Light-sheet fluorescence microscopy (LSFM) can quickly generate stunning 3-D images of intact organs and tiny organisms like zebrafish and mouse brains. However, the samples must typically be immobilized in a stiff gel to obtain those images. This requirement limits the technique’s use in some studies of biological dynamics and aspects of drug discovery.
A team of researchers has now developed a method to combine light-sheet fluorescence microscopy with a different technique for holding the specimen in place: a contact-free ultrasound trap. The researchers also demonstrated the approach’s utility by measuring the effect of specific drugs on the heartbeat of zebrafish larvae suspended in the trap using the LSFM-ultrasound combination.
Light-sheet fluorescence microscopy shapes an excitation laser into a thin sheet, then excites fluorescence only in a micrometer-thick sample slice. The fluorescence signal from that thin slice of sample is then collected in a microscope objective and routed to a CCD or other image sensor. It is possible to build up a high-resolution, 3-D image of the specimen by taking multiple sections from different angles and orientations. LSFM has relatively low photobleaching and photodamage of delicate biological specimens, in addition to its speed and resolution. It is a novel approach to drug-based research in cardiovascular disease and developmental biology.