Magnetic lab-on-a-drop

Nanomaterials

June 25, 2008

Surface-functionalized superparamagnetic particles emulsified in mineral oil turn a free-standing droplet into a flexible virtual laboratory with (sub)microliter volumes. By using magnetic forces, rare acute monocytic leukaemia cells are extracted from blood, preconcentrated, purified, lysed and subjected to a real-time PCR in minutes. The PCR works like a clockwork by rotating the droplet over different temperature zones. (© 2008 Wiley-VCH.)

Researchers from the Institute of Bioengineering and Nanotechnology in Singapore have developed a handheld diagnostic system that is able to perform sample preparation and analysis on the same chip [Pipper et al., Angew. Chem. Int. Ed. (2008).

The miniaturized instrument, which is built mainly from the components of a compact disc read-only memory (CD-ROM) drive, promises much faster polymerase chain reaction (PCR) times.

The ‘laboratory device’ devised by Juergen Pipper and colleagues is essentially an aqueous suspension of antibody-coated, superparamagnetic particles sealed in mineral oil. This single droplet can be moved, merged, mixed and split by an external magnetic field. The superparamagnetic particles also act as a solid support for biochemical processes, such as solid phase extraction.

To test the system, the researchers used a 25 μL blood sample containing 30 human leukemia cells expressing a green fluorescent protein (CD15-bound GFP-transfected THP-1). When placed on the chip, anti-CD15-coated superparamagnetic particles bound to the target cells, which could then be extracted within a smaller droplet.

This concentrated sample was purified twice in washing-solution and then added to reagents for PCR. The magnetic droplet was finally moved clockwise through four different temperature zones (eight seconds per thermocycle) whilst a fluorescence detector indicated the presence and quantity of the desired gene sequence.

The whole process took just 17 minutes from start to finish. In contrast, bench-scale PCR typically takes hours.

Biofouling is also unlikely with the lab-on-a-drop because the magnetic droplet only comes into contact with fresh solutions and uncontaminated surfaces, according to Pipper.

“The presence of an additional positive internal control is crucial to rule-out ‘false negatives’ within a PCR,” Pipper tells Materials Today. He then adds, “to address this issue, we are working on a small-footprint detector which is able to simultaneously monitor the fluorescence signal of two different fluorescent probes.”

Paula Gould