A sample detection system including an anti-resonant waveguide, including a sample having a first index of refraction, a top layer and a substrate surrounding the sample, where the top layer has a second index of refraction, and the substrate has a third index of refraction. The second index of refraction, and the third index of refraction are both greater than the first index of refraction. A detection device of the system includes a low power light source used to direct light into the sample and generate an anti-resonant optical mode in the sample, and an analyzing system to detect the interaction of the light propagating in the sample.