Automatic concentration and reformulation of PET tracers via microfluidic membrane distillation.

Short-lived radiolabeled tracers for positron emission tomography (PET) must be rapidly synthesized, purified, and formulated into injectable solution just prior to imaging. Current radiosynthesizers are generally designed for clinical use, and the HPLC purification and SPE formulation processes often result in a final volume that is too large for preclinical and emerging in vitro applications. Conventional technologies and techniques for reducing this volume tend to be slow, resulting in radioactive decay of the product, and often require manual handling of the radioactive materials. We present a fully-automated microfluidic system based on sweeping gas membrane distillation to rapidly perform the concentration and formulation process. After detailed characterization of the system, we demonstrate fast and efficient concentration and formulation of several PET tracers, evaluate residual solvent content to establish the safety of the formulated tracers for injection, and show that the formulated tracer can be used for in vivo imaging.

Compact microfluidic device for rapid concentration of PET tracers.

HPLC purification and reformulation of positron emission tomography (PET) tracers can lead to significant dilution of the final product, making it difficult to produce a sufficiently high radioactivity concentration for some applications (e.g. small animal imaging, in vitro assays, and labelling of proteins with prosthetic groups). This is especially true for molecules with lengthy or low-yield syntheses. Starting the synthesis with more radioactivity increases the final radioactivity concentration but increases hazards and complexity of handling. An alternative is to concentrate the final product by a process such as rotary evaporation prior to downstream use. Because a rotovap requires significant space within a hot cell that could be put to more productive use, we developed a compact microfluidic system for concentration of PET tracers. This system also provides advantages in terms of repeatability, interfacing and potential for automation. We present here the design and performance characterization of the system, and demonstrate the concentration of several tracers in aqueous-based HPLC mobile phases.

A microreactor with phase-change microvalves for batch chemical synthesis at high temperatures and pressures.

We present a simple microreactor with dimethyl sulfoxide (DMSO) phase-change valves suitable for performing batch organic chemistry under high temperature and pressure conditions. As a proof of principle, we demonstrate a radiofluorination reaction important in the synthesis of [(18)F]FAC, a new positron emission tomography biomarker for immune system monitoring and prediction of chemotherapy response. We achieved high radioactivity recovery (97 ± 1%, n = 3) and conversion efficiency (83 ± 1%, n = 3), comparable to that achieved with macroscale systems, but with a volume 30× smaller. This platform overcomes the limitations of previously reported phase-change valves in terms of compatibility with organic chemistry, and extends the range of reaction conditions for carrying out harsh batch chemistry at the microscale.

Identification of Salmonella using colony-print and detection with antibody-coated gold nanoparticles.

In this study, we developed an easy screening test that identifies Salmonella in 2 h after colony-print which is a procedure based on the transfer of surface cells of the colonies to a nitrocellulose membrane. Gold nanoparticles coated with the anti-Salmonella antibody were used to highlight the Salmonella spp. on the membrane to facilitate the selectivity. On Hektoen agar, 134 stool samples containing black or crystalloid colonies were identified using the proposed method. Without any equipment, such as microscope, the red dots corresponding Salmonella were observed. After colony-print test, 22 of the isolates were correctly identified as Salmonella to achieve 100% sensitivity. 111 samples were correctly identified as non-Salmonella spp., but one was incorrectly identified as Salmonella. The specificity is 99.1%. This method is simple, straightforward, inexpensive, and fast. It can be easily applied to the routine workload of clinical laboratories, and can be very useful when large amounts of fecal samples should be evaluated for rapid screening and diagnosis.

Alternating droplet generation and controlled dynamic droplet fusion in microfluidic device for CdS nanoparticle synthesis.

A multifunctional and high-efficiency microfluidic device for droplet generation and fusion is presented. Through unique design of the micro-channels, the device is able to alternately generate droplets, generating droplet ratios ranging from 1 ratio 5 to 5 ratio 1, and fuse droplets, enabling precise chemical reactions in several picoliters on a single chip. The controlled fusion is managed by passive control based on the channel geometry and liquid phase flow. The synthesis of CdS nanoparticles utilizing each fused droplet as a microreactor for rapid and efficient mixing of reagents is demonstrated in this paper. Following alternating droplet generation, the channel geometry allows the exclusive fusion of alternate droplets with concomitant rapid mixing and produces supersaturated solution of Cd2+ and S2- ions to form CdS nanoparticles in each fused droplet. The spectroscopic properties of the CdS nanoparticles produced by this method are compared with CdS prepared by bulk mixing.