Introduction to bioanalytical sensors for real-world applications

We are excited to present this Analytical Methods collection on bioanalytical sensors for real-world applications. In soliciting submissions, we aimed to gather papers demonstrating the use of sensors to measure analytes in complex matrices, using robust technologies with high sensitivity and specificity. We sought to explicitly address the gap between the idealized proof-of-concept experiments—where analytical method development typically begins—and the messy, interference-prone world in which we hope our measurements will ultimately prove valuable. The scope of this collection is intentionally broad to cover a wide range of applications, both biomedical and environmental.

Despite the diverse challenges faced by researchers during the submission window, as the COVID-19 pandemic forced an upheaval of life both in and out of the lab, we have assembled a remarkable set of papers. In this collection you will find 16 research papers and one review, contributed by research labs around the world.

The collection opens with a critical review from Netzahualcoyotl Arroyo-Currás on electrochemical aptamer-based sensors. These sensors have been demonstrated in matrices as complex as whole blood and have been coupled with feedback-controlled drug release, but making this technology routine will require surmounting numerous challenges, as the authors describe (DOI: 10.1039/D0AY00026D). Another application of DNA aptamers comes from Pengfei Pang, who used dsDNA templated copper nanoclusters, aptamers and complementary strands, and fluorescence quenching to detect microcystin-LR, a toxin produced by freshwater cyanobacteria (DOI: 10.1039/C9AY02250C).

Infections caused by pathogens in seafood is a public health concern that is expected to grow more serious as temperatures rise in bodies of water globally. Kimberly Hamad-Schifferli reports a field-deployable dipstick immunoassay method to detect pathologic bacteria in oyster hemolymph with a readout based on gold nanoparticles (DOI: 10.1039/D0AY00725K). Also in the area of instrument-free methods to monitor food quality, Jean-Francois Masson reports a plasmonic tongue to detect organic compounds responsible for off-flavors in maple syrup. Based on gold nanoparticle aggregation, the test uses nonspecific interactions and can be deployed on-site in sugar shacks (DOI: 10.1039/C9AY01942A). Alan O’Riordan reports a label-free impedimetric immunosensor device usable on farms to monitor bovine IgG in the serum of newborn calves during the crucial first hours after birth (DOI: 10.1039/D0AY00194E).

Several of the papers focus on the detection of clinically relevant analytes. John Lowry has developed an electrochemical O₂ sensor usable in vivo, for applications such as monitoring perfusion during surgery, and has demonstrated its use during carpal tunnel release surgery (DOI: 10.1039/D0AY00206B). B. Jill Venton and Yuanyu Chang report a method to improve the fabrication of graphene oxide-modified carbon-fiber microelectrodes and demonstrate their use to detect dopamine through fast-scan cyclic voltammetry in mouse brain slices (DOI: 10.1039/D0AY00310G). Detecting large and small molecules with a single sensing platform is an outstanding challenge. Benjamin Miller reports an arrayed image reflectometry method to detect antiretrovirals (protease inhibitors) and inflammatory biomarkers in serum, addressing an important clinical challenge for people living with HIV (DOI: 10.1039/D0AY00098A). Heather Clark and Wenjun Di use an optode-based nanosensor to detect chloride in interstitial fluid, and applies the detector in a cystic fibrosis mouse model. This in vivo fluorescence imaging approach could be used to assess the efficacy of novel cystic fibrosis treatments (DOI: 10.1039/C9AY02717C). Charles Mace developed a paper-based device to perform in situ chemical hemolysis and quantify haemoglobin liberated from whole blood (DOI: 10.1039/C9AY02292A).

Several contributors made inroads into challenging analytical problems through the use of innovative materials and design approaches. Xiliang Luo performs nitrite sensing in a 3D porous polyaniline/carbon nanotube conductive hydrogel. The hydrogel is both a wearable sensor and an electrolyte reservoir (DOI: 10.1039/C9AY02442E). In the lab of Matthew Lockett, block-layered oxygen-controlled chips (BLOCCs) were assembled from laser cut acrylic and silicone and used to impose physiologically relevant oxygen gradients across 3D cell cultures. These BLOCCs were used to quantify cell-microenvironment relationships (DOI: 10.1039/C9AY01690B). Jakoah Brgoch deployed two persistent luminescent nanophosphors and immobilized antibodies in a lateral flow assay paired with a smartphone for signal detection. This dual detection platform is demonstrated using PSA and human chorionic gonadotropin as the model analytes (DOI: 10.1039/C9AY02247C). Martyn Boutelle and Xize Niu provide a cautionary tale in assay miniaturization. They found that long-established conditions useful for real-time enzymatic measurement of lactate need to be carefully re-optimized to be usable in the format of miniaturized droplet microfluidics, which encapsulates samples in droplets to preserve the temporal detail of chemical variation in this important metabolic marker (DOI: 10.1039/C9AY02070E).

Marya Lieberman’s lab made three outstanding contributions to this collection. In one paper (DOI: 10.1039/C9AY01547G), Lieberman and a team of global collaborators report a field screening test for the beta-lactam pharmaceuticals amoxicillin and ampicillin. This device may be useful to identify adulterated or substandard antibiotics in low and middle-income countries. In a second study, they report a paper analytical device (PAD) to detect degraded, adulterated, and falsified ceftriaxone injectable formulations. Considering that ceftriaxone is often administered after resistance to other antibiotics has developed, detection of bad quality formulations is of considerable interest to the global health community (DOI: 10.1039/C9AY01489F). Finally, Lieberman and Holly Goodson describe a paper-immobilized fluorescence whole-cell yeast biosensor for detection of doxycycline in technology limited settings (DOI: 10.1039/D0AY00001A).

Taken together, these papers illustrate the innovation and creativity of the bioanalytical sensors community. We hope you enjoy reading the papers in this collection as much as we did.

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