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Superconducting detectors for particles from atoms to proteins
Physica C 468 (2008) 1987–1991
Contents lists available at ScienceDirect
Physica C journal homepage: www.elsevier.com/locate/physc
Superconducting detectors for particles from atoms to proteins M. Ohkubo * Research Institute of Instrumentation Frontier, National Institute of Advanced Industrial Science and Technology (AIST), Central 2, 1-1-1, Umezono, Tsukuba, Ibaraki 305-8568, Japan
a r t i c l e
i n f o
Article history: Available online 3 June 2008 PACS: 07.75.+h 07.77.Gx 85.30.Mn 85.25.j Keywords: Mass spectrometer Superconducting tunnel junction Superconducting stripline Biomolecule TOF-MS
a b s t r a c t Superconducting detectors are ideal for detecting low-energy particles from atoms to proteins of which kinetic energies range from less than 1 keV to 30 keV compatible with analytical instruments for ordinary laboratory use. The superconducting detectors have the advantages of detecting low energy quanta, because a threshold equivalent to the gap parameter (D) is extremely small: meV that is one-thousandth of the band gap of semiconductor detectors. Any low-energy quanta including phonons created by individual particle hit-events on the detector surface can be detected through Cooper-pair breaking. Such detectors as superconducting tunnel junctions (STJs) and superconducting stripline detectors (SSLDs) are promising for developing advanced analytical instruments for nuclear physics, basic chemistry, and biology. Especially, mass spectrometry (MS) equipped with the superconducting detectors has been producing the remarkable results, which have never been obtained by conventional MS instruments. Ó 2008 Elsevier B.V. All rights reserved.
1. Introduction Particle detection with superconductivity has a rather long history. We focus on such particles as atoms or molecules. The superconducting particle detection began with high-energy a-particles of MeV. The detection of low energy particles of a few keV or less, which is compatible with analytical instruments for ordinary laboratory use, by using the superconducting detectors has been made possible only in the last decade as the nanofabrication techniques have developed. The first particle detection with superconductivity was reported in 1949 by Andrews et al. who used a columbium(niobium)-nitride superconducting stripline detector (SSLD) with a size of 3.5 mm 0.4 mm 6 lm in order to count 5.3-MeV a-particles [1]. Although time response was as slow as 100 ls, the pulse response to the a-particles was obtained through a superconducting-normal transition of the stripline, as proposed by Sherman [2]. Wood and White reported an experiment on the detection of 5.1-MeV a-particles with a tin-based superconducting tunnel junction (STJ) in 1969 [3]. Although there was no data about kinetic energy measurement in that paper, they proposed the concept of a high-resolution particle spectrometer with superconductivity. In their proposal, the kinetic energies of high-energy particles that penetrate deep into superconductors would be measured through the electronic excitations due to the energy loss of energetic particles. * Tel.: +81 29 861 5685; fax: +81 29 861 5730. E-mail address: [email protected] 0921-4534/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.physc.2008.05.225
The high energy-resolution is expected from the small threshold that corresponds to the energy gap necessary for the creation of quasiparticles. When an energy quantum above the threshold is absorbed in a superconductor, Cooper-pair breaking takes place during relaxation processes. It is expected that the number of the quasiparticles is proportional to the energy deposited on the detector material. The quasiparticles are similar to the carriers in such semiconductor detectors as silicon particle detectors. The energy gaps in superconductors are in the order of meV expected from the superconducting gap parameters (D), while the band gaps in semiconductors are eV. The number of the quasiparticles is one thousand times larger than the carrier number in the semiconductor. Therefore, the energy resolution of the superconducting detectors is thirty times better than that of the semiconductor detectors because of a statistical reason in principle, if we assume the Poisson process [3]. In addition, the smallness of the energy gaps realizes the detection of low energy quanta of meV, for example phonons, as will be mentioned below. After the above pioneering works, Kurakado precisely calculated the threshold that is called the e value for a superconductor. The e value is the deposited energy divided by the number of created quasiparticles [4]. The calculated value was 1.7D. He also pointed out that superconducting detectors would be useful to detect low energy atoms that produce no carriers in semiconductors but phonons on the occasion of atom impact. The maximum energy of the phonons roughly corresponds to the Debye energy, which is 24 meV in Nb. The phonons with the energies over 1.7D are able to break Cooper pairs. In fact, the STJ detectors were
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employed to measure phonons in germanium [5]. Therefore, the detection of low energy atoms would be feasible through the phonons. Research activities on the superconducting detectors are collected in a series of workshops on low temperature detectors (LTD) started from 1985. The proceedings of the recent workshops in 2005 or 2007 can be found in Ref. [6]. Some of the superconducting detectors are STJs, microcalorimeters with transition edge sensors (TESs), magnetic microcalorimeters (MMCs), microwave kinetic inductance detectors (MKIDs), and superconducting single photon detectors (SSPDs). The recent advancement of the nanofabrication techniques has realized the remarkable improvement of the detector performance in energy and time resolution. Furthermore, the objects to be measured rapidly expand from elementary particles to biomolecules. The first STJ application to the detection of biomolecules was reported by Twerenbold in 1996 [7]. The works on the biomolecule detection before 1999 were reviewed by Frank [8]. The advantages of the STJ detectors are unity detection efficiency independent on molecular weight (MW) and a capability to measure the kinetic energies of molecules. The above advantages are very attractive in the application to mass spectrometry (MS). However, the junctions, which have a typical size of 100 lm, are very smaller than that of such conventional ion detectors as microchannel plates (MCPs) with a centimeter scale. The small size results in a low throughput for sample analysis. One of the solutions is to fabricate large-scale array detectors to compensate the small pixel size [9]. The array of small STJ pixels gives an additional advantage that is the analysis of fragments generated from precursor molecules [10]. The fragment analysis is indispensable for proteomics that means systematic analysis of all protein expressions in a cell or tissue. In contrast to the above-mentioned advantages of the STJ detectors, one of the drawbacks is that the kinetic energy measurement requires a relatively long charge-collection-time. The charge-collection-time is equivalent to a relaxation time or a falltime of an current output pulse, which is in a range of ls and considerably slower than ns of MCPs. It has been known that, concerning high time-resolution, the SSPD that is based on the same concept as the SSLD performs well. A relaxation time less than 100 ps for photons was reported in an NbN nanostripline detector [11]. We tried to use the SSLD as a biomolecule detector. A detection experiment of peptides and proteins was successful by using an NbN-based SSLD [12]. The time resolution is expected to be well better than 1 ns, which is comparable with the best MCP detector and can be improved by controlling kinetic inductance. In fact, we have recently recorded a time resolution of 360 ps [13]. However, the present SSLDs are very small: 50 50 lm2. The development of large SSLDs or array detectors is in progress. Two kinds of the superconducting particle detectors: STJs and SSLDs having the advantages to conventional particle detectors, will play an important role in such fields as nuclear physics, basic chemistry, and biology. Mass spectroscopy with the superconducting detectors has been producing remarkable results these days. In this paper, we report a conceptual difference between the superconducting detectors and the semiconductor detectors in details, and some of the latest results obtained using the STJs and the SSLDs at our institute. 2. Operating principle difference between conventional detectors and superconducting detectors The first step of particle detection is the interaction between a particle and a detector material, which is illustrated in Fig. 1. The conventional particle detectors such as Si surface barrier detectors employ the carrier generation inside the semiconductor crystal.
Fig. 1. Schematic drawing of two extreme cases of particle detection: a high energy nucleus of meV in nuclear physics and a low energy molecule of keV in analytical instruments for biology. The meV particle first undergoes electronic stopping with electrons and then nuclear stopping with nuclear collisions just before a complete stop. The keV molecule impinges on the detector surface and sticks on it while inducing the emission of a secondary electron or a secondary ion at a probability of less than unity.
The carriers of electron–hole pairs are generated by the energy-loss processes of energetic atomic ions or nuclei such as a-particles of meV. An energetic particle penetrates deep into the crystal, so that the particle forms the trace of electronic excitations and finally the cascades of atomic displacements before a stop, as shown in Fig. 1. The stopping of the energetic particle leads to the carrier production. The number of the carriers is proportional to the kinetic energy of the particle. The carriers generate a current pulse, which can be read out by a semiconductor-based amplifier. In this detector operation, the detection efficiency is unity, and we can obtain both of the arrival time and the kinetic energy on each particle hit event. These particle detectors are often used for an energy range of MeV in nuclear physics. If the particle kinetic energy decreases and is as low as less than keV, the atomic particles stop within surface dead-layers such as thin electrodes on the semiconductor detector surface. High-mass protein particles of keV land on the detector surface without penetration. In this case, the semiconductor detectors have essentially no sensitivity for the low energy particles, although the total kinetic energy of a particle is considerably larger than the semiconductor gap energy of eV. Other class of particle detectors relies on the emission of a secondary electron or a secondary ion from the surface at a particle hit event. The number of electrons or ions is multiplied by a factor of 106 with an electron multiplier in order to produce the charge number enough for semiconductor-based amplifiers. The particle energy in this detection mechanism can be less than keV, at which the particles cannot penetrate into the detector material. The efficiency of the secondary electron emission is roughly proportional to the particle velocity. Therefore, the detection efficiency drops with increasing molecular mass at a constant kinetic energy. For example, an MCP detector has a detection efficiency of 1–5% for a protein, bovine serum albumin (BSA) of 66,430 Da [14]. The unit of Da is used in biology, and equivalent to atomic mass unit. An example of the low energy particle impact is shown in Fig. 2, which is a differential interference contrast micrograph of an STJ detector surface after the detection of particles from atoms to such biomolecules as peptides and proteins with kinetic energies of 3–20 keV. Fig. 2 is the part of an array detector that has been used for time-of-flight mass spectrometry (TOF MS) for over one year. The small white dots in the bottom half of the micrograph indicate the remains of the particle hit events. It is certain that the incoming particles exist on the detector surface, since the white dots were
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structure with a thickness of less than 10 nm and a line width of less than 1 lm. This fine structure gives the fast relaxation of the deposited energy, which is quickly transferred to the substrate. Actual response time is governed by kinetic inductance of striplines [13]. 3. Analysis of low energy particles with superconducting detectors on TOF MS configuration The concept of the MS analysis using a STJ detector is illustrated in Fig. 3. Atoms or precursor molecules are ionized and accelerated by a static voltage of V, which is normally kV. Atoms or small molecules are ionized by electron impact (EI), fast-atom bombardment (FAB), etc., while biomolecules are ionized by matrix-assisted laser desorption/ionization (MALDI) or electrospray ionization (ESI) without decomposing into fragments in the ion source. The accelerated ions fly for a length of l. The time of flight (TOF) is given by Fig. 2. Differential interference contrast micrograph of the surface of a superconducting tunnel junction (STJ) detector used in time-of-flight mass spectrometry (TOF MS) for over one year. The array of the 200 lm-square junctions and wiring for the bottom and top electrodes are seen as the white lines. After the detection of particles from atoms to proteins with energies from 3 to 20 keV, the white dots which are the remains of the particle impact appeared on the detector surface.
easily removed by organic-solvent-washing or ozone-cleaning. Even in this particle landing situation, the STJ detectors generate current pulses for the particle hit events, as can be realized in the situation of the deep penetration of meV energetic nuclei into the Si detectors. The pulse height values correspond to the kinetic energies of particles. This spectroscopic particle detection with the STJ detector can be realized by the extremely small gap energy (2D). A difference in the electronic states between superconductors and semiconductors was discussed in Ref. [9]. The readout of the quasiparticle number is performed by measuring the increase of the subgap current between two electrodes of a junction, which is cooled at 0.3 K so that there are almost no thermally excited quasiparticles. The current pulses are usually amplified by a semiconductor-based amplifier, while a SQUID amplifier was also effective [15]. Other superconducting detectors such as normalinsulator-superconductor (NIS) junctions or transition edge sensors (TESs) were also used for TOF MS [16,17]. However, these detectors need very low operating temperatures less than 0.1 K, and have slow relaxation times, e.g., 17 ls, which is more than ten times longer than that of the STJ. The low operating temperatures and the slow response times are bottlenecks for practical use. Another possible superconducting detector that can be operated at 4 K is kinetic inductance detectors [18]. The time resolution of less than 1 ns is favorable for TOF MS in order to realize a high mass resolution. The conventional MCP detectors have a time resolution of 1 ns or better, although the unity detection efficiency is kept only up to approximately 4000 Da [15]. One of the candidates for detectors with a high time resolution and a unity detection efficiency is the SSLD. The operating principle of the SSLD is the same as that of the SSPD [11], but we use the acronym of SSLD for the particle detection in this paper because the SSPD assume the photon detection. The fast response is due to a hotspot formation leading to a resistive barrier across the stripline and its fast recovery to the superconducting state. The resistive barrier results in a voltage pulse formation, when a bias current of is applied just below the critical current of a stripline. The subsequent relaxation can be as fast as less than 100 ps. This operating principle is similar to that in Ref. [1], but it is very much faster. The operation of the Andrew’s detector may be calorimetric due to the bulky stripline and the meV energy deposition. The SSLDs fabricated recently have the sophisticated
TOF ¼
pffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi m=2zeV l;
ð1Þ
where m is the mass of the particle, z is the charge number of the ion, e is the electron charge. The TOF is proportional to the square root of m/z, and the particle velocity v is inversely proportional to the square root of m/z. The m/z value is the so-called mass-to-charge ratio, which is the dimensionless ratio of the relative mass to the charge number. The TOF measurement gives us only the m/z values of the intactions. Since the efficiency of the secondary electron emission is roughly proportional to the velocity, the detection efficiency of the conventional ion detectors decreases with increasing MW [19]. It is expected, on the other hand, that the superconducting detectors have unity detection efficiency independent on MW because of the meV threshold value. The threshold value is considerably smaller than the kinetic energies divided into the individual atoms forming a large molecule. Each atomic collision at the large molecule impact has a deposited energy enough for Cooper-pair breaking. The total energy deposition seems to be almost independent on MW, when the charge numbers of the ions are the same. Therefore, no MW dependence of the output pulse height is expected. An experimental result that supports the unity detection efficiency up to at least 1 M Da can be found in Ref. [10]. In addition to the analysis of intact ions, such dissociation processes as post-source decay (PSD), collision induced dissociation (CID), electron transfer dissociation (ETD), etc. are frequently employed to make fragments for structural analysis or molecule identification. The fragment patterns depend on molecular structures. For example, the fragmentation analysis makes possible to identify the amino acid orders of small biomolecules of peptides, which have the chains consisting of a few to over ten amino acids. The amino acid order corresponds to a DNA base sequence. This analysis is called ‘‘sequencing.” The fragments produced by dissociation carry the kinetic energies that are proportional to the MW values of fragments so that a equation of E = E1 + E2 + E3 is held for a simple dissociation example shown in Fig. 3. All of the fragments have the same velocity as that of the intact ion, so that they arrive at the detector surface simultaneously. It is, therefore, impossible to separate different fragments by using a conventional detector that is placed on the liner mode. It is necessary to add extra ion optics or the second MS instrument to analyze ionic fragments. On the other hand, the STJ detectors are able to measure the kinetic energies E1, E2, E3 of the fragments directly, so that we can analyze all the fragments including neutrals as well as ions. The analysis of neutrals is impossible in conventional MS instruments. We can realize mass spectroscopy for neutral particles without reionization by using superconducting detectors. The details which will be published elsewhere.
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Fig. 3. New concept of mass spectroscopy with superconducting detectors. The superconducting detectors have unity detection efficiency independent on molecular weight (MW). In addition, the analysis of both ionic fragments and neutral fragments can be performed through kinetic energy measurement with the array of small STJ pixels.
The kinetic energy of each fragment can be measured with the STJ array detector with a small pixel size of a few 100 lm, as shown in Fig. 3. At a dissociation event, each fragment has a slightly different deviation from the original flight direction because of kinetic energy release upon dissociation. The deviation results in the fact that individual fragments hit different pixels. Thus, the TOF values and the kinetic energies of the fragments can simultaneously be measured one by one. This new measurement method enables the fragment analysis for different precursor ions at the same time. The conventional MCP particle detectors have millions of microchannels, but the readout circuit is essentially single. The flight direction deviation is small, which means that all fragments arrive at the MCP surface at the same time. Moreover, the MCP detectors have no capability to measure the kinetic energies of the fragments. Therefore, the MCP detectors cannot distinguish the fragments produced from an intact precursor ion. The MS data of bovine serum albumin (BSA) of 66,430 Da with the STJ detector is shown in Fig. 4. The TOF values and the kinetic energies of the incoming particles including the intact ions and the fragment particles were measured. The TOF values were converted to the m/z values by Eq. (1). The individual particle hit events are plotted according to the m/z values and the kinetic energies in
Fig. 4b and e. The kinetic energy spectra in (a) and (d) show the ion count histograms against the kinetic energies for the data surrounded by the dotted lines in the scatter plots of (b) and (e). These selected events originate only from the singly charged intact BSA ions and the fragments produced from the BSA+. The mass spectra in (c) and (f) show the ion count histograms against the m/z values for all events. The upper three graphs, (a–c), were taken at the ionization condition of a pulsed UV laser energy of 8 lJ in the MALDI process. The laser energy was increased to 12 lJ in the lower three graphs, (d–f). The mass spectra for both laser energies are essentially the same except for more pronounced background at 12 lJ. In contrast to the similarity of the mass spectra, the m/z versus kinetic energy scatter plots in (b) and (e) exhibit a large difference between 8 and 12 lJ. The vertical streak at the m/z value of 66,430 for 12 lJ indicates the presence of the large number of fragments that have the same TOF value but different kinetic energies less than that of the precursor ion. The fragmentation is also clearly observed in the kinetic energy spectra in Fig. 4a and d. The single peak is observed at 8 lJ, which indicates that almost all particles are the intact BSA molecules that carry the energy of 17.5 keV. On the other hand, no peak corresponding to the intact BSA is recognized at 12 lJ, and the low energy events less than 17.5 keV
Fig. 4. Mass spectra and related data measured by an STJ for a protein, bovine serum albumin (BSA) of 66,430 Da: kinetic energy spectra (a) (d), m/z versus kinetic energy scatter plots (b) (e), and mass spectra (c) (f). The protein was ionized by the matrix-assisted laser desorption/ionization (MALDI). The particles accelerated at 17.5 keV were detected by the STJ detector. The energies of UV laser pulses in the MALDI process were 8 lJ for the upper three graphs (a–c) and 12 lJ for the lower three graphs (d–f). The laser pulse energies greatly affect the extent of the fragmentation due to post-source decay (PSD).
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conductor-based particle detectors operating above 77 K and MCP at room temperature. The superconducting particle detectors will play an important role for advanced mass spectroscopy. Superconducting particle detectors of superconducting tunnel junctions (STJs) as particle spectrometers and superconducting stripline detectors (SSLDs) as ultrafast particle counters are promising for developing new MS instruments. Both superconducting particle detectors have already been producing the remarkable results that cannot be obtained with the conventional MS instruments. A large market of the MS instruments with superconductivity is expected for many fields from industries to sciences. Acknowledgments
Fig. 5. Temporal response of the superconducting NbN stripline detector (SSLD) to a peptide, Angiotensin I of 1296 Da and BSA of 66,430 Da.
are significant for the fragments. This fragmentation process is called PSD, which originates from a molecular excitation upon the ionization or during the acceleration. The excited molecules decay into the small fragments during the free flight period after the acceleration. At this stage, we have obtained the time resolution of several 10 ns with the STJ detectors [20]. Better time response is desirable for high mass–resolution, and has been realized with the 50 lmsquare NbN SSLD with a thickness of 7 nm and a stripline width of 200 nm. Fig. 5 shows a comparison of temporal response between a peptide, Angiotensin I of 1296 Da, and a protein, BSA of 66,430 Da. It was confirmed that the pulses have a risetime of 540 ps and a falltime of 20–40 ns. The first mass spectra measured with the SSLD are reported in Ref. [21]. The SSLDs are expected to have both of fast response time and unity detection efficiency independent on MW, although additional experiments are required to confirm unity detection efficiency. Other merit of the NbN SSLDs is that the operating temperature is 4 K, which is considerably higher than 0.3 K for the STJ detectors. The SSLDs with oxide superconductors having higher Tc are attractive for the operation at higher temperatures. The STJ and SSLD are effective at different positions in MS instruments. The STJ is powerful in analyzing the fragments for structural analysis of molecules at the linear mode position shown in Fig. 3. The kinetic energy measurement with the STJ is also useful for discrimination of the different charge states with the same m/z value. This performance has realized the clear separation between 14N2++ and 14N+, which have never been separately measured before [22], and the fragment analysis of Immunoglobulin G (IgG) [23]. In addition, the STJ can be used to observe microscopic particle-surface interactions through the measurement of the energies deposited to the detector surface [24]. The SSLD with the ultrafast response may be effective after additional optics such as reflectron to improve mass resolution.
The author would like to thank M. Ukibe, A. Kurokawa, Yigang Chen, Yiner Chen, K. Chiba, Y. Kobayashi, Y. Shimizugawa, K. Suzuki, S. Shiki of Superspectroscopy System Research Group at AIST for experimental works and fruitful discussion. Many thanks go to H. Sato, T. Kinumi, Y. Shigeri, Z. Wang, S. Miki, S. Hayakawa, S. Tomita, Y. Sato, K. Teramoto, and M. Setou for performing novel MS experiments. This work was supported by the JST-SENTAN Project (Japan Science and Technology Agency). References [1] [2] [3] [4] [5] [6]
[7] [8] [9] [10]
[11]
[12] [13] [14] [15] [16] [17] [18] [19] [20] [21]
4. Conclusion
[22]
It has been demonstrated that superconducting detectors operating below 4 K provide the outstanding particle detection performance, which cannot be realized by the conventional semi-
[23] [24]
D. Andrews, R. Fowler, M. Williams, Phys. Rev. 76 (1949) 154. N. Sherman, Phys. Rev. Lett. 8 (1962) 438. G. Wood, B. White, Appl. Phys. Lett. 15 (1969) 237. M. Kurakado, Nucl. Instrum. Meth. 196 (1982) 275. W. Dietsche, G. Northrop, J. Wolfe, Phys. Rev. Lett. 47 (1981) 660. M. Ohkubo, K. Mitsuda, H. Takahashi (Ed.), in: Proceedings of the 11th International Workshops on Low Temperature Detectors. Nucl. Instrum. Meth. Phys. Res. A 559 (2006) 329,; M. Chapellier, G. Chardin (Ed.), in: Proceedings of the 12th International Workshops on Low Temperature Detectors. J. Low Temp. Phys. 151 (2008) 5. D. Twerenbold, J. Vuilleumier, D. Gerber, A. Tadsen, B. Brandt, P. Gillevet, Appl. Phys. Lett. 68 (1996) 3503. M. Frank, S. Labov, G. Westmacott, W. Benner, Mass Spec. Rev. 18 (1999) 155. M. Ohkubo, IEICE Trans. Electron. E90-C (2007) 550. M. Ohkubo, Y. Shigeri, T. Kinumi, N. Saito, M. Ukibe, Y. Chen, A. Kushino, A. Kurokawa, H. Sato, S. Ichimura, Nucl. Instrum. Meth. Phys. Res. A 559 (2006) 779. G.N. Gol’tsman, O. Okunev, G. Chulkova, A. Lipatov, A. Semenov, K. Smirnov, B. Voronov, A. Dzardanov, C. Williams, R. Sobolewski, Appl. Phys. Lett. 79 (2001) 705. K. Suzuki, S. Miki, S. Shiki, Y. Kobayashi, K. Chiba, Z. Wang, M. Ohkubo, J. Low Temp. Phys. 151 (2008) 766. K. Suzuki, S. Shigetomo, Z. Wang, M. Ohkubo, Appl. Phys. Exp. 1 (2008) 031702. G. Westmacott, M. Frank, S.E. Labov, W.H. Benner, Rapid Commun. Mass Spectrom. 14 (2000) 1854. C. Mears, S. Labov, M. Frank, M. Lindeman, L. Hiller, H. Netel, A. Barfknecht, Nucl. Instrum. Meth. Phys. Res. A 370 (1996) 53. G. Hilton, J. Martinis, D. Wollman, K. Irwin, L. Dulcie, D. Gerber, P. Gillevet, D. Twerenbold, Nature 391 (1998) 672. S. Rutzinger, P. Christ, F. Proebst, W. Seidel, S. Uchiaikin, M. Stark, Nucl. Instrum. Meth. Phys. Res. A 520 (2004) 625. S. Pagano, E. Esposito, M. Ejrnaes, C. Nappi, R. Cristiano, IEEE Trans. Appl. Super. 15 (2005) 940. I. Gilmore, M. Seah, Int. J. Mass Spectrom. 202 (2000) 217. M. Ohkubo, M. Ukibe, N. Saito, A. Kushino, S. Ichimura, S. Friedrich, IEEE Trans. Appl. Super. 15 (2005) 932. K. Suzuki, S. Miki, S. Shiki, Y. Kobayashi, K. Chiba, Z. Wang, M. Ohkubo, Physica C, in these proceedings. S. Shiki, M. Ukibe, Y. Sato, S. Tomita, S. Hayakawa, M. Ohkubo, J. Am. Soc. Mass Spectrom., in press. Y. Kobayashi, M. Ukibe, K. Chiba, H. Nakanishi, S. Shiki, K. Suzuki, M. Ohkubo, Physica C, in these proceedings. S. Tomita, Y. Sato, M. Ohkubo, M. Ukibe, S. Hayakawa, Appl. Phys. Lett. 91 (2007) 053507.
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Physica C journal homepage: www.elsevier.com/locate/physc
Superconducting detectors for particles from atoms to proteins M. Ohkubo * Research Institute of Instrumentation Frontier, National Institute of Advanced Industrial Science and Technology (AIST), Central 2, 1-1-1, Umezono, Tsukuba, Ibaraki 305-8568, Japan
a r t i c l e
i n f o
Article history: Available online 3 June 2008 PACS: 07.75.+h 07.77.Gx 85.30.Mn 85.25.j Keywords: Mass spectrometer Superconducting tunnel junction Superconducting stripline Biomolecule TOF-MS
a b s t r a c t Superconducting detectors are ideal for detecting low-energy particles from atoms to proteins of which kinetic energies range from less than 1 keV to 30 keV compatible with analytical instruments for ordinary laboratory use. The superconducting detectors have the advantages of detecting low energy quanta, because a threshold equivalent to the gap parameter (D) is extremely small: meV that is one-thousandth of the band gap of semiconductor detectors. Any low-energy quanta including phonons created by individual particle hit-events on the detector surface can be detected through Cooper-pair breaking. Such detectors as superconducting tunnel junctions (STJs) and superconducting stripline detectors (SSLDs) are promising for developing advanced analytical instruments for nuclear physics, basic chemistry, and biology. Especially, mass spectrometry (MS) equipped with the superconducting detectors has been producing the remarkable results, which have never been obtained by conventional MS instruments. Ó 2008 Elsevier B.V. All rights reserved.
1. Introduction Particle detection with superconductivity has a rather long history. We focus on such particles as atoms or molecules. The superconducting particle detection began with high-energy a-particles of MeV. The detection of low energy particles of a few keV or less, which is compatible with analytical instruments for ordinary laboratory use, by using the superconducting detectors has been made possible only in the last decade as the nanofabrication techniques have developed. The first particle detection with superconductivity was reported in 1949 by Andrews et al. who used a columbium(niobium)-nitride superconducting stripline detector (SSLD) with a size of 3.5 mm 0.4 mm 6 lm in order to count 5.3-MeV a-particles [1]. Although time response was as slow as 100 ls, the pulse response to the a-particles was obtained through a superconducting-normal transition of the stripline, as proposed by Sherman [2]. Wood and White reported an experiment on the detection of 5.1-MeV a-particles with a tin-based superconducting tunnel junction (STJ) in 1969 [3]. Although there was no data about kinetic energy measurement in that paper, they proposed the concept of a high-resolution particle spectrometer with superconductivity. In their proposal, the kinetic energies of high-energy particles that penetrate deep into superconductors would be measured through the electronic excitations due to the energy loss of energetic particles. * Tel.: +81 29 861 5685; fax: +81 29 861 5730. E-mail address: [email protected] 0921-4534/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.physc.2008.05.225
The high energy-resolution is expected from the small threshold that corresponds to the energy gap necessary for the creation of quasiparticles. When an energy quantum above the threshold is absorbed in a superconductor, Cooper-pair breaking takes place during relaxation processes. It is expected that the number of the quasiparticles is proportional to the energy deposited on the detector material. The quasiparticles are similar to the carriers in such semiconductor detectors as silicon particle detectors. The energy gaps in superconductors are in the order of meV expected from the superconducting gap parameters (D), while the band gaps in semiconductors are eV. The number of the quasiparticles is one thousand times larger than the carrier number in the semiconductor. Therefore, the energy resolution of the superconducting detectors is thirty times better than that of the semiconductor detectors because of a statistical reason in principle, if we assume the Poisson process [3]. In addition, the smallness of the energy gaps realizes the detection of low energy quanta of meV, for example phonons, as will be mentioned below. After the above pioneering works, Kurakado precisely calculated the threshold that is called the e value for a superconductor. The e value is the deposited energy divided by the number of created quasiparticles [4]. The calculated value was 1.7D. He also pointed out that superconducting detectors would be useful to detect low energy atoms that produce no carriers in semiconductors but phonons on the occasion of atom impact. The maximum energy of the phonons roughly corresponds to the Debye energy, which is 24 meV in Nb. The phonons with the energies over 1.7D are able to break Cooper pairs. In fact, the STJ detectors were
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employed to measure phonons in germanium [5]. Therefore, the detection of low energy atoms would be feasible through the phonons. Research activities on the superconducting detectors are collected in a series of workshops on low temperature detectors (LTD) started from 1985. The proceedings of the recent workshops in 2005 or 2007 can be found in Ref. [6]. Some of the superconducting detectors are STJs, microcalorimeters with transition edge sensors (TESs), magnetic microcalorimeters (MMCs), microwave kinetic inductance detectors (MKIDs), and superconducting single photon detectors (SSPDs). The recent advancement of the nanofabrication techniques has realized the remarkable improvement of the detector performance in energy and time resolution. Furthermore, the objects to be measured rapidly expand from elementary particles to biomolecules. The first STJ application to the detection of biomolecules was reported by Twerenbold in 1996 [7]. The works on the biomolecule detection before 1999 were reviewed by Frank [8]. The advantages of the STJ detectors are unity detection efficiency independent on molecular weight (MW) and a capability to measure the kinetic energies of molecules. The above advantages are very attractive in the application to mass spectrometry (MS). However, the junctions, which have a typical size of 100 lm, are very smaller than that of such conventional ion detectors as microchannel plates (MCPs) with a centimeter scale. The small size results in a low throughput for sample analysis. One of the solutions is to fabricate large-scale array detectors to compensate the small pixel size [9]. The array of small STJ pixels gives an additional advantage that is the analysis of fragments generated from precursor molecules [10]. The fragment analysis is indispensable for proteomics that means systematic analysis of all protein expressions in a cell or tissue. In contrast to the above-mentioned advantages of the STJ detectors, one of the drawbacks is that the kinetic energy measurement requires a relatively long charge-collection-time. The charge-collection-time is equivalent to a relaxation time or a falltime of an current output pulse, which is in a range of ls and considerably slower than ns of MCPs. It has been known that, concerning high time-resolution, the SSPD that is based on the same concept as the SSLD performs well. A relaxation time less than 100 ps for photons was reported in an NbN nanostripline detector [11]. We tried to use the SSLD as a biomolecule detector. A detection experiment of peptides and proteins was successful by using an NbN-based SSLD [12]. The time resolution is expected to be well better than 1 ns, which is comparable with the best MCP detector and can be improved by controlling kinetic inductance. In fact, we have recently recorded a time resolution of 360 ps [13]. However, the present SSLDs are very small: 50 50 lm2. The development of large SSLDs or array detectors is in progress. Two kinds of the superconducting particle detectors: STJs and SSLDs having the advantages to conventional particle detectors, will play an important role in such fields as nuclear physics, basic chemistry, and biology. Mass spectroscopy with the superconducting detectors has been producing remarkable results these days. In this paper, we report a conceptual difference between the superconducting detectors and the semiconductor detectors in details, and some of the latest results obtained using the STJs and the SSLDs at our institute. 2. Operating principle difference between conventional detectors and superconducting detectors The first step of particle detection is the interaction between a particle and a detector material, which is illustrated in Fig. 1. The conventional particle detectors such as Si surface barrier detectors employ the carrier generation inside the semiconductor crystal.
Fig. 1. Schematic drawing of two extreme cases of particle detection: a high energy nucleus of meV in nuclear physics and a low energy molecule of keV in analytical instruments for biology. The meV particle first undergoes electronic stopping with electrons and then nuclear stopping with nuclear collisions just before a complete stop. The keV molecule impinges on the detector surface and sticks on it while inducing the emission of a secondary electron or a secondary ion at a probability of less than unity.
The carriers of electron–hole pairs are generated by the energy-loss processes of energetic atomic ions or nuclei such as a-particles of meV. An energetic particle penetrates deep into the crystal, so that the particle forms the trace of electronic excitations and finally the cascades of atomic displacements before a stop, as shown in Fig. 1. The stopping of the energetic particle leads to the carrier production. The number of the carriers is proportional to the kinetic energy of the particle. The carriers generate a current pulse, which can be read out by a semiconductor-based amplifier. In this detector operation, the detection efficiency is unity, and we can obtain both of the arrival time and the kinetic energy on each particle hit event. These particle detectors are often used for an energy range of MeV in nuclear physics. If the particle kinetic energy decreases and is as low as less than keV, the atomic particles stop within surface dead-layers such as thin electrodes on the semiconductor detector surface. High-mass protein particles of keV land on the detector surface without penetration. In this case, the semiconductor detectors have essentially no sensitivity for the low energy particles, although the total kinetic energy of a particle is considerably larger than the semiconductor gap energy of eV. Other class of particle detectors relies on the emission of a secondary electron or a secondary ion from the surface at a particle hit event. The number of electrons or ions is multiplied by a factor of 106 with an electron multiplier in order to produce the charge number enough for semiconductor-based amplifiers. The particle energy in this detection mechanism can be less than keV, at which the particles cannot penetrate into the detector material. The efficiency of the secondary electron emission is roughly proportional to the particle velocity. Therefore, the detection efficiency drops with increasing molecular mass at a constant kinetic energy. For example, an MCP detector has a detection efficiency of 1–5% for a protein, bovine serum albumin (BSA) of 66,430 Da [14]. The unit of Da is used in biology, and equivalent to atomic mass unit. An example of the low energy particle impact is shown in Fig. 2, which is a differential interference contrast micrograph of an STJ detector surface after the detection of particles from atoms to such biomolecules as peptides and proteins with kinetic energies of 3–20 keV. Fig. 2 is the part of an array detector that has been used for time-of-flight mass spectrometry (TOF MS) for over one year. The small white dots in the bottom half of the micrograph indicate the remains of the particle hit events. It is certain that the incoming particles exist on the detector surface, since the white dots were
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structure with a thickness of less than 10 nm and a line width of less than 1 lm. This fine structure gives the fast relaxation of the deposited energy, which is quickly transferred to the substrate. Actual response time is governed by kinetic inductance of striplines [13]. 3. Analysis of low energy particles with superconducting detectors on TOF MS configuration The concept of the MS analysis using a STJ detector is illustrated in Fig. 3. Atoms or precursor molecules are ionized and accelerated by a static voltage of V, which is normally kV. Atoms or small molecules are ionized by electron impact (EI), fast-atom bombardment (FAB), etc., while biomolecules are ionized by matrix-assisted laser desorption/ionization (MALDI) or electrospray ionization (ESI) without decomposing into fragments in the ion source. The accelerated ions fly for a length of l. The time of flight (TOF) is given by Fig. 2. Differential interference contrast micrograph of the surface of a superconducting tunnel junction (STJ) detector used in time-of-flight mass spectrometry (TOF MS) for over one year. The array of the 200 lm-square junctions and wiring for the bottom and top electrodes are seen as the white lines. After the detection of particles from atoms to proteins with energies from 3 to 20 keV, the white dots which are the remains of the particle impact appeared on the detector surface.
easily removed by organic-solvent-washing or ozone-cleaning. Even in this particle landing situation, the STJ detectors generate current pulses for the particle hit events, as can be realized in the situation of the deep penetration of meV energetic nuclei into the Si detectors. The pulse height values correspond to the kinetic energies of particles. This spectroscopic particle detection with the STJ detector can be realized by the extremely small gap energy (2D). A difference in the electronic states between superconductors and semiconductors was discussed in Ref. [9]. The readout of the quasiparticle number is performed by measuring the increase of the subgap current between two electrodes of a junction, which is cooled at 0.3 K so that there are almost no thermally excited quasiparticles. The current pulses are usually amplified by a semiconductor-based amplifier, while a SQUID amplifier was also effective [15]. Other superconducting detectors such as normalinsulator-superconductor (NIS) junctions or transition edge sensors (TESs) were also used for TOF MS [16,17]. However, these detectors need very low operating temperatures less than 0.1 K, and have slow relaxation times, e.g., 17 ls, which is more than ten times longer than that of the STJ. The low operating temperatures and the slow response times are bottlenecks for practical use. Another possible superconducting detector that can be operated at 4 K is kinetic inductance detectors [18]. The time resolution of less than 1 ns is favorable for TOF MS in order to realize a high mass resolution. The conventional MCP detectors have a time resolution of 1 ns or better, although the unity detection efficiency is kept only up to approximately 4000 Da [15]. One of the candidates for detectors with a high time resolution and a unity detection efficiency is the SSLD. The operating principle of the SSLD is the same as that of the SSPD [11], but we use the acronym of SSLD for the particle detection in this paper because the SSPD assume the photon detection. The fast response is due to a hotspot formation leading to a resistive barrier across the stripline and its fast recovery to the superconducting state. The resistive barrier results in a voltage pulse formation, when a bias current of is applied just below the critical current of a stripline. The subsequent relaxation can be as fast as less than 100 ps. This operating principle is similar to that in Ref. [1], but it is very much faster. The operation of the Andrew’s detector may be calorimetric due to the bulky stripline and the meV energy deposition. The SSLDs fabricated recently have the sophisticated
TOF ¼
pffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi m=2zeV l;
ð1Þ
where m is the mass of the particle, z is the charge number of the ion, e is the electron charge. The TOF is proportional to the square root of m/z, and the particle velocity v is inversely proportional to the square root of m/z. The m/z value is the so-called mass-to-charge ratio, which is the dimensionless ratio of the relative mass to the charge number. The TOF measurement gives us only the m/z values of the intactions. Since the efficiency of the secondary electron emission is roughly proportional to the velocity, the detection efficiency of the conventional ion detectors decreases with increasing MW [19]. It is expected, on the other hand, that the superconducting detectors have unity detection efficiency independent on MW because of the meV threshold value. The threshold value is considerably smaller than the kinetic energies divided into the individual atoms forming a large molecule. Each atomic collision at the large molecule impact has a deposited energy enough for Cooper-pair breaking. The total energy deposition seems to be almost independent on MW, when the charge numbers of the ions are the same. Therefore, no MW dependence of the output pulse height is expected. An experimental result that supports the unity detection efficiency up to at least 1 M Da can be found in Ref. [10]. In addition to the analysis of intact ions, such dissociation processes as post-source decay (PSD), collision induced dissociation (CID), electron transfer dissociation (ETD), etc. are frequently employed to make fragments for structural analysis or molecule identification. The fragment patterns depend on molecular structures. For example, the fragmentation analysis makes possible to identify the amino acid orders of small biomolecules of peptides, which have the chains consisting of a few to over ten amino acids. The amino acid order corresponds to a DNA base sequence. This analysis is called ‘‘sequencing.” The fragments produced by dissociation carry the kinetic energies that are proportional to the MW values of fragments so that a equation of E = E1 + E2 + E3 is held for a simple dissociation example shown in Fig. 3. All of the fragments have the same velocity as that of the intact ion, so that they arrive at the detector surface simultaneously. It is, therefore, impossible to separate different fragments by using a conventional detector that is placed on the liner mode. It is necessary to add extra ion optics or the second MS instrument to analyze ionic fragments. On the other hand, the STJ detectors are able to measure the kinetic energies E1, E2, E3 of the fragments directly, so that we can analyze all the fragments including neutrals as well as ions. The analysis of neutrals is impossible in conventional MS instruments. We can realize mass spectroscopy for neutral particles without reionization by using superconducting detectors. The details which will be published elsewhere.
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Fig. 3. New concept of mass spectroscopy with superconducting detectors. The superconducting detectors have unity detection efficiency independent on molecular weight (MW). In addition, the analysis of both ionic fragments and neutral fragments can be performed through kinetic energy measurement with the array of small STJ pixels.
The kinetic energy of each fragment can be measured with the STJ array detector with a small pixel size of a few 100 lm, as shown in Fig. 3. At a dissociation event, each fragment has a slightly different deviation from the original flight direction because of kinetic energy release upon dissociation. The deviation results in the fact that individual fragments hit different pixels. Thus, the TOF values and the kinetic energies of the fragments can simultaneously be measured one by one. This new measurement method enables the fragment analysis for different precursor ions at the same time. The conventional MCP particle detectors have millions of microchannels, but the readout circuit is essentially single. The flight direction deviation is small, which means that all fragments arrive at the MCP surface at the same time. Moreover, the MCP detectors have no capability to measure the kinetic energies of the fragments. Therefore, the MCP detectors cannot distinguish the fragments produced from an intact precursor ion. The MS data of bovine serum albumin (BSA) of 66,430 Da with the STJ detector is shown in Fig. 4. The TOF values and the kinetic energies of the incoming particles including the intact ions and the fragment particles were measured. The TOF values were converted to the m/z values by Eq. (1). The individual particle hit events are plotted according to the m/z values and the kinetic energies in
Fig. 4b and e. The kinetic energy spectra in (a) and (d) show the ion count histograms against the kinetic energies for the data surrounded by the dotted lines in the scatter plots of (b) and (e). These selected events originate only from the singly charged intact BSA ions and the fragments produced from the BSA+. The mass spectra in (c) and (f) show the ion count histograms against the m/z values for all events. The upper three graphs, (a–c), were taken at the ionization condition of a pulsed UV laser energy of 8 lJ in the MALDI process. The laser energy was increased to 12 lJ in the lower three graphs, (d–f). The mass spectra for both laser energies are essentially the same except for more pronounced background at 12 lJ. In contrast to the similarity of the mass spectra, the m/z versus kinetic energy scatter plots in (b) and (e) exhibit a large difference between 8 and 12 lJ. The vertical streak at the m/z value of 66,430 for 12 lJ indicates the presence of the large number of fragments that have the same TOF value but different kinetic energies less than that of the precursor ion. The fragmentation is also clearly observed in the kinetic energy spectra in Fig. 4a and d. The single peak is observed at 8 lJ, which indicates that almost all particles are the intact BSA molecules that carry the energy of 17.5 keV. On the other hand, no peak corresponding to the intact BSA is recognized at 12 lJ, and the low energy events less than 17.5 keV
Fig. 4. Mass spectra and related data measured by an STJ for a protein, bovine serum albumin (BSA) of 66,430 Da: kinetic energy spectra (a) (d), m/z versus kinetic energy scatter plots (b) (e), and mass spectra (c) (f). The protein was ionized by the matrix-assisted laser desorption/ionization (MALDI). The particles accelerated at 17.5 keV were detected by the STJ detector. The energies of UV laser pulses in the MALDI process were 8 lJ for the upper three graphs (a–c) and 12 lJ for the lower three graphs (d–f). The laser pulse energies greatly affect the extent of the fragmentation due to post-source decay (PSD).
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conductor-based particle detectors operating above 77 K and MCP at room temperature. The superconducting particle detectors will play an important role for advanced mass spectroscopy. Superconducting particle detectors of superconducting tunnel junctions (STJs) as particle spectrometers and superconducting stripline detectors (SSLDs) as ultrafast particle counters are promising for developing new MS instruments. Both superconducting particle detectors have already been producing the remarkable results that cannot be obtained with the conventional MS instruments. A large market of the MS instruments with superconductivity is expected for many fields from industries to sciences. Acknowledgments
Fig. 5. Temporal response of the superconducting NbN stripline detector (SSLD) to a peptide, Angiotensin I of 1296 Da and BSA of 66,430 Da.
are significant for the fragments. This fragmentation process is called PSD, which originates from a molecular excitation upon the ionization or during the acceleration. The excited molecules decay into the small fragments during the free flight period after the acceleration. At this stage, we have obtained the time resolution of several 10 ns with the STJ detectors [20]. Better time response is desirable for high mass–resolution, and has been realized with the 50 lmsquare NbN SSLD with a thickness of 7 nm and a stripline width of 200 nm. Fig. 5 shows a comparison of temporal response between a peptide, Angiotensin I of 1296 Da, and a protein, BSA of 66,430 Da. It was confirmed that the pulses have a risetime of 540 ps and a falltime of 20–40 ns. The first mass spectra measured with the SSLD are reported in Ref. [21]. The SSLDs are expected to have both of fast response time and unity detection efficiency independent on MW, although additional experiments are required to confirm unity detection efficiency. Other merit of the NbN SSLDs is that the operating temperature is 4 K, which is considerably higher than 0.3 K for the STJ detectors. The SSLDs with oxide superconductors having higher Tc are attractive for the operation at higher temperatures. The STJ and SSLD are effective at different positions in MS instruments. The STJ is powerful in analyzing the fragments for structural analysis of molecules at the linear mode position shown in Fig. 3. The kinetic energy measurement with the STJ is also useful for discrimination of the different charge states with the same m/z value. This performance has realized the clear separation between 14N2++ and 14N+, which have never been separately measured before [22], and the fragment analysis of Immunoglobulin G (IgG) [23]. In addition, the STJ can be used to observe microscopic particle-surface interactions through the measurement of the energies deposited to the detector surface [24]. The SSLD with the ultrafast response may be effective after additional optics such as reflectron to improve mass resolution.
The author would like to thank M. Ukibe, A. Kurokawa, Yigang Chen, Yiner Chen, K. Chiba, Y. Kobayashi, Y. Shimizugawa, K. Suzuki, S. Shiki of Superspectroscopy System Research Group at AIST for experimental works and fruitful discussion. Many thanks go to H. Sato, T. Kinumi, Y. Shigeri, Z. Wang, S. Miki, S. Hayakawa, S. Tomita, Y. Sato, K. Teramoto, and M. Setou for performing novel MS experiments. This work was supported by the JST-SENTAN Project (Japan Science and Technology Agency). References [1] [2] [3] [4] [5] [6]
[7] [8] [9] [10]
[11]
[12] [13] [14] [15] [16] [17] [18] [19] [20] [21]
4. Conclusion
[22]
It has been demonstrated that superconducting detectors operating below 4 K provide the outstanding particle detection performance, which cannot be realized by the conventional semi-
[23] [24]
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