(1) Bhalla, N.; Jolly, P.; Formisano, N.; Estrela, P. Essays Biochem. 2016, 60, 1–8.
(2) Udugama, B.; Kadhiresan, P.; Kozlowski, H. N.; Malekjahani, A.; Osborne, M.;
Li, V. Y.; Chen, H.; Mubareka, S.; Gubbay, J. B.; Chan, W. C. ACS nano 2020,
14, 3822–3835.
(3) Kevadiya, B. D. et al. Nat. Mater. 2021, 20, 593–605.
(4) Masterson, A. N.; Muhoberac, B. B.; Gopinadhan, A.; Wilde, D. J.; Deiss, F. T.;
John, C. C.; Sardar, R. Anal. Chem. 2021, 93, 8754–8763.
(5) Homola, J. Anal. Bioanal. Chem. 2003, 377, 528–539.
(6) Wang, J.; Zhou, H. S. Anal. Chem. 2008, 80, 7174–7178.
(7) Piliarik, M.; Bocková, M.; Homola, J. Biosens. Bioelectron. 2010, 26, 1656–1661.
(8) Qu, J. H.; Dillen, A.; Saeys, W.; Lammertyn, J.; Spasic, D. Anal. Chim. Acta 2020,
1104, 10–27.
14
(9) Watanabe, S.; Murozaki, Y.; Sugiura, H.; Sato, Y.; Honbe, K.; Arai, F. Sens. Actuators
A: Phys. 2021, 317, 112475.
(10) Chappanda, K. N.; Shekhah, O.; Yassine, O.; Patole, S. P.; Eddaoudi, M.; Salama, K. N.
Sens. Actuators B: Chem. 2018, 257, 609–619.
(11) Yao, Y.; Huang, X.; Zhang, B.; Zhang, Z.; Hou, D.; Zhou, Z. Sens. Actuators B: Chem.
2020, 302, 127192.
(12) Jin, X.; Huang, Y.; Mason, A.; Zeng, X. Anal. Chem. 2009, 81, 595–603.
(13) Rianjanu, A.; Fauzi, F.; Triyana, K.; Wasisto, H. S. ACS Appl. Nano Mater. 2021, 4,
9957–9975.
(14) Zhou, L.; Nakamura, N.; Nagakubo, A.; Ogi, H. Appl. Phys. Lett. 2019, 115, 171901.
(15) Chen, D.; Li, H.; Su, X.; Li, N.; Wang, Y.; Stevenson, A. C.; Hu, R.; Li, G. Sens.
Actuators B: Chem. 2019, 287, 35–41.
(16) Reviakine, I.; Johannsmann, D.; Richter, R. P. Anal. Chem. 2011, 83, 8838–8848.
(17) Ogi, H. Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. 2013, 89, 401–417.
(18) Sauerbrey, G. Z. Phys. 1959, 55, 206–222.
(19) Ogi, H.; Fukunishi, Y.; Omori, T.; Hatanaka, K.; Hirao, M.; Nishiyama, M. Anal.
Chem. 2008, 80, 5494–5500.
(20) Ogi, H.; Nagai, H.; Fukunishi, Y.; Hirao, M.; Nishiyama, M. Anal. Chem. 2009, 81,
8068–8073.
(21) Zhang, Y.; Rojas, O. J. Biomacromolecules 2017, 18, 526–534.
(22) Hampitak, P.; Jowitt, T. A.; Melendrez, D.; Fresquet, M.; Hamilton, P.; Iliut, M.;
Nie, K.; Spencer, B.; Lennon, R.; Vijayaraghavan, A. ACS Sens. 2020, 5, 3520–3532.
15
(23) Hu, J.; Yesilbas, G.; Li, Y.; Geng, X.; Li, P.; Chen, J.; Wu, X.; Knoll, A.; Ren, T. L.
Anal. Chem. 2022, 94, 5760–5768.
(24) Kato, F.; Ogi, H.; Yanagida, T.; Nishikawa, S.; Hirao, M.; Nishiyama, M. Biosens.
Bioelectron. 2012, 33, 139–145.
(25) Kato, F.; Noguchi, H.; Kodaka, Y.; Oshida, N.; Ogi, H. Jpn. J. Appl. Phys. 2018, 57,
07LD14.
(26) Zhou, L.; Kato, F.; Ogi, H. Jpn. J. Appl. Phys. 2021, 60, SDDB03.
(27) Noi, K.; Iwata, A.; Kato, F.; Ogi, H. Anal. Chem. 2019, 91, 9398–9402.
(28) Jiang, X.; Wang, R.; Wang, Y.; Su, X.; Ying, Y.; Wang, J.; Li, Y. Biosens. Bioelectron.
2011, 29, 23–28.
(29) Chen, Q.; Tang, W.; Wang, D.; Wu, X.; Li, N.; Liu, F. Biosens. Bioelectron. 2010, 26,
575–579.
(30) Dong, Z. M.; Jin, X.; Zhao, G. C. Biosens. Bioelectron. 2018, 106, 111–116.
(31) Yang, H.; Li, Y.; Wang, D.; Liu, Y.; Wei, W.; Zhang, Y.; Liu, S.; Li, P. ChemComm.
2019, 55, 5994–5997.
(32) Ogi, H.; Yanagida, T.; Hirao, M.; Nishiyama, M. Biosens. Bioelectron. 2011, 26, 4819–
4822.
(33) Thies, J. W.; Kuhn, P.; Thürmann, B.; Dübel, S.; Dietzel, A. Microelectron. Eng. 2017,
179, 25–30.
(34) Noi, K.; Iijima, M.; Kuroda, S.; Ogi, H. Sens. Actuators B: Chem. 2019, 293, 59–62.
(35) Lee, D.; Yoo, M.; Seo, H.; Tak, Y.; Kim, W. G.; Yong, K.; Rhee, S. W.; Jeon, S. Sens.
Actuators B: Chem. 2009, 135, 444–448.
16
(36) Yan, J.; Zhao, C.; Ma, Y.; Yang, W. Biomacromolecules 2022, 23, 2614–2623.
(37) Liu, Y.; Yu, J. Microchim. Acta 2016, 183, 1–19.
(38) Park, M. Biochip J. 2019, 13, 82–94.
(39) Yuan, Y.; He, H.; Lee, L. J. Biotechnol. Bioeng. 2009, 102, 891–901.
(40) Tajima, N.; Takai, M.; Ishihara, K. Anal. Chem. 2011, 83, 1969–1976.
(41) Neubert, H.; Jacoby, E. S.; Bansal, S. S.; Iles, R. K.; Cowan, D. A.; Kicman, A. T.
Anal. Chem. 2002, 74, 3677–3683.
(42) Kausaite-Minkstimiene, A.; Ramanaviciene, A.; Kirlyte, J.; Ramanavicius, A. Anal.
Chem. 2010, 82, 6401–6408.
(43) Iijima, M.; Nakayama, T.; Kuroda, S. Biosens. Bioelectron. 2020, 150, 111860.
(44) Iijima, M.; Matsuzaki, T.; Kadoya, H.; Hatahira, S.; Hiramatsu, S.; Jung, G.;
Tanizawa, K.; Kuroda, S. Anal. Biochem. 2010, 396, 257–261.
(45) Nilsson, B.; Moks, T.; Jansson, B.; Abrahmsen, L.; Elmblad, A.; Holmgren, E.; Henrichson, C.; Jones, T. A.; Uhlén, M. Prot. Eng. 1987, 1, 107–113.
(46) Iijima, M.; Somiya, M.; Yoshimoto, N.; Niimi, T.; Kuroda, S. Sci. Rep. 2012, 2, 00790.
(47) Noi, K.; Iijima, M.; Kuroda, S.; Kato, F.; Ogi, H. Jpn. J. Appl. Phys. 2020, 59,
SKKB03.
(48) Iijima, M. et al. Biomaterials 2011, 32, 1455–1464.
(49) Kato, F.; Ogi, H.; Yanagida, T.; Nishikawa, S.; Nishiyama, M.; Hirao, M. Jpn. J. Appl.
Phys. 2011, 50, 07HD03.
(50) Liu, Y.; Yu, X.; Zhao, R.; Shangguan, D. H.; Bo, Z.; Liu, G. Biosens. Bioelectron.
2003, 19, 9–19.
17
(51) Ogi, H.; Motohisa, K.; Hatanaka, K.; Ohmori, T.; Hirao, M.; Nishiyama, M. Biosens.
Bioelectron. 2007, 22, 3238–3242.
(52) Christodoulides, N.; Mohanty, S.; Miller, C. S.; Langub, M. C.; Floriano, P. N.; Dharshan, P.; Ali, M. F.; Bernard, B.; Romanovicz, D.; Anslyn, E.; Fox, P. C.; McDevitt, J. T. Lab Chip 2005, 5, 261–269.
(53) Vashist, S. K.; Venkatesh, A. G.; Schneider, E. M.; Beaudoin, C.; Luppa, P. B.; Luong, J. H. Biotechnol. Adv. 2016, 34, 272–290.
(54) Zhang, L.; Li, H. Y.; Li, W.; Shen, Z. Y.; Wang, Y. D.; Ji, S. R.; Wu, Y. Front.
immunol. 2018, 9, 1–5.
(55) Vashist, S. K.; Czilwik, G.; Oordt, T. V.; Stetten, F. V.; Zengerle, R.; Schneider, E. M.;
Luong, J. H. Anal. Biochem. 2014, 456, 32–37.
(56) Gupta, R. K.; Periyakaruppan, A.; Meyyappan, M.; Koehne, J. E. Biotechnol. Bioeng.
2014, 59, 112–119.
(57) Boonkaew, S.; Chaiyo, S.; Jampasa, S.; Rengpipat, S.; Siangproh, W.; Chailapakul, O.
Microchim. Acta 2019, 186, 1–10.
(58) Baradoke, A.; Hein, R.; Li, X.; Davis, J. J. Anal. Chem. 2020, 92, 3508–3511.
(59) Aray, A.; Chiavaioli, F.; Arjmand, M.; Trono, C.; Tombelli, S.; Giannetti, A.; Cennamo, N.; Soltanolkotabi, M.; Zeni, L.; Baldini, F. J. Biophotonics 2016, 9, 1077–1084.
(60) Bini, A.; Centi, S.; Tombelli, S.; Minunni, M.; Mascini, M. Anal. Bioanal. Chem. 2008,
390, 1077–1086.
(61) Vashist, S. K.; Schneider, E. M.; Luong, J. H. Analyst 2015, 140, 4445–4452.
(62) Ding, P.; Liu, R.; Liu, S.; Mao, X.; Hu, R.; Li, G. Sens. Actuators B: Chem. 2013, 188,
1277–1283.
18
(63) Gao, K.; Cui, S.; Liu, S. Int. J. Electrochem. Sci. 2018, 13, 812–821.
19
!"##
(#$))
*#$%&'
+",-$.#-/01',$1-
$"##
!"##
'(
+(-#&+.-/0"$$%*&
!" #$%
&'
&''/-#,'$/'',
)(%*+,
#$%&&
!"
'(
!"#$%&'#(&)*
(#$))
*#$%&
"--.*/%-+.--%
*&2-12%,''/)
Figure 1: (A) Illustration of the fabricated MEMS QCM biosensor chip and (B) its crosssection view. (C) Explanation of the three-layer structure of the chip.
Figure 2: (A) Illustration of the MEMS QCM functionalization process. (B) Schematic of
the QCM surface functionalized by SAM and protein A for IgG detection. (C) Frequency
responses of the 125-MHz MEMS QCM biosensor in IgG detection during the binding reaction.
20
Figure 3: (A) Illustration of the cross-section of the ZZ-BNC. (B) Schematic of the QCM
surface functionalized by ZZ-BNC for IgG detection. (C) Frequency responses of the 125MHz MEMS QCM biosensor in IgG detection during the binding reaction. (D) Frequency
decreases measured by the 125-MHz MEMS QCM in IgG detection using protein A and
ZZ-BNC at 30 min. (E) Exponential coefficients of the frequency decrease curves in IgG
detection using protein A and ZZ-BNC as functions of the IgG concentration. The inset
shows the binding affinity between IgG and protein A and between IgG and ZZ-BNC.
21
&53IORZ
$QWL&53
&RQWURO
&53
SJ P/
∆II SSP
∆II SSP
7LPHKRXU
&53FRQFHQWUDWLRQ QJိP/
Figure 4: (A) Schematic of the QCM surface functionalized by ZZ-BNC and anti-CRP antibody for CRP detection. (B) Frequency responses of the 166-MHz MEMS QCM biosensor
in CRP detection during the binding reaction. (C) Frequency decreases at 10 min against
the logarithm of CRP concentration.
22
For Table of Contents Only
23
Mass-fabrication scheme of highly sensitive wireless
electrodeless MEMS QCM biosensor with antennas on inner
walls of microchannel
Lianjie Zhou,†,⊥ Fumihito Kato,‡,⊥ Masumi Iijima,¶ Tomoyuki Nonaka,§ Shun’ichi Kuroda,∥ and Hirotsugu Ogi∗,† †Graduate School of Engineering, Osaka University, Yamadaoka 2-1, Suita, Osaka 565-0871, Japan ‡Department of Mechanical Engineering, Nippon Institute of Technology, Gakuendai 4-1, Miyashiro-machi, Minamisaitama, Saitama 345-8501, Japan ¶Department of Nutritional Science and Food Safety, Tokyo University of Agriculture, Sakuragaoka 1-1-1, Setagaya-ku, Tokyo 156-8502, Japan §Samco Inc., Waraya-cho 36, Takeda, Fushimi-ku, Kyoto 612-8443, Japan ∥The Institute of Scientific and Industrial Research, Osaka University, Mihogaoka 81, Ibaraki, Osaka 567-0047, Japan ⊥Contributed equally to this work *E-mail: ogi@prec.eng.osaka-u.ac.jp Supporting Figure S1
Supporting Figure S2
••••••••••••••••••••••••••••••
••••••••••••••••••••••••••••••
S-1
S-2
S-3
Figure S1
4-inch wafer-level MEMS process for fabricating ~180 ultra-high sensitive QCM
biosensors. This MEMS process consists of four processes: (i) Glass-wafer process for fabricating
upper and bottom glass wafers with microchannels and inner and outer antennas, (ii) silicon-oninsulator (SOI) wafer process for making the middle Si layer as the bonding layer, (iii) quartz-wafer
process for patterning the isolated thin quartz resonators, and (iv) packaging process.
S-2
Df/f0 (ppm)
IgG (1 ng/mL) GHB IgG (10 ng/mL)
GHB
IgG (100 ng/mL)
HBS
GHB
HBS
HBS
-50
HBS
HBS
-100
HBS
HBS
10
12
Time (hour)
Figure S2 Frequency response of a 125 MHz MEMS QCM in a long-term measurement of IgG
detection.
S-3
...