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.

References

1.
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
.10.1021/ac202611x
2.
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
.10.1021/ac3031543
3.
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
.10.1021/ac049214f
4.
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
.10.1021/ac101106m
5.
Liu
,
P.
, and
Mathies
,
R. A.
,
2009
, “
Integrated Microfluidic Systems for High-Performance Genetic Analysis
,”
Trends Biotechnol.
,
27
(
10
), pp.
572
581
.10.1016/j.tibtech.2009.07.002
6.
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
.10.1016/j.bios.2006.10.030
7.
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
8.
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
.10.1080/10408340008984163
9.
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
.10.1021/ac9029086
10.
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
.10.1016/j.snb.2008.04.005
11.
Wang
,
J.
,
Polsky
,
R.
,
Tian
,
B. M.
, and
Chatrathi
,
M. P.
,
2000
, “
Voltammetry on Microfluidic Chip Platforms
,”
Anal. Chem.
,
72
(
21
), pp.
5285
5289
.10.1021/ac000484h
12.
Rogers
,
K. R.
,
2006
, “
Recent Advances in Biosensor Techniques for Environmental Monitoring
,”
Anal. Chim. Acta
,
568
(
1–2
), pp.
222
231
.10.1016/j.aca.2005.12.067
13.
Banerjee
,
P.
,
Franz
,
B.
, and
Bhunia
,
A. K.
,
2010
, “
Mammalian Cell-Based Sensor System
,”
Adv. Biochem. Eng. Biotechnol.
,
117
, pp.
21
55
.10.1007/10_2009_21
14.
Wang
,
P.
,
2010
,
Cell-Based Biosensors Principles and Applications
,
Artech House, Norwood, MA
.
15.
Lagarde
,
F.
, and
Jaffrezic-Renault
,
N.
,
2011
, “
Cell-Based Electrochemical Biosensors for Water Quality Assessment
,”
Anal. Bioanal. Chem.
,
400
(
4
), pp.
947
964
.10.1007/s00216-011-4816-7
16.
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
.10.1016/j.biomaterials.2013.01.092
17.
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
.10.1002/jbt.10010
18.
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
.10.1002/jbt.10025
19.
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
.10.1039/b300102d
20.
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
.10.1039/b808179d
21.
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
.10.1021/ac802209e
22.
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
.10.1021/nl0494811
23.
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
.10.1021/ac060031y
24.
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
.10.1021/ac050321z
25.
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
.10.1021/ac071162h
26.
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
.10.1021/ac7019927
27.
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
.10.1021/ja0374776
28.
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
.10.1039/b509063f
29.
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
.10.1021/ac981161c
30.
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
.10.1021/ac049136w
31.
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
.10.1039/b800549d
32.
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
.10.1007/s10404-008-0281-9
33.
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
.10.1039/b802778a
34.
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
.10.1039/b717220f
35.
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
.10.1021/nl902228p
36.
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
.10.1021/ac801245n
37.
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
.10.1039/b717900f
38.
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
.10.1002/elps.200900027
39.
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
.10.1021/ja802692x
40.
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
.10.1021/ac701759f
41.
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
.10.1021/ac800157q
42.
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
.10.1002/elps.200305906
43.
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
.10.1002/elps.200410132
44.
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
.10.1002/pmic.200600230
45.
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
.10.1021/la010552a
46.
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
.10.1021/ac052121t
47.
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
.10.1002/elps.200800005
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