 µl sample of whole blood in less than 20 min. This study marks the first use of label-free nanosensors with physiological solutions, positioning this technology for rapid translation to clinical settings.

19 page pdf of supplemental information

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