The Quest for Monitoring our Environment: Portable Arrayed Biosensors
Prof. Levi A. Gheber
Department of Biotechnology Engineering, The Ilse Katz Institute for Meso and Nanoscale Science and Technology, BGU
Monitoring our environment for biological threats is a growing need, largely unmet. Currently, biosensing platforms suffer from a myriad of shortcomings, regarding various basic requirements, which ultimately lead to the same end-result: the need for trained, expensive human intervention and the transport of the technologies to large facilities.
One of the chief shortcomings of present technologies is the size of sensing elements. The smallest ones are produced by microarray technology: 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, a drastic reduction in sizes is required. While nano-biolithography techniques have the ability to fabricate structures of biomolecules as small as ~ 40 nm, the loss in Signal to Noise Ratio (SNR) accompanying miniaturization leads to very few examples of working biosensors of these sizes.
Autonomy of biosensing platforms requires vast integration of subsystems, like sample collection, purification, amplification, liquid handling, read-out, analysis and remote transmission of results. Such integration does not exist presently.
The vast majority of biosensing systems use some form of labeling, for the detection of the bound target. Labeling is opposed to the concept of continuous monitoring of target levels in a sample. For this purpose label-free detection methods are being developed, so far with relatively poor sensitivity and specificity.
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 other optical methods, and integrating on-chip polymer microlenses-as part of the read-out system[9] and microfluidics for liquid sampling.
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.
10. 10. Kantarovich K., et al., Plasmonics, 2013. 8: p. 3-12
