Cryogenic Detectors: Detection of Single Molecules


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).



Benner WH, Horn DM, Jaklevic JM, et al. (1997) Simultaneous measurement of flight time and energy of large MALDI ions with a superconducting tunnel junction detector. Journal of the American Society for Mass Spectrometry 8: 1094–1102.

Burlingame AL, Boyd RK and Gaskell SJ (1998) Mass spectrometry. Analytical Chemistry 70: 647R–716R.

Frank M, Mears CA, Labov SE, et al. (1996) High‐efficiency detection of 66,000‐Da protein molecules using a cryogenic detector in a matrix‐assisted‐laser‐desorption‐ionization (MALDI) time‐of‐flight mass spectrometer. Rapid Communications in Mass Spectrometry 10: 1946–1950.

Gritti D (2002) Mass Spectrometry with Cryogenic Detectors. PhD Thesis, University of Neuchâtel.

Hilton GC, Martinis JM, Wollmann DA, et al. (1998) Impact energy measurement in time‐of‐flight mass spectrometry with cryogenic microcalorimeters. Nature 391: 672–675.

Siuzdak G (1994) The emergence of mass spectrometry in biochemical research. Proceedings of the National Academy of Sciences of the United States of America 91: 11290–11297.

Twerenbold D (1996a) Biopolymer mass spectrometer with cryogenic particle detectors. Nuclear Instruments and Methods A 370: 253–255.

Twerenbold D (1996b) Cryogenic particle detectors. Reports in Progress in Physics 59: 349–426.

Twerenbold D, Vuilleumier JL, Gerber D, et al. (1996) Detection of single macromolecules using a cryogenic particle detector coupled to a biopolymer mass spectrometer. Applied Physics Letters 68: 3503–3505.

Twerenbold D, Gerber D, Gritti D, et al. (2001) Single molecule detector for mass spectrometry with mass independent detection efficiency. Proteomics 1: 66–69.

Westmacott G, Ens W and Standing KG (1996) Secondary ion and electron yield measurements for surfaces bombarded with large molecular ions. Nuclear Instruments and Methods B 108: 282–289.

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

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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. [doi: 10.1002/9780470015902.a0006203]