Highly Sensitive Metamaterials for Molecular Chirality Sensing
Physical Sciences : Materials and Compounds
Available for licensing
- Andrea Alu, Ph.D. , Electrical and Computer Engineering
- Yang Zhao , University of Texas at Austin
In the last 20 years the market for single-enantiomer drugs has substantially grown, and today over 50 percent of drugs currently in use are chiral compounds. Handedness of enantiomers is strongly related to their pharmacological effects, especially their potency and toxicity: single-enantiomer drugs are more effective than their racemic mixtures and, more importantly, while one chirality can form a powerful medication, the other one may cause serious side effects.
To date, molecular chirality is conventionally determined using circular dichroism (CD) measurements. Chiral molecules on their own typically possess extremely small CD, with only a small CD resonance with magnitude in the range of few tens of millidegrees, observable in the UV range. There are other important challenges in conventional CD measurements: they are inherently indefinite--i.e., they cannot directly detect the chiral handedness, they are time consuming (often taking up to 30 minutes), and they involve large amounts of analytes, typically requiring sub-milliliter volumes at a molecular concentration in the micromolar range.
These measurements need to be carried out during and after each synthetic step of a chiral drug, becoming particularly challenging at the beginning of a synthetic approach, when large amounts of analytes are hard to realize due to limited production efficiency. Therefore, being able to detect the absolute handedness of enantiomers with significantly less concentration in microsecond time scales would be groundbreaking for pharmaceutical applications.
A group in the Electrical and Computing Engineering Department at UT Austin, led by Dr. Andrea Alu, has invented a method to detect the chirality of molecules with unprecedented sensitivity, ultra-fast processing time, and absolute detection of molecular chirality. The new proposed method involves a pair of plasmonic twisted metamaterials with complementary chiral properties, which allow proper tuning of the local optical response of the metamaterials to enhance the electromagnetic chirality leading to enhanced sensitivity to molecular chirality.
By adsorbing a monolayer of chiral molecules on the surface of the metamaterial with opposite twist angles, and combining the total measured circular dichroism from the pair, significantly enhanced circular dichroism can be achieved, with a sign unequivocally indicating the chirality of the molecule. Experiments show that the chirality of as few as only 5 molecules per unit cell can be accurately and absolutely sensed. This method can also be extended to sense the concentration of a particular chiral molecule in an achiral mixture.
- Orders of magnitude higher sensitivity: only a few zeptomoles (10-21) of analytes needed, equivalent to about 5 molecule per unit cell
- Significantly faster measurement rate: reduced from 30 min to microseconds
- CD measurement can be shifted from UV to the visible range, eliminating the concerns of damaging the molecules
- Enhanced chiral assignment purely a near field effect, sensitive to only a monolayer of analytes adsorbed on the metamaterial surface, eliminating the interference from water absorbance
Pharmaceutical drug discovery and characterization; biomedical analysis of small quantity of specimens