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Title: Machine learning enabled acoustic detection of sub-nanomolar concentration of trypsin and plasmin in solution

Abstract

Here, we demonstrate a machine learning enabled low-cost acoustic detection of protease which may find application in assuring quality and safety of dairy products, drug screening, molecular profiling, and disease diagnostics. A hydrophilic SiO2-coated quartz crystal microbalance (QCM) acts as a substrate to assemble α-, β-, and κ-casein layers (protease reporters) and as a transducer for measuring changes in frequency as casein is removed by protease. We demonstrate that α-, β-, and κ-caseins can form stable assembly on SiO2 from phosphate-buffered solution (PBS) solution. Exposure to protease results in cleaving of casein which changes the frequency of the 1st–11th odd harmonics of QCM. Monitoring β-casein cleavage allows ~0.2 nM detection of trypsin and ~0.5 nM detection of plasmin and enables differentiation between trypsin and plasmin after <2 min of protease exposure. The casein-coated QCM allows sub-nanomolar detection and classification of protease.

Authors:
 [1];  [2];  [1]; ORCiD logo [2]; ORCiD logo [2];  [1]; ORCiD logo [2]
  1. Comenius Univ., Bratislava (Slovakia)
  2. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Publication Date:
Research Org.:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
OSTI Identifier:
1482462
Alternate Identifier(s):
OSTI ID: 1591683
Grant/Contract Number:  
AC05-00OR22725
Resource Type:
Accepted Manuscript
Journal Name:
Sensors and Actuators. B, Chemical
Additional Journal Information:
Journal Volume: 272; Journal Issue: C; Journal ID: ISSN 0925-4005
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
47 OTHER INSTRUMENTATION; Casein; Plasmin; Trypsin; Protease; QCM; Biosensor; Machine learning

Citation Formats

Tatarko, Marek, Muckley, Eric S., Subjakova, Veronika, Goswami, Monojoy, Sumpter, Bobby G., Hianik, Tibor, and Ivanov, Ilia N. Machine learning enabled acoustic detection of sub-nanomolar concentration of trypsin and plasmin in solution. United States: N. p., 2018. Web. doi:10.1016/j.snb.2018.05.100.
Tatarko, Marek, Muckley, Eric S., Subjakova, Veronika, Goswami, Monojoy, Sumpter, Bobby G., Hianik, Tibor, & Ivanov, Ilia N. Machine learning enabled acoustic detection of sub-nanomolar concentration of trypsin and plasmin in solution. United States. https://doi.org/10.1016/j.snb.2018.05.100
Tatarko, Marek, Muckley, Eric S., Subjakova, Veronika, Goswami, Monojoy, Sumpter, Bobby G., Hianik, Tibor, and Ivanov, Ilia N. Sat . "Machine learning enabled acoustic detection of sub-nanomolar concentration of trypsin and plasmin in solution". United States. https://doi.org/10.1016/j.snb.2018.05.100. https://www.osti.gov/servlets/purl/1482462.
@article{osti_1482462,
title = {Machine learning enabled acoustic detection of sub-nanomolar concentration of trypsin and plasmin in solution},
author = {Tatarko, Marek and Muckley, Eric S. and Subjakova, Veronika and Goswami, Monojoy and Sumpter, Bobby G. and Hianik, Tibor and Ivanov, Ilia N.},
abstractNote = {Here, we demonstrate a machine learning enabled low-cost acoustic detection of protease which may find application in assuring quality and safety of dairy products, drug screening, molecular profiling, and disease diagnostics. A hydrophilic SiO2-coated quartz crystal microbalance (QCM) acts as a substrate to assemble α-, β-, and κ-casein layers (protease reporters) and as a transducer for measuring changes in frequency as casein is removed by protease. We demonstrate that α-, β-, and κ-caseins can form stable assembly on SiO2 from phosphate-buffered solution (PBS) solution. Exposure to protease results in cleaving of casein which changes the frequency of the 1st–11th odd harmonics of QCM. Monitoring β-casein cleavage allows ~0.2 nM detection of trypsin and ~0.5 nM detection of plasmin and enables differentiation between trypsin and plasmin after <2 min of protease exposure. The casein-coated QCM allows sub-nanomolar detection and classification of protease.},
doi = {10.1016/j.snb.2018.05.100},
journal = {Sensors and Actuators. B, Chemical},
number = C,
volume = 272,
place = {United States},
year = {2018},
month = {5}
}

Journal Article:

Citation Metrics:
Cited by: 2 works
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Figures / Tables:

Fig. 1 Fig. 1: Kinetics of casein adsorption and removal from SiO⁠2, as measured by frequency shift ($Δ$f) of 1st–11th odd harmonics of the QCM. Exposure and removal of $α$-casein (left panel), $β$-casein (middle panel), and κ-casein (right panel) are marked by the first and second vertical dashed lines respectively.

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Works referenced in this record:

Heat stability of plasmin (milk proteinase) and plasminogen
journal, May 1986

  • Alichanidis, Efstathios; Wrathall, Julia H. M.; Andrews, Anthony T.
  • Journal of Dairy Research, Vol. 53, Issue 2
  • DOI: 10.1017/S0022029900024869

Relationship Between Physical Properties of Casein Micelles and Rheology of Skim Milk Concentrate
journal, November 2005


Invited review: Plasmin protease in milk: Current knowledge and relevance to dairy industry
journal, November 2010


Antibodies against dengue virus E protein peptide bind to human plasminogen and inhibit plasmin activity
journal, September 1997


Electrochemical assay of plasmin activity and its kinetic analysis
journal, February 2009

  • Ohtsuka, Keiichi; Maekawa, Iwao; Waki, Michinori
  • Analytical Biochemistry, Vol. 385, Issue 2
  • DOI: 10.1016/j.ab.2008.11.006

Electrochemical and Photometric Detection of Plasmin by Specific Peptide Substrate
journal, January 2015

  • Castillo, Gabriela; Pribransky, Kinga; Mező, Gábor
  • Electroanalysis, Vol. 27, Issue 3
  • DOI: 10.1002/elan.201400622

Tear fluid plasmin activity of dry eye patients with Sjögren's syndrome
journal, April 1997


A sensitive fluorometric assay for plasminogen, plasmin, and streptokinase
journal, September 1974


Human Plasmin Enzymatic Activity Is Inhibited by Chemically Modified Dextrans
journal, September 2000

  • Ledoux, Dominique; Papy-Garcia, Dulce; Escartin, Quentin
  • Journal of Biological Chemistry, Vol. 275, Issue 38
  • DOI: 10.1074/jbc.M000837200

Plasmin Activates Epithelial Na+ Channels by Cleaving the γ Subunit
journal, December 2008

  • Passero, Christopher J.; Mueller, Gunhild M.; Rondon-Berrios, Helbert
  • Journal of Biological Chemistry, Vol. 283, Issue 52
  • DOI: 10.1074/jbc.M805676200

Contact lens wear is associated with the appearance of plasmin in the tear fluid — preliminary results
journal, January 1989

  • Tervo, T.; van Setten, G. -B.; Andersson, R.
  • Graefe's Archive for Clinical and Experimental Ophthalmology, Vol. 227, Issue 1
  • DOI: 10.1007/BF02169824

Tc-99m PLASMIN FOR RAPID DETECTION OF DEEP VEIN THROMBOSIS
journal, January 1982


Labeling plasmin with technetium-99m for scintigraphic localization of thrombi
journal, January 1977

  • Persson, Bertil R. R.; Darte, Lennart
  • The International Journal of Applied Radiation and Isotopes, Vol. 28, Issue 1-2
  • DOI: 10.1016/0020-708X(77)90163-6

Health systems and policy research in Europe: Horizon 2020
journal, August 2013


Verwendung von Schwingquarzen zur W�gung d�nner Schichten und zur Mikrow�gung
journal, April 1959


PEDOT:PSS/QCM-based multimodal humidity and pressure sensor
journal, November 2016


Nonlabeled Quartz Crystal Microbalance Biosensor for Bacterial Detection Using Carbohydrate and Lectin Recognitions
journal, March 2007

  • Shen, Zhihong; Huang, Mingchuan; Xiao, Caide
  • Analytical Chemistry, Vol. 79, Issue 6
  • DOI: 10.1021/ac061986j

Sensor materials for the detection of proteases
journal, March 2009

  • Stair, Jacqueline L.; Watkinson, Michael; Krause, Steffi
  • Biosensors and Bioelectronics, Vol. 24, Issue 7
  • DOI: 10.1016/j.bios.2008.11.002

Detection of plasmin based on specific peptide substrate using acoustic transducer
journal, February 2016

  • Poturnayova, Alexandra; Karpisova, Ivana; Castillo, Gabriela
  • Sensors and Actuators B: Chemical, Vol. 223
  • DOI: 10.1016/j.snb.2015.09.143

Friction Force Spectroscopy of β- and κ-Casein Monolayers
journal, February 2011

  • Sotres, Javier; Svensson, Olof; Arnebrant, Thomas
  • Langmuir, Vol. 27, Issue 3
  • DOI: 10.1021/la1043377

Adsorption of β-casein to hydrophilic silica surfaces. Effect of pH and electrolyte
journal, May 2014


Scalable molecular dynamics with NAMD
journal, January 2005

  • Phillips, James C.; Braun, Rosemary; Wang, Wei
  • Journal of Computational Chemistry, Vol. 26, Issue 16, p. 1781-1802
  • DOI: 10.1002/jcc.20289

Using support vector machines for prediction of protein structural classes based on discrete wavelet transform
journal, June 2009

  • Qiu, Jian-Ding; Luo, San-Hua; Huang, Jian-Hua
  • Journal of Computational Chemistry, Vol. 30, Issue 8
  • DOI: 10.1002/jcc.21115

Surface-Bound Casein Modulates the Adsorption and Activity of Kinesin on SiO2 Surfaces
journal, April 2009


β-Casein Adsorption at the Silicon Oxide−Aqueous Solution Interface
journal, September 2001

  • Tiberg, F.; Nylander, T.; Su, T. J.
  • Biomacromolecules, Vol. 2, Issue 3
  • DOI: 10.1021/bm0155221

Interactions between casein layers adsorbed on hydrophobic surfaces from self consistent field theory: κ-casein versus para-κ-casein
journal, January 2014


Plasmin Activity in UHT Milk: Relationship between Proteolysis, Age Gelation, and Bitterness
journal, July 2014

  • Rauh, Valentin M.; Johansen, Lene B.; Ipsen, Richard
  • Journal of Agricultural and Food Chemistry, Vol. 62, Issue 28
  • DOI: 10.1021/jf502088u

Micelle Stability: κ-Casein Structure and Function
journal, November 1998


Interfacial Behavior of Goat Kappa Casein: Ellipsometry and Atomic Force Microscopy Study
journal, June 2002


Works referencing / citing this record:

Machine Learning‐Enabled Correlation and Modeling of Multimodal Response of Thin Film to Environment on Macro and Nanoscale Using “Lab‐on‐a‐Crystal”
journal, January 2020

  • Muckley, Eric S.; Collins, Liam; Srijanto, Bernadeta R.
  • Advanced Functional Materials, Vol. 30, Issue 10
  • DOI: 10.1002/adfm.201908010

Figures/Tables have been extracted from DOE-funded journal article accepted manuscripts.