Design and ex vivo characterization of narrow implants with custom piezo-activated osteotomy for patients with substantial bone loss.

OBJECTIVE: Bone augmentation delays implant placement and increases risks due to additional surgeries. Implant systems compatible with reduced alveolar bone volume are required. To design, manufacture, and test a non-cylindrical dental implant system using piezotomes and custom-designed matching titanium mini-implants to address the needs of patients with missing teeth and narrow jawbone. MATERIALS AND METHODS: Tapered mini-implants with a rectangular cross-section (4.6 mm × 2.1 mm) were machined with dimensions that could accommodate narrow alveolar ridges. The performance of the implants were tested in both static and fatigue cycle 30° compression tests. Tapered, rectangular cutting tools that matched the overall trapezoidal morphology of the implant were also designed. These novel tools were engineered to be compatible with commercially available piezoelectric osteotomes. Tools were optimized using finite element analysis and were manufactured accordingly and were used by a periodontal surgery team in a pork rib bone model to monitor utility of the device and ease of use. RESULTS: The rectangular design of the implant allows for a full occlusal load due to the larger implant flexural rigidity compared to a similar diameter mini-implant with a standard cylindrical design. During 30° compression fatigue tests, the implant tested at 340 N did not fail after 5M cycles as shown in Kaplan-Meier survival curves. Finite element analysis allowed for functional optimization of the roughing and finishing tools. In the pork rib model, these tools successfully cut trapezoidal holes that matched the dimensions of the implant. CONCLUSIONS: The implant system here demonstrates the feasibility of a mini-implant system that has superior flexural rigidity and potentially circumvents the need for patient bone augmentation.

A novel device for collecting and dispensing fingerstick blood for point of care testing.

The increased world-wide availability of point-of-care (POC) tests utilizing fingerstick blood has led to testing scenarios in which multiple separate fingersticks are performed during a single patient encounter, generating cumulative discomfort and reducing testing efficiency. We have developed a device capable of a) collection of up to 100 µL of fingerstick blood from a single fingerstick by capillary action, and b) dispensing this blood in variable increments set by the user. We tested the prototype device both in a controlled laboratory setting and in a fingerstick study involving naive device users, and found it to have accuracy and precision similar to a conventional pipettor. The users also found the device to be easy to use, and recommended minor ergonomic improvements. Our device would allow performance of multiple POC tests from a single fingerstick blood sample, thus providing a novel functionality that may be of use in many testing settings worldwide.

Rapid microbial sample preparation from blood using a novel concentration device.

Appropriate care for bacteremic patients is dictated by the amount of time needed for an accurate diagnosis. However, the concentration of microbes in the blood is extremely low in these patients (1-100 CFU/mL), traditionally requiring growth (blood culture) or amplification (e.g., PCR) for detection. Current culture-based methods can take a minimum of two days, while faster methods like PCR require a sample free of inhibitors (i.e., blood components). Though commercial kits exist for the removal of blood from these samples, they typically capture only DNA, thereby necessitating the use of blood culture for antimicrobial testing. Here, we report a novel, scaled-up sample preparation protocol carried out in a new microbial concentration device. The process can efficiently lyse 10 mL of bacteremic blood while maintaining the microorganisms' viability, giving a 30-µL final output volume. A suite of six microorganisms (Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Haemophilus influenzae, Pseudomonas aeruginosa, and Candida albicans) at a range of clinically relevant concentrations was tested. All of the microorganisms had recoveries greater than 55% at the highest tested concentration of 100 CFU/mL, with three of them having over 70% recovery. At the lowest tested concentration of 3 CFU/mL, two microorganisms had recoveries of ca. 40-50% while the other four gave recoveries greater than 70%. Using a Taqman assay for methicillin-sensitive S. aureus (MSSA)to prove the feasibility of downstream analysis, we show that our microbial pellets are clean enough for PCR amplification. PCR testing of 56 spiked-positive and negative samples gave a specificity of 0.97 and a sensitivity of 0.96, showing that our sample preparation protocol holds great promise for the rapid diagnosis of bacteremia directly from a primary sample.

Automated production of plant-based vaccines and pharmaceuticals.

A fully automated "factory" was developed that uses tobacco plants to produce large quantities of vaccines and other therapeutic biologics within weeks. This first-of-a-kind factory takes advantage of a plant viral vector technology to produce specific proteins within the leaves of rapidly growing plant biomass. The factory's custom-designed robotic machines plant seeds, nurture the growing plants, introduce a viral vector that directs the plant to produce a target protein, and harvest the biomass once the target protein has accumulated in the plants-all in compliance with Food and Drug Administration (FDA) guidelines (e.g., current Good Manufacturing Practices). The factory was designed to be time, cost, and space efficient. The plants are grown in custom multiplant trays. Robots ride up and down a track, servicing the plants and delivering the trays from the lighted, irrigated growth modules to each processing station as needed. Using preprogrammed robots and processing equipment eliminates the need for human contact, preventing potential contamination of the process and economizing the operation. To quickly produce large quantities of protein-based medicines, we transformed a laboratory-based biological process and scaled it into an industrial process. This enables quick, safe, and cost-effective vaccine production that would be required in case of a pandemic.