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Where are you now? Intelligence Services > 21 CFR Part 11 > Products > Evolving Technology

QCM Systems 21 CFR Part 11 Compliant


Introduction to QCM - a New Device for an Evolving Technology

Direct measurement, real-time analysis, high sensitivity, high specificity, wide dynamic range, hyphenated methods, broad range of applications, and cost effectiveness are all desirable characteristics in high performance analytical systems. Unfortunately, in most cases only some of the above capabilities are available for the scientists in a single instrument to optimise their needs. Acoustic devices offer a unique opportunity & challenges, where all of the above characteristics can be combined.

Acoustics waves cover very broad range of frequencies form below 1Hz to well beyond GHz. From practical point of view, based on current state of technology, cost, and availability, we shall focus on thickness-shear-mode (TSM) resonators, which are also known as quartz-crystal-microbalances or QCMs. The heart of a QCM device is the coated quartz crystal designed for an appropriate frequency range and application. Most measurements have been conducted from 5MHz to 20MHz, providing nanogram or in some cases better sensitivities.

What are the applications of QCM based devices?

Initially QCM was used for mass sensing & thickness monitoring of adsorption processes in vacuum and air. With the advancement of electronics QCM was made operable in liquids and a new category of applications evolved in the areas analytical and physical chemistries, including:

  • Biomolecular adsorption
  • Molecular interactions
  • Antibody-antigen interactions
  • Immunoassays
  • Testing the presence of antigens in blood
  • Polymer science
  • Toxic gas sensing
  • Adsorption and hybridization of oligonucleotides
  • Characterization of adsorbed proteins
  • Biofilm formation
  • Kinetic of cell spreading
  • Electrochemical applications
  • Studying solid state phase transition
  • Measurement of trace quantities of volatile compounds in water
  • Monitoring air pollution
  • Measurment of film thickness
  • Measurement of dissolution
  • Clean room applications

What are some the unique advantages of QCM over other methods?

QCM, by its inherent nature, can be used to study

  • Immunochemical & immuno-biological characteristics in neat mode without the enzyme labels used in ELISA based tests
  • Cell adhesion characteristics in neat mode
  • QCM-PCR integration
  • Viscoelastic kinetics in the evaluation of coagulation & anticoagulation processes
  • Real-time monitoring & rapid analysis of contaminants.

What are some the main challenges QCM faces?

  • The development of high-throughput capability
  • The assurance of quality in the raw data & test results
  • The development of a functional system that can be used in a flexible & reliable manner to integrate the various capabilities

Our intention is to develop a QCM knowledge base to assist the advancement of this new evolving technology and to provide a platform via OVAL (OPULUS Virtual Application Laboratory) for future collaborative studies.

OVAL has been developed recently for Web-based proficiency testing. The first application has been added for LAL methodologies; see LALPT. With the inclusion of QCM, we hope to catalyse the evolutionary process both in the development of suitable analytical systems and in the standardization of the measurement protocols.


DQ-IQ-OQ-PQ and 21 CFR part 11

Regulatory compliance in the pharmaceutical, biotechnology, and medical device, industries is the foundation of good business practices. DQ-IQ-OQ-PQ documents for QCM Systems provide significant support to reduce the risk of non-compliance.

DQ (Design Qualification) - is the foundation of good science & good compliance practices. You cannot get more out of a system that has been built into it. DQ is the tool & methodology to make the evaluation of suitability for specific requirements, including worst-case-scenario. DQ also provides the baseline for meaningful Performance Qualification (PQ) monitoring; without DQ, PQ flounders, it does not exist. 21 CFR Part 11 compliance is a major functionality relative to Design Qualification.
In the first part let us consider what may be the most important questions to ask relative to 21 CFR Part 11 DQ. STOP

DQ supports the functional & quality specifications designed into QCM Systems. Documentary proof of DQ compliance includes:

  1. Software Validation Plan,
  2. Software Validation Summary,
  3. 21 CFR Part 11 Validation Summary,
  4. Measurement Performance Design Summary, and
  5. Measurement Compliance Summary

IQ (Installation Qualification) - IQ supports the requirement for proper installation and acceptance qualification for QCM Systems. Documentary proof of IQ compliance includes:

  1. Receipt & acceptance checklist,
  2. Physical & electrical compliance checklist,
  3. Environmental compliance checklist,
  4. Training compliance checklist, and
  5. Final IQ Summary

OQ (Operational Qualification) - OQ supports the specification compliant functioning of the system. Documentary proof of OQ compliance includes:

  1. 21 CFR Part 11 operational specification checklist,
  2. Software operational specification checklist,
  3. Instrument interface operational specification checklist,
  4. Instrument operational specification checklist, and
  5. Final OQ Summary

PQ (Performance Qualification) - PQ supports quality evaluation & quality compliance management of the system. PQ compliance models include:

  1. 21 CFR Part 11 compliance models,
  2. SQC models for instrument qualification review,
  3. SQC models for method qualification review,
  4. SQC models for vendor qualification review, and
  5. SQC models for OOS investigations

Application Publications - Alzheimer

  • Acoustic sensor for monitoring adhesion of Neuro-2A cells in real-time
    Massoud Louis Khraiche, Anhong Zhou, Jit Muthuswamy
    Journal of Neuroscience Methods 144 (2005) 1–10
  • AFM for structure and dynamics of biomembranes
    Emel I. Goksu, Juan M. Vanegas, Craig D. Blanchette, Wan-Chen Lin, Marjorie L. Longo
    Biochimica et Biophysica Acta (2008), article in press
  • Amyloid-β detection with saccharide immobilized gold nanoparticle on carbon electrode
    Miyuki Chikae, Tomohiro Fukuda, Kagan Kerman, Koutarou Idegami, Yoshiko Miura, Eiichi Tamiya
    Bioelectrochemistry 74 (2008) 118–123
  • A novel detection method for DNA point mutation using QCM based on Fe3O4/Au core/shell nanoparticle and DNA ligase reaction
    Lan-Lan Pang, Ji-Shan Li, Jian-Hui Jiang, Yuan Le, Guo Li Shen, Ru-Qin Yu
    Sensors and Actuators B 127 (2007) 311–316
  • A Novel Method for the Detection of Point Mutation in DNA Using Single-base Coded CdS Nanoprobles
    Min Ye, Youyu Zhang, Haitao Li, Yuqin Zhang, Ping Tan, Hao Tang, Shouzhuo Yao
    Biosensors and Bioelectronics (2008), doi:10.1016/j.bios.2008.12.002 (accepted manuscript)
  • A thin-film transistor based acetylcholine sensor using self-assembled carbon nanotubes and SiO2 nanoparticles
    Wei Xue, Tianhong Cui
    Sensors and Actuators B 134 (2008) 981–987
  • Biochemical characterization of tau protein and its associated syndapin 1 and protein kinase Cε for their functional regulation in rat brain
    Kanzo Suzuki, Fumitaka Kawakami, Hisashi Sasaki, Hiroko Maruyama, Kenzo Ohtsuki
    BBA -General Subjects (2008), doi:10.1016/j.bbagen.2008.11.007 (accepted manuscript)
  • Detection of Alzheimer’s tau protein using localised surface plasmon resonance-based immunochip
    Mun’delanji Vestergaard, Kagan Kerman, Do-Kyun Kim, Ha Minh Hiep, Eiichi Tamiya
    Talanta 74 (2008) 1038–1042
  • Detection of nicotine based on molecularly imprinted TiO2-modified electrodes
    Cheng-TarWu, Po-Yen Chen, Jian-Ging Chen, Vembu Suryanarayanan, Kuo-Chuan Ho
    Analytica Chimica Acta(2008), in press
  • Development of a bifunctional sensor using haptenized acetylcholinesterase and application for the detection of cocaine and organophosphates
    Carsten Teller, Jan Halámek, Jiri Zeravík, Walter F.M. Stöcklein, FriederW. Scheller
    Biosensors and Bioelectronics 24 (2008) 111–117
  • Electrochemical detection of point mutation based on surface ligation reaction and biometallization
    Peng Zhang, Xia Chu, Xiangmin Xu, Guoli Shen, Ruqin Yu
    Biosensors and Bioelectronics 23 (2008) 1435–1441
  • Glutamate sensing with enzyme-modified floating-gate field effect transistors
    D. Braeken, D.R. Rand, A. Andrei, R. Huys, M.E. Spira, S. Yitzchaik, J. Shappir, G. Borghs, G. Callewaert, C. Bartic
    Biosensors and Bioelectronics (2008), doi:10.1016/j.bios.2008.12.012 (accepted manuscript)
  • Imprinting unique motifs formed from protein–protein associations
    John Rick, Tse-Chuan Chou
    Analytica Chimica Acta 542 (2005) 26–31
  • Islet Amyloid Polypeptide Forms Rigid Lipid–Protein Amyloid Fibrils on Supported Phospholipid Bilayers
    Yegor A. Domanov and Paavo K. J. Kinnunen
    J. Mol. Biol. (2008) 376, 42–54
  • Label-free bioelectronic immunoassay for the detection of human telomerase reverse transcriptase in urine
    Masayuki Takata, Kagan Kerman, Naoki Nagatani, Hiroyuki Konaka, Mikio Namiki, Eiichi Tamiya
    Journal of Electroanalytical Chemistry 596 (2006) 109–116
  • Modification of nanostructured materials for biomedical applications
    Tao Xu, Ning Zhang, Heather L. Nichols, Donglu Shi, Xuejun Wen
    Materials Science and Engineering C 27 (2007) 579–594
  • Nonfibrous β-structured aggregation of an Aβ model peptide (Ad-2α) on GM1/DPPC mixed monolayer surfaces
    Takayoshi Kawasaki, Kentaro Asaoka, Hisakazu Mihara, Yoshio Okahata
    Journal of Colloid and Interface Science 294 (2006) 295–303
  • Protective effects of genistein on proinflammatory pathways in human brain microvascular endothelial cells
    Yong W. Lee, Won H. Lee
    Journal of Nutritional Biochemistry 19 (2008) 819–825
  • Protein-nanoparticle interactions
    Iseult Lynch and Kenneth A. Dawson
  • Proton-assisted iron(III) recognition with 4,40-(4,5-diaminonaphthalen-1,8-yldiazo)-bisbenzenesulfonate
    Yu Jiuan Cheng, Wei Ching Liao, Chong Mou Wang
    Journal of Electroanalytical Chemistry 612 (2008) 15–21
  • Quartz crystal microbalance analysis of growth kinetics for aggregation intermediates of the amyloid-β protein
    Joseph A. Kotarek, Kathryn C. Johnson, Melissa A. Moss
    Analytical Biochemistry 378 (2008) 15–24
  • Recent advancements in surface plasmon resonance immunosensors for detection of small molecules of biomedical, food and environmental interest
    Dhesingh Ravi Shankaran, K. Vengatajalabathy Gobi, Norio Miura
    Sensors and Actuators B 121 (2007) 158–177
  • Smart polymeric gels: Redefining the limits of biomedical devices
    Somali Chaterji, Il Keun Kwon, Kinam Park
    Prog. Polym. Sci. 32 (2007) 1083–1122
  • Structure and dynamics of the full-length M1 muscarinic acetylcholine receptor studied by molecular dynamics simulations
    L. Michel Espinoza-Fonseca, Alessandro Pedretti, Giulio Vistoli
    Archives of Biochemistry and Biophysics 469 (2008) 142–150
  • Study of interaction of curcumin, a potential antineuroinflammatory agent, with C3 and C3b using QCM-D technology
    Amod P. Kulkarni, Krishna H. Murthy, Girish J. Kotwal
    Abstracts / Molecular Immunology 44 (2007) 147–266
  • Synergie between molecular imprinted polymer based on solid-phase extraction and quartz crystal microbalance technique for 8-OHdG sensing
    Arzu Ersöz, S. Emir Diltemiz, A. Atilir Özcan, Adil Denizli, Ridvan Say
    Biosensors and Bioelectronics 24 (2008) 742–747
  • Synergistic Ca2+ and Cu2+ requirements of the FGF1–S100A13 interaction measured by quartz crystal microbalance: An initial step in amlexanox-reversible non-classical release of FGF1
    Hayato Matsunaga, Hiroshi Ueda
    Neurochemistry International 52 (2008) 1076–1085

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