development of a time-of-flight mass spectrometer
TRANSCRIPT
INTEGRATED PAPERINTEGRATED PAPER
��������� ���������������
Development of a Time-of-Flight Mass Spectrometer Utilizing aSpiral Ion Trajectory
����Takaya S6ID=
�������� JEOL Ltd., Akishima, TOKYO, JAPAN
A novel time-of-flight mass spectrometer that utilizes a spiral ion trajectory was developed. In this massspectrometer, the ions sequentially pass through four toroidal electrostatic sectors and revolve along a figure-eight-shaped orbit on a particular projection plane. Each toroidal electrostatic sector has eight stories, andduring multiple revolutions, the ion trajectory shifted perpendicular to the projection plane in every cycle,thereby generating a spiral trajectory. Two prototypes, orthogonal acceleration time-of-flight mass spectrome-ter (OA-TOFMS) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (MALDI-TOFMS) were made and tested. The total flight path lengths were 20 and 17 m for OA-TOFMS and MALDI-TOFMS, respectively. By adopting an ion optical system that has a flight path length more than five timeslonger than that of the commonly used reflectron ion optical system, the m/z-dependent mass resolving powerwas reduced while improving the mass accuracy of the mass measurements.
(Received April 7, 2009; Accepted June 23, 2009)
1. � �
���� (time-of-flight mass spectrome-
try) ��� ��������������� m/z ��� ���!�� "��# $%&��'�()*�+���,� -.���/0�1����2�3 -.���/���� ���/ m/z�/��4������56� m/z �/7�8���$%9:-.���;,� ���!� m/z �����<=>�?�3���� @ (time-of-flight mass spectrometer:
TOFMS) /��A��� �0/ m/z ��� ���!B���(CDEF /-.��/��� DT B��GH-.��/��I/���(CDE/J���K>L�"�F� MNOP/QR� T BS��F ��8T T/
2DT��U��<=>�?�3 TOFMS� 1964�����'TV 1)� T�W?X��<=� DT�7�X��<=�NL��A�/IY>Z%'T?53 1955������[�/\]^_/���`�I�ab�2����>c��'� DT�7�X��<=>d�=�L��A�>IY,52)3 �5 1970�\!��� P/���
�N�abe"�# =,� ���fgh3) ijk�l4)
�mn�'�o#pq)rhabs�� ���tuv�w$�%��<=���1���GH�� T�x��2� �5 DT/&7y�z'��<=�� ��A�>IY,T8�3 U{/|(}"/~=������fgh�)�,TML�1� 1�3 m�"�3 ������*�������� ��,5��+�[��� ���/��+*�D������ �����)@������ DT�7�X��<=���,T8�3�%����A�/IY/56�� �1���+�� TOFMS�,��'� ��-��'T8�3 0 ��0����.�/����2��)����� ¡��¢B£Q�¤¢F5) i�)��h�¢ B£Q¥�¢F6), 7) /���tuv>"�3 �5�¦0 ��� ���fgh/§L0,�£$�,5��¨�¢8)� �)��h�¢���tuv/�.�¥�©=�Gª$�ª%,5%2��.¢/���tuv>"�9)�11)3 �)����� ¡��¢i�)��h�¢���tuv�� «�(�E�J�1�23Y4¬W/�1��U�?� �5'T8�3 ,$,� �0�.���2�56� ��*/W?8���Bm/z �/7�8���F >� ��*/7�8���Bm/z�/W?8���F �68®�/�� ��7¯>¬��'T,�¦8° >"�3 ��¨�¢i%2��.¢/���tuv�� </68®,/8°�A±�?� $ ² /���fgh�)�����³��´T�A������*�U��<=>�?�3
Correspondence to: Takaya S6ID=, JEOL Ltd., Musashino 3�1�2, Akishima, Tokyo 196�8558, JAPAN, e-mail: [email protected]����� ��������� µ196�8558 9¶:·;|<¸= 3�1�2�¹º� 2008�*���� u�»>¼�½¼,53
J. Mass Spectrom. Soc. Jpn. Vol. 57, No. 5, 2009
�363�
����� ������ ���������������������� TOFMS ����� TOFMS!� ��"#�$%&'
2. ����� TOFMS���
(�)� *+,-(�./ T! �01*&2�3��45�67�8&�9��� DT �:;�+#<=�>?��@#����ABCD�(�E6���FGH*&2IJ��K&' �����LM�>?N�OPQ�RS�GTU+&�9� VWXY� Z�9��� (�6�[��\]+��@^&���ABCD��_��`&2IJ�2+&' �<=+ab���*���cde2��� fgfd���T� “perfect focusing” 2hijklm�n12) �opq,��K&' ����cde�rstu�vwT� TOFMS 2��xyFz3��45�r{��@|� ����� TOFMS }�~���F�2�`��'ijklm������cde��������� *
&�9��� 1 ���2����������2�\]
6�����#U���K&' ��� f�U�^� 2
������`�&' � 1 ��� ����}�������SW��������[��\]��-� 1 ���2�����l+���6�������#U��K|� � 2 ����SW��������[���9�����SW�I������������#U��K&'���� ��������l��u*&���K|� ���+���� �+&=`� ����l���6�<&���ABCD�¡�|��¢T+#2#=£¤I¥¦*&' §�¨��Ff��¤�� �����*�9�������+2�K&' ��©�� �9���<&ijklm������cdeM����ª«T&�� ¬�SW�W2®U�"2���¯°�GTU*&2���&2�±T�' ���� ���cde�������²�³j���#2��`�I2¨��´µ��'�$�fgfd� �T� “perfect focusing” 2 hi
jklm�n �opq,��r{��tu2��� ¶·��2¸"�¹Jº��»�opq,�� MULTUM
Linear plus6) 2�¶·��2 2��i¼½³�mD�op
Fig. 1. Schema of the ion optical system utilizing a spiral ion trajectory. (a) The configuration of the four toroidalelectrostatic sectors is shown along with beam defining slit, detector, and spiral ion trajectory. (b) Extendedfigure of TES1 (without outer electrode) which shows configuration of Matsuda plates inside TES. (Reprintedwith permission from ref. 11, �2007 Elsevier.)
T. Satoh
�364�
���������� ������ MULTUM II7)
���� ������������ !"#$%&�'�� ($")*+,8��-./�0%��1�������2'3 #$"�����%45621�78��9�:3 ;�<=2��%��8'>?@�A>����� %BC�9��D����<E�78%F8D�83 ������������ %G��H�BC'��� MULTUM II������ %IJK21��� ���"456����� �2'3 +��L���M����
� �����"3 N����2�OP2 3GQ�2RS'�TUA/J�%��'�456������BC1��
����� �V�W% Fig. 1 2X1� Y�Y" 1)*Z82������[�\?]�Y��^3 _*�`a�"b��Y2c�'�� ����� "�d�� �456����� (toroidal electrostatic sector: TES)
1e4���'�� TES"3 ���.8=��.�OP Lx
23 �'?fO Ly%cg\�h��� i)*+j1k ��TUA/J������\?�� Fig. 1a � TES1"=��.%='�6�%X'\l^3 Fig. 1b 2 TES1�m�W%X'�� ���" Lx8 Ly8�n����fO��o%�p1�� �45� TES1e4%qG r'3 TES4
r#3 TES1�G45!�M1�� ;�%)*+!s^"178�3 ���6������%#9tuv2$%1� iFig. 1a �&�wx������k� TUA/J��y�% Lm3 )*��'% Lc81�83 1)*Z82 Y�Y2[��z("3 LyjLm��^3456�����!��ML q"3 1)*���' Lc%�?\3
tan q{(LyjLm)/Lc (1)
8���178��9��TES1e4!�|R�}"3 ���.�}3 =��.�}3 TUA/J��}� 3~)��^3 ;��� TES
1e4�1h\�TUA/J�3 TES1e4�����.l���=��.2����\?��
TES1�* 15�+(2"3 ����J�%��1��D2��K���%cg\?�� 7�"TUA/J�8N����n�1�������N���3 TUA/J�������fO��O,-.����/�>�D����
3. �������
(��c���2��93 ������0 (electron
ionization: EI) l���/���KA/J����0(electrospray ionization: ESI)8�1'��+R2�p�3!�� (orthogonal acceleration time-of-flight mass
spectrometer: OA-TOFMS)3 l��T���K��/J�J4(/����0 (matrix-assisted laser desorption/
ionization: MALDI) 8�1'�MALDI��p�O�3!�� (MALDI-TOFMS)�`a%p �� 5$2l?\¡¢£¤¥�����%6�'�� <¦2;�c�§72 ?\¨81��3 5$�9©% Table 1 2ªF8D��F[ OA-TOFMS�§72 ?\«h�� OA-TOFMS
����R2:% Fig. 2 2X1� 7����R2:" EI,
ESI 8��1�¬ ��^3 ����®����R2:F��;¯"3 EI8��1�"/�0 3 ESI�"���°�±�p �� ���R2:2"3 �,�²®� j30
V ��²³�R2���<1����J��3 ´'u'�.8�,�. i�,�²k ��O²�2�M1�� �M'�����J�"3 ´'u'�.8�,�.O2 1 kHz
�|R��� j0.7 kV �µK�}2\ TES1�Y2R
Table 1. Comparison Table of Two Types of Time-of-flight Mass Spectrometer, OA-TOFMS and MALDI-TOFMS, UsingSpiral Ion Trajectory
OA-TOFMS MALDI-TOFMS
¶��pz( 20 m 17 m
�ML q 2.2 deg 1.6 deg
R2�} j7.4 kV j20.0 kV
456�����n6 *=>· 50 mm 80 mm*=L� 157.1 deg 157.1 degN���OP Lx 10 mm 16 mm1)*�'� Lc 1,308 mm 2,093 mmTUA/J�Oz( Ly 40 mm 50 mmTUA/J�y Lm 10 mm 8 mm¶�)*+ 15 cycle 8 cycle
|R�} ���. j1,477 V j4,000 V=��. ¸1,477 V ¸4,000 VTUA/J� j610 V j850 V
��K���? �.¹º�A�Y 1 mm 1 mmTUA/J��Y 6 mm 1 mm
tuv 14,882 option1 DM167»@¼�/
���6������%A�'��p�O�3!���½B
�365�
����� ���� ��������� �� ������������ !"#$%�� & '�� 9(�)�*"#+,�� -."#� /7.0 kV �"0+1)��234� !"#5-."#�6� 8(�"#�� 7489"#:;<:=>?@ AB� "C<DEFGB�HI4 OA-TOFMS@�)�"0�� J7.4 kV @,4�TOFMS�� KLMN��� OPQR"C�� /7.0
kV @,�� �� )�ST�UV�� WXY�)�"0 J30 V 5���Z[��T�)�"0J7.4 kV����� � 3.6\�]\<^_2`ab�� B�Bcdb�e9� TES1f 1gT�UV]\� 2.2\@,��@� �� )�S[c�FhBijklm�2�� OP�n
o<a_�OA-TOFMS�pg��q�rs"t�� MULTUM II
�uv5:w5B� OPQRxyz{ 50 mm� xy]\157.1\� N|/}|"#6�6~< 10 mm5B� 1�x���� 1.308 m @,�� OA-TOFMS@��������u<�)B� �x��C@`a��+����@,�� ��-��x�� 15�x@,4� -�`a��� 20
m�\@,�� ��r�kX�� Lm � 10 mm� ��r�kX�6~ Ly � 40 mm 5B� HI4� � (1)���� �pg��q�rs�"tT�UV]\� 2.2\@,��pg��q�rs"t�N|"#�}|"#���r�kX��������� OPQR"C�� /1,477 V,
Fig. 2. Schema of acceleration region of OA-TOFMS. The ion beam from ion source was orthogonally accelerated. Theincident angle to first layer of TES1 was adjusted by deflector after the acceleration. (Reprinted with permissionfrom ref. 9, �2005 Elsevier.)
Fig. 3. Schema of the MALDI ion source. This diagram includes acceleration region comprising of MALDI target, gridelectrode and grounded electrode 1, and the Einzel lens system comprising the lens electrode, and groundedelectrodes 1 and 2. (Reprinted with permission from ref. 11, �2007 Elsevier.)
T. Satoh
�366�
�1,477 V,�610 V ������� �� ��������� 1������������ 1�6 mm ��������� �!"#��$%&'�()*+ �,-�.�/0��,-��1%�234 567%�+ETP89 TOFMS 2:�;<= 14,880 option1 �> ?�@�.�� 3 ns (full width at half maxi-
mum: FWHM) 2A4:% MALDI-TOFMS �B �CD4 Fig. 3 %
MALDI-TOFMS��,-�.��EF �,-�.��G-!�!"#�+ H��I�J+ KL�J 12MNOP(>4 MALDI-TOFMS2�QRS36���T�()*+ "#U#V�WX�G-!�!"#�)YZH��I�J%� �20 kV ���[��OP(>4 "#U#V�/0QP4\�]� nsX%H��I�J����17 kV ��^%�_O`4\�2�,-��.�abF4 KL�J 1�cdX+ "-e�J)YZKL�J 2
2MNOP4"-ef2ghOP+ TES1� 1�i$/j TES1� 1�i���k��XC�Yj% 1.6�2A4[+ �,-�.��l� mY�$n /0 1.6�op4\�2qr�(>4
MALDI-TOFMS2�+ �� ��������stk� 157.1��?�uu��+ v�wxst�y 80 mm+�z/{z�J|�|}� 16 mm�F4\�2+ ~sv� Lc � OA-TOFMS� 1.6� 2.093 m �� u+� �!"#�|} Ly � 50 mm+ � �!"#�� Lm
� 8 mm ��+ ~s]� 8~s m����� 17 mn �� � (1)/0�,-��� ��������i���k�� 1.6�2A4 �� ���������z�J+{z�J+ � �!"#�%�?P�P�,-v�wx�^ mKL�^n /0 �4,000 V, �4,000 V, �750 V ������� �� ��������� 1������������+ 1�1 mm �� 567%�+ ETP89TOFMS 2:�;<= DM167�> ?�@�.�� 1 ns (FWHM) 2A4
4. OA-TOFMS�����
EI, ESI �K�����+ m/z ����������� Fig. 4%EF EI���+�#��,����- (PFK)
[F(CF2)nF] �+ ESI���+ ����,����������,-_� ��+ m/z 1002����� 20,000
(FWHM), m/z�1,0002 40,000�50,000 (FWMH)��N�:% OA-TOFMS��(������:���2��� u� EI 2�,-_��#��,����-�m/z 69�381� 18���#�%�>(+ ¡��¢|�£N�/0�0P4¤¥m/z�� 1�4:�¦§� (2)2�¨�©¨-H�+:]%@ª(�] a�e�¥6F4 m�«¬+ 3:�2AP¬+ a, b, c, d�¥6F4n
�m/zm/za�bt�ct2�dt3�et4 (2)
:%�0P¦§� (2)%?P�P��#�� ¡��¢|�®��+ ¡ m/z��¥6F4 ¯X% ¡ m/z ��¤¥ m/z��°±�²³2´µ+ ?� rms (root mean
square) ��²:]%�>(¥6� � �¶·2 ESI
%(�,-_�����,��������� m/z
703�3,014� 18���#��>(���������>+ ��� Table 2 %u�µ EI, ESI �¸%:]2¹3º»>�º'°±� 0.3�0.5 ppm�qr�
Table 2. Comparison between the Theoretical andCalibrated m/z Values in Terms of the RootMean Square (rms) Values Using Di#erentNumbers of Terms up to the Fourth Order forthe Calibration Equations. Eighteen Peaks ofm/z and m/z Was Used for EI and ESI,Respectively
Order
1st 2nd 3rd 4th
EI 0.5 ppm 0.5 ppm 0.4 ppm 0.4 ppmESI 0.4 ppm 0.3 ppm 0.3 ppm 0.3 ppm
Fig. 4. Relationship between the mass resolving power and m/z value utilizing EI and ESI.
0`¼ ��,-v������¢|���½¤�a
�367�
TOFMS������ ��� m/z�� ��������� 1��������� ���� � ! "#$�%&��'()*�+,-�.��/012#3"�45167� ���"189:;��� 1�.����<=">?@A1B8CDE,� ��� m/z�� ���<7FGH1��I31J�C�� I�I3�� K"7LM��NOPQRSTUV1WX���I3YJZ�D7��[\]�^_Y`a��I3�bcMY`a�� EI�deVf�� CF3
g (m / z 69), ESI �deVf��C33H41N2O9
g (m/z 609)�hSi�-�3jk��lmYno��pqYJ� (Fig. 5)� rs�pq�tuvw��x�� 1bcy z�"{|}~�P���~���CD7�� �8 15bcy�jk��tu`f�"7��� I���deV���� 100� Y���D7�37���
���"18� bcY�����xDhSi�1�1���� -�3�D� 60�70� �A������
5. MALDI-TOFMS�����
��MALDI-TOFMS��9HX����7D����m/z �3>?��X���Y Fig. 6 �J�� :���bradykinin1�9, angiotensin II, angiotensin I, P14R�,
adrenocorticotropic hormone (ACTH)18�39��5���,� C¡C�¢£�V¤¥deV�¦§¨d©�h�ideV�ª« m/z ��� 757.3991, 1,046.5418,
1,296.6848, 1,533.8576, 2,465.1983���� ¬�Pi��� a-CHCAY7�� Fig. 6 �� ®¯°\±�²³Y�
�P14R: Pro-Pro-Pro-Pro-Pro-Pro-Pro-Pro-Pro-Pro-Pro-Pro-Pro-Pro-Arg
Fig. 5. Variation in peak area and height of PFK (m/z 69) and reserpine (m/z 609) from EI and ESI ion source,respectively.
Fig. 6. The variation in mass resolving power (FWHM) of five standard peptides by adjusting the delay time atBradikinin1�9, P14R and ACTH18�39. (Reprinted with permission from ref. 11, �2007 Elsevier.)
T. Satoh
�368�
bradykinin1�9, angiotensin I, ACTH18�39������������ ������� ���� ����������������� � !"#��������$� ��� ��� m/z�%������ m/z
�&��"'()�������*+,- .� ���/%�,-0./��� m/z 757� 33,000
143,000, m/z 2,465� 60,000180,000���������23+4���"�56�789:;6<=>�?@:���A�BC�
m/z 67912,769� 37 �8=D���� OA-TOFMS
����������� ���� ����E��FG�Table 3 �+� MALDI-TOFMS���� 1HI� 2HI�J�K��A�BC� 2HI14HI�0�"��0LM�� 1HI� 2HI�������K�0� 1HI��� �N�"LM�� � !#� �O�P&�� 2HI��N�"��$�.4��QLM��
MALDI-TOFMS�R��STUV>WX:�Y6�Z:[�������E��� \=]^Y�9=Y_�`��� 50 fmol La 0.1 fmol b���Bc�� ����defg:h=�6:ig:;� �j�k��� FG�Table 4 �+� l=\m=eno 0MASCOT����� %�FG� `�� 50 fmol �0� Z=p:eqr=�75s td^�������u 52v�e<V 570� `�� 0.1
fmol �/Z=p:eqr=� 18s td^�������u 12v� e<V 92��w+4���"��
6. � � � �
xy� z{J���!|0�"#����!|����.�0� }?W6^�~����!|���$����� z{J���!|0� dee�DY>�%�$ e��:+&'�'� b��(�)����.4��*+�.� xy/� ,u����.�0���=q=��(�� ����� �~�),��-����-��zM��� ��0� %������� �-+/��.�
� � �0� .��/ 0�t�v �zM� �ac��1 TOFMS���2�b�$�/��+����3|�`� ���� ,���4����"b�����!|�2��� R����b+� OA-TOFMS�`� �"b��0� ���� 5w 166�7¡¢£��89¤¥�2�¦§� �jz�b��� b�� y¨:��©;�/ 0�<ª«� ���¬ .�j� �©;®��4����"b��� ¯=>?°±� ²³´>?°±� @µ¶°±� A=¶°±�0·$��b+�¸�¨�¨¹B¨��º�B¨C»���!;>=��¼� R����b+�
�
1) W. E. Stephens, Phys. Rev., 69, 691 (1946).2) W. C. Wiley and I. H. McLaren, Rev. Sci. Instrum., 26,
1150 (1955).3) B. A. Mamyrin, V. I. Karataev, D. V. Shmikk, and V. A.
Zagulin, Sov. Phys. JETP, 37, 45 (1973).4) W. P. Poschenrieder, Int. J. Mass Spectrom. Ion. Phys., 6,
357 (1972).5) H. Wollnik and A. Casares, Int. J. Mass Spectrometry, 227,
217 (2003).6) M. Toyoda, M. Ishihara, S. Yamaguchi, H. Ito, T. Matsuo,
R. Reinhard, and H. Rosenbauer, J. Mass Spectrom., 35,163 (2000).
7) D. Okumura, M. Toyoda, M. Ishihara, and I. Katakuse, J.
Mass Spectom. Soc. Jpn., 51, 349 (2003).8) M. Yavor, A. Verentchikov, J. Hasin, B. Kozlov, M.
Gavrik, and A. Trufanov, Physics Procedia, 1, 391 (2008).9) T. Satoh, H. Tsuno, M. Iwanaga, and Y. Kammei, J. Am.
Soc. Mass Spectrom., 16, 1969 (2005).10) T. Satoh, H. Tsuno, M. Iwanaga, and Y. Kammei, J. Mass
Spectrom. Soc. Jpn., 54, 11 (2006).11) T. Satoh, T. Sato, and J. Tamura, J. Am. Soc. Mass
Spectrom., 18, 1318 (2007).12) M. Ishihara, M. Toyoda, and T. Matsuo, Int. J. Mass
Spectrom., 197, 179 (2000).
Keywords: Time-of-flight mass spectrometer, Spiral ion tra-jectory, MALDI, Orthogonal acceleration
Table 3. Comparison between the Theoretical andCalibrated m/z Values in Terms of the RootMean Square (rms) Values of 37 Peaks UsingDi#erent Numbers of Terms up to the FourthOrder for the Calibration Equations
Order
1st 2nd 3rd 4th
1.2 ppm 0.8 ppm 0.8 ppm 0.8 ppm
Table 4. Search Result of Protein Identification byPeptide Mass Fingerprinting Using MASCOT(Reprinted with permission from ref. 11,�2007Elsevier.)
`��(fmol)
Z=p:eqr=�(s)
d^�������u e<V
50 75 52 57010 64 41 390
5 54 36 3511 43 28 2550.5 46 31 3060.1 18 12 92
ac�½�?@:�1���� z{J���!|��2
�369�