Sara Kazemi

The advent of bioprocessing has revolutionized the biomanufacturing industry, leading to the rise of biotherapeutics derived from biologic products such as chimeric antigen receptor (CAR) T-cells used for targeted cancer treatment and the Vero cell line for the production of viral vectors and vaccines. Despite these promising developments, most biologic products are characterized by fragile macromolecular structures that are heterogenous with a purity profile that varies with each batch making them susceptible to microorganism contamination. Regulatory oversight of biologic products is imperative to ensure adherence to good manufacturing practices and compliance with quality management systems. Current quality assurance protocols during production include monoclonality during cell line development, real-time monitoring of process parameters, flow cytometry for microbial monitoring, polymerase chain reaction, and immunoassay techniques to amplify DNA sequences related to bacterial or biological contaminants. FDA guidance recommends the implementation of process analytical technology within biomanufacturing production to measure critical quality parameters, which includes screening for potential biological contamination. Future advancements in bioprocess monitoring and control should capitalize on providing cheap, real-time, and sensitive detection. Biosensors, mass spectrometry, and polymerase chain reaction present robust, rapid, and real-time capabilities for multiplexed detection of contaminant analytes and have shown promise in meeting these needs. This review discusses the main biological contaminants of bioprocesses, European Union and FDA regulatory guidelines for monitoring and control within biologics production, existing methods and their limitations, and future advancements for biological contamination detection.

Wearable biosensors are becoming increasingly popular due to the rise in demand for non-invasive, real-time monitoring of health and personalized medicine. Traditionally, wearable biosensors have explored protein-based enzymatic and affinity-based detection strategies. However, in the past decade, with the success of nucleic acid-based point-of-care diagnostics, a paradigm shift has been observed in integrating nucleic acid-based assays into wearable sensors, offering better stability, enhanced analytical performance, and better clinical applicability. This narrative review builds upon the current state and advances in utilizing nucleic acid-based assays, including oligonucleotides, nucleic acid, aptamers, and CRISPR-Cas, in wearable biosensing. The review also discusses the three fundamental blocks, i.e., fabrication requirements, biomolecule integration, and transduction mechanism, for creating nucleic acid integrated wearable biosensors.