Dielectrophoresis: Applications and future outlook in point of care

Dielectrophoresis (DEP) is a label free, noninvasive, stand alone, rapid, and sensitive particle manipulation and characterization technique. Improvements in micro-electro-mechanical systems technology have enabled the biomedical applications of DEP over the past decades. By this way, integration of DEP into lab-on-a-chip systems has become achievable, creating a potential tool for point-of-care (POC) systems. DEP can be utilized in many different POC applications including early detection and prognosis of various cancer types, diagnosis of infectious diseases, blood cell analysis, and stem cell therapy. However, there are still some challenges to be resolved to have DEP-based devices available in POC market. Today, researchers have focused on these challenges to have this powerful theory as a solution for many POC applications. Here, DEP theory, cell modeling, and most common device structures are introduced briefly. Next, POC applications of DEP theory, such as cell (blood, cancer, stem, and fetal) and microorganism separation, manipulation, and enrichment for diagnosis and prognosis, are explained. Integration of DEP with other detection techniques to have more sensitive systems is summarized. Finally, future outlook for DEP-based systems are discussed with some challenges, which are currently preventing these systems to be a common tool for POC applications, and possible solutions

A high-throughput microfluidic rare cell enrichment system based on dielectrophoresis and filtering

In this study, a MEMS-based microfluidic device combining DEP-based cell manipulation with size-based filtration for the enrichment of CTCs from blood with high-throughput was developed. Positive-DEP (pDEP) force and the hydrodynamic force have been used to fine-tune the cell movement over the planar electrodes (sliding) at a high flow rate (30 mu l/min). While smaller sized RBCs passed through the gaps and were directed to the waste channels, cancer cells (K562 cells) were filtered and directed to the cancer cell outlet. A cell enrichment factor and depletion rate of RBCs were calculated as 1.45 and 60%, respectively

Label-free detection of multidrug resistance in K562 cells through isolated 3D-electrode dielectrophoresis

Dielectrophoresis (DEP), a technique used to separate particles based on different sizes and/or dielectric properties under nonuniform electric field, is a promising method to be applied in label-free, rapid, and effective cell manipulation and separation. In this study, a microelectromechanical systems-based, isolated 3D-electrode DEP device has been designed and implemented for the label-free detection of multidrug resistance in K562 leukemia cells, based on the differences in their cytoplasmic conductivities. Cells were hydrodynamically focused to the 3D-electrode arrays, placed on the side walls of the microchannel, through V-shaped parylene-C obstacles. 3D-electrodes extruded along the z-direction provide uniformly distributed DEP force through channel depth. Cell suspension containing resistant and sensitive cancer cells with 1:100 ratio was continuously flown through the channel at a rate of 10 L/min. Detection was realized at 48.64 MHz, the cross-over frequency of sensitive K562 cells, at which sensitive cells flow with the fluid, while the resistant ones are trapped by positive DEP force. Device can be operated at considerably low voltages (<9 V-pp). This is achieved by means of a very thin (0.5 m) parylene coating on electrodes, providing the advantages offered by the isolation of electrodes from the sample, while the working voltage can still be kept low. Results prove that the presented DEP device can provide an efficient platform for the detection of multidrug resistance in leukemia, in a label-free manner

Prolongation of Neoadjuvant Chemotherapy before Surgery: Seeking the Optimal Number of Cycles in Serous Ovarian Cancer

Aim: The optimal number of neoadjuvant chemotherapy (NACT) cycles is unclear in epithelial ovarian cancer. Our study aimed to evaluate the effect of the number of NACT cycles before interval debulking surgery on survival. Methods: Data of 221 patients with advanced-stage serous epithelial ovarian cancer (EOC) were retrospectively evaluated. The patients were divided into groups as who received 3 cycles of NACT (group A), 4-5 cycles of NACT (group B), and 6 cycles of NACT (group C). Results: There were 67 (30%) patients in group A, 70 (32%) in group B, and 84 (38%) in group C. Median overall survival (OS) was 61 (range 43-79) months for group A, 44 (range 36-52) months for group B, and 39 (range 27-50) months for group C. In addition, median disease-free survival (DFS) was 23.1 (range 8.5-32.1) months for group A, 19.2 (range 10.1-28.4) months for group B, and 21.5 (range 16-27) months for group C. Patients receiving >3 NACT cycles had worse OS than patients who received 3 NACT cycles (for group A vs. B, p = 0.018; for group A vs. C, p = 0.049). However, in terms of DFS, patients receiving 3 NACT cycles had no statistically significant difference compared to patients who received >3 NACT cycles. Conclusions: Patients with advanced-stage serous EOC who received more than 3 cycles of NACT had poor OS. However, there was no statistical difference in terms of DFS. In addition, >3 cycles of NACT did not increase the probability of achieving complete cytoreduction at the time of surgery

Predictors of high-grade residual disease after repeat conization in patients with positive surgical margins

Objectives: No consensus exists on the subsequent management strategy of patients who exhibit positive surgical margin (PSM) after re-excision of high-grade cervical intraepithelial neoplasia (CIN). The aim of the study is to examine the predictors related to the persistence of high-grade CIN lesions after re-excision, where PSM was left behind. Material and methods: The present retrospective study included patients with PSM who underwent repeated conization due to residual high-grade CIN lesions between January 2005 and December 2019. The SPSS software v20.0 was used for data interpretation and statistical analysis. P values less than 0.05 were accepted as statistically significant. Results: Repeat conization was performed in 91 patients, 43 (47.3%) presented with PSM with high-grade CIN, 6 (6.5%) presented with micro-invasive carcinoma, and 42 (46.2%) presented with clear surgical margin or CIN 1 at the surgical margin. At the time of conization, patients who presented with lesions &gt; 5 mm in repeat cone specimens, exhibited a significantly higher rate of residual disease (p &lt; 0.001). Besides, the involvement of the endocervical margin with high-grade CIN was the predictor of residual disease in repeat cone specimens (p = 0.006). Conclusions: In the cone specimen, the presence of lesion size greater than 5 mm and involvement of the endocervical margin were the predictors of high-grade residual disease after re-excision. Whether it is the first or second procedure, great care must be given to excise the lesion entirely at the time of the conization, preferably in one piece

İnsülinomanin Cerrahi Yönetiminde Uzun Dönem Sonuçlar: Tek Merkez Deneyimi

Objective: Limited data are available in regards to the surgical management and outcomes of insulinoma. This study aimed to assess the outcomes associated with surgical treatment of insulinoma, as the most common pancreatic endocrine tumor Methods: Medical records of patients who diagnosed as insulinoma from 2000 to 2010 at General Surgery Department of Cukurova University Hospital were retrospectively reviewed. Surgical treatment (resection vs. enucleation) was based on preoperative radiological investigations (abdominal spiral contrast tomography, ultrasound, selective angiography for selected cases) and intra-operative ultrasound imaging once indicated. Conclusion: Surgical treatment of insulinoma is associated with favorable outcomes.Intra-operative ultrasound with manual palpation is still the gold standard for localizing insulinoma. Location, size and relationship with main pancreatic duct of the lesions are key components for the selection of optimal surgical procedure.Giriş: İnsülinomanin cerrahi yönetimi ve sonuçlarıyla ilişkili olarak sınırlı miktarda bilgiler mevcuttur.Bu çalısma en sık pankreatik endokrin tümör olan insülinomaların cerrahi tedavisiyle ilgili sonuçları değerlendirmeyi amaçlamıştır Yöntemler: Çukurova Üniverstitesi Genel Cerrahi Departmanında 2000 ile 2010 yılları arasında insulinoma tanısıyla ameliyat edilen hastalar geriye dönük olarak değerlendirildi. Rezeksiyon yada enükleasyondan oluşan cerrahi tedavi kararı preoperatif radyolojik değerlendirme (abdominalkontrastlı tomografi, ultrason ve endikasyou olan hastaraselektifanjiografi) ve intraoperatifultrasonografik görüntülemeye göre yapıldı. Bulgular: Cerrahi olarak tedavi edilen, insulinoma tanısı alan ve ortalama takip süresi 5.3 yıl (0.5-10) olan 13 hasta (K/E:9/4) calışmayadahil edildi. Enükleasyon 11 hastaya uygulanırken 2 hastaya distalpankreatektomi (biri dalak koruycu) uygulandı. Mortalite izlenmedi. Cerrahi sonrası tüm hastalar tekrar ameliyat gereksinimi olmaksızın kabul edilebilir komplikasyon oranları (panreatik fistül, n=3; pankreatit, n=1) ile normoglisemik hale geldi. Sonuç: İnsülinomanin cerrahi tedavisi olumlu klinik sonuçlarla ilişkilidir. İnsulinomanin lokalizasyonunu saptamada intraoperatifultrasonla birlikte palpasyonla yapılan değerlendirme altın standarda sahiptir. Uygun cerrahi prosedürü belirlemede lezyonun lokalizasyonu, boyutu ve ana pankreatik kanal ile ilişkisi kritik öneme sahiptir

Long-term Outcomes of Surgical Management of Insulinoma: Single Center Experience

Objective: Limited data are available in regards to the surgical management and outcomes of insulinoma. This study aimed to assess the outcomes associated with surgical treatment of insulinoma, as the most common pancreatic endocrine tumor. Methods: Medical records of patients who diagnosed as insulinoma from 2000 to 2010 at General Surgery Department of Cukurova University Hospital were retrospectively reviewed. Surgical treatment (resection vs. enucleation) was based on preoperative radiological investigations (abdominal spiral contrast tomography, ultrasound, selective angiography for selected cases) and intra-operative ultrasound imaging once indicated. Results: Surgically treated thirteen patients (F/M:9/4) who diagnosed with insulinoma were assessed with a mean follow-up of 5.3 (0.5-10) years. Enucleation and distal pancreatectomywere performed for 11 and 2 (one of those is spleen-preserving) patients, respectively. No mortality was recorded. All patients became normoglycemic after surgery without re-operation and with acceptable complication rates (n=3 pancreatic fistula, n=1 pancreatitis). Conclusion: Surgical treatment of insulinoma is associated with favorable outcomes.Intra-operative ultrasound with manual palpation is still the gold standard for localizing insulinoma. Location, size and relationship with main pancreatic duct of the lesions are key components for the selection of optimal surgical procedure

A Novel Microfluidic Method Utilizing a Hydrofoil Structure to Improve Circulating Tumor Cell Enrichment: Design and Analytical Validation

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. View Full-Text Keywords: circulating tumor cells; cancer; liquid biopsy; microfluidics; inertial particle focusin