The present microarray technology produces active spots with a diameter of ~100 µm and separation of 300 – 400 µm. These sizes are the main reason for the fact that microarray handling requires heavy machines within well equipped laboratories with well trained personnel. To harness the potential of parallel, multiplexed assays and produce portable, deployable, multiplexed sensors, for the monitoring of the environment, a drastic reduction in sizes is required. While nano-biolithography techniques have the ability to fabricate structures of biomolecules as small as ~ 40 nm, very few examples of working biosensors of these sizes have been demonstrated.

We are developing nano-biolithography techniques to produce spots of sub-µm diameters[1-3], while maintaining a high SNR[4], aided with mathematical modeling. We are also tackling additional factors impeding portability of arrayed biosensors, by using polymeric detection elements (molecularly imprinted polymers – MIPs) for stability and regenerative properties[5], detecting binding of analytes using label-free surface-enhanced Raman spectroscopy (SERS)[6-8], and integrating on-chip polymer microlenses-as part of the read-out system[9].

We present results from each of these, discuss the complex inter-dependencies between the various factors, and ways to overcome some difficulties.

References

1.             1. Taha, H., et al., Applied Physics Letters, 2003. 83(5): p. 1041-1043.

2.             2. Ionescu, R.E., R.S. Marks, and L.A. Gheber, Nano Letters, 2003. 3(12): p. 1639-1642.

3.             3. Ionescu, R.E., R.S. Marks, and L.A. Gheber, Nano Letters, 2005. 5(5): p. 821-827.

4.             4. Tsarfati-BarAd, I., et al., Biosensors and Bioelectronics, 2011. 26(9): p. 3774-3781.

5.             5. Belmont, A.-S., et al., Applied Physics Letters, 2007. 90(193101): p. 1-3.

6.             6. Kantarovich, K., et al., Analytical Chemistry, 2009. 81: p. 5686-5690.

7.             7. Kantarovich, K., et al., Applied Physics Letters, 2009. 94(194103): p. 1-3.

8.             8. Kantarovich, K., et al.,. Biosensors and Bioelectronics, 2010. 26: p. 809-814.

9.             9. Sokuler, M. and L.A. Gheber, Nano Letters, 2006. 6(4): p. 848-853.

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