Scientists studying marine bacteria have discovered an easy way of segregating right- and left-handed microbes - a discovery that could lead to a new way of isolating chirals. Susan Birks reports
Many biochemically active molecules are naturally chiral, which means they can bind only to target chiral molecules of a specific "handedness". The other enantiomer (i.e. the molecule having opposite handedness), if used in pharmaceuticals, for example, may be inactive or cause undesirable effects, as happened in the case of the drug thalidomide.
Chemical synthesis of chiral molecules usually produces a racemic mixture, with equal amounts of both enantiomers. Their separation based on chirality is of importance to the pharmaceutical industry as it must ensure that the wrong enantiomer is never present.
Currently favoured approaches for separation rely on gas, liquid or capillary electro-migration chromatography1, requiring costly chiral media. Thus, simpler alternative approaches to chiral separation are desirable. Now scientists at MIT and Brown University believe they might have found that alternative solution.
The scientists in question were studying how marine bacteria move in water, and they discovered that a sharp variation in water current segregates "right-handed" bacteria from their "left-handed" brethren, impelling the microbes in opposite directions.
While single-celled bacteria do not have hands, their helical-shaped flagella, with which they propel themselves through water, spiral either clockwise or counter-clockwise. This makes these opposite-turning flagella similar to human hands in that they are mirror images of one another and cannot be superimposed - ie they exhibit chirality.
quick segregation
The scientists believe this finding opens up the possibility of quickly and cheaply implementing the segregation of "two-handed" objects in the laboratory, and that this could have a big impact on the pharmaceutical sector, where the separation of chiral molecules can be crucial to a drug;s safety.
"This discovery is important for several industries that rely upon the ability to separate two-handed molecules," said Roman Stocker*, the Doherty assistant professor of Ocean Utilisation in the MIT Department of Civil and Environmental Engineering, and a principal investigator in the research.
Stocker and MIT mechanical engineering graduate student Marcos**, along with co-authors Henry Fu *** and associate professor Thomas Powers*** of Brown University, published their findings in the April 17 issue of Physical Review Letters.
In the paper, the researchers describe how they designed a microfluidic environment - a device about the size of an iPod nano that has channels containing water and bacteria - to create a "shear" flow of adjacent layers of water moving at different speeds. In their tests, Stocker and Marcos used a non-motile mutant of the bacterium Leptospira biflexa, whose entire body has the shape of a right-handed helix. They injected the Leptospira organisms into the centre of the microfluidic device and demonstrated that they drift off-course in a direction dictated by their chirality.
But the researchers did much more than observe the microbes under a microscope. In addition to the experimental data they gathered with their Brown colleagues, the MIT researchers also developed a rigorous mathematical model of the process. They are currently implementing this new approach to separate objects at molecular scales.
past attempts
According to the researchers, several previous proposals for chiral separation have looked to exploit hydrodynamic forces. Some of these are, as yet, untested experimentally and rely on the presence of a surface2 or array of micro-vortices,3 and there has been successful chiral separation of centimetre-sized crystals in a rotating drum.4
Other methods5,6 stem from the prediction that a chiral particle in a simple shear flow experiences a lateral drift.7 However, according to the MIT and Brown University researchers, the feasibility of this approach has remained questionable, as measurements in Couette cells reported that the drift of millimetre-sized chiral objects8 and the forces on centimetre-sized ones9 differ from predictions by two orders of magnitude8 or even in sign.9
The team say they have found that micro-scale chiral objects, three orders of magnitude smaller than previous studies,8,9 experience a lateral drift in a microfluidic shear flow and that the magnitude of the drift is in agreement with their theory.
Their method uses micro-channels to sort particles by chirality, and they claim to have shown that an enantiomer drifts with direction determined by the local shear and demonstrated the feasibility of this method for chiral separation. They claim that the high shear rates achievable in micro-channels
(>10-6 s-1)10 allow the method to be extended to smaller scales (<40 nm).
"The methods currently used to separate chiral molecules are far more expensive and far slower than the microfluidic option. While we still have some way to go to separate actual chiral molecules, we think our work is very promising for the pharmaceutical, agriculture and food industries," said Marcos.
This work was partially supported by grants from the National Science Foundation.