Search for: All records

While implantable medical devices offer tremendous potential for treating a myriad of diseases and disorders, there are many situations in which such devices are only needed for short time periods, with extended presence or surgical removal leading to a host of undesired complications. To address this concern, researchers are working to develop implantable circuitry that eventually disintegrates. Prior work in this area leveraged known bioresorbable materials, but the lifetime of circuits formed from such materials is determined upon fabrication, and on‐demand, triggered disintegration is not possible. To better match the lifetime of an implanted device to the status of the condition it is monitoring or treating, it would be advantageous to be able to noninvasively trigger disintegration at a particular time, avoiding situations in which the device lifetime is either too short or too long. Thus, to enable implantable circuitry with wireless capabilities that can disintegrate upon external stimuli, thermoresponsive transient RF antennas are formed that exhibit stable wireless response in warm aqueous environments but disintegrate and irreversibly lose functionality when cooled below a critical temperature. Antennas are formed by embedding patterned networks of silver nanowires in a thermoresponsive polymeric binder, which maintains network conductivity in warm solution but disintegrates and releases the nanowires when solution temperature drops. Mild sintering enhances electrical properties of the conductive nanowire network and antenna response while maintaining the capability for disintegration. To reduce the undesired effects of swelling, devices are sandwiched between two parylene films. These thermoresponsive transient devices represent an important step toward the realization of wireless medical implants whose disintegration can be triggered at any time by an external cooling stimulus.

 

Fabrication of microfluidic devices by photolithography generally requires specialized training and access to a cleanroom. As an alternative, 3D printing enables cost-effective fabrication of microdevices with complex features that would be suitable for many biomedical applications. However, commonly used resins are cytotoxic and unsuitable for devices involving cells. Furthermore, 3D prints are generally refractory to elastomer polymerization such that they cannot be used as master molds for fabricating devices from polymers ( e.g. polydimethylsiloxane, or PDMS). Different post-print treatment strategies, such as heat curing, ultraviolet light exposure, and coating with silanes, have been explored to overcome these obstacles, but none have proven universally effective. Here, we show that deposition of a thin layer of parylene, a polymer commonly used for medical device applications, renders 3D prints biocompatible and allows them to be used as master molds for elastomeric device fabrication. When placed in culture dishes containing human neurons, regardless of resin type, uncoated 3D prints leached toxic material to yield complete cell death within 48 hours, whereas cells exhibited uniform viability and healthy morphology out to 21 days if the prints were coated with parylene. Diverse PDMS devices of different shapes and sizes were easily cast from parylene-coated 3D printed molds without any visible defects. As a proof-of-concept, we rapid prototyped and tested different types of PDMS devices, including triple chamber perfusion chips, droplet generators, and microwells. Overall, we suggest that the simplicity and reproducibility of this technique will make it attractive for fabricating traditional microdevices and rapid prototyping new designs. In particular, by minimizing user intervention on the fabrication and post-print treatment steps, our strategy could help make microfluidics more accessible to the biomedical research community. 

Precise monitoring of specific biomarkers in biological fluids with accurate biodiagnostic sensors is critical for early diagnosis of diseases and subsequent treatment planning. In this work, we demonstrated an innovative biodiagnostic sensor, portable reusable accurate diagnostics with nanostar antennas (PRADA), for multiplexed biomarker detection in small volumes (~50 μl) enabled in a microfluidic platform. Here, PRADA simultaneously detected two biomarkers of myocardial infarction, cardiac troponin I (cTnI), which is well accepted for cardiac disorders, and neuropeptide Y (NPY), which controls cardiac sympathetic drive. In PRADA immunoassay, magnetic beads captured the biomarkers in human serum samples, and gold nanostars (GNSs) “antennas” labeled with peptide biorecognition elements and Raman tags detected the biomarkers via surface‐enhanced Raman spectroscopy (SERS). The peptide‐conjugated GNS‐SERS barcodes were leveraged to achieve high sensitivity, with a limit of detection (LOD) of 0.0055 ng/ml of cTnI, and a LOD of 0.12 ng/ml of NPY comparable with commercially available test kits. The innovation of PRADA was also in the regeneration and reuse of the same sensor chip for ~14 cycles. We validated PRADA by testing cTnI in 11 de‐identified cardiac patient samples of various demographics within a 95% confidence interval and high precision profile. We envision low‐cost PRADA will have tremendous translational impact and be amenable to resource‐limited settings for accurate treatment planning in patients.