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

Abstract

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: (I) 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 nonlaboratoiy 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 hasalso 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 ate 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.

Supramolecular Luminescent Sensors

“…506 Synthetic derivatives of fluorescein have also been reported, 507 including caged fluorescein variants that can be released via an external stimulus at targeted time points. 508 The use of fluorescein as a sensor for metal cations, 509 anions, 510 and small molecule toxicants 511 has also been reported. 512 3.2.2.…”

Chemical Sensing Platforms Based on Organic Thin-Film Transistors Functionalized with Artificial Receptors

“…Hence, the development of easy-to-use DNA sensors is crucial for point-of-care diagnostics 127,128 or biothreat detection. 129 Basically, the DNA polynucleotide consists of the two types of base pairs through hydrogen bonds: the Watson−Crick base pair of adenine (A)-thymine (T) or guanine (G)-cytosine (C). To achieve the detection of a specific base sequence in the target DNA, the probe DNA with homology to a target base sequence should be immobilized in sensor devices.…”

“…The DNA detection results in the inference of the onset risk for hereditary diseases or cancers because DNA plays a key role in the storage and transmission of genetic information. Hence, the development of easy-to-use DNA sensors is crucial for point-of-care diagnostics , or biothreat detection . Basically, the DNA polynucleotide consists of the two types of base pairs through hydrogen bonds: the Watson–Crick base pair of adenine (A)-thymine (T) or guanine (G)-cytosine (C).…”

Handheld Raman Spectrometer Instrumentation for Quantitative Tuberculosis Biomarker Detection: A Performance Assessment for Point-of-Need Infectious Disease Diagnostics

“…The development of point-of-need (PON) tests for disease markers has emerged as a global research effort. [1][2][3][4][5] The goal is to translate the strengths of today's most effective in vitro diagnostic tests (e.g., enzyme-linked immunosorbent assays [ELISAs] and nucleic acid amplification tests [NAATs]) to platforms that can be deployed outside of formal clinical settings. 1 The challenge in reaching this goal reflects the fact that most in vitro diagnostic tests require sophisticated infrastructure and highly trained personnel, which limit PON applicability.…”