Sensitive and multiplexed detection of disease specific protein markers is important for clinical diagnosis. ELISA remains the gold standard for protein detection however the need for multiplexing, higher sensitivity, low sample requirement and capability of point of care testing (POC) is driving the innovations for new biosensing platforms. Changes are coming fast and furious at every level including: a) novel capture agents that include Bio-Mimetic/Antibody-Mimetic Recognition Elements; b) novel surfaces and immobilization methods for oriented and functional immobilization of capture proteins while minimizing non-specific binding; c) new signal transducers like quantum dots, brighter fluorescent dyes, multicolored photonic crystals and up-converting nanoparticles and barcoded nano/micro particles; d) signal amplification methods like rolling circle amplifications and tyramide based amplification; e) new multiplexed sensor platforms like protein arrays, bead arrays and microfluidics and f) label free biosensors based on gold nanoparticles, nanowires, microcantilevers.
To this list can now be added a new biosensor; Magnetic Nanotag Biosensors developed by Shan X Wang group at Stanford. The sensor is a typical sandwich based immunoassay with two critical differences: a) capture antibody is immobilized on a microarray of Giant magnetoresistive (GMR) sensors and b) secondary antibody is labeled with biotin that binds streptavidin tagged with super paramagnetic nanoparticles. Magnetic field induced by paramagnetic nanoparticle is detected by GMR sensors. Concentration as low as 50 attomolar (10-18 M) can be detected using this biosensor and for multiplexing 10 analytes were detected in parallel in quadruplicates (40 reactions). The biosensor is also “Matrix-insensitive” means analyte can be detected with equal sensitivity either from buffer or from complex biological samples like serum.
Though novel and impressive research, I had problem understanding the claim of “Matrix-insensitive protein assay”. Since multiple washings are involved the matrices is long gone before the sensor ever sees paramagnetic nanoparticle for detection. A homogenous assay that is matrix-insensitive makes more sense. Moreover, the problem of auto-fluorescence from biological matrices has been mostly solved by the use of long wavelength fluorescent dyes. Other statement that bothered me is the broad claim that biosensor is 1000 times more sensitive than ELISA. In reality the biosensor performed 1000 fold better for one analyte against one commercially available ELISA kit. It is foreseeable that the commercial ELISA kit used for comparison was the worst kit in the market. Ideally the authors should have created their own ELISA assays (very easy) using the same set of primary and secondary antibodies as used in their biosensor.
Still, a cool technology that avoids the use of any complex optical design and may be ideal for POC devices.