Point-of-care (POC) device development is a growing field that aims to develop low-cost, rapid, sensitive in-vitro diagnostic testing platforms that are portable, selfcontained, and can be used anywhere -from modern clinics to remote and low resource areas. In this review, surface enhanced Raman spectroscopy (SERS) is discussed as a solution to facilitating the translation of bioanalytical sensing to the POC. The potential for SERS to meet the widely accepted "ASSURED" (Affordable, Sensitive, Specific, Userfriendly, Rapid, Equipment-free, and Deliverable) criterion provided by the World Health Organization is discussed based on recent advances in SERS in vitro assay development. As SERS provides attractive characteristics for multiplexed sensing at low concentration limits with a high degree of specificity, it holds great promise for enhancing current efforts in rapid diagnostic testing. In outlining the progression of SERS techniques over the past years combined with recent developments in smart nanomaterials, high-throughput microfluidics, and low-cost paper diagnostics, an extensive number of new possibilities show potential for translating SERS biosensors to the POC.
Wearable devices have found widespread applications in recent years as both medical devices as well as consumer electronics for sports and health tracking. A metric of health that is often overlooked in currently available technology is the direct measurement of molecular oxygen in living tissue, a key component in cellular energy production. Here, we report on the development of a wireless wearable prototype for transcutaneous oxygenation monitoring based on quantifying the oxygen-dependent phosphorescence of a metalloporphyrin embedded within a highly breathable oxygen sensing film. The device is completely self-contained, weighs under 30 grams, performs on-board signal analysis, and can communicate with computers or smartphones. The wearable measures tissue oxygenation at the skin surface by detecting the lifetime and intensity of phosphorescence, which undergoes quenching in the presence of oxygen. As well as being insensitive to motion artifacts, it offers robust and reliable measurements even in variable atmospheric conditions related to temperature and humidity. Preliminary in vivo testing in a porcine ischemia model shows that the wearable is highly sensitive to changes in tissue oxygenation in the physiological range upon inducing a decrease in limb perfusion.
Surface-enhanced Raman scattering (SERS) optical nanoprobes offer a number of advantages for ultrasensitive analyte detection. These functionalized colloidal nanoparticles are a multifunctional assay component. providing a platform for conjugation to spectral tags, stabilizing polymers, and biorecognition elements such as aptamers or antibodies. We demonstrate the design and characterization of a SERS-active nanoprobe and investigate the nanoparticles’ biorecognition capabilities for use in a competitive binding assay. Specifically, the nanoprobe is designed for the quantification of bisphenol A (BPA) levels in the blood after human exposure to the toxin in food and beverage plastic packaging. The nanoprobes demonstrated specific affinity to a BPA aptamer with a dissociation constant Kd of 54 nM, and provided a dose-dependent SERS spectra with a limit of detection of 3 nM. Our conjugation approach shows the versatility of colloidal nanoparticles in assay development, acting as detectable spectral tagging elements and biologically active ligands concurrently.
Blood, saliva, mucus, sweat, sputum, and other biological fluids are often hindered in their ability to be used in point-of-care (POC) diagnostics because their assays require some form of off-site sample pre-preparation to effectively separate biomarkers from larger components such as cells. The rapid isolation, identification, and quantification of proteins and other small molecules circulating in the blood plasma from larger interfering molecules are therefore particularly important factors for optical blood diagnostic tests, in particular, when using optical approaches that incur spectroscopic interference from hemoglobin-rich red blood cells (RBCs). In this work, a sequential spiral polydimethylsiloxane (PDMS) microfluidic device for rapid (∼1 min) on-chip blood cell separation is presented. The chip utilizes Dean-force induced migration via two 5-loop Archimedean spirals in series. The chip was characterized in its ability to filter solutions containing fluorescent beads and silver nanoparticles and further using blood solutions doped with a fluorescent protein. Through these experiments, both cellular and small molecule behaviors in the chip were assessed. The results exhibit an average RBC separation efficiency of ∼99% at a rate of 5.2 × 10 cells per second while retaining 95% of plasma components. This chip is uniquely suited for integration within a larger point-of-care diagnostic system for the testing of blood plasma, and the use of multiple filtering spirals allows for the tuning of filtering steps, making this device and the underlying technique applicable for a wide range of separation applications.
Flaps are common in plastic surgery to reconstruct large tissue defects in cases such as trauma or cancer. However, most tissue oximeters used for monitoring ischemia in postoperative flaps are bulky, wired devices, which hinder direct flap observation. Here, we present the results of a clinical trial using a previously untried paintable transparent phosphorescent bandage to assess the tissue’s partial pressure of oxygen (pO2). Statistical analysis revealed a strong relationship (P < 0.0001) between the rates of change of tissue oxygenation measured by the bandage and blood oxygen saturation (%stO2) readings from a standard-of-care ViOptix near-infrared spectroscopy oximeter. In addition, the oxygen-sensing bandage showed no adverse effects, proved easy handling, and yielded bright images across all skin tones with a digital single-lens reflex (DSLR) camera. This demonstrates the feasibility of using phosphorescent materials to monitor flaps postoperatively and lays the groundwork for future exploration in other tissue oxygen sensing applications.
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