Lab-on-a-Chip Demonstrates Potential to Detect Isolated Cancer Cells

A lab-on-a-chip that combines nanotechnology with microfluidics and surface plasmonic resonance spectroscopy has the potential of detecting isolated cancer cells before they can begin to form tumors.

Investigators at the Institute of Photonic Sciences (Castelldefels, Spain) created a chip coated with minute channels lined with antibody-labeled gold nanoparticles. A drop of blood applied to the chip circulates through the microchannels and specific cancer markers in the serum bind to the antibody-labeled nanoparticles. Binding of cancer biomarker proteins trigger changes in the reflectivity of the gold nanoparticles that is detected by plasmonic resonance spectroscopy.

Plasmonic resonance is a phenomenon that occurs when light is reflected off thin metal films, which may be used to measure interaction of biomolecules on the surface. An electron charge density wave arises at the surface of the film when light is reflected at the film under specific conditions. A fraction of the light energy incident at a defined angle can interact with the delocalized electrons in the metal film (plasmon) thus reducing the reflected light intensity. The angle of incidence at which this occurs is influenced by the refractive index close to the backside of the metal film, to which target molecules are immobilized. If ligands in a mobile phase running along a flow cell bind to the surface molecules, the local refractive index changes in proportion to the mass being immobilized. This can be monitored in real time by detecting changes in the intensity of the reflected light.

The investigators tested a prototype chip that was able to carry out parallel, real-time inspection of 32 sensing sites distributed across eight independent microfluidic channels with very high reproducibility/repeatability. The chip was able to rapidly detect relevant cancer biomarkers (human alpha-feto-protein and prostate specific antigen) down to concentrations of 500 picograms per milliliter in a complex matrix consisting of 50% human serum.

Senior author Dr. Romain Quidant, leader of the nanophotonics group at the Institute of Photonic Sciences, said, "The most fascinating finding is that we are capable of detecting extremely low concentrations of these proteins in a matter of minutes, making this device an ultra-high sensitivity, state-of-the-art, powerful instrument that will benefit early detection and treatment monitoring of cancer."

A detailed description of the device was published in the April 14, 2014, online edition of the journal Nano Letters.

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