Direct analysis of neutrals using superconducting detector in tandem - PDF document

Direct analysis of neutrals using superconducting detector in tandem mass spectrometry � TOD: Novel Developments in Mass Spectrometry Instrumentation: Analyzers, Detectors, Tandem Instruments ! City hall, May 31, 2009 � ASMS2009, Philadelphia ! Neutral loss in MS � • � MS analyzes ions only. � • � Ion reactions in MS/MS produce metastable molecules and then ionic and neutral fragments. � [R. Cooks, ASMS2008 tutorial lecture, Metastable Ions: Past and Future in Mass Spectrometry] ! ABA + *( < life time ) � ABA *( < life time ) � � AB + + A � � AB + A � � ABA + + N � ABA * + N + � ABA + � ABA + * � AB + A + � � A + B + A � � A + + B + A AA + B � � � � ... CAD ! ETD ! � • � ETD requires multiply-charged precursor ions so that at least one of the fragments has a charge. � • � Neutral products are lost, which is called “ neutral loss .” �

Re-ionization MS (indirect MS for neutral fragments) � • � Neutralization re-ionization mass spectroscopy (NRMS) � • � Charge inversion mass spectroscopy (CIMS) � in 1980 � s. � • � Additional fragmentation during the re-ionization process may take place. � • � Efficiency of electron multiplier detectors depends on charge states; quantitative analysis of reaction branches may be difficult. ! Ref. e.g. C. Wesdemiotis, F. McLafferty, Chem. Rev . 87 , 485 (1987). S. Hayakawa, J. Mass Spectrom . 39 , 111 (2004). ! A method of direct analysis for neutral fragments � Kinetic energy sensitive � + � Si surface barrier detector � E � (100% detection efficiency, � + � � E = 20 keV) � � A l u � A Heavy ion synchrotron storage ring � S i � E 1 � + � (MeV, d > 10 m ) � E 2 � E 3 � e – or ions � r a l � n e u t l y O n ~ cm � V ) � M e t s ( d u c p r o E = E 1 + E 2 + E 3 � Dissociative recombination (DR) or (with eV KER) � Merged-beams experiments � Ref. e.g.: R. Thomas, Mass Spectrom. Rev ., 27 , 485 (2008). A. Florescu-Mitchella, J. Mitchella, Phys. Rep . 430 , 277 (2006). N. Adams, V. Poterya, and L. Babcock, Mass Spectrom. Rev . 25 , 798 (2006). R. Phaneuf et al ., Rep. Prog. Phys . 62, 1143 (1999). !

C 4 H + DR experiment at ASTRID(Denmark) � a. C 4 H + + e � � C 4 H Au � Al � C 4 � b. � � C 3 + C Si � c. � � C 2 + C 2 d. � C 2 + C + C ! ~ cm � T � C 2 � C � C 3 � Ref. G. Angelova et al. , Int. J. Mass Spectrom . 232, 195 (2004). K. Berkner et al., Proc. 7 th Int. Conf. on Phys. of Electronic and Atomic Collisions, 422 (1971). ! Heavy-ion storage ring facilities � FLAIR hall, GSI ! CRYRING (Stockholm), H. Danared et al ., Proceedings of EPAC2006,Edinburgh !

Our method, kinetic energy ( KE ) spectroscopy for neutrals in keV � Kinetic energy � MS-II: E = E 1 + E 2 + E 3 � sensitive � cryodetector � (with eV KER) � (KEMS) � Cryostat � ( � E = 200 eV) � (0.3 K) � Single molecule hit for each pixel � E 2 � E 3 � + � E 1 � E 3 � Electrostatic sector � Ion deflector � + � + � ! E 3 � Collision chamber � + � + � (CAD, ETD) � E � Xe � ion source � (3 keV, EI) � MS-I Magnetic sector � 3 m � A cryodetector for neutrals as well as ions � ! ! ! ! 1 ! ! ! -./$/$0 ! 300 nm � Nb ! 1 nm AlO x � Al � Al � "#$$%&'$()*#++%$,) ! fabricated at AIST ! Nb ! Si substrate ! • � operates in a keV range. Ref. � M. Frank et al , Mass Spectrom. Rev . 18 , 155 (1999). � • � 100% detection efficiency D. Koppenaal et al ., Anal. Chem . 419A (2005). � for both neutrals and ions M. Ohkubo, Physica C 468 , 1987 (2008). � S. Shiki et al ., J. Mass Spectrom . 43 , 1686 (2008). � • � 100 times better KE resolution ! S. Tomita et al ., Appl. Phys. Lett. 91 , 053507 (2007). � K. Suzuki et al ., Appl. Phys. Exp. 1 , 031702 (2008). � A. Casaburi et al ., Appl. Phys. Lett. 94 , 212502 (2009). �

Instruments for direct neutral analysis � Circumference = 52 m ! CRYRING, Stockholm ! http://www.msi.se/MSL_files/Cryring.html ! 3 m � Observed physical phenomena are different, but the compact lab-based MS/MS instrument is unique; ions and neutrals without re-ionization. � (The cryodetector is also useful for electrostatic storage rings at ~20 keV.) � MS/KEMS instrument, AIST, Tsukuba ! Artificial peak � (3 keV CH 3 CO + ) without Xe target gas � SiO 2 (700 nm) � 100 µm � 32% m / � m = 14 �

Two modifications to eliminate the artificial peak � 1. � bigger size to reduce � 2. insertion of a phonon the flame ratio � converter layer into the SiO 2 film � 200 µm � M. Ohkubo et al ., J Low Temp Phys 151 , 760 (2008). ! Improved response � 3 keV CH 3 CO + without Xe target �

MS/KEMS experiment � • � 3 keV singly-charge precursor ions: acetyl and acetone � – � (non QET molecules, dissociation from electronically excited state) � • � Target gas: Xe 10 -5 Pa ( < 20 % reduction of precursor flux ) � – � A high charge-exchange neutralization; CAD + ETD � • � Precursor ions, neutralized precursor, ionic fragments, neutral fragments were separated by the ion deflector and kinetic energies. � E 1 � E E 2 � E 3 � CH 3 CO E = E 1 + E 2 + E 3 ! (CH 3 ) 2 CO � CO CH 3 Reaction of acetyl (CH 3 CO) � Raw data � Precursor � subtracted � Molecule yield [counts /s] ! E 2 ! E 1 ! E ! • � Life time of metastable CH 3 CO(A) = a few µs � E = E 1 + E 2 ! • � Neutral CO, CH 3 + : CH 3 = 7 : 3 � • � CH 3 + (CAD), neutral CH 3 (ETD) � E 1 � E � E 2 � • � CH 3 CO + (A) � CH 3 + + CO(CAD) � 70% � CH 3 CO � CO + CH 3 ! • � CH 3 CO • (A) � CH 3 • + CO(ETD) � 30% �

Reaction of acetone (CH 3 COCH 3 ) � Raw data � Precursor � subtracted � E = E 1 + E 2 + E 3 ! • � Life time of metastable CH 3 CO(A) = ~ 100 � s E 1 � E • � neutral CH 3 and CO, CH 3 CO + : CH 3 CO : CO = 7 : 1 : 2 ! E 2 � • � (CH 3 ) 2 CO + • (A) � CH 3 CO + + CH 3 • (CAD) � 70% � E 3 � CH 3 CO • � (CH 3 ) 2 CO (A) � CH 3 CO • + CH 3 • (ETD) � 10% � (CH 3 ) 2 CO � CO • � (CH 3 ) 2 CO (A) � CH 3 • + CH 3 • + CO (ETD) � 20% � CH 3 Summary � • � Lab-based MS/KEMS instrument for both ionic and neutral fragments realized no “ neutral loss” . • � Cryodetector has 100 times better KE resolution than Si detector. • � Collision of acetyl and acetone with Xe leads to CAD and ETD. • � Branching ratios were directly determined even when only neutral fragments are produced. • � In future, – � statistics and KE resolution must be improved (CH 2 , CH, C). – � artificial peak must be eliminated completely. – � coincidence experiment with array detector ( KE and scattering angle). !

MS instruments equipped with cryodetectors, AIST � < 4,500 Da, < 3 keV > 1 MDa, 20 keV Double-focusing MS (EI/CI/FAB) MALDI TOF MS (100 channels) ! > 1 MDa, 20 keV MALDI for sub-nano second response < ~200k Da with mass-independent sensitivity ! ESI TOF MS (100 channels) Acknowledgement �