Ionization Mass

Application of Matrix-Assisted Laser Desorption/Ionization Mass...

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Application of Matrix-Assisted Laser Desorption/Ionization Mass Spectrometric Imaging for Photolithographic Structuring Anna C. Crecelius,*,†,‡,§ Ralf Steinacker,†,‡ Alexander Meier,†,‡ Theodore Alexandrov,∥,⊥,⊗ Jürgen Vitz,†,‡,§ and Ulrich S. Schubert†,‡,§ †

Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich-Schiller-University Jena, Humboldtstrasse 10, 07743 Jena, Germany ‡ Jena Center for Soft Matter (JCSM), Friedrich-Schiller-University Jena, Humboldtstrasse 10, 07743 Jena, Germany § Dutch Polymer Institute (DPI), John F. Kennedylaan 2, 5612 AB Eindhoven, The Netherlands ∥ Steinbeis Innovation Center for Scientific Computing in Life Sciences (SCiLS), Bremen, Germany ⊥ Center for Industrial Mathematics, University of Bremen, Bremen, Germany ⊗ MALDI Imaging Lab, University of Bremen, Bremen, Germany S Supporting Information *

ABSTRACT: The aim of this contribution is the application of matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI) in the area of photolithographic structuring. As proof of concept, this method was used to image an UV exposed negative photoresist layer, which is generally used to manufacture printed circuit boards (PCB) for electronic components. The negative photoresist layer consisting of the main component novolac, benzophenone as the active component, and the solvent tetrahydrofuran was mixed with the matrix dithranol and the salt additive LiTFA and spin-coated onto an ITO-conductive glass slide. To imprint an image on the created surface, a transparency with a printed wiring diagram was placed on top of it and irradiated by UV light for 15 min. The inspection of the efficient imprinting of the microstructure onto the photoresist layer was performed by MALDI-MSI. This unique application represents a further step toward the surface analysis of polymer films by this emerging life science imaging technique.


performed solvent removal steps. Because of the small size of the ion beam, a resolution of about 4 μm could be achieved. This is not possible with commercial MALDI-TOF instruments, which can perform MSI experiments, since the current ion optics can focus in most cases only the laser down to 10 μm. The soft ionization technique MALDI used for MSI enables the detection of intact ions, which is not possible by SIMS-MSI, as shown by the Castner group.9,10 In the present study, the surface analysis of a photoresist is elucidated by employing MALDI-MSI as the imaging technique. Photoresists can be either positive or negative. In a positive photoresist, the area exposed to light becomes soluble to the photoresist developer, which is typically a basic aqueous solution used to remove only the soluble areas and the rest remains insoluble. In a negative photoresist the behavior is vice versa. Both photoresists are used, e.g., in the production of printed circuit boards (PCB) for electronic components. Different companies (for an example, see ref 11) are producing

atrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI) is on the way to become a mainstream analytical technique in life science related areas.1,2 It is commonly used to monitor endogenous or administered compounds, such as lipids,3 metabolites,4 peptides,5 proteins,6 and xenobiotics,7 within biological tissues. A new application field of MALDI-MSI has been recently presented,8 which involves the surface analysis of polymer films. Poly(styrene) (PS) films were irradiated by UV light for several times and caused a reduction of the recorded PS signals until finally no signals of PS in the irradiated area could be recorded due to the cross-linking of the treated PS film. A correlation between the UV irradiation time and the signal decrease of PS could be established. The presented investigation was considered as a first example for the application of this new approach of MALDI-MSI in polymer science. The analysis of polymer surfaces by MSI using secondary ion mass spectrometry (SIMS) instead of the soft ionization technique MALDI was already presented by the Castner group.9,10 In their studies the authors nicely demonstrated that the photoresist, which is a light-sensitive material, used commonly in photolithography, still remains on the surface despite commonly © 2012 American Chemical Society

Received: June 12, 2012 Accepted: July 26, 2012 Published: July 26, 2012 6921 | Anal. Chem. 2012, 84, 6921−6925

Analytical Chemistry


Figure 1. Schematic representation of the synthesis of the novolac resin. The methylene bridges are attached in the ortho/ortho or ortho/para position relative to the hydroxyl-substituted carbon atom.

these photoresists, which are also optimized for different coating-methods like roll, spin-, or slit coating. Since we were unable to analyze the commercial available positive photoresist (Positiv 20, e.g., see ref 12) by MALDI time-of-flight mass spectrometry (TOF MS) due to the containing dye, which was suppressing all ion signals of the other components, we formulated our own negative photoresist, consisting of a novolac resin, a photoactive compound, and a solvent.13,14 The surface analysis of the negative photoresist layer by MALDIMSI verified that the anticipated imprinting of an audio operational amplifier (OPA) wiring diagram successfully occurred by UV irradiation of the surface. This second example of MALDIMSI for the surface analysis of polymers highlights the potential of the technique in the described field and should inspire more researchers to pursue this new approach.

EXPERIMENTAL SECTION Synthesis of the Novolac Resist. The novolac resin, also known as phenol resin or Bakelit, was synthesized based on the classical route using a mixture of phenol, formaldehyde, and an acid.15−22 In our optimized procedure, the phenol (50 mL, 568 mmol) was melted in a water bath at 60 °C and then added into a 250 mL round-bottom flask. The 35% formaldehyde solution (35 mL, 455 mmol) and the 37% HCl solution (1 mL, 12 mmol) were added to the melted phenol, and the mixture was heated at 90 °C under reflux for several hours. After phase separation into two phases, the upper aqueous phase was decanted and the lower resin phase was washed several times with hot water to remove traces of HCl. Afterward, the resin was filled in an aluminum pan and slowly heated up to 200 °C to remove the unreacted formaldehyde. After the resin became clear, the temperature was shortly increased to 260 °C to remove traces of unreacted phenol. Subsequently, the resin was cooled to room temperature. The top red layer was removed by grinding, and the remaining resin was converted into a powder with a mortar and a pestle (35.12 g, 331 mmol, 58%). The elemental analysis results showed a small deviation from the expected values for the carbon and hydrogen content, which can be explained by the hygroscopic nature of the novolac resin. Assuming that all phenol could be removed by the abovementioned heating procedure, approximately 2.5% of water is attracted to the resin. However, this represents no problem for the later applied MALDI-MSI analysis; therefore, the novolac resin was not further dried. Preparation of a Negative Photoresist Layer. A solution of the novolac resin (10 mg/mL in tetrahydrofuran, THF) containing 10% w/w benzophenone was mixed with the matrix solution (dithranol, 20 mg/mL in THF) and the salt solution (LiTFA, 100 mg/mL in THF) in a volume ratio of 1:3:1 (v/v/v). A volume of 100 μL of this mixture was spincoated onto an indium−tin-oxide (ITO) glass slide at 2 000 rpm for 30 s using a standard spin-coater (model WS-400B-6NPP/ LITE, Laurell Technologies Corporation).

Figure 2. MALDI-TOF mass spectra of the novolac resin, prepared with the matrix dithranol and (a) NaI and (b) LiTFA as salt additives.

UV Irradiation. A transparency with a printed wiring diagram was placed on top of the ITO glass-slide with the negative photoresist layer and irradiated for 15 min with UV light (Hönle UVA cube 100). The printed transparency was acting as a mask, and the UV light was penetrating through the areas which were not colored black. MALDI-MSI Data Acquisition. Prior to the MALDI-MSI analysis, the transparency was removed. The MALDI-MSI analysis was performed on an Ultraflex III MALDI-TOF/TOF mass spectrometer (Bruker Daltonics, Bremen, Germany) equipped with a “smartbeam” laser (λ = 355 nm, repetition rate 200 Hz). The laser energy was in the range of the threshold energy for the novolac resin, thus avoiding any fragmentation of the polymer/cross-linked surface. Fleximaging software version 3.0 (Bruker Daltonics) was used for spectral acquisition and evaluation throughout all experiments. Before every measurement, the instrument was calibrated with an external standard (poly(methyl methacrylate), PSS GmbH). All spectra were measured in the positive reflectron mode, and the m/z range 100 to 4 500 was scanned. Typically, 200 shots were 6922 | Anal. Chem. 2012, 84, 6921−6925

Analytical Chemistry


Figure 3. MALDI-MSI analysis of a prepared negative photoresist layer, spin-coated onto an ITO glass-slide and covered by a transparency, on which a wiring diagram of an OPA was printed with a laser printer.

Figure 4. Results of the multivariate analysis of the MALDI-MSI data using two clusters which were colocalized with the conducting path applying the segmentation method. (A) The m/z-values shown on the data set mean spectrum; the annotation 1479 +1 + 2 denotes three ions 1479, 1480, and 1481. (B) The resulting average m/z image for all m/z values between 1 000 and 2 500.

SCiLS Lab software (SCiLS, Bremen, Germany) was used with the following settings: TIC-normalization, peak picking with the OMP algorithm, 100 peaks per spectrum, each 50th spectrum, threshold 1%, peaks alignment to the mean spectrum; clustering with the bisecting k-means algorithm, Euclidean distance, see ref 24 for more details on the algorithms and parameters.

accumulated for a spectrum; about 13 200 positions were recorded for two selected areas with a spatial resolution of 100 μm. The size of the two imaged areas was approximately 60 and 70 mm2, respectively. The acquisition time was in the range of 15 h. MALDI-MSI Data Analysis and Interpretation. For analysis and interpretation of the obtained MALDI-MSI data, we used the spatial segmentation method.23 First, we processed the spectra and grouped them into seven clusters by similarity using a multivariate clustering algorithm. Then, pixels of each cluster were represented with one pseudocolor, creating the so-called segmentation map (see the Supporting Information, Figure S-1A). After visual examination of the segmentation map overlaid with the optical image, we selected clusters corresponding to the conducting paths (see the Supporting Information, Figure S-1B). Then, we found m/z-values colocalized with the complement of these clusters, i.e., those m/z-values which have low intensity in the selected regions (conducting paths) and high intensity in the rest of the sample. For the analysis, the

RESULTS AND DISCUSSION Since the MALDI-TOF MS analysis of a commercial photoresist (Positiv 2012) was unsuccessful due to the blue ink, which was suppressing all other ions in the positive photoresist, a negative photoresist was prepared by synthesizing the main component, novolac, based on the classical route by L. H. Baekeland using a mixture of phenol, formaldehyde, and acid.15−22 From the 1H NMR and 13C NMR spectroscopy data (see the Supporting Information, Figures S-2−S-4) it could be concluded that the methylene bridges were attached in the polymer 6923 | Anal. Chem. 2012, 84, 6921−6925

Analytical Chemistry


wiring diagrams. The described study shows that the imaging technique MALDI-MSI can indeed be applied in the field of lithographic structuring to follow the success of the imprinting step, in particular in the field of PCB manufacturing for singleor double-sided boards or even flexible plastics, which we have chosen as an example. In this area, different techniques are used to create conducting copper layers on substrates. In most cases, a copper layer is bonded over the whole substrate and the unwanted copper is removed by subtractive processes, e.g., silk screen printing, photoengraving or milling, or additive processes, e.g., electroplating.29,30 In particular the illumination step of the photoengraving technique could benefit in our view by direct analysis without the need to chemically develop and etch the circuit to remove the unwanted copper surface as presented in Figure 5 (after step 3). This helps to reduce both

chain at the ortho/ortho or ortho/para positions relative to the hydroxyl-substituted carbon atom, as already described by Ottenbourgs et al.25 The synthesis of the polymer novolac is shown in Figure 1. For the MALDI-TOF MS analysis of the novolac, a solution (10 mg/mL in THF) was mixed with various matrixes (dithranol, DCTB, DHB, IAA, HABA; 20 up to 40 mg/mL in THF) and salt additives (NaI, KCl, LiTFA; 100 mg/mL in acetone or THF) in the volume ratios 1:3:1 (v/v/v) and spotted onto a MALDI target (dried-droplet method).26 The best spectra (good signal-to-noise levels, 25, and adequate resolution, 23 654) were obtained by using the matrix dithranol and the salt additives NaI or LiTFA, as presented in parts a and b of Figure 2, respectively. The novolac resist could be detected in both mass spectra from 3 to 16 repeating units with the correct spacing of m/z 106. The next step in this study was to prepare a layer of the negative photoresist with the matrix dithranol and the salt additive LiTFA by spin-coating the mixture onto an ITO glassslide. As the photoactive compound, initially triarylsulfonium hexafluoroantimonate was mixed at 10% w/w to the novolac resist; however, ion suppression27 of the novolac signals occurred during the MALDI-TOF MS determination (data not shown). Hence, benzophenenone was used instead at 10% w/w. To imprint the wiring diagram of the operational amplifier (OPA), which was designed with the PCB layout software Target 3001!,28 on the negative photoresist layer, a mirror inverted transparency black-and-white print-out was used. The aura and the conducting paths shown in the optical image of Figure 3 are transparent, which means that UV light could pass through the transparency at these positions. The rest was colored in black protecting the negative photoresist layer from UV light. The manual analysis of MALDI-MSI data revealed that the signal intensities of the undecamer and the tridecamer of the novolac resist is lower in the areas where the UV light was penetrating through the mask. The reasons for this signal decrease can be explained by the cross-linking occurring as a result of the UV irradiation.8 The MALDI-MSI images of the undecamer and tridecamer signals of the novolac resin are presented in Figure 3 with a spectrum (sum of 200 shots) acquired at a position protected from UV light. The multivariate analysis of the MALDI-MSI data revealed that in the m/z region from 730 to 2 500 all repeating units of the novolac resin were detected (from pentamer to henicosane) as having low intensity in the conducting paths and high intensity in the rest of the sample (Figure 4A). Note that only few other ions in this m/z range with the same spatial distribution pattern were detected, namely, m/z 743, 747, 849, 955, 958, 959, and 960. In Figure 4B the average MALDI-MSI image for all m/z values between 1 000 and 2 500 colocalized with the conducting paths using the segmentation approach is presented. As discussed, these colocalized m/z values correspond to the different repeating units of the novolac resin. Note the low intensities inside the conducting paths. The higher quality of the image as compared to individual m/z images for the undecamer and tridecamer (see Figure 3) can be explained by the noise-suppressing effect of averaging of many m/z images. Only two areas of the whole wiring diagram have been imaged with a resolution of 100 μm, since the analysis time was already over 15 h. The aura and the conducting paths were 300 μm thick in diameter and, therefore, consisted of three pixels in the MALDI-MSI images. This scale is usually used in

Figure 5. General production steps for a PCB (one sided) using a photo mask. 6924 | Anal. Chem. 2012, 84, 6921−6925

Analytical Chemistry


(8) Crecelius, A. C.; Alexandrov, T.; Schubert, U. S. Rapid Commun. Mass Spectrom. 2011, 25, 2809−2814. (9) Takahashi, H.; Emoto, K.; Dubey, M.; Castner, D. G.; Grainger, D. W. Adv. Funct. Mater. 2008, 18, 2079−2088. (10) Dubey, M.; Emoto, K.; Cheng, F.; Gamble, L. J.; Takahashia, H.; Grainger, D. W.; Castner, D. G. Surf. Interface Anal. 2009, 41, 645− 652. (11) AZ Electronic Materials, (12) CRC. Industries Kontakt Chemie,, purchased from Conrad Electronic SE. (13) Shaw, J. M.; Gelorme, J. D.; LaBianca, N. C.; Conley, W. E.; Holmes, S. J. IBM J. Res. Dev. 1997, 41, 81−94. (14) Wilson, C. G.; Trinque, B. C. J. Photopolym. Sci. Technol. 2003, 16, 621−628. (15) Baekeland, L. H. Ind. Eng. Chem. 1909, 1, 149−161. (16) Baekeland, L. H. Ind. Eng. Chem. 1909, 1, 545−549. (17) Kleeberg, W. Annalen 1891, 263, 283−286. (18) Bayer, A. Chem. Ber. 1872, 5, 1095. (19) Bayer, A. Chem. Ber. 1872, 19, 3004. (20) Bayer, A. Chem. Ber. 1872, 19, 3009. (21) Bayer, A. Chem. Ber. 1872, 25, 3477. (22) Bayer, A. Chem. Ber. 1872, 27, 2411. (23) Alexandrov, T.; Becker, M.; Deininger, S. O.; Ernst, G.; Wehder, L.; Grasmair, M.; von Eggeling, F.; Thiele, H.; Maass, P. J. Proteome Res. 2010, 9, 6535−6546. (24) Trede, D.; Schiffler, S.; Becker, M.; Wirtz, S.; Steinhorst, K.; Strehlow, J.; Aichler, M.; Kobarg, J. H.; Oetjen, J.; Dyatlov, A.; Heldmann, S.; Walch, A.; Thiele, H.; Maass, P.; Alexandrov, T. Anal. Chem. 2012, 84, 6079−6087. (25) Ottenbourgs, B.; Adriaensens, P.; Carleer, R.; Vanderzande, D.; Gelan, J. Polymer 1998, 39, 5293−5300. (26) Raeder, H. J.; Schrepp, W. Acta Polym. 1998, 49, 272−293. (27) Zenobi, R.; Knochenmuss, R. Mass Spectrom. Rev. 1998, 17, 337−366. (28) Target 3001! V15 discover, Ing.-Buero Friedrich, http://www. (29) Harper, C. A. Electronic Materials and Processes Handbook; McGraw-Hill: New York, 2003. (30) Coombs, C. F., Jr. Printed Circuits Handbook; McGraw-Hill Professional: New York, 2007. (31) Davis, B. Circuit World 1983, 10, 32−34. (32) Ryan, A.; Lewis, H. Robotics Comput.-Integrated Manuf. 2007, 23, 720−726. (33) Perelaer, J.; Smith, P. J.; Mager, D.; Soltman, D.; Volkman, S. K.; Subramanian, V.; Korvink, J. G.; Schubert, U. S. J. Mater. Chem. 2010, 20, 8446−8453.

time and waste using either positive or negative photoresists besides reducing the so-called etch-back effect. Furthermore, in case of an unsuccessful illumination, the nonetched coppersubstrate can be used again by applying new photoresist and a mask; this is potentially interesting when using expensive PCB materials, e.g., polyimides, and helps to improve quality, to increase productivity, and therefore to also reduce costs for the production of PCBs.31 Furthermore, this technique could be used in the field of printing conductive inks and adhesives.32,33

CONCLUSIONS The successful surface analysis of a negative photoresist layer was presented by MALDI-MSI for the first time. This is a further step toward the development of new applications of MALDI-MSI in the field of polymer science in addition to a potential improvement of the illumination step in the field of PCB manufacturing. Future experiments will be conducted to image wiring diagrams imprinted on a negative photoresist layer, which is spin-coated on a copper plate, commonly used for photolitographic structuring. Further areas could be the MSI-analysis of organic light-emitting diode (OLED) layers, based on both small molecules and polymers or organic solar cell layers, which represents growing fields in electronics and energy technology.


S Supporting Information *

Additional information as noted in the text. This material is available free of charge via the Internet at


Corresponding Author

*E-mail: [email protected]. Notes

The authors declare no competing financial interest.

ACKNOWLEDGMENTS The authors Ulrich S. Schubert, Jürgen Vitz, and Anna C. Crecelius thank the Dutch Polymer Institute (DPI, Technology Area High Throughput Experimentation) and the Thüringer Ministerium für Bildung, Wissenschaft und Kultur (Grant No. B515-07008) for the financial support of this study. Anna C. Crecelius additionally is grateful for the funding provided by the ProChance 2010 Project of the Friedrich-Schiller-University Jena. Furthermore, the authors acknowledge Stefan Schiffler (SCiLS, Bremen) for his help with the multivariate analysis of the data.


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