2017 Young Chemist Award Winner


Congratulations to our $10,000 winner: Aldin Malkoc, Arizona State University

Metrohm USA is pleased to announce the winner of the 2017 Young Chemist Award, Aldin Malkoc. Aldin is completing his graduate work at Arizona State University where he works under the supervision of Professors Michael Caplan, Chair of the Biomedical Engineering Department, and Jeffrey LaBelle, Assistant Professor.

 

Abstract:

Cooperative DNA-based Molecular Recognition Elements for Electrochemical Biosensors

There is a monumental need for a transformative technology to enhance biosensor diagnostics. However, when attempting to enhance biosensor diagnosis the confounding factor leading to 9% – 57% increase in false positives and false negatives is attempting to address simultaneously issues with specificity and sensitivity. False positives and negatives occurring in current state-of-the-art (SOTA) biosensor detection methods can have negative medical consequences. Development of thermodynamic models employing next generation molecular recognition elements (MREs) would revolutionize disease detection by addressing key issues with current methods, such as specificity and sensitivity. Thermodynamic models creating next generation MREs quickens and replaces the slow pan-and-sift approaches for harvesting antibodies from animal, displaying phages in bacteria, and identifying apatmers through SELEX can replace or better SOTA techniques. Analytical models that are based on thermodynamic laws will help facilitate the development and improvement of next generation biosensors. These models can be applied to validate and verify the design and efficacy of biosensors and ultimately help understand abstract ideas.
The development of a biosensor combined with the high specificity and high sensitivity of cooperative probes, called Tentacle Probe using Electrochemical Impedance Spectroscopy (EIS) would allow for hundreds of various sensor applications. This is predominantly due to low cost in addition to making it applicable for use in developing countries, homes, underrepresented clinics where cost would become less of an issue and treatment could begin immediately.
The label-free technique EIS applies a steady-state alternating current by executing a small sinusoidal voltage at a range of frequencies to measures the electrical impedance or voltage:current ratio. Label-free detection reduces the need for various reagents allowing for rapid and robust detection of numerous molecular recognition elements (MREs). Due to the high sensitivity capabilities of EIS most MREs will have a single optimal frequency that can generate concentration calibration curves. While EIS is a sensitive technique it lags in MRE specificity due to monovalent binding. Tentacle probes offer a solution due to divalent binding to increase specificity without a decrease in sensitivity. ‘Tentacle Probes’ two binding components offers a linear DNA capture region and a Molecular Beacon (MB) detection region. For binding to occur on both the linear and MB region the analyte must first bind to the capture region and in order to bind to the MB region the affinity is tuned to be stronger then the local concentration of the analyte already bound to the detection region so initial binding facilities the opening of the MB region producing a divalent binding event.
Previous work with EIS and TPs resulted in a publication in the Journal of Biosensor and Bioelectronics. With this work integration of the two techniques and produce an enhanced specificity and sensitivity biosensor. TP combined with EIS detected, with statistical significance of p<3.0*10-13, the difference between B Anthracis gyrA gene and B. Cereus gyrA Single Nucleotide Polymorphism sequence at a lower limit of detection of 20 nM. However, the next step would be to further enhance the optimization of the technique and develop thermodynamic models to develop TPs and potentially integrate as single or multimarker detection.
This type of research would do two important things. The first is that it would support discovery and lead to an essential new technology by developing a rapid, point-of-care low-cost and highly specific and sensitive method of genetic mutation detection. Second, it could revolutionize the existing field by developing a new gold standard for molecular recognition. The understanding that TPs will advance a radically different approach to detection of genes in both the scientific and medical disciplines will lead to a new paradigms or science fields.