Sustained release and replenishment of the drug depot are essential for the long-term functionality of implantable drug-delivery devices. This study demonstrates the use nanoporous gold (np-Au) thin films for in-plane transport of fluorescein (a small-molecule drug surrogate) over large (mm-scale) distances from a distal reservoir to the site of delivery, thereby establishing a constant flux of molecular release. In the absence of halides, the fluorescein transport is negligible due to a strong non-specific interaction of fluorescein with the pore walls. However, in the presence of physiologically relevant concentration of ions, halides preferentially adsorb onto the gold surface, minimizing the fluorescein-gold interactions and thus enabling in-plane fluorescein transport. In addition, the nanoporous film serves as an intrinsic size-exclusion matrix and allows for sustained release in biofouling conditions (dilute serum). The molecular release is reproducibly controlled by gating it in response to the presence of halides at the reservoir (source) and the release site (sink) without external triggers (e.g., electrical and mechanical).

Background

Biological systems have complicated environmental conditions that vary both spatially and temporally. It becomes necessary to impose time-varying soluble factor concentrations to study such systems, including cellular responses to pharmaceuticals, inflammation with waxing and waning cytokine concentrations, as well as circadian rhythms and their metabolic manifestations. There is therefore a need for platforms that can achieve time-varying concentrations with arbitrary waveforms.

Results

To address this need, we developed a microfluidic system that can deliver concentration waveforms in a fast and accurate manner by adopting concepts and tools from electrical engineering and fluid mechanics. Specifically, we employed pulse width modulation (PWM), a commonly used method for generating analog signals from digital sources. We implement this technique using three microfluidic components via laser ablation prototyping: low-pass filter (lower frequency signals permitted, high frequency signals blocked), resistor, and mixer. Each microfluidic component was individually studied and iteratively tuned to generate desired concentration waveforms with high accuracy. Using fluorescein as a small-molecule soluble factor surrogate, we demonstrated a series of concentration waveforms, including square, sawtooth, sinusoidal, and triangle waves with frequencies ranging from 100 mHz to 400 mHz.

Conclusion

We reported the fabrication and characterization of microfluidic platform that can generate time-varying concentrations of fluorescein with arbitrary waveforms. We envision that this platform will enable a wide range of biological studies, where time-varying soluble factor concentrations play a critical role. In addition, the technology is expected to assist in the development of biomedical devices that allow precise dosing of pharmaceuticals for enhanced therapeutic efficacy and reduced toxicity.

Point-of-care serological and direct antigen testing offers actionable insights for diagnosing challenging illnesses, empowering distributed health systems. Here, we report a POC-compatible serologic test for Lyme disease (LD), leveraging synthetic peptides specific to LD antibodies and a paper-based platform for rapid, and cost-effective diagnosis. Antigenic epitopes conserved across Borrelia burgdorferi genospecies, targeted by IgG and IgM antibodies, are selected to develop a multiplexed panel for detection of LD antibodies from patient sera. Multiple peptide epitopes, when combined synergistically with a machine learning-based diagnostic model achieve high sensitivity without sacrificing specificity. Blinded validation with 15 LD-positive and 15 negative samples shows 95.5% sensitivity and 100% specificity. Blind testing with the CDCs LD repository samples confirms the test accuracy, matching lab-based two-tier results, correctly differentiating between LD and look-alike diseases. This LD diagnostic test could potentially replace the cumbersome two-tier testing, improving diagnosis and enabling earlier treatment while facilitating immune monitoring and surveillance.