Research Papers

Development of Fieldable Lab-on-a-Chip Systems for Detection of a Broad Array of Targets From Toxicants to Biowarfare Agents

[+] Author and Article Information
Aaron T. Timperman

U.S. Army Engineer Research
and Development Center,
Construction Engineering Research
Champaign, IL 61826

Manuscript received May 14, 2013; final manuscript received September 18, 2013; published online October 18, 2013. Assoc. Editor: Shaurya Prakash.

J. Nanotechnol. Eng. Med 4(2), 020904 (Oct 18, 2013) (8 pages) Paper No: NANO-13-1029; doi: 10.1115/1.4025539 History: Received May 14, 2013; Revised September 18, 2013

In today's world, there is an ever growing need for lightweight, portable sensor systems to detect chemical toxicants and biological toxins. The challenges encountered with such detection systems are numerous, as there are a myriad of potential targets in various sample matrices that are often present at trace-level concentrations. At ERDC-CERL, the Lab-on-a-Chip (LoaC) group is working with a number of academic and small business collaborators to develop solutions to meet these challenges. This report will focus on recent advances in three distinct areas: (1) the development of a flexible platform to allow fieldable LoaC analyses of water samples, (2) cell-, organelle-, and synthetic biology-based toxicity sensors, and (3) nanofluidic/microfluidic interface (NMI) sample enrichment devices. To transition LoaC-based sensors from the laboratory bench to the field, a portable hardware system capable of operating a wide variety of microfluidic chip-based assays has been developed. As a demonstration of the versatility of this approach assays for the separation and quantitation of anionic contaminants (i.e., perchlorate), quantitation of heavy metals (Pb and Cd), and cell-based toxicity sensors have been developed and demonstrated. Sensors harboring living cells provide a rapid means of assessing water toxicity. Cell-based sensors exploit the sensitivity of a living cell to discrete changes in its environment to report the presence of toxicants. However, this sensitivity of cells to environmental changes also hinders their usability in nonlaboratory settings. Therefore, isolating intact organelles (i.e., mitochondria) offers a nonliving alternative that preserves the sensitivity of the living cells and allows the electrochemical reporting of the presence of a contaminant. Pursuing a synthetic biology approach has also allowed the development of nonliving reporting mechanisms that utilize engineered biological pathways for novel sensing and remediation applications. To help overcome the challenges associated with the detection of target species at trace-level concentrations, NMIs are being developed for the enrichment of charged species in solution. NMI concentrators can be classified as either electroosmotic flow or electrophoresis-dominant devices. Further advances in electrophoresis-dominant concentrators will aid in the analysis of samples that contain proteins and other substances prone to surface adsorption. These recent advances illustrate how LoaC systems provide a suitable platform for development of fieldable sensors to detect a broad range of chemical/biological pollutants and threats.

Copyright © 2013 by ASME
Your Session has timed out. Please sign back in to continue.


Kovarik, M. L., Gach, P. C., Ornoff, D. M., Wang, Y., Balowski, J., Farrag, L., and Allbritton, N. L., 2012, “Micro Total Analysis Systems for Cell Biology and Biochemical Assays,” Anal. Chem., 84(2), pp. 516–540. [CrossRef] [PubMed]
Kovarik, M. L., Ornoff, D. M., Melvin, A. T., Dobes, N. C., Wang, Y., Dickinson, A. J., Gach, P. C., Shah, P. K., and Allbritton, N. L., 2013, “Micro Total Analysis Systems: Fundamental Advances and Applications in the Laboratory, Clinic, and Field,” Anal. Chem., 85(2), pp. 451–472. [CrossRef] [PubMed]
Renzi, R. F., Stamps, J., Horn, B. A., Ferko, S., Vandernoot, V. A., West, J. A. A., Crocker, R., Wiedenman, B., Yee, D., and Fruetel, J. A., 2005, “Hand-Held Microanalytical Instrument for Chip-Based Electrophoretic Separations of Proteins,” Anal. Chem., 77(2), pp. 435–441. [CrossRef] [PubMed]
Hecht, A. H., Sommer, G. J., Durland, R. H., Yang, X., Singh, A. K., and Hatch, A. V., 2010, “Aptamers as Affinity Reagents in an Integrated Electrophoretic Lab-on-a-Chip Platform,” Anal. Chem., 82(21), pp. 8813–8820. [CrossRef]
Liu, P., and Mathies, R. A., 2009, “Integrated Microfluidic Systems for High-Performance Genetic Analysis,” Trends Biotechnol., 27(10), pp. 572–581. [CrossRef] [PubMed]
Chinowsky, T. M., Grow, M. S., Johnston, K. S., Nelson, K., Edwards, T., Fu, E., and Yager, P., 2007, “Compact, High Performance Surface Plasmon Resonance Imaging System,” Biosens. Bioelectron., 22(9–10), pp. 2208–2215. [CrossRef] [PubMed]
U.S.E.P. Agency, 2011, “Final Regulatory Determination for Perchlorate, 5/6,” https://www.federalregister.gov/articles/2011/02/11/2011-2603/drinking-water-regulatory-determination-on-perchlorate
Urbansky, E. T., 2000, “Quantitation of Perchlorate Ion: Practices and Advances Applied to the Analysis of Common Matrices,” Crit. Rev. Anal. Chem., 30(4), pp. 311–343. [CrossRef]
Gertsch, J. C., Noblitt, S. D., Cropek, D. M., and Henry, C. S., 2010, “Rapid Analysis of Perchlorate in Drinking Water at Parts Per Billion Levels Using Microchip Electrophoresis,” Anal. Chem., 82(9), pp. 3426–3429. [CrossRef] [PubMed]
Zou, Z. W., Jang, A., Macknight, E., Wu, P. M., Do, J., Bishop, P. L., and Ahn, C. H., 2008, “Environmentally Friendly Disposable Sensors With Microfabricated on-Chip Planar Bismuth Electrode for In Situ Heavy Metal Ions Measurement,” Sens. Actuators B, 134(1), pp. 18–24. [CrossRef]
Wang, J., Polsky, R., Tian, B. M., and Chatrathi, M. P., 2000, “Voltammetry on Microfluidic Chip Platforms,” Anal. Chem., 72(21), pp. 5285–5289. [CrossRef] [PubMed]
Rogers, K. R., 2006, “Recent Advances in Biosensor Techniques for Environmental Monitoring,” Anal. Chim. Acta, 568(1–2), pp. 222–231. [CrossRef] [PubMed]
Banerjee, P., Franz, B., and Bhunia, A. K., 2010, “Mammalian Cell-Based Sensor System,” Adv. Biochem. Eng. Biotechnol., 117, pp. 21–55. [CrossRef] [PubMed]
Wang, P., 2010, Cell-Based Biosensors Principles and Applications, Artech House, Norwood, MA.
Lagarde, F., and Jaffrezic-Renault, N., 2011, “Cell-Based Electrochemical Biosensors for Water Quality Assessment,” Anal. Bioanal. Chem., 400(4), pp. 947–964. [CrossRef] [PubMed]
Lin, L. J., Grimme, J. M., Sun, J., Lu, S., Gai, L., Cropek, D. M., and Wang, Y., 2013, “The Antagonistic Roles of Pdgf and Integrin Alphavbeta3 in Regulating Ros Production at Focal Adhesions,” Biomaterials, 34(15), pp. 3807–3815. [CrossRef] [PubMed]
Vicente, J. A., Peixoto, F., Lopes, M. L., and Madeira, V. M., 2001, “Differential Sensitivities of Plant and Animal Mitochondria to the Herbicide Paraquat,” J. Biochem. Mol. Toxicol., 15(6), pp. 322–330. [CrossRef] [PubMed]
Fernandes, M. A., Santos, M. S., Alpoim, M. C., Madeira, V. M., and Vicente, J. A., 2002, “Chromium(Vi) Interaction With Plant and Animal Mitochondrial Bioenergetics: A Comparative Study,” J. Biochem. Mol. Toxicol., 16(2), pp. 53–63. [CrossRef] [PubMed]
Zhang, Y., and Timperman, A. T., 2003, “Integration of Nanocapillary Arrays into Microfluidic Devices for Use as Analyte Concentrators,” Analyst, 128(6), pp. 537–542. [CrossRef] [PubMed]
Miller, S. A., Kelly, K. C., and Timperman, A. T., 2008, “Ionic Current Rectification and Analyte Concentration in an Asymmetric Nanofluidic/Microfluidic Interface,” Lab Chip, 8, pp. 1729–1732. [CrossRef] [PubMed]
Kelly, K. C., Miller, S. A., and Timperman, A. T., 2009, “Investigation of Zone Migration in a Current Rectifying Nanofluidic/Microfluidic Analyte Concentrator,” Anal. Chem., 81, pp. 732–738. [CrossRef] [PubMed]
Pu, Q., Yun, J., Temkin, H., and Liu, S., 2004, “Ion-Enrichment and Ion-Depletion Effect of Nanochannel Structures,” Nano Lett., 4(6), pp. 1099–1103. [CrossRef]
Kim Sun, M., Burns Mark, A., and Hasselbrink Ernest, F., 2006, “Electrokinetic Protein Preconcentration Using a Simple Glass/Poly(Dimethylsiloxane) Microfluidic Chip,” Anal. Chem., 78(14), pp. 4779–4785. [CrossRef] [PubMed]
Wang, Y.-C., Stevens, A. L., and Han, J., 2005, “Million-Fold Preconcentration of Proteins and Peptides by Nanofluidic Filter,” Anal. Chem., 77(14), pp. 4293–4299. [CrossRef] [PubMed]
Lee, J. H., Chung, S., Kim, S. J., and Han, J., 2007, “Poly(Dimethylsiloxane)-Based Protein Preconcentration Using a Nanogap Generated by Junction Gap Breakdown,” Anal. Chem., 79(17), pp. 6868–6873. [CrossRef] [PubMed]
Dhopeshwarkar, R., Crooks, R. M., Hlushkou, D., and Tallarek, U., 2008, “Transient Effects on Microchannel Electrokinetic Filtering With an Ion-Permselective Membrane,” Anal. Chem., 80(4), pp. 1039–1048. [CrossRef] [PubMed]
Dai, J., Ito, T., Sun, L., and Crooks, R. M., 2003, “Electrokinetic Trapping and Concentration Enrichment of DNA in a Microfluidic Channel,” J. Am. Chem. Soc., 125(43), pp. 13026–13027. [CrossRef] [PubMed]
Dhopeshwarkar, R., Sun, L., and Crooks, R. M., 2005, “Electrokinetic Concentration Enrichment Within a Microfluidic Device Using a Hydrogel Microplug,” Lab Chip, 5(10), pp. 1148–1154. [CrossRef] [PubMed]
Khandurina, J., Jacobson, S. C., Waters, L. C., Foote, R. S., and Ramsey, J. M., 1999, “Microfabricated Porous Membrane Structure for Sample Concentration and Electrophoretic Analysis,” Anal. Chem., 71(9), pp. 1815–1819. [CrossRef] [PubMed]
Foote, R. S., Khandurina, J., Jacobson, S. C., and Ramsey, J. M., 2005, “Preconcentration of Proteins on Microfluidic Devices Using Porous Silica Membranes,” Anal. Chem., 77(1), pp. 57–63. [CrossRef] [PubMed]
Hlushkou, D., Dhopeshwarkar, R., Crooks Richard, M., and Tallarek, U., 2008, “The Influence of Membrane Ion-Permselectivity on Electrokinetic Concentration Enrichment in Membrane-Based Preconcentration Units,” Lab Chip, 8(7), pp. 1153–1162. [CrossRef] [PubMed]
Huang, K.-D., and Yang, R.-J., 2008, “Formation of Ionic Depletion/Enrichment Zones in a Hybrid Micro-/Nano-Channel,” Microfluid. Nanofluid., 5(5), pp. 631–638. [CrossRef]
Yu, H., Lu, Y., Zhou, Y.-G., Wang, F.-B., He, F.-Y., and Xia, X.-H., 2008, “A Simple, Disposable Microfluidic Device for Rapid Protein Concentration and Purification via Direct-Printing,” Lab Chip, 8(9), pp. 1496–1501. [CrossRef] [PubMed]
Wang, Y.-C., and Han, J., 2008, “Pre-Binding Dynamic Range and Sensitivity Enhancement for Immuno-Sensors Using Nanofluidic Preconcentrator,” Lab Chip, 8(3), pp. 392–394. [CrossRef] [PubMed]
Stein, D., Deurvorst, Z., Van Der Heyden, F. H. J., Koopmans, W. J. A., Gabel, A., and Dekker, C., 2010, “Electrokinetic Concentration of DNA Polymers in Nanofluidic Channels,” Nano Lett., 10(3), pp. 765–772. [CrossRef] [PubMed]
Yamamoto, S., Hirakawa, S., and Suzuki, S., 2008, “In Situ Fabrication of Ionic Polyacrylamide-Based Preconcentrator on a Simple Poly(Methyl Methacrylate) Microfluidic Chip for Capillary Electrophoresis of Anionic Compounds,” Anal. Chem, 80(21), pp. 8224–8230. [CrossRef] [PubMed]
Lee, J. H., Song, Y.-A., and Han, J., 2008, “Multiplexed Proteomic Sample Preconcentration Device Using Surface-Patterned Ion-Selective Membrane,” Lab Chip, 8(4), pp. 596–601. [CrossRef] [PubMed]
Hoeman, K. W., Lange, J. J., Roman, G. T., Higgins, D. A., and Culbertson, C. T., 2009, “Electrokinetic Trapping Using Titania Nanoporous Membranes Fabricated Using Sol-Gel Chemistry on Microfluidic Devices,” Electrophoresis, 30(18), pp. 3160–3167. [CrossRef] [PubMed]
Zhou, K., Kovarik, M. L., and Jacobson, S. C., 2008, “Surface-Charge Induced Ion Depletion and Sample Stacking Near Single Nanopores in Microfluidic Devices,” J. Am. Chem. Soc., 130(27), pp. 8614–8616. [CrossRef] [PubMed]
Kovarik, M. L., and Jacobson, S. C., 2008, “Integrated Nanopore/Microchannel Devices for AC Electrokinetic Trapping of Particles,” Anal. Chem, 80(3), pp. 657–664. [CrossRef] [PubMed]
Kim, S. J., and Han, J., 2008, “Self-Sealed Vertical Polymeric Nanoporous-Junctions for High-Throughput Nanofluidic Applications,” Anal. Chem, 80(9), pp. 3507–3511. [CrossRef] [PubMed]
Moini, M., and Huang, H., 2004, “Application of Capillary Electrophoresis/Electrospray Ionization-Mass Spectrometry to Subcellular Proteomics of Escherichia Coli Ribosomal Proteins,” Electrophoresis, 25(13), pp. 1981–1987. [CrossRef] [PubMed]
Simpson, D. C., and Smith, R. D., 2005, “Combining Capillary Electrophoresis With Mass Spectrometry for Applications in Proteomics,” Electrophoresis, 26(7–8), pp. 1291–1305. [CrossRef] [PubMed]
Schiffer, E., Mischak, H., and Novak, J., 2006, “High Resolution Proteome/Peptidome Analysis of Body Fluids by Capillary Electrophoresis Coupled With Ms,” Proteomics, 6(20), pp. 5615–5627. [CrossRef] [PubMed]
Ostuni, E., Chapman, R. G., Liang, M. N., Meluleni, G., Pier, G., Ingber, D. E., and Whitesides, G. M., 2001, “Self-Assembled Monolayers That Resist the Adsorption of Proteins and the Adhesion of Bacterial and Mammalian Cells,” Langmuir, 17(20), pp. 6336–6343. [CrossRef]
Razunguzwa, T. T., Warrier, M., and Timperman, A. T., 2006, “ESI-MS Compatible Permanent Coating of Glass Surfaces Using Poly(Ethylene Glycol)-Terminated Alkoxysilanes for Capillary Zone Electrophoretic Protein Separations,” Anal. Chem., 78(13), pp. 4326–4333. [CrossRef] [PubMed]
Sun, X., Liu, J., and Lee, M. L., 2008, “Surface Modification of Polymer Microfluidic Devices Using in-Channel Atom Transfer Radical Polymerization,” Electrophoresis, 29(13), pp. 2760–2767. [CrossRef] [PubMed]


Grahic Jump Location
Fig. 1

(Top) Early prototype of SafePort™ hardware showing electronic component housing, chip carrier, and microfluidic chip. (Bottom) SafePort™ compatible microfluidic chip composed of hot embossed polymer on a printed circuit board base.

Grahic Jump Location
Fig. 2

Electropherograms showing separation of drinking water samples spiked with 0.12 ppm PDS and concentrations of perchlorate between 1 and 1000 ppb. Conditions: −350 V/cm, 10 s injection, background electrolyte = 10 mM nicotinic acid, 1.0 mM TDAPS, pH 3.6. Reprinted with permission from Gertsch et al. [9]. Copyright (2010) American Chemical Society.

Grahic Jump Location
Fig. 3

Schematic representation of the IdEA for impedance-based detection of contaminants in water. (Left) Representation of the working sensor device showing positions of all gold electrodes, the IdEA pad where the monolayer of cells are seeded onto the extracellular matrix-coated gold electrode array. (Middle) Monolayer of trout gill cells grown on the IdEA pad. (Right) Live (light) versus dead (dark) cell staining of the cells following toxicant exposure.

Grahic Jump Location
Fig. 4

Individual mouse embryonic fibroblast cells harboring FRET-based reporter targeted to focal adhesion sites. (Left) The ECFP (donor)/YPet (acceptor) ratio images in response to the oxidizing agent, diamide, over time. (Right) Time course of the normalized ECFP/YPet ratio upon treatment with diamide (0.5 mM).

Grahic Jump Location
Fig. 5

Schematic representation of a mitochondrial bioelectrode showing electron and ATP production during substrate (pyruvate or fatty acid) oxidation through the four complexes of the electron transport chain and ATPase

Grahic Jump Location
Fig. 6

Synthetic polymer nanoreactor. A polymer-based shell with protein gates for controlled influx and efflux. The encapsulated proteins are responsible for transformation of the targeted substrate, perchlorate. Image created by Dr. Manish Kumar, Pennsylvania State University.

Grahic Jump Location
Fig. 7

Examples of high (a) and low EOF (b) NMI sample concentrators are shown. The signs in the reservoirs near the microchannel ends show the polarity of the applied electric field. In both cases, the permselectivity of the nanofluidic element and electric field drive the formation of the depleted and enriched CP zones on opposite sides of the nanofluidic element. In the high EOF system, the microchannel EOF is greater in magnitude than the electrophoretic mobility of the anions, driving the anions to the interface of the bulk solution with the depleted CP zone. At this interface, the reverse electrophoretic velocity of the analyte increases as the local electric field increases, and the analyte is enriched in a forced balanced zone. In the low EOF system, the nanofluidic element is in the flow path and sufficiently reduces the EOF, and electrophoresis drives the analyte toward the nanofluidic element where it is concentrated in the enriched CP zone.

Grahic Jump Location
Fig. 8

Two similar NMI concentrators with integrated NCMs. (a) The anionic fluorescein is transported towards the negative electrode by EOF. The separation between the NCM and the enriched zone is NCM is caused by presence of the CP depleted zone. (b) The EOF is lower and the fluorescein migrates toward the NCM by electrophoresis. The highest intensity is in the vertical microchannel via.



Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging and repositioning the boxes below.

Related Journal Articles
Related eBook Content
Topic Collections

Sorry! You do not have access to this content. For assistance or to subscribe, please contact us:

  • TELEPHONE: 1-800-843-2763 (Toll-free in the USA)
  • EMAIL: asmedigitalcollection@asme.org
Sign In