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Aligned with the medical device industry's trend of miniaturization, academic and commercial researchers are constantly attempting to reduce device sizes. Many applications require miniature actuators (2 mm range) to perform mechanical work; however, biocompatible micromotors are not readily available. To that end, a hydraulic motor-driven cutting module that aims to combine cutting and drug delivery is presented. The hydraulic motor prototype developed has an outside diameter (OD) of ~4 mm (twice the target size) and a 1 mm drive shaft to attach a cutter. Four different designs were explored and fabricated using additive manufacturing. The benchtop experimental data of the prototypes are presented herein. For the prototype motor with fluid inlet perpendicular to the blades, the average angular velocity was 10,593 RPM at a flowrate of 3.6 mL/s and 42,597 RPM at 10.1 mL/s. This design was numerically modeled using 3D-transient simulations in ANSYS CFX (version 2022 R2) to determine the performance characteristics and the internal resistance of the motor. Simplified mathematical models were also used to compute and compare the peak torque with the simulation estimates. The viability of current design represents a crucial milestone in scaling the hydraulic motor to a 2 mm OD to power a microcutter. [ABSTRACT FROM AUTHOR]

Miniaturization of multifunctional instruments is key to evolving less invasive medical procedures. The current work outlines steps towards developing a miniature motor to power a cutting tool of a millimeter-scale robot/device (target outside diameter ~2 mm) for minimally invasive procedures. Multiple motor concepts were explored and ranked using a Pugh matrix. The single-rotor hydraulic design was deemed most viable for prototyping and scale-down to the target size. Prototypes were manufactured to be progressively smaller using additive manufacturing. The smallest prototype fabricated was 2:1 scale of the desired final size with a 2 mm outside diameter (OD) rotor and a device OD of 4 mm. The scaled prototypes with an 8 mm rotor were lab tested and achieved average speeds of 5000–6000 RPM at a flowrate of 15–18 mL/s and 45 PSI water pressure. Ansys CFX was used as a design tool to explore the parameter space and 3D transient simulations were implemented using the immersed solid method. The predicted rotor RPM from the modeling matched the experimental values within 3% error. The model was then used to develop performance curves for the miniature hydraulic motor. In summary, the single-rotor hydraulic design shows promise for miniaturization to the target 2 mm size. [ABSTRACT FROM AUTHOR]

Background: Several studies suggest that patients with KRAS-mutant NSCLC fail to benefit from standard systemic therapies and do not respond to EGFR inhibitors. Most recently, KRAS 12c data suggest specific treatment for improving ORR and OS. There is a clear need for therapies specifically developed for these patients. Moreover, data that might be suggestive of a response to specific therapies, such as BRCA1, are needed, and two mutations that were studied in other malignancies show more response to PARP inhibitors. Molecular profiling has the potential to identify other potential targets that may provide better treatment and novel targeted therapy for KRAS-mutated NSCLC. Methods: We purified RNA from archived tissues of patients with stage I and II NSCLC with wild-type (wt) and mutant (mt) KRAS tumors; paired normal tissue adjacent to the tumor from 20 and 17 patients, respectively, and assessed, using real-time reverse transcriptase–polymerase chain reaction (RT-PCR), the expression of four genes involved in DNA synthesis and repair, including thymidylate synthase (TS), BRCA1, ECCR1, RAP80, and the proto-oncogene SRC. Additionally, we assessed the expression of PD-L1 in mt KRAS tumors with immunohistochemistry using an antibody against PD-L1. Results: Our results show that in mtKRAS tumors, the level of expression of ERCC1, TS, and SRC was significantly increased in comparison to paired normal lung tissue (p ≤ 0.04). The expression of BRCA1 and RAP80 was similar in both mt KRAS tumors and paired normal tissue. Furthermore, the expression of BRCA1, TS, and SRC was significantly increased in wt KRAS tumors relative to their expression in the normal lung tissue (p < 0.044). The expression of ERCC1 and RAP80 was similar in wt KRAS tumors and paired normal tissue. Interestingly, SRC expression in mtKRAS tumors was decreased in comparison to wt KRAS tumors. Notably, there was an expression of PD-L1 in the tumor and stromal cells in a few (5 out of 20) mtKRAS tumors. Our results suggest that a greater ERCC1 expression in mt KRAS tumors might increase platinum resistance in this group of patients, whereas the greater expression of BRCA1 in wt KRAS tumor might be suggestive of the sensitivity of taxanes. Our data also suggest that the combination of an SRC inhibitor with a TS inhibitor, such as pemetrexed, might improve the outcome of patients with NSCLC and in particular, patients with wt KRAS tumors. PD-L1 expression in tumors, and especially stromal cells, suggests a better outcome. Conclusion: mt KRAS NSCLC patients might benefit from a treatment strategy that targets KRAS in combination with therapeutic agents based on pharmacogenomic markers, such as SRC and BRCA1. mtKRAS tumors are likely to be platinum-, taxane-, and pemetrexed-resistant, as well as having a low level of PD-L1 expression; thus, they are less likely to receive single-agent immunotherapy, such as pembrolizumab, as the first-line therapy. wt KRAS tumors with BRCA1 positivity tend to be sensitive to taxane therapy and, potentially, platinum. Our results suggest the need to develop targeted therapies for KRAS-mutant NSCLC or combine the targeting of oncogenic KRAS in addition to other therapeutic agents specific to the molecular profile of the tumor. [ABSTRACT FROM AUTHOR]