ABSTRACT
Secreted metabolites are an important class of bio-process analytical technology (PAT) targets that can correlate to cell conditions. However, current strategies for measuring metabolites are limited to discrete measurements, resulting in limited understanding and ability for feedback control strategies. Herein, a continuous metabolite monitoring strategy is demonstrated using a single-use metabolite absorbing resonant transducer (SMART) to correlate with cell growth. Polyacrylate is shown to absorb secreted metabolites from living cells containing hydroxyl and alkenyl groups such as terpenoids, that act as a plasticizer. Upon softening, the polyacrylate irreversibly conformed into engineered voids above a resonant sensor, changing the local permittivity which is interrogated, contact-free, with a vector network analyzer. Compared to sensing using the intrinsic permittivity of cells, the SMART approach yields a 20-fold improvement in sensitivity. Tracking growth of many cell types such as Chinese hamster ovary, HEK293, K562, HeLa, and E. coli cells as well as perturbations in cell proliferation during drug screening assays are demonstrated. The sensor is benchmarked to show continuous measurement over six days, ability to track different growth conditions, selectivity to transducing active cell growth metabolites against other components found in the media, and feasibility to scale out for high throughput campaigns.
ABSTRACT
Inexpensive and accurate tools for monitoring conditions in enclosed environments (through garments, bandages, tissue, etc.) have been a long-standing goal of medicine. Passive resonant sensors are a promising solution for such wearable health sensors as well as off-body diagnostics. They are simple circuits with inherent inductance and capacitance (LC tank) that have a measurable resonant frequency. Changes in local parameters, e.g., permittivity or geometry, effect inductance and capacitance which cause a resonant frequency shift response. This signal transduction has been applied to several biomedical applications such as intracranial pressure, hemodynamics, epidermal hydration, etc. Despite these many promising applications presented in the literature, resonant sensors still do not see widespread adoption in biomedical applications, especially as wearable or embedded sensing devices. This perspective highlights some of the current challenges facing LC resonant sensors in biomedical applications, such as positional sensitivity, and potential strategies that have been developed to overcome them. An outlook on adoption in medicine and health monitoring is presented, and a perspective is given on next steps for research in this field.
