Liposome-based chemical barcodes for single molecule DNA detection using imaging mass spectrometry.
We report on a mass-spectrometry (time-of-flight secondary ion mass spectrometry, TOF-SIMS) based method for multiplexed DNA detection utilizing a random array, where the lipid composition of small unilamellar liposomes act as chemical barcodes to identify unique DNA target sequences down to the single molecule level. In a sandwich format, suspended target-DNA to be detected mediates the binding of capture-DNA modified liposomes to surface-immobilized probe-DNA. With the lipid composition of each liposome encoding a unique target-DNA sequence, TOF-SIMS analysis was used to determine the chemical fingerprint of the bound liposomes. Using high-resolution TOF-SIMS imaging, providing sub-200 nm spatial resolution, single DNA targets could be detected and identified via the chemical fingerprint of individual liposomes. The results also demonstrate the capability of TOF-SIMS to provide multiplexed detection of DNA targets on substrate areas in the micrometer range. Together with a high multiplexing capacity, this makes the concept an interesting alternative to existing barcode concepts based on fluorescence, Raman, or graphical codes for small-scale bioanalysis.
Gunnarsson
Anders
A
Department of Applied Physics, Division of Biological Physics, Chalmers University of Technology, Göteborg, Sweden.
Sjövall
Peter
P
Höök
Fredrik
F
D000818:Animals; D004247:DNA / Q000737:chemistry*; D001330:Electronic Data Processing; D005453:Fluorescence; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D013058:Mass Spectrometry / Q000379:methods*; D053768:Metal Nanoparticles / Q000737:chemistry; D036103:Nanotechnology / Q000379:methods*; D020411:Oligonucleotide Array Sequence Analysis / Q000295:instrumentation* / Q000379:methods*
D008055:Lipids; D008081:Liposomes; D004247:DNA