Direct genetic analysis of ten cancer cells: tuning sensor structure and molecular probe design for efficient mRNA capture.

In order to facilitate the use of biomolecular markers in clinical medicine, devices are urgently needed that are highly sensitive, specific, cost effective, and automated. Great strides have been made in this area with elegant sensing systems employing nanomaterials, microfluidics, and increasingly sophisticated device design. The direct analysis of most types of clinical samples requires femtomolar detection limits to sense scarce analytes with an acceptably low level of false negatives. Very high levels of specificity are required to ensure low levels of false positives. From a practical perspective, equally important is a streamlined approach to sample workup, since the need for extensive sample processing can diminish the benefits of a sensor s innately high sensitivity and specificity. In the development of a sensing approach, several components can be tuned at the molecular and chemical level to optimize the performance of the system and refine requirements for sample processing. These components include the actual sensors used for detection, the probe molecules that specifically bind a given target, and the approach to sample workup (chemical, enzymatic, mechanical, fluidic, etc). We recently reported a new approach to biomolecular detection utilizing a microchip-based platform for ultrasensitive nucleic acids detection. Nanostructured microsensors deposited on the surface of the chip served as specific detectors of oligonucleotides, mRNAs, and microRNAs when used in conjunction with an electrochemical reporter system (Figure 1). Attomolar sensitivity was obtained with small oligonucleotides and microRNAs.