Şebnem Şahin

The isolation of circulating tumor cells (CTCs) from peripheral blood with high efficiency remains a challenge hindering the utilization of CTC enrichment methods in clinical practice. Here, we propose a microfluidic channel design for the size-based hydrodynamic enrichment of CTCs from blood in an epitope-independent and high-throughput manner. The microfluidic channel comprises a spiral-shaped part followed by a widening part, incorporating successive streamlined pillars, that improves the enrichment efficiency. The design was tested against two benchmark designs, a spiral microfluidic channel and a spiral microfluidic channel followed by a widening channel without the hydrofoils, by processing 5 mL of healthy blood samples spiked with 100 MCF-7 cells. The results proved that the design with hydrofoil-shaped pillars perform significantly better in terms of recovery (recovery rate of 67.9% compared to 23.6% in spiral and 56.7% in spiral with widening section), at a cost of slightly lower white blood cell (WBC) depletion (depletion rate of 94.2% compared to 98.6% in spiral and 94.2% in spiral with widening section), at 1500 µL/min flow rate. For analytical validation, the design was further tested with A549, SKOV-3, and BT-474 cell lines, yielding recovery rates of 62.3 ± 8.4%, 71.0 ± 6.5%, and 82.9 ± 9.9%, respectively. The results are consistent with the size and deformability variation in the respective cell lines, where the increasing size and decreasing deformability affect the recovery rate in a positive manner. The analysis before and after the microfluidic chip process showed that the process does not affect cell viability.

Being one of the major pillars of liquid biopsy, isolation and characterization of circulating tumor cells (CTCs) during cancer management provides critical information on the evolution of cancer and has great potential to increase the success of therapies. In this article, we define a novel strategy to effectively enrich CTCs from whole blood based on size, utilizing a spiral microfluidic channel embedded with a hydrofoil structure at the downstream of the spiral channel. The hydrofoil increases the distance between the streams of CTCs and peripheral blood cells, which are already distributed about two focal axes by the spiral channel, thereby improving the resolution of the separation. Analytical validation of the system has been carried out using Michigan Cancer Foundation-7 (MCF7) breast cancer cell lines spiked into blood samples from healthy donors, and the performance of the system in terms of white blood cell (WBC) depletion, CTC recovery rate and cell viability has been shown in single or two-step process: by passing the sample once or twice through the microfluidic chip. Single step process yielded high recovery (77.1%), viable (84.7%) CTCs. When the collected cell suspension is re-processed by the same chip, recovery decreases to 65.5%, while the WBC depletion increases to 88.3%, improving the purity. Cell viability of >80% was preserved after two-step process. The novel microfluidic chip is a good candidate for CTC isolation applications requiring high recovery rate and viability, including functional downstream analyses for variety of cancer types.

Osteoarthritis (OA) is a common form of arthritis, which is characterized by progressive degradation of joint cartilage resulting in pain, joint stiffness, deformity and disability that is also recently related to an increased incidence of mortality. Inhibition of the extracellular matrix (ECM) production by chondrocytes and accumulation of catabolic mediators associated with matrix degradation are the cause of OA. Nonsurgical treatments for OA can be characterised as symptom-modifying or disease-modifying approaches. It’s estimated that 10% of the world population older than 60 years demonstrated symptoms of OA (Messier SP, Callahan LF, Beavers DP et al., BMC Musculoskelet Disord 18(1):91, 2017). A virtue of chondrocytes has a limited proliferation capability; nonsurgical OA therapies mostly include native cartilage extracellular component injections like hyaluronic acid, anti-inflammatory effected autologous cell implantations, platelet rich plasma injections and medicals like corticosteroids. Stem cells are searched to cure OA recently. Also nowadays we can develop injectable release systems, biocompatible hydrogels and micro/nano sized carriers to make these medicals more effective. In this review we cover injectable alternatives to modify the natural course of OA that gives a window for patients between conventional treatment methods and joint replacement surgery.