Cryogenic Detectors: Detection of Single Molecules

Abstract

To extend the technique of mass spectrometry for analyzing large protein complexes, more sensitive detectors are required. Cryogenic detectors operate by measuring the energy deposition of a single molecule. Their detection sensitivity is independent of mass, and both the arrival time and energy of an individual molecule are measured in a MALDI‐TOF mass spectrometer.

Keywords: MALDI‐TOF; mass spectrometry; detector; protein complexes; sensitivity; cryodetector

Figure 1.

Principle of operation of a superconducting tunnel junction cryodetector. The absorption of the molecule energy on impact induces internal energy excitations (quasiparticles) in the absorber, which diffuse quickly to the quasiparticle sensing device.

Figure 2.

Time‐of‐flight histogram of an IgG sample (mass= 135 kDa), accelerated to a voltage of 12 kV, obtained with a tantalum/Al‐ox/niobium STJ cryodetector. 2M+ denotes the IgG molecule with a single positive charge and M++ the IgG molecule with two positive charges. 2M+ represents the singly charged IgG dimer.

Figure 3.

Comparison of the intrinsic detection sensitivity of classical ionizing detectors with a cryodetector, as a function of molecule velocity. The ionizing detector efficiency decreases exponentially with decreasing velocity (increasing mass). For more details on this figure, see Twerenbold et al..

Figure 4.

The effect of using pulse height selection of cryodetector signals in the case of a 40‐mer deoxyribonucleic acid (DNA) oligonucleotide sample. Both time‐of‐flight histograms are from the same data set (insert showing the pulse height to time‐of‐flight scatter plot).

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References

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Further Reading

Cotter RJ (ed.) (1994) Time‐of‐Flight Mass Spectrometry. ACS Symposium Series 549. Washington DC: American Chemical Society.

Frank M, Labov SE, Westmacott G and Benner WH (1999) Energy‐sensitive cryogenic detectors for high‐mass biomolecule mass spectrometry. Mass Spectrometry Reviews 18: 155–186.

Larsen BS and McEwen CN (eds.) (1998) Mass Spectrometry of Biological Materials. New York, NY: Marcel Dekker.

Senko MW and McLafferty FW (1994) Mass spectrometry of macromolecules: has its time now come? Annual Review of Biophysics and Biomolecular Structure 23: 763–785.

Watson JT (1997) Introduction to Mass Spectrometry. Philadelphia, PA: Lippincott‐Raven Publishers.

Wilkins MR, Williams KL, Appel RD and Hochstrasser D (eds.) (1997) Proteome Research: New Frontiers in Functional Genomics. Berlin: Springer‐Verlag.

Web Links

GenSpec SA. Company website with information about a cryodetector for a biomolecule mass spectrometer http://www.genspec.ch

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How to Cite close
Twerenbold, Damian(Sep 2006) Cryogenic Detectors: Detection of Single Molecules. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0006203]