Nanosensors for diagnosis with optical, electric and mechanical transducers

Abstract

Nanosensors with high sensitivity utilize electrical, optical, and acoustic properties to improve the detection limits of analytes. The unique and exceptional properties of nanomaterials (large surface area to volume ratio, composition, charge, reactive sites, physical structure and potential) are exploited for sensing purposes. High-sensitivity in analyte recognition is achieved by preprocessing of samples, signal amplification and by applying different transduction approaches. In this review, types of signals produced and amplified by nanosensors (based on transducers) are presented, to sense exceptionally small concentrations of analytes present in a sample. The use of such nanosensors, sensitivity and selectivity can offer different advantages in biomedical applications like earlier detection of disease, toxins or biological threats and create significant improvements in clinical as well as environmental and industrial outcomes. The emerging discipline of nanotechnology at the boundary of life sciences and chemistry offers a wide range of prospects within a number of fields like fabrication and characterization of nanomaterials, supramolecular chemistry, targeted drug supply and early detection of disease related biomarkers.

Fig. 1. Different shapes of nanomaterials according to their dimensions and their applications.

Fig. 2. Schematic illustration of the sensing process. Sensors main elements are recognition element and a transduction element. The sensor receives input from the sample, which is converted into a signal. If the recognition element is a nanomaterial (at least one dimension is between 1–100 nm) we obtain a nanosensor.

Fig. 3. Real-time protein detection by using silicon nanowires (SiNW). (a) Graphic representation of protein attachment (right) to the biotin-functionalized SiNW (left). (b and c) Conductance plotted against time while the buffer solution contains silicon nanowire (region 1) (b) 250 nM to 25 pM of streptavidin protein attracted towards the silicon nanowire (region 2) and as a final point the silicon nanowire releases in buffer solution (region 3). The arrows point toward the changing in solution. (This figure has been reproduced from ref. 48, with permission from AAAS Publishing Group.)

Fig. 4. Whole blood analysis for cancer biomarker detection. The device empowers the purification and cancer antigens capture, successive release and transference of the concentrated marker of interest towards the sensing device. Antigens are restrained in the bigger chamber of the microfluidic device. (a) Primary antibodies to multiple biomarkers, are bound with a photocleavable crosslinker. The chip is placed in a plastic housing and a valve (pink) directs fluid flow exiting the chip to either a waste receptacle or the nanosensor chip. (b) The blood sample is introduced in microfluidic device, specific antigens are apprehended by their antibodies. Then washing steps were performed. Antibodies are functionalized by a light sensitive molecule, (c) UV light irradiation used to release these molecules. (d) Conjugates of antigen and antibody are transported towards nanosensors, and an electronic system is used to record the signal. (This figure has been reproduced from ref. 51, with permission from Nature Publishing Group.)

Fig. 5. Chemical “nose” sensor. Graphic representation of gold NPs interaction with fluorescent polymer. When the fluorescent polymer intermingles with gold nanoparticles the fluorescence is quenched. When a targeted protein attacks and displaces the polymer, fluorescence is restored. Reprinted with permission from ref. 71, ACS Publishing Group.

Fig. 6. Ag film on nanoparticles sensor: first nanoparticles are coated with silver (blue), then with 1-decanethiol 80 acting as an effective partition layer. The process continues with incubation in (6-mercaptohexane 1-ol) which improves biocompatibility, then the analyte is captured on the surface. Atomic force microscopy is used to show sensor morphology. Reprinted with permission from ref. 80, ACS Publishing Group.

Fig. 7. Suspended micro-array resonator. (a) Graphical depiction of suspended microchannel. These channels provide a continuous flow of fluid. Under high vacuum accumulation of mass on cantilever can be detected down to subfemto gram. These mechanical nanosensors solve the issue of detection in fluid. (b) Sandwich assay, targeted molecule accumulate in microchannel resulted in increase of mass (right) while non-targeted molecules continue their flow without any disturbance (left) due to increase in mass frequency shifts. Adapted with permission from ref. 90, Nature Publishing Group.