A five-pound, hand-held medical diagnostic device being developed at the US National Nuclear Security Administration’s Sandia National Laboratories promises let doctors know in minutes if their patient is prone to heart disease, gum disease, or cancer.
“We have taken technology that we’ve worked on for several years – Sandia’s lab-on-a-chip devices – and are adapting them for use in medical diagnostics,” says Anup Singh, project leader. “We’ve tested saliva samples from healthy patients for gum disease, and within the next few months we will begin using the diagnostic tool to test diseased samples.”
Lab-on-a-chip technologies were developed in the mid-1990s for detecting biotoxins and chemical agents. In new incarnations they are used in the analysis of bodily fluids, such as saliva and blood, for detecting certain diseases. Expanding on established microchip-based separation technologies, the research team adapted a method known as immunoassay to a chip. The combination of the lab-on-a-chip and the immunoassay technique allows for fast and sensitive analysis of biomarkers specific to certain diseases.
As part of the immunoassay process, antibodies specific for biomarkers of interest, such as gum or heart disease, are tagged with a fluorescent dye and then mixed with a patient’s saliva or blood. Biomarkers present in the sample attach themselves to the fluorescent antibody. The mixture is injected into a microchip using a syringe. An applied electric field forces the sample to flow through a microchannel that is two to five centimetres long, tens of microns deep, and a few hundred microns wide.
As the sample moves through the channel, cast-in-place porous polymers in the microchannel sort molecules based on their sizes and electrical charges. If biomarkers for the disease are present in the patient’s sample, the lab-on-a-chip analysis will separate fluorescent antibodies bound to the biomarker from unbound antibodies.
A photomultiplier tube then detects the fluorescence emission with extreme sensitivity. After quantifying the relative fluorescence of the two species – bound and unbound antibodies – researchers can determine the amount of biomarker present in the patient’s sample. If the sample contains significant fluorescence emission from a bound antibody, indicating that biomarkers are present above a certain level, a doctor could conclude that the patient has or will eventually get the disease for which he or she is being tested. At the conclusion of the test, while the patient is still in the doctor’s office, preventive or therapeutic care could begin.
The entire device, including the channelled glass chips, photomultiplier, and electronics, will fit into a hand-held package that weighs less than five pounds.
“The beauty of this device is that it has everything required to make it useful – sensitivity, portability, and the ability to run tests quickly,” Singh says. “It is small and can be carried with ease almost everywhere. It’s also very sensitive and works fast. Within a few minutes you can tell if you have a diseased sample.”
In addition to biomarkers for gum disease, Sandia researchers are also developing assays for cardiovascular disease markers such as C-Reactive protein. Singh says that although the primary goal is to analyse saliva, “we have shown that our device can work with blood as well.” Having the ability to analyse multiple bodily fluids makes the device useful for a wide variety of clinical applications.
Having already studied saliva samples from healthy people, the Sandia researchers will begin studying samples from 50 to 100 diseased patients in January.
“Working with samples from actual patients will give us the opportunity to see how accurate our immunoassay method works,” Singh says.