Figure 1 (A) A schematic of ovarian cancer metastases involving tumor cells or clusters (yellow) shedding from a primary site and disseminating along ascitic currents of peritoneal fluid (green arrows) in the abdominal cavity. Ovarian cancer typically disseminates in four common abdomino-pelvic sites: (1) cul-de-sac (an extension of the peritoneal cavity between the rectum and back wall of the uterus); (2) right infracolic space (the apex formed by the termination of the small intestine of the small bowel mesentery at the ileocecal junction); (3) left infracolic space (superior site of the sigmoid colon); (4) Right paracolic gutter (communication between the upper and lower abdomen defined by the ascending colon and peritoneal wall). (B) The schematic of a perfusion model used to study the impact of sustained fluid flow on treatment resistance and molecular features of 3D ovarian cancer nodules (Top left). A side view of the perfusion model and growth of ovarian cancer nodules to a stromal bed (Top right). The photograph of a perfusion model used in the experiments (Bottom left) and depth-informed confocal imaging of ovarian cancer nodules in channels with and without carboplatin treatment (Bottom right). The perfusion model is 24 × 40 mm, with three channels that are 4 × 30 mm each and a height of 254 μm. The inlet and outlet ports of channels are 2.2 mm in diameter and positioned 5 mm from the edge of the chip. (C) A schematic of a 24-well plate model used to study the treatment resistance and molecular features of 3D ovarian cancer nodules under static conditions (without flow) (Top left). A side view of the static models and growth of ovarian cancer nodules on a stromal bed (Top right). Confocal imaging of 3D ovarian cancer nodules in a 24-well plate without and with carboplatin treatment (Bottom). Scale bars: 1 mm.

Flow-induced Shear Stress Confers Resistance to Carboplatin in an Adherent Three-Dimensional Model for Ovarian Cancer: A Role for EGFR-Targeted Photoimmunotherapy Informed by Physical Stress

난소암에 대한 일관된 3차원 모델에서 카보플라틴에 대한 유동에 의한 전단응력변화에 관한 연구

Abstract

A key reason for the persistently grim statistics associated with metastatic ovarian cancer is resistance to conventional agents, including platinum-based chemotherapies. A major source of treatment failure is the high degree of genetic and molecular heterogeneity, which results from significant underlying genomic instability, as well as stromal and physical cues in the microenvironment. Ovarian cancer commonly disseminates via transcoelomic routes to distant sites, which is associated with the frequent production of malignant ascites, as well as the poorest prognosis. In addition to providing a cell and protein-rich environment for cancer growth and progression, ascitic fluid also confers physical stress on tumors. An understudied area in ovarian cancer research is the impact of fluid shear stress on treatment failure. Here, we investigate the effect of fluid shear stress on response to platinum-based chemotherapy and the modulation of molecular pathways associated with aggressive disease in a perfusion model for adherent 3D ovarian cancer nodules. Resistance to carboplatin is observed under flow with a concomitant increase in the expression and activation of the epidermal growth factor receptor (EGFR) as well as downstream signaling members mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK) and extracellular signal-regulated kinase (ERK). The uptake of platinum by the 3D ovarian cancer nodules was significantly higher in flow cultures compared to static cultures. A downregulation of phospho-focal adhesion kinase (p-FAK), vinculin, and phospho-paxillin was observed following carboplatin treatment in both flow and static cultures. Interestingly, low-dose anti-EGFR photoimmunotherapy (PIT), a targeted photochemical modality, was found to be equally effective in ovarian tumors grown under flow and static conditions. These findings highlight the need to further develop PIT-based combinations that target the EGFR, and sensitize ovarian cancers to chemotherapy in the context of flow-induced shear stress.

전이성 난소 암과 관련된 지속적으로 암울한 통계의 주요 이유는 백금 기반 화학 요법을 포함한 기존 약제에 대한 내성 때문입니다. 치료 실패의 주요 원인은 높은 수준의 유전적 및 분자적 이질성이며, 이는 중요한 기본 게놈 불안정성과 미세 환경의 기질 및 물리적 단서로 인해 발생합니다.

난소 암은 흔히 transcoelomic 경로를 통해 먼 부위로 전파되며, 이는 악성 복수의 빈번한 생산과 가장 나쁜 예후와 관련이 있습니다. 암 성장 및 진행을위한 세포 및 단백질이 풍부한 환경을 제공하는 것 외에도 복수 액은 종양에 물리적 스트레스를 부여합니다. 난소 암 연구에서 잘 연구되지 않은 분야는 유체 전단 응력이 치료 실패에 미치는 영향입니다.

여기, 우리는 백금 기반 화학 요법에 대한 반응과 부착 3D 난소 암 결절에 대한 관류 모델에서 공격적인 질병과 관련된 분자 경로의 변조에 대한 유체 전단 응력의 효과를 조사합니다.

카르보플라틴에 대한 내성은 상피 성장 인자 수용체 (EGFR)의 발현 및 활성화의 수반되는 증가 뿐만 아니라 다운 스트림 신호 구성원인 미토겐 활성화 단백질 키나제/세포 외 신호 조절 키나제 (MEK) 및 세포 외 신호 조절과 함께 관찰됩니다. 키나아제 (ERK). 3D 난소 암 결절에 의한 백금 흡수는 정적 배양에 비해 유동 배양에서 상당히 높았습니다.

포스 포-포컬 접착 키나제 (p-FAK), 빈 쿨린 및 포스 포-팍 실린의 하향 조절은 유동 및 정적 배양 모두에서 카보 플 라틴 처리 후 관찰되었습니다. 흥미롭게도, 표적 광 화학적 양식 인 저용량 항 EGFR 광 면역 요법 (PIT)은 유동 및 정적 조건에서 성장한 난소 종양에서 똑같이 효과적인 것으로 밝혀졌습니다.

이러한 발견은 EGFR을 표적으로하는 PIT 기반 조합을 추가로 개발하고 흐름 유도 전단 응력의 맥락에서 화학 요법에 난소 암을 민감하게 할 필요성을 강조합니다.

Keywords: ovarian cancer, epidermal growth factor receptor (EGFR), mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK), extracellular signal-regulated kinase (ERK), chemoresistance, fluid shear stress, ascites, perfusion model, photoimmunotherapy (PIT), photodynamic therapy (PDT), carboplatin

Figure 1 (A) A schematic of ovarian cancer metastases involving tumor cells or clusters (yellow) shedding from a primary site and disseminating along ascitic currents of peritoneal fluid (green arrows) in the abdominal cavity. Ovarian cancer typically disseminates in four common abdomino-pelvic sites: (1) cul-de-sac (an extension of the peritoneal cavity between the rectum and back wall of the uterus); (2) right infracolic space (the apex formed by the termination of the small intestine of the small bowel mesentery at the ileocecal junction); (3) left infracolic space (superior site of the sigmoid colon); (4) Right paracolic gutter (communication between the upper and lower abdomen defined by the ascending colon and peritoneal wall). (B) The schematic of a perfusion model used to study the impact of sustained fluid flow on treatment resistance and molecular features of 3D ovarian cancer nodules (Top left). A side view of the perfusion model and growth of ovarian cancer nodules to a stromal bed (Top right). The photograph of a perfusion model used in the experiments (Bottom left) and depth-informed confocal imaging of ovarian cancer nodules in channels with and without carboplatin treatment (Bottom right). The perfusion model is 24 × 40 mm, with three channels that are 4 × 30 mm each and a height of 254 μm. The inlet and outlet ports of channels are 2.2 mm in diameter and positioned 5 mm from the edge of the chip. (C) A schematic of a 24-well plate model used to study the treatment resistance and molecular features of 3D ovarian cancer nodules under static conditions (without flow) (Top left). A side view of the static models and growth of ovarian cancer nodules on a stromal bed (Top right). Confocal imaging of 3D ovarian cancer nodules in a 24-well plate without and with carboplatin treatment (Bottom). Scale bars: 1 mm.
Figure 1 (A) A schematic of ovarian cancer metastases involving tumor cells or clusters (yellow) shedding from a primary site and disseminating along ascitic currents of peritoneal fluid (green arrows) in the abdominal cavity. Ovarian cancer typically disseminates in four common abdomino-pelvic sites: (1) cul-de-sac (an extension of the peritoneal cavity between the rectum and back wall of the uterus); (2) right infracolic space (the apex formed by the termination of the small intestine of the small bowel mesentery at the ileocecal junction); (3) left infracolic space (superior site of the sigmoid colon); (4) Right paracolic gutter (communication between the upper and lower abdomen defined by the ascending colon and peritoneal wall). (B) The schematic of a perfusion model used to study the impact of sustained fluid flow on treatment resistance and molecular features of 3D ovarian cancer nodules (Top left). A side view of the perfusion model and growth of ovarian cancer nodules to a stromal bed (Top right). The photograph of a perfusion model used in the experiments (Bottom left) and depth-informed confocal imaging of ovarian cancer nodules in channels with and without carboplatin treatment (Bottom right). The perfusion model is 24 × 40 mm, with three channels that are 4 × 30 mm each and a height of 254 μm. The inlet and outlet ports of channels are 2.2 mm in diameter and positioned 5 mm from the edge of the chip. (C) A schematic of a 24-well plate model used to study the treatment resistance and molecular features of 3D ovarian cancer nodules under static conditions (without flow) (Top left). A side view of the static models and growth of ovarian cancer nodules on a stromal bed (Top right). Confocal imaging of 3D ovarian cancer nodules in a 24-well plate without and with carboplatin treatment (Bottom). Scale bars: 1 mm.
Figure 2 (A) Geometry of the micronodule located at the center of the microchannel. The flow velocity is in the X-direction. The nodule is modeled as an ellipse with a semi-minor axis of 40 μm in the Z-direction. The semi-major axis varies from 40-100 μm in the X-direction. The section over which the fluid dynamics are studied is the middle part of the channel with dimensions 4 mm along the Y-axis and 250 μm along the Z-axis. The nodule is located at (0, 20 μm). The black dotted line shows the centerline of the largest nodule. (B) Shear stress distribution over the surface of the solid micro-nodule on the XZ-plane. (C) Shear stress distribution over the surface of the porous micro-nodule on the XZ-plane. (D) Flow flux distribution over the centerline of the porous micro-nodule on the XZ-plane. The flux enters the surface at the left and leaves at the right.
Figure 2 (A) Geometry of the micronodule located at the center of the microchannel. The flow velocity is in the X-direction. The nodule is modeled as an ellipse with a semi-minor axis of 40 μm in the Z-direction. The semi-major axis varies from 40-100 μm in the X-direction. The section over which the fluid dynamics are studied is the middle part of the channel with dimensions 4 mm along the Y-axis and 250 μm along the Z-axis. The nodule is located at (0, 20 μm). The black dotted line shows the centerline of the largest nodule. (B) Shear stress distribution over the surface of the solid micro-nodule on the XZ-plane. (C) Shear stress distribution over the surface of the porous micro-nodule on the XZ-plane. (D) Flow flux distribution over the centerline of the porous micro-nodule on the XZ-plane. The flux enters the surface at the left and leaves at the right.
Figure 3 Cytotoxic response in carboplatin-treated 3D OVCAR-5 cultures under static conditions. (A) Representative confocal images of 3D tumors treated with carboplatin (0-500 μM) for 96 h showing a dose-dependent reduction in viable tumor (calcein signal). (B) Image-based quantification of normalized viable tumor area in 3D OVCAR-5 cultures following treatment with increasing doses of carboplatin. A minimum nodule size cut-off of 2000 µm2 (clusters of ~15–20 cells) was applied to the fluorescence images for quantitative analysis of the normalized viable tumor area. (One-way ANOVA with Dunnett’s post hoc test; n.s., not significant; * p < 0.05; *** p < 0.001; N = 9) (C) Inductively coupled plasma mass spectrometry (ICP-MS)-based quantification of carboplatin uptake in static 3D OVCAR-5 tumors shows a dose-dependent increase in platinum levels, up to 9774 ± 3,052 ng/mg protein at an incubation concentration of 500 μM carboplatin. (One-way ANOVA with Dunn’s multiple comparisons test; n.s., not significant; * p < 0.05; ** p < 0.01; N = 3). Results are expressed as mean ± standard error of mean (SEM). Scale bars: 500 μm.
Figure 3 Cytotoxic response in carboplatin-treated 3D OVCAR-5 cultures under static conditions. (A) Representative confocal images of 3D tumors treated with carboplatin (0-500 μM) for 96 h showing a dose-dependent reduction in viable tumor (calcein signal). (B) Image-based quantification of normalized viable tumor area in 3D OVCAR-5 cultures following treatment with increasing doses of carboplatin. A minimum nodule size cut-off of 2000 µm2 (clusters of ~15–20 cells) was applied to the fluorescence images for quantitative analysis of the normalized viable tumor area. (One-way ANOVA with Dunnett’s post hoc test; n.s., not significant; * p < 0.05; *** p < 0.001; N = 9) (C) Inductively coupled plasma mass spectrometry (ICP-MS)-based quantification of carboplatin uptake in static 3D OVCAR-5 tumors shows a dose-dependent increase in platinum levels, up to 9774 ± 3,052 ng/mg protein at an incubation concentration of 500 μM carboplatin. (One-way ANOVA with Dunn’s multiple comparisons test; n.s., not significant; * p < 0.05; ** p < 0.01; N = 3). Results are expressed as mean ± standard error of mean (SEM). Scale bars: 500 μm.
Figure 4 flow-induced chemo-resistance
Figure 4 flow-induced chemo-resistance
Figure 5 The effects of flow-induced shear stress on 3D ovarian cancer biology. (A) Western blot analysis of OVCAR-5 tumors was performed 7 days after culture under static or flow conditions. A flow-induced increase in EGFR and p-ERK, compared to static cultures, was observed. Conversely, a reduction in p-FAK, p-Paxillin, and Vinculin was observed under flow, relative to static conditions. (B) Western blot analysis of 3D OVCAR-5 tumors was performed 11 days after culture under static or flow conditions, including 4 days of treatment with 500 µM carboplatin, and respective controls. In both static and flow 3D cultures, carboplatin treatment resulted in downregulation of EGFR, FAK, p-Paxillin, Paxillin, and Vinculin. Upregulation of p-ERK was observed after carboplatin treatment in both static and flow 3D cultures. (C) Baseline levels of EGFR activity and expression are maintained by a complex array of factors, including recycling and degradation of the activated receptor complex. Flow-induced shear stress has been shown to cause a posttranslational up-regulation of EGFR expression and activation, likely resulting from increased receptor recycling and decreased EGFR degradation. Activation of EGFR results in ERK phosphorylation to induce gene expression, ultimately leading to cell proliferation, survival, and chemoresistance. FAK and other tyrosine kinases are activated by the engagement of integrins with the ECM. Subsequent phosphorylation of paxillin by FAK not only influences the remodeling of the actin cytoskeleton, but also modulates vinculin activation to regulate mitogen-activated protein kinase (MAPK) cascades, thereby stimulating pro-survival gene expression.
Figure 5 The effects of flow-induced shear stress on 3D ovarian cancer biology. (A) Western blot analysis of OVCAR-5 tumors was performed 7 days after culture under static or flow conditions. A flow-induced increase in EGFR and p-ERK, compared to static cultures, was observed. Conversely, a reduction in p-FAK, p-Paxillin, and Vinculin was observed under flow, relative to static conditions. (B) Western blot analysis of 3D OVCAR-5 tumors was performed 11 days after culture under static or flow conditions, including 4 days of treatment with 500 µM carboplatin, and respective controls. In both static and flow 3D cultures, carboplatin treatment resulted in downregulation of EGFR, FAK, p-Paxillin, Paxillin, and Vinculin. Upregulation of p-ERK was observed after carboplatin treatment in both static and flow 3D cultures. (C) Baseline levels of EGFR activity and expression are maintained by a complex array of factors, including recycling and degradation of the activated receptor complex. Flow-induced shear stress has been shown to cause a posttranslational up-regulation of EGFR expression and activation, likely resulting from increased receptor recycling and decreased EGFR degradation. Activation of EGFR results in ERK phosphorylation to induce gene expression, ultimately leading to cell proliferation, survival, and chemoresistance. FAK and other tyrosine kinases are activated by the engagement of integrins with the ECM. Subsequent phosphorylation of paxillin by FAK not only influences the remodeling of the actin cytoskeleton, but also modulates vinculin activation to regulate mitogen-activated protein kinase (MAPK) cascades, thereby stimulating pro-survival gene expression.
Figure 6 PIT efficacy in 3D tumors. (A) Dose-dependent change in normalized viable tumor area in static 3D cultures treated with PIC (1 μM BPD equivalent) and increasing energy densities (10–50 J/cm2 @ 50 mW/cm2). Significant tumoricidal efficacy is observed in a light-dose-dependent manner, starting at 15 J/cm2. (One-way ANOVA with Dunnett’s post hoc test; n.s., not significant; ** p < 0.01, *** p < 0.001, N = 9) (B) Comparison of cytotoxic response in PIT-treated 3D cultures under static and flow conditions. For quantitative analysis of fluorescence images, a minimum nodule size cut-off of 2000 µm2 (clusters of ~15–20 cells) was used to establish normalized viable tumor area. PIT is equally effective in 3D tumors grown in static cultures (green) and under flow-induced shear stress (blue) (in contrast to flow-induced chemo-resistance shown in Figure 4) (Two-tailed t test; n.s., not significant; N = 9).
Figure 6 PIT efficacy in 3D tumors. (A) Dose-dependent change in normalized viable tumor area in static 3D cultures treated with PIC (1 μM BPD equivalent) and increasing energy densities (10–50 J/cm2 @ 50 mW/cm2). Significant tumoricidal efficacy is observed in a light-dose-dependent manner, starting at 15 J/cm2. (One-way ANOVA with Dunnett’s post hoc test; n.s., not significant; ** p < 0.01, *** p < 0.001, N = 9) (B) Comparison of cytotoxic response in PIT-treated 3D cultures under static and flow conditions. For quantitative analysis of fluorescence images, a minimum nodule size cut-off of 2000 µm2 (clusters of ~15–20 cells) was used to establish normalized viable tumor area. PIT is equally effective in 3D tumors grown in static cultures (green) and under flow-induced shear stress (blue) (in contrast to flow-induced chemo-resistance shown in Figure 4) (Two-tailed t test; n.s., not significant; N = 9).

References

  1. Siegel R.L., Miller K.D., Jemal A. Cancer statistics, 2019. CA Cancer J. Clin. 2019;69:7–34. doi: 10.3322/caac.21551. [PubMed] [CrossRef] [Google Scholar]
  2. Foley O.W., Rauh-Hain J.A., Del Carmen M.G. Recurrent epithelial ovarian cancer: An update on treatment. Oncology. 2013;27:288–294, 298. [PubMed] [Google Scholar]
  3. Kipps E., Tan D.S., Kaye S.B. Meeting the challenge of ascites in ovarian cancer: New avenues for therapy and research. Nat. Rev. Cancer. 2013;13:273–282. doi: 10.1038/nrc3432. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  4. Tan D.S., Agarwal R., Kaye S.B. Mechanisms of transcoelomic metastasis in ovarian cancer. Lancet Oncol. 2006;7:925–934. doi: 10.1016/S1470-2045(06)70939-1. [PubMed] [CrossRef] [Google Scholar]
  5. Ahmed N., Stenvers K.L. Getting to know ovarian cancer ascites: Opportunities for targeted therapy-based translational research. Front. Oncol. 2013;3:256. doi: 10.3389/fonc.2013.00256. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  6. Shield K., Ackland M.L., Ahmed N., Rice G.E. Multicellular spheroids in ovarian cancer metastases: Biology and pathology. Gynecol. Oncol. 2009;113:143–148. doi: 10.1016/j.ygyno.2008.11.032. [PubMed] [CrossRef] [Google Scholar]
  7. Naora H., Montell D.J. Ovarian cancer metastasis: Integrating insights from disparate model organisms. Nat. Rev. Cancer. 2005;5:355–366. doi: 10.1038/nrc1611. [PubMed] [CrossRef] [Google Scholar]
  8. Lengyel E. Ovarian cancer development and metastasis. Am. J. Pathol. 2010;177:1053–1064. doi: 10.2353/ajpath.2010.100105. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  9. Javellana M., Hoppenot C., Lengyel E. The road to long-term survival: Surgical approach and longitudinal treatments of long-term survivors of advanced-stage serous ovarian cancer. Gynecol. Oncol. 2019;152:228–234. doi: 10.1016/j.ygyno.2018.11.007. [PubMed] [CrossRef] [Google Scholar]
  10. Al Habyan S., Kalos C., Szymborski J., McCaffrey L. Multicellular detachment generates metastatic spheroids during intra-abdominal dissemination in epithelial ovarian cancer. Oncogene. 2018;37:5127–5135. doi: 10.1038/s41388-018-0317-x. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  11. Kim S., Kim B., Song Y.S. Ascites modulates cancer cell behavior, contributing to tumor heterogeneity in ovarian cancer. Cancer Sci. 2016;107:1173–1178. doi: 10.1111/cas.12987. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  12. Bowtell D.D., Bohm S., Ahmed A.A., Aspuria P.J., Bast R.C., Beral V., Berek J.S., Birrer M.J., Blagden S., Bookman M.A., et al. Rethinking ovarian cancer II: Reducing mortality from high-grade serous ovarian cancer. Nat. Rev. Cancer. 2015;15:668–679. doi: 10.1038/nrc4019. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  13. Hoppenot C., Eckert M.A., Tienda S.M., Lengyel E. Who are the long-term survivors of high grade serous ovarian cancer? Gynecol. Oncol. 2018;148:204–212. doi: 10.1016/j.ygyno.2017.10.032. [PubMed] [CrossRef] [Google Scholar]
  14. Zhao Y., Cao J., Melamed A., Worley M., Gockley A., Jones D., Nia H.T., Zhang Y., Stylianopoulos T., Kumar A.S., et al. Losartan treatment enhances chemotherapy efficacy and reduces ascites in ovarian cancer models by normalizing the tumor stroma. Proc. Natl. Acad. Sci. USA. 2019;116:2210–2219. doi: 10.1073/pnas.1818357116. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  15. Ayantunde A.A., Parsons S.L. Pattern and prognostic factors in patients with malignant ascites: A retrospective study. Ann. Oncol. 2007;18:945–949. doi: 10.1093/annonc/mdl499. [PubMed] [CrossRef] [Google Scholar]
  16. Latifi A., Luwor R.B., Bilandzic M., Nazaretian S., Stenvers K., Pyman J., Zhu H., Thompson E.W., Quinn M.A., Findlay J.K., et al. Isolation and characterization of tumor cells from the ascites of ovarian cancer patients: Molecular phenotype of chemoresistant ovarian tumors. PLoS ONE. 2012;7:e46858. doi: 10.1371/journal.pone.0046858. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  17. Ahmed N., Greening D., Samardzija C., Escalona R.M., Chen M., Findlay J.K., Kannourakis G. Unique proteome signature of post-chemotherapy ovarian cancer ascites-derived tumor cells. Sci. Rep. 2016;6:30061. doi: 10.1038/srep30061. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  18. Gjorevski N., Boghaert E., Nelson C.M. Regulation of Epithelial-Mesenchymal Transition by Transmission of Mechanical Stress through Epithelial Tissues. Cancer Microenviron. 2012;5:29–38. doi: 10.1007/s12307-011-0076-5. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  19. Polacheck W.J., Charest J.L., Kamm R.D. Interstitial flow influences direction of tumor cell migration through competing mechanisms. Proc. Natl. Acad. Sci. USA. 2011;108:11115–11120. doi: 10.1073/pnas.1103581108. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  20. Polacheck W.J., German A.E., Mammoto A., Ingber D.E., Kamm R.D. Mechanotransduction of fluid stresses governs 3D cell migration. Proc. Natl. Acad. Sci. USA. 2014;111:2447–2452. doi: 10.1073/pnas.1316848111. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  21. Polacheck W.J., Zervantonakis I.K., Kamm R.D. Tumor cell migration in complex microenvironments. Cell Mol. Life Sci. 2013;70:1335–1356. doi: 10.1007/s00018-012-1115-1. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  22. Swartz M.A., Lund A.W. Lymphatic and interstitial flow in the tumour microenvironment: Linking mechanobiology with immunity. Nat. Rev. Cancer. 2012;12:210–219. doi: 10.1038/nrc3186. [PubMed] [CrossRef] [Google Scholar]
  23. Pisano M., Triacca V., Barbee K.A., Swartz M.A. An in vitro model of the tumor-lymphatic microenvironment with simultaneous transendothelial and luminal flows reveals mechanisms of flow enhanced invasion. Integr. Biol. 2015;7:525–533. doi: 10.1039/C5IB00085H. [PubMed] [CrossRef] [Google Scholar]
  24. Follain G., Herrmann D., Harlepp S., Hyenne V., Osmani N., Warren S.C., Timpson P., Goetz J.G. Fluids and their mechanics in tumour transit: Shaping metastasis. Nat. Rev. Cancer. 2020;20:107–124. doi: 10.1038/s41568-019-0221-x. [PubMed] [CrossRef] [Google Scholar]
  25. Rizvi I., Gurkan U.A., Tasoglu S., Alagic N., Celli J.P., Mensah L.B., Mai Z., Demirci U., Hasan T. Flow induces epithelial-mesenchymal transition, cellular heterogeneity and biomarker modulation in 3D ovarian cancer nodules. Proc. Natl. Acad. Sci. USA. 2013;110:E1974–E1983. doi: 10.1073/pnas.1216989110. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  26. Novak C., Horst E., Mehta G. Mechanotransduction in ovarian cancer: Shearing into the unknown. APL Bioeng. 2018;2 doi: 10.1063/1.5024386. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  27. Carmignani C.P., Sugarbaker T.A., Bromley C.M., Sugarbaker P.H. Intraperitoneal cancer dissemination: Mechanisms of the patterns of spread. Cancer Metastasis Rev. 2003;22:465–472. doi: 10.1023/A:1023791229361. [PubMed] [CrossRef] [Google Scholar]
  28. Sugarbaker P.H. Observations concerning cancer spread within the peritoneal cavity and concepts supporting an ordered pathophysiology. Cancer Treatment Res. 1996;82:79–100. [PubMed] [Google Scholar]
  29. Feki A., Berardi P., Bellingan G., Major A., Krause K.H., Petignat P., Zehra R., Pervaiz S., Irminger-Finger I. Dissemination of intraperitoneal ovarian cancer: Discussion of mechanisms and demonstration of lymphatic spreading in ovarian cancer model. Crit. Rev. Oncol./Hematol. 2009;72:1–9. doi: 10.1016/j.critrevonc.2008.12.003. [PubMed] [CrossRef] [Google Scholar]
  30. Holm-Nielsen P. Pathogenesis of ascites in peritoneal carcinomatosis. Acta Pathol. Microbiol. Scand. 1953;33:10–21. doi: 10.1111/j.1699-0463.1953.tb04805.x. [PubMed] [CrossRef] [Google Scholar]
  31. Ahmed N., Riley C., Oliva K., Rice G., Quinn M. Ascites induces modulation of alpha6beta1 integrin and urokinase plasminogen activator receptor expression and associated functions in ovarian carcinoma. Br. J. Cancer. 2005;92:1475–1485. doi: 10.1038/sj.bjc.6602495. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  32. Woodburn J.R. The epidermal growth factor receptor and its inhibition in cancer therapy. Pharmacol. Ther. 1999;82:241–250. doi: 10.1016/S0163-7258(98)00045-X. [PubMed] [CrossRef] [Google Scholar]
  33. Servidei T., Riccardi A., Mozzetti S., Ferlini C., Riccardi R. Chemoresistant tumor cell lines display altered epidermal growth factor receptor and HER3 signaling and enhanced sensitivity to gefitinib. Int. J. Cancer J. Int. Cancer. 2008;123:2939–2949. doi: 10.1002/ijc.23902. [PubMed] [CrossRef] [Google Scholar]
  34. Chen A.P., Zhang J., Liu H., Zhao S.P., Dai S.Z., Sun X.L. Association of EGFR expression with angiogenesis and chemoresistance in ovarian carcinoma. Zhonghua zhong liu za zhi [Chinese journal of oncology] 2009;31:48–52. [PubMed] [Google Scholar]
  35. Alper O., Bergmann-Leitner E.S., Bennett T.A., Hacker N.F., Stromberg K., Stetler-Stevenson W.G. Epidermal growth factor receptor signaling and the invasive phenotype of ovarian carcinoma cells. J. Natl. Cancer Inst. 2001;93:1375–1384. doi: 10.1093/jnci/93.18.1375. [PubMed] [CrossRef] [Google Scholar]
  36. Zeineldin R., Muller C.Y., Stack M.S., Hudson L.G. Targeting the EGF receptor for ovarian cancer therapy. J. Oncol. 2010;2010:414676. doi: 10.1155/2010/414676. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  37. Alper O., De Santis M.L., Stromberg K., Hacker N.F., Cho-Chung Y.S., Salomon D.S. Anti-sense suppression of epidermal growth factor receptor expression alters cellular proliferation, cell-adhesion and tumorigenicity in ovarian cancer cells. Int. J. Cancer. 2000;88:566–574. doi: 10.1002/1097-0215(20001115)88:4<566::AID-IJC8>3.0.CO;2-D. [PubMed] [CrossRef] [Google Scholar]
  38. Posadas E.M., Liel M.S., Kwitkowski V., Minasian L., Godwin A.K., Hussain M.M., Espina V., Wood B.J., Steinberg S.M., Kohn E.C. A phase II and pharmacodynamic study of gefitinib in patients with refractory or recurrent epithelial ovarian cancer. Cancer. 2007;109:1323–1330. doi: 10.1002/cncr.22545. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  39. Psyrri A., Kassar M., Yu Z., Bamias A., Weinberger P.M., Markakis S., Kowalski D., Camp R.L., Rimm D.L., Dimopoulos M.A. Effect of epidermal growth factor receptor expression level on survival in patients with epithelial ovarian cancer. Clin. Cancer Res. 2005;11:8637–8643. doi: 10.1158/1078-0432.CCR-05-1436. [PubMed] [CrossRef] [Google Scholar]
  40. Dimou A., Agarwal S., Anagnostou V., Viray H., Christensen S., Gould Rothberg B., Zolota V., Syrigos K., Rimm D. Standardization of epidermal growth factor receptor (EGFR) measurement by quantitative immunofluorescence and impact on antibody-based mutation detection in non-small cell lung cancer. Am. J. Pathol. 2011;179:580–589. doi: 10.1016/j.ajpath.2011.04.031. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  41. Anagnostou V.K., Welsh A.W., Giltnane J.M., Siddiqui S., Liceaga C., Gustavson M., Syrigos K.N., Reiter J.L., Rimm D.L. Analytic variability in immunohistochemistry biomarker studies. Cancer Epidemiol Biomarkers Prev. 2010;19:982–991. doi: 10.1158/1055-9965.EPI-10-0097. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  42. Del Carmen M.G., Rizvi I., Chang Y., Moor A.C., Oliva E., Sherwood M., Pogue B., Hasan T. Synergism of epidermal growth factor receptor-targeted immunotherapy with photodynamic treatment of ovarian cancer in vivo. J. Natl. Cancer Inst. 2005;97:1516–1524. doi: 10.1093/jnci/dji314. [PubMed] [CrossRef] [Google Scholar]
  43. Armstrong D.K., Bundy B., Wenzel L., Huang H.Q., Baergen R., Lele S., Copeland L.J., Walker J.L., Burger R.A., Gynecologic Oncology G. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N. Engl. J. Med. 2006;354:34–43. doi: 10.1056/NEJMoa052985. [PubMed] [CrossRef] [Google Scholar]
  44. Verwaal V.J., Van Ruth S., De Bree E., Van Sloothen G.W., Van Tinteren H., Boot H., Zoetmulder F.A. Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J. Clin. Oncol. 2003;21:3737–3743. doi: 10.1200/JCO.2003.04.187. [PubMed] [CrossRef] [Google Scholar]
  45. Van Driel W.J., Koole S.N., Sikorska K., Schagen van Leeuwen J.H., Schreuder H.W.R., Hermans R.H.M., De Hingh I., Van der Velden J., Arts H.J., Massuger L., et al. Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer. N. Engl. J. Med. 2018;378:230–240. doi: 10.1056/NEJMoa1708618. [PubMed] [CrossRef] [Google Scholar]
  46. Verwaal V.J., Bruin S., Boot H., Van Slooten G., Van Tinteren H. 8-year follow-up of randomized trial: Cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy in patients with peritoneal carcinomatosis of colorectal cancer. Ann. Surg. Oncol. 2008;15:2426–2432. doi: 10.1245/s10434-008-9966-2. [PubMed] [CrossRef] [Google Scholar]
  47. DeLaney T.F., Sindelar W.F., Tochner Z., Smith P.D., Friauf W.S., Thomas G., Dachowski L., Cole J.W., Steinberg S.M., Glatstein E. Phase I study of debulking surgery and photodynamic therapy for disseminated intraperitoneal tumors. Int. J. Radiat. Oncol. Biol. Phys. 1993;25:445–457. doi: 10.1016/0360-3016(93)90066-5. [PubMed] [CrossRef] [Google Scholar]
  48. Celli J.P., Spring B.Q., Rizvi I., Evans C.L., Samkoe K.S., Verma S., Pogue B.W., Hasan T. Imaging and photodynamic therapy: Mechanisms, monitoring, and optimization. Chem. Rev. 2010;110:2795–2838. doi: 10.1021/cr900300p. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  49. Spring B.Q., Rizvi I., Xu N., Hasan T. The role of photodynamic therapy in overcoming cancer drug resistance. Photochem. Photobiol. Sci. 2015;14:1476–1491. doi: 10.1039/C4PP00495G. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  50. Liang B.J., Pigula M., Baglo Y., Najafali D., Hasan T., Huang H.C. Breaking the Selectivity-Uptake Trade-Off of Photoimmunoconjugates with Nanoliposomal Irinotecan for Synergistic Multi-Tier Cancer Targeting. J. Nanobiotechnol. 2020;18:1. doi: 10.1186/s12951-019-0560-5. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  51. Huang H.C., Rizvi I., Liu J., Anbil S., Kalra A., Lee H., Baglo Y., Paz N., Hayden D., Pereira S., et al. Photodynamic Priming Mitigates Chemotherapeutic Selection Pressures and Improves Drug Delivery. Cancer Res. 2018;78:558–571. doi: 10.1158/0008-5472.CAN-17-1700. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  52. Huang H.C., Mallidi S., Liu J., Chiang C.T., Mai Z., Goldschmidt R., Ebrahim-Zadeh N., Rizvi I., Hasan T. Photodynamic Therapy Synergizes with Irinotecan to Overcome Compensatory Mechanisms and Improve Treatment Outcomes in Pancreatic Cancer. Cancer Res. 2016;76:1066–1077. doi: 10.1158/0008-5472.CAN-15-0391. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  53. Cengel K.A., Glatstein E., Hahn S.M. Intraperitoneal photodynamic therapy. Cancer Treat. Res. 2007;134:493–514. [PubMed] [Google Scholar]
  54. Obaid G., Broekgaarden M., Bulin A.-L., Huang H.-C., Kuriakose J., Liu J., Hasan T. Photonanomedicine: A convergence of photodynamic therapy and nanotechnology. Nanoscale. 2016;8:12471–12503. doi: 10.1039/C5NR08691D. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  55. Ogata F., Nagaya T., Nakamura Y., Sato K., Okuyama S., Maruoka Y., Choyke P.L., Kobayashi H. Near-infrared photoimmunotherapy: A comparison of light dosing schedules. Oncotarget. 2017;8:35069–35075. doi: 10.18632/oncotarget.17047. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  56. Mitsunaga M., Ogawa M., Kosaka N., Rosenblum L.T., Choyke P.L., Kobayashi H. Cancer cell-selective in vivo near infrared photoimmunotherapy targeting specific membrane molecules. Nat. Med. 2011;17:1685–1691. doi: 10.1038/nm.2554. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  57. Inglut C.T., Baglo Y., Liang B.J., Cheema Y., Stabile J., Woodworth G.F., Huang H.-C. Systematic Evaluation of Light-Activatable Biohybrids for Anti-Glioma Photodynamic Therapy. J. Clin. Med. 2019;8:1269. doi: 10.3390/jcm8091269. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  58. Huang H.C., Pigula M., Fang Y., Hasan T. Immobilization of Photo-Immunoconjugates on Nanoparticles Leads to Enhanced Light-Activated Biological Effects. Small. 2018:e1800236. doi: 10.1002/smll.201800236. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  59. Spring B.Q., Abu-Yousif A.O., Palanisami A., Rizvi I., Zheng X., Mai Z., Anbil S., Sears R.B., Mensah L.B., Goldschmidt R., et al. Selective treatment and monitoring of disseminated cancer micrometastases in vivo using dual-function, activatable immunoconjugates. Proc. Natl. Acad. Sci. USA. 2014;111:E933–E942. doi: 10.1073/pnas.1319493111. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  60. Abu-Yousif A.O., Moor A.C., Zheng X., Savellano M.D., Yu W., Selbo P.K., Hasan T. Epidermal growth factor receptor-targeted photosensitizer selectively inhibits EGFR signaling and induces targeted phototoxicity in ovarian cancer cells. Cancer Lett. 2012;321:120–127. doi: 10.1016/j.canlet.2012.01.014. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  61. Rizvi I., Dinh T.A., Yu W., Chang Y., Sherwood M.E., Hasan T. Photoimmunotherapy and irradiance modulation reduce chemotherapy cycles and toxicity in a murine model for ovarian carcinomatosis: Perspective and results. Israel J. Chem. 2012;52:776–787. doi: 10.1002/ijch.201200016. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  62. Quirk B.J., Brandal G., Donlon S., Vera J.C., Mang T.S., Foy A.B., Lew S.M., Girotti A.W., Jogal S., LaViolette P.S., et al. Photodynamic therapy (PDT) for malignant brain tumors–where do we stand? Photodiagnosis Photodyn. Ther. 2015;12:530–544. doi: 10.1016/j.pdpdt.2015.04.009. [PubMed] [CrossRef] [Google Scholar]
  63. Eljamel M.S., Goodman C., Moseley H. ALA and Photofrin fluorescence-guided resection and repetitive PDT in glioblastoma multiforme: A single centre Phase III randomised controlled trial. Lasers Med. Sci. 2008;23:361–367. doi: 10.1007/s10103-007-0494-2. [PubMed] [CrossRef] [Google Scholar]
  64. Varma A.K., Muller P.J. Cranial neuropathies after intracranial Photofrin-photodynamic therapy for malignant supratentorial gliomas-a report on 3 cases. Surg. Neurol. 2008;70:190–193. doi: 10.1016/j.surneu.2007.01.060. [PubMed] [CrossRef] [Google Scholar]
  65. Akimoto J. Photodynamic Therapy for Malignant Brain Tumors. Neurol. Medico-Chirurgica. 2016;56:151–157. doi: 10.2176/nmc.ra.2015-0296. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  66. Kercher E.M., Nath S., Rizvi I., Spring B.Q. Cancer Cell-targeted and Activatable Photoimmunotherapy Spares T Cells in a 3D Coculture Model. Photochem. Photobiol. 2019 doi: 10.1111/php.13153. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  67. Savellano M.D., Hasan T. Targeting cells that overexpress the epidermal growth factor receptor with polyethylene glycolated BPD verteporfin photosensitizer immunoconjugates. Photochem. Photobiol. 2003;77:431–439. doi: 10.1562/0031-8655(2003)077<0431:TCTOTE>2.0.CO;2. [PubMed] [CrossRef] [Google Scholar]
  68. Molpus K.L., Hamblin M.R., Rizvi I., Hasan T. Intraperitoneal photoimmunotherapy of ovarian carcinoma xenografts in nude mice using charged photoimmunoconjugates. Gynecol. Oncol. 2000;76:397–404. doi: 10.1006/gyno.1999.5705. [PubMed] [CrossRef] [Google Scholar]
  69. Savellano M.D., Hasan T. Photochemical targeting of epidermal growth factor receptor: A mechanistic study. Clin. Cancer Res. 2005;11:1658–1668. doi: 10.1158/1078-0432.CCR-04-1902. [PubMed] [CrossRef] [Google Scholar]
  70. Nath S., Saad M.A., Pigula M., Swain J.W.R., Hasan T. Photoimmunotherapy of Ovarian Cancer: A Unique Niche in the Management of Advanced Disease. Cancers. 2019;11:1887. doi: 10.3390/cancers11121887. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  71. Calibasi Kocal G., Guven S., Foygel K., Goldman A., Chen P., Sengupta S., Paulmurugan R., Baskin Y., Demirci U. Dynamic Microenvironment Induces Phenotypic Plasticity of Esophageal Cancer Cells Under Flow. Sci. Rep. 2016;6:38221. doi: 10.1038/srep38221. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  72. Tasoglu S., Gurkan U.A., Wang S., Demirci U. Manipulating biological agents and cells in micro-scale volumes for applications in medicine. Chem. Soc. Rev. 2013;42:5788–5808. doi: 10.1039/c3cs60042d. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  73. Moon S., Gurkan U.A., Blander J., Fawzi W.W., Aboud S., Mugusi F., Kuritzkes D.R., Demirci U. Enumeration of CD4+ T-cells using a portable microchip count platform in Tanzanian HIV-infected patients. PLoS ONE. 2011;6:e21409. doi: 10.1371/journal.pone.0021409. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  74. White F.M. Fluid Mechanics. McGraw-Hill; Boston, MA, USA: 2011. [Google Scholar]
  75. Luo Q., Kuang D., Zhang B., Song G. Cell stiffness determined by atomic force microscopy and its correlation with cell motility. Biochim Biophys Acta. 2016;1860:1953–1960. doi: 10.1016/j.bbagen.2016.06.010. [PubMed] [CrossRef] [Google Scholar]
  76. Sarntinoranont M., Rooney F., Ferrari M. Interstitial Stress and Fluid Pressure Within a Growing Tumor. Ann. Biomed. Eng. 2003;31:327–335. doi: 10.1114/1.1554923. [PubMed] [CrossRef] [Google Scholar]
  77. Baxter L.T., Jain R.K. Transport of fluid and macromolecules in tumors. I. Role of interstitial pressure and convection. Microvasc. Res. 1989;37:77–104. doi: 10.1016/0026-2862(89)90074-5. [PubMed] [CrossRef] [Google Scholar]
  78. Malik R., Khan A.P., Asangani I.A., Cieślik M., Prensner J.R., Wang X., Iyer M.K., Jiang X., Borkin D., Escara-Wilke J., et al. Targeting the MLL complex in castration-resistant prostate cancer. Nat. Med. 2015;21:344. doi: 10.1038/nm.3830. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  79. Nath S., Christian L., Tan S.Y., Ki S., Ehrlich L.I., Poenie M. Dynein Separately Partners with NDE1 and Dynactin To Orchestrate T Cell Focused Secretion. J. Immunol. 2016;197:2090–2101. doi: 10.4049/jimmunol.1600180. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  80. Celli J.P., Rizvi I., Evans C.L., Abu-Yousif A.O., Hasan T. Quantitative imaging reveals heterogeneous growth dynamics and treatment-dependent residual tumor distributions in a three-dimensional ovarian cancer model. J. Biomed. Opt. 2010;15:051603. doi: 10.1117/1.3483903. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  81. Rizvi I., Celli J.P., Evans C.L., Abu-Yousif A.O., Muzikansky A., Pogue B.W., Finkelstein D., Hasan T. Synergistic Enhancement of Carboplatin Efficacy with Photodynamic Therapy in a Three-Dimensional Model for Micrometastatic Ovarian Cancer. Cancer Res. 2010;70:9319–9328. doi: 10.1158/0008-5472.CAN-10-1783. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  82. Glidden M.D., Celli J.P., Massodi I., Rizvi I., Pogue B.W., Hasan T. Image-Based Quantification of Benzoporphyrin Derivative Uptake, Localization, and Photobleaching in 3D Tumor Models, for Optimization of PDT Parameters. Theranostics. 2012;2:827–839. doi: 10.7150/thno.4334. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  83. Celli J.P., Rizvi I., Blanden A.R., Massodi I., Glidden M.D., Pogue B.W., Hasan T. An imaging-based platform for high-content, quantitative evaluation of therapeutic response in 3D tumour models. Sci. Rep. 2014;4:3751. doi: 10.1038/srep03751. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  84. Bulin A.L., Broekgaarden M., Hasan T. Comprehensive high-throughput image analysis for therapeutic efficacy of architecturally complex heterotypic organoids. Sci. Rep. 2017;7:16645. doi: 10.1038/s41598-017-16622-9. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  85. Rahmanzadeh R., Rai P., Celli J.P., Rizvi I., Baron-Luhr B., Gerdes J., Hasan T. Ki-67 as a molecular target for therapy in an in vitro three-dimensional model for ovarian cancer. Cancer Res. 2010;70:9234–9242. doi: 10.1158/0008-5472.CAN-10-1190. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  86. Anbil S., Rizvi I., Celli J.P., Alagic N., Pogue B.W., Hasan T. Impact of treatment response metrics on photodynamic therapy planning and outcomes in a three-dimensional model of ovarian cancer. J. Biomed. Opt. 2013;18:098004. doi: 10.1117/1.JBO.18.9.098004. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  87. Di Pasqua A.J., Goodisman J., Dabrowiak J.C. Understanding how the platinum anticancer drug carboplatin works: From the bottle to the cell. Inorg. Chim. Acta. 2012;389:29–35. doi: 10.1016/j.ica.2012.01.028. [CrossRef] [Google Scholar]
  88. Rabik C.A., Dolan M.E. Molecular mechanisms of resistance and toxicity associated with platinating agents. Cancer Treat. Rev. 2007;33:9–23. doi: 10.1016/j.ctrv.2006.09.006. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  89. Ozols R.F. Carboplatin and paclitaxel in ovarian cancer. Semin. Oncol. 1995;22:78–83. [PubMed] [Google Scholar]
  90. Neijt J.P., Lund B. Paclitaxel with carboplatin for the treatment of ovarian cancer. Semin. Oncol. 1996;23:2–4. [PubMed] [Google Scholar]
  91. Subauste C.M., Pertz O., Adamson E.D., Turner C.E., Junger S., Hahn K.M. Vinculin modulation of paxillin–FAK interactions regulates ERK to control survival and motility. J. Cell Biol. 2004;165:371–381. doi: 10.1083/jcb.200308011. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  92. Eke I., Cordes N. Focal adhesion signaling and therapy resistance in cancer. Semin. Cancer Biol. 2015;31:65–75. [PubMed] [Google Scholar]
  93. McCubrey J.A., Steelman L.S., Chappell W.H., Abrams S.L., Wong E.W., Chang F., Lehmann B., Terrian D.M., Milella M., Tafuri A., et al. Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim. Biophys. Acta. 2007;1773:1263–1284. doi: 10.1016/j.bbamcr.2006.10.001. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  94. Duska L.R., Hamblin M.R., Miller J.L., Hasan T. Combination photoimmunotherapy and cisplatin: Effects on human ovarian cancer ex vivo. J. Natl. Cancer Inst. 1999;91:1557–1563. doi: 10.1093/jnci/91.18.1557. [PubMed] [CrossRef] [Google Scholar]
  95. Spring B., Mai Z., Rai P., Chang S., Hasan T. Theranostic nanocells for simultaneous imaging and photodynamic therapy of pancreatic cancer. Proc. SPIE. 2010;7551:755104. [Google Scholar]
  96. Kessel D., Oleinick N.L. Photodynamic therapy and cell death pathways. Methods Mol. Biol. 2010;635:35–46. doi: 10.1007/978-1-60761-697-9_3. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  97. Van Dongen G.A., Visser G.W., Vrouenraets M.B. Photosensitizer-antibody conjugates for detection and therapy of cancer. Adv. Drug Deliv. Rev. 2004;56:31–52. doi: 10.1016/j.addr.2003.09.003. [PubMed] [CrossRef] [Google Scholar]
  98. Ayhan A., Gultekin M., Taskiran C., Dursun P., Firat P., Bozdag G., Celik N.Y., Yuce K. Ascites and epithelial ovarian cancers: A reappraisal with respect to different aspects. Int. J. Gynecol. Cancer. 2007;17:68–75. doi: 10.1111/j.1525-1438.2006.00777.x. [PubMed] [CrossRef] [Google Scholar]
  99. Shen-Gunther J., Mannel R.S. Ascites as a predictor of ovarian malignancy. Gynecol. Oncol. 2002;87:77–83. doi: 10.1006/gyno.2002.6800. [PubMed] [CrossRef] [Google Scholar]
  100. Pourgholami M.H., Ataie-Kachoie P., Badar S., Morris D.L. Minocycline inhibits malignant ascites of ovarian cancer through targeting multiple signaling pathways. Gynecol. Oncol. 2013;129:113–119. doi: 10.1016/j.ygyno.2012.12.031. [PubMed] [CrossRef] [Google Scholar]
  101. Shender V., Arapidi G., Butenko I., Anikanov N., Ivanova O., Govorun V. Peptidome profiling dataset of ovarian cancer and non-cancer proximal fluids: Ascites and blood sera. Data Brief. 2019;22:557–562. doi: 10.1016/j.dib.2018.12.056. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  102. Parsons S.L., Watson S.A., Steele R.J.C. Malignant ascites. Br. J. Surg. 1996;83:6–14. doi: 10.1002/bjs.1800830104. [PubMed] [CrossRef] [Google Scholar]
  103. Becker G., Galandi D., Blum H.E. Malignant ascites: Systematic review and guideline for treatment. Eur. J. Cancer. 2006;42:589–597. doi: 10.1016/j.ejca.2005.11.018. [PubMed] [CrossRef] [Google Scholar]
  104. Huang H., Li Y.J., Lan C.Y., Huang Q.D., Feng Y.L., Huang Y.W., Liu J.H. Clinical significance of ascites in epithelial ovarian cancer. Neoplasma. 2013;60:546–552. doi: 10.4149/neo_2013_071. [PubMed] [CrossRef] [Google Scholar]
  105. Blagden S.P. Harnessing Pandemonium: The Clinical Implications of Tumor Heterogeneity in Ovarian Cancer. Front. Oncol. 2015;5:149. doi: 10.3389/fonc.2015.00149. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  106. Ahmed N., Latifi A., Riley C.B., Findlay J.K., Quinn M.A. Neuronal transcription factor Brn-3a(l) is over expressed in high-grade ovarian carcinomas and tumor cells from ascites of patients with advanced-stage ovarian cancer. J. Ovarian Res. 2010;3:17. doi: 10.1186/1757-2215-3-17. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  107. Mahmood N., Mihalcioiu C., Rabbani S.A. Multifaceted Role of the Urokinase-Type Plasminogen Activator (uPA) and Its Receptor (uPAR): Diagnostic, Prognostic, and Therapeutic Applications. Front. Oncol. 2018;8:24. doi: 10.3389/fonc.2018.00024. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  108. Jeffrey B., Udaykumar H.S., Schulze K.S. Flow fields generated by peristaltic reflex in isolated guinea pig ileum: Impact of contraction depth and shoulders. Am. J. Physiol. Gastrointest. Liver Physiol. 2003;285:G907–G918. doi: 10.1152/ajpgi.00062.2003. [PubMed] [CrossRef] [Google Scholar]
  109. Nagy J.A., Herzberg K.T., Dvorak J.M., Dvorak H.F. Pathogenesis of malignant ascites formation: Initiating events that lead to fluid accumulation. Cancer Res. 1993;53:2631–2643. [PubMed] [Google Scholar]
  110. Ahmed N., Abubaker K., Findlay J., Quinn M. Epithelial mesenchymal transition and cancer stem cell-like phenotypes facilitate chemoresistance in recurrent ovarian cancer. Curr. Cancer Drug Targets. 2010;10:268–278. doi: 10.2174/156800910791190175. [PubMed] [CrossRef] [Google Scholar]
  111. Latifi A., Abubaker K., Castrechini N., Ward A.C., Liongue C., Dobill F., Kumar J., Thompson E.W., Quinn M.A., Findlay J.K., et al. Cisplatin treatment of primary and metastatic epithelial ovarian carcinomas generates residual cells with mesenchymal stem cell-like profile. J. Cell Biochem. 2011;112:2850–2864. doi: 10.1002/jcb.23199. [PubMed] [CrossRef] [Google Scholar]
  112. Chan D.W., Hui W.W., Cai P.C., Liu M.X., Yung M.M., Mak C.S., Leung T.H., Chan K.K., Ngan H.Y. Targeting GRB7/ERK/FOXM1 signaling pathway impairs aggressiveness of ovarian cancer cells. PLoS ONE. 2012;7:e52578. doi: 10.1371/journal.pone.0052578. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  113. Mebratu Y., Tesfaigzi Y. How ERK1/2 activation controls cell proliferation and cell death: Is subcellular localization the answer? Cell Cycle. 2009;8:1168–1175. doi: 10.4161/cc.8.8.8147. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  114. Zebisch A., Czernilofsky A.P., Keri G., Smigelskaite J., Sill H., Troppmair J. Signaling through RAS-RAF-MEK-ERK: From basics to bedside. Curr. Med. Chem. 2007;14:601–623. doi: 10.2174/092986707780059670. [PubMed] [CrossRef] [Google Scholar]
  115. Jo H., Sipos K., Go Y.M., Law R., Rong J., McDonald J.M. Differential effect of shear stress on extracellular signal-regulated kinase and N-terminal Jun kinase in endothelial cells. Gi2- and Gbeta/gamma-dependent signaling pathways. J. Biol. Chem. 1997;272:1395–1401. doi: 10.1074/jbc.272.2.1395. [PubMed] [CrossRef] [Google Scholar]
  116. Surapisitchat J., Hoefen R.J., Pi X., Yoshizumi M., Yan C., Berk B.C. Fluid shear stress inhibits TNF-alpha activation of JNK but not ERK1/2 or p38 in human umbilical vein endothelial cells: Inhibitory crosstalk among MAPK family members. Proc. Natl. Acad. Sci. USA. 2001;98:6476–6481. doi: 10.1073/pnas.101134098. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  117. Kim C.H., Jeung E.B., Yoo Y.M. Combined Fluid Shear Stress and Melatonin Enhances the ERK/Akt/mTOR Signal in Cilia-Less MC3T3-E1 Preosteoblast Cells. Int. J. Mol. Sci. 2018;19:2929. doi: 10.3390/ijms19102929. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  118. Persons D.L., Yazlovitskaya E.M., Cui W., Pelling J.C. Cisplatin-induced activation of mitogen-activated protein kinases in ovarian carcinoma cells: Inhibition of extracellular signal-regulated kinase activity increases sensitivity to cisplatin. Clin. Cancer Res. 1999;5:1007–1014. [PubMed] [Google Scholar]
  119. Hayakawa J., Ohmichi M., Kurachi H., Ikegami H., Kimura A., Matsuoka T., Jikihara H., Mercola D., Murata Y. Inhibition of extracellular signal-regulated protein kinase or c-Jun N-terminal protein kinase cascade, differentially activated by cisplatin, sensitizes human ovarian cancer cell line. J. Biol. Chem. 1999;274:31648–31654. doi: 10.1074/jbc.274.44.31648. [PubMed] [CrossRef] [Google Scholar]
  120. Yeh P.Y., Chuang S.E., Yeh K.H., Song Y.C., Ea C.K., Cheng A.L. Increase of the resistance of human cervical carcinoma cells to cisplatin by inhibition of the MEK to ERK signaling pathway partly via enhancement of anticancer drug-induced NF kappa B activation. Biochem. Pharmacol. 2002;63:1423–1430. doi: 10.1016/S0006-2952(02)00908-5. [PubMed] [CrossRef] [Google Scholar]
  121. Wang X., Martindale J.L., Holbrook N.J. Requirement for ERK activation in cisplatin-induced apoptosis. J. Biol. Chem. 2000;275:39435–39443. doi: 10.1074/jbc.M004583200. [PubMed] [CrossRef] [Google Scholar]
  122. Qin X., Liu C., Zhou Y., Wang G. Cisplatin induces programmed death-1-ligand 1(PD-L1) over-expression in hepatoma H22 cells via Erk /MAPK signaling pathway. Cell Mol. Biol. 2010;56:OL1366-72. doi: 10.1170/156. [PubMed] [CrossRef] [Google Scholar]
  123. Basu A., Tu H. Activation of ERK during DNA damage-induced apoptosis involves protein kinase Cdelta. Biochem. Biophys. Res. Commun. 2005;334:1068–1073. doi: 10.1016/j.bbrc.2005.06.199. [PubMed] [CrossRef] [Google Scholar]
  124. Nowak G. Protein kinase C-alpha and ERK1/2 mediate mitochondrial dysfunction, decreases in active Na+ transport, and cisplatin-induced apoptosis in renal cells. J. Biol. Chem. 2002;277:43377–43388. doi: 10.1074/jbc.M206373200. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  125. Chaudhury A., Tan B.J., Das S., Chiu G.N. Increased ERK activation and cellular drug accumulation in the enhanced cytotoxicity of folate receptor-targeted liposomal carboplatin. Int. J. Oncol. 2012;40:703–710. doi: 10.3892/ijo.2011.1262. [PubMed] [CrossRef] [Google Scholar]
  126. Lok G.T., Chan D.W., Liu V.W., Hui W.W., Leung T.H., Yao K.M., Ngan H.Y. Aberrant activation of ERK/FOXM1 signaling cascade triggers the cell migration/invasion in ovarian cancer cells. PLoS ONE. 2011;6:e23790. doi: 10.1371/journal.pone.0023790. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  127. Lafky J.M., Wilken J.A., Baron A.T., Maihle N.J. Clinical implications of the ErbB/epidermal growth factor (EGF) receptor family and its ligands in ovarian cancer. Biochim. Biophys. Acta. 2008;1785:232–265. doi: 10.1016/j.bbcan.2008.01.001. [PubMed] [CrossRef] [Google Scholar]
  128. Secord A.A., Blessing J.A., Armstrong D.K., Rodgers W.H., Miner Z., Barnes M.N., Lewandowski G., Mannel R.S., Gynecologic Oncology G. Phase II trial of cetuximab and carboplatin in relapsed platinum-sensitive ovarian cancer and evaluation of epidermal growth factor receptor expression: A Gynecologic Oncology Group study. Gynecol. Oncol. 2008;108:493–499. doi: 10.1016/j.ygyno.2007.11.029. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  129. Bae G.-Y., Choi S.-J., Lee J.-S., Jo J., Lee J., Kim J., Cha H.-J. Loss of E-cadherin activates EGFR-MEK/ERK signaling, which promotes invasion via the ZEB1/MMP2 axis in non-small cell lung cancer. Oncotarget. 2013;4:2512. doi: 10.18632/oncotarget.1463. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  130. Pece S., Gutkind J.S. Signaling from E-cadherins to the MAPK pathway by the recruitment and activation of epidermal growth factor receptors upon cell-cell contact formation. J. Biol. Chem. 2000;275:41227–41233. doi: 10.1074/jbc.M006578200. [PubMed] [CrossRef] [Google Scholar]
  131. Lifschitz-Mercer B., Czernobilsky B., Feldberg E., Geiger B. Expression of the adherens junction protein vinculin in human basal and squamous cell tumors: Relationship to invasiveness and metastatic potential. Hum. Pathol. 1997;28:1230–1236. doi: 10.1016/S0046-8177(97)90195-7. [PubMed] [CrossRef] [Google Scholar]
  132. Raz A., Geiger B. Altered organization of cell-substrate contacts and membrane-associated cytoskeleton in tumor cell variants exhibiting different metastatic capabilities. Cancer Res. 1982;42:5183–5190. [PubMed] [Google Scholar]
  133. Fukada T., Sakajiri H., Kuroda M., Kioka N., Sugimoto K. Fluid shear stress applied by orbital shaking induces MG-63 osteosarcoma cells to activate ERK in two phases through distinct signaling pathways. Biochem. Biophys. Rep. 2017;9:257–265. doi: 10.1016/j.bbrep.2017.01.004. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  134. Wu D.W., Wu T.C., Wu J.Y., Cheng Y.W., Chen Y.C., Lee M.C., Chen C.Y., Lee H. Phosphorylation of paxillin confers cisplatin resistance in non-small cell lung cancer via activating ERK-mediated Bcl-2 expression. Oncogene. 2014;33:4385–4395. doi: 10.1038/onc.2013.389. [PubMed] [CrossRef] [Google Scholar]
  135. Kessel D. Apoptosis and associated phenomena as a determinants of the efficacy of photodynamic therapy. Photochem. Photobiol. Sci. 2015;14:1397–1402. doi: 10.1039/C4PP00413B. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  136. Agostinis P., Berg K., Cengel K.A., Foster T.H., Girotti A.W., Gollnick S.O., Hahn S.M., Hamblin M.R., Juzeniene A., Kessel D., et al. Photodynamic therapy of cancer: An update. CA Cancer J. Clin. 2011;61:250–281. doi: 10.3322/caac.20114. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  137. Sorrin A.J., Ruhi M.K., Ferlic N.A., Karimnia V., Polacheck W.J., Celli J.P., Huang H.C., Rizvi I. Photodynamic Therapy and the Biophysics of the Tumor Microenvironment. Photochem. Photobiol. 2020 doi: 10.1111/php.13209. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  138. Niu C.J., Fisher C., Scheffler K., Wan R., Maleki H., Liu H., Sun Y., C A.S., Birngruber R., Lilge L. Polyacrylamide gel substrates that simulate the mechanical stiffness of normal and malignant neuronal tissues increase protoporphyin IX synthesis in glioma cells. J. Biomed. Opt. 2015;20:098002. doi: 10.1117/1.JBO.20.9.098002. [PubMed] [CrossRef] [Google Scholar]
  139. Perentes J.Y., Wang Y., Wang X., Abdelnour E., Gonzalez M., Decosterd L., Wagnieres G., Van den Bergh H., Peters S., Ris H.B., et al. Low-Dose Vascular Photodynamic Therapy Decreases Tumor Interstitial Fluid Pressure, which Promotes Liposomal Doxorubicin Distribution in a Murine Sarcoma Metastasis Model. Transl. Oncol. 2014;7 doi: 10.1016/j.tranon.2014.04.010. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  140. Leunig M., Goetz A.E., Gamarra F., Zetterer G., Messmer K., Jain R.K. Photodynamic therapy-induced alterations in interstitial fluid pressure, volume and water content of an amelanotic melanoma in the hamster. Br. J. Cancer. 1994;69:101–103. doi: 10.1038/bjc.1994.15. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  141. Foster T.H., Murant R.S., Bryant R.G., Knox R.S., Gibson S.L., Hilf R. Oxygen consumption and diffusion effects in photodynamic therapy. Radiat Res. 1991;126:296–303. doi: 10.2307/3577919. [PubMed] [CrossRef] [Google Scholar]
  142. Foster T.H., Hartley D.F., Nichols M.G., Hilf R. Fluence rate effects in photodynamic therapy of multicell tumor spheroids. Cancer Res. 1993;53:1249–1254. [PubMed] [Google Scholar]
  143. Nichols M.G., Foster T.H. Oxygen diffusion and reaction kinetics in the photodynamic therapy of multicell tumour spheroids. Phys. Med. Biol. 1994;39:2161–2181. doi: 10.1088/0031-9155/39/12/003. [PubMed] [CrossRef] [Google Scholar]
  144. Cavin S., Wang X., Zellweger M., Gonzalez M., Bensimon M., Wagnieres G., Krueger T., Ris H.B., Gronchi F., Perentes J.Y. Interstitial fluid pressure: A novel biomarker to monitor photo-induced drug uptake in tumor and normal tissues. Lasers Surg. Med. 2017;49:773–780. doi: 10.1002/lsm.22687. [PubMed] [CrossRef] [Google Scholar]
  145. Garcia Calavia P., Chambrier I., Cook M.J., Haines A.H., Field R.A., Russell D.A. Targeted photodynamic therapy of breast cancer cells using lactose-phthalocyanine functionalized gold nanoparticles. J. Colloid Interface Sci. 2018;512:249–259. doi: 10.1016/j.jcis.2017.10.030. [PubMed] [CrossRef] [Google Scholar]
  146. Kato T., Jin C.S., Ujiie H., Lee D., Fujino K., Wada H., Hu H.P., Weersink R.A., Chen J., Kaji M., et al. Nanoparticle targeted folate receptor 1-enhanced photodynamic therapy for lung cancer. Lung Cancer. 2017;113:59–68. doi: 10.1016/j.lungcan.2017.09.002. [PubMed] [CrossRef] [Google Scholar]
  147. Sebak A.A., Gomaa I.E.O., ElMeshad A.N., AbdelKader M.H. Targeted photodynamic-induced singlet oxygen production by peptide-conjugated biodegradable nanoparticles for treatment of skin melanoma. Photodiagnosis Photodyn. Ther. 2018;23:181–189. doi: 10.1016/j.pdpdt.2018.05.017. [PubMed] [CrossRef] [Google Scholar]
  148. Fernandes S.R.G., Fernandes R., Sarmento B., Pereira P.M.R., Tome J.P.C. Photoimmunoconjugates: Novel synthetic strategies to target and treat cancer by photodynamic therapy. Org. Biomol. Chem. 2019;17:2579–2593. doi: 10.1039/C8OB02902D. [PubMed] [CrossRef] [Google Scholar]
  149. Hamblin M.R., Miller J.L., Hasan T. Effect of charge on the interaction of site-specific photoimmunoconjugates with human ovarian cancer cells. Cancer Res. 1996;56:5205–5210. [PubMed] [Google Scholar]
  150. Flont M., Jastrzebska E., Brzozka Z. Synergistic effect of the combination therapy on ovarian cancer cells under microfluidic conditions. Anal. Chim. Acta. 2020;1100:138–148. doi: 10.1016/j.aca.2019.11.047. [PubMed] [CrossRef] [Google Scholar]
Figure 1.1: A water droplet with a radius of 1 mm resting on a glass substrate. The surface of the droplet takes on a spherical cap shape. The contact angle θ is defined by the balance of the interfacial forces.

Effect of substrate cooling and droplet shape and composition on the droplet evaporation and the deposition of particles

기판 냉각 및 액적 모양 및 조성이 액적 증발 및 입자 증착에 미치는 영향

by Vahid Bazargan
M.A.Sc., Mechanical Engineering, The University of British Columbia, 2008
B.Sc., Mechanical Engineering, Sharif University of Technology, 2006
B.Sc., Chemical & Petroleum Engineering, Sharif University of Technology, 2006

고착 방울은 평평한 기판에 놓인 액체 방울입니다. 작은 고정 액적이 증발하는 동안 액적의 접촉선은 고정된 접촉 영역이 있는 고정된 단계와 고정된 접촉각이 있는 고정 해제된 단계의 두 가지 단계를 거칩니다. 고정된 접촉 라인이 있는 증발은 액적 내부에서 접촉 라인을 향한 흐름을 생성합니다.

이 흐름은 입자를 운반하고 접촉 선 근처에 침전시킵니다. 이로 인해 일반적으로 관찰되는 “커피 링”현상이 발생합니다. 이 논문은 증발 과정과 고착성 액적의 증발 유도 흐름에 대한 연구를 제공하고 콜로이드 현탁액에서 입자의 침착에 대한 통찰력을 제공합니다. 여기서 우리는 먼저 작은 고착 방울의 증발을 연구하고 증발 과정에서 기판의 열전도도의 중요성에 대해 논의합니다.

현재 증발 모델이 500µm 미만의 액적 크기에 대해 심각한 오류를 생성하는 방법을 보여줍니다. 우리의 모델에는 열 효과가 포함되어 있으며, 특히 증발 잠열의 균형을 맞추기 위해 액적에 열을 제공하는 기판의 열전도도를 포함합니다. 실험 결과를 바탕으로 접촉각의 진화와 관련된 접촉 선의 가상 움직임을 정의하여 고정 및 고정 해제 단계의 전체 증발 시간을 고려합니다.

우리의 모델은 2 % 미만의 오차로 500 µm보다 작은 물방울에 대한 실험 결과와 일치합니다. 또한 유한한 크기의 라인 액적의 증발을 연구하고 증발 중 접촉 라인의 복잡한 동작에 대해 논의합니다. 에너지 공식을 적용하고 접촉 선이 구형 방울의 후퇴 접촉각보다 높은 접촉각을 가진 선 방울의 두 끝에서 후퇴하기 시작 함을 보여줍니다. 그리고 라인 방울 내부의 증발 유도 흐름을 보여줍니다.

마지막으로, 계면 활성제 존재 하에서 접촉 라인의 거동을 논의하고 입자 증착에 대한 Marangoni 흐름 효과에 대해 논의합니다. 열 Marangoni 효과는 접촉 선 근처에 증착 된 입자의 양에 영향을 미치며, 기판 온도가 낮을수록 접촉 선 근처에 증착되는 입자의 양이 많다는 것을 알 수 있습니다.

Figure 1.1: A water droplet with a radius of 1 mm resting on a glass substrate. The surface of the droplet takes on a spherical cap shape. The contact angle θ is defined by the balance of the interfacial forces.
Figure 1.1: A water droplet with a radius of 1 mm resting on a glass substrate. The surface of the droplet takes on a spherical cap shape. The contact angle θ is defined by the balance of the interfacial forces.
Figure 2.1: Evaporation modes of sessile droplets on a substrate: (a) evaporation at constant contact angle (de-pinned stage) and (b) evaporation at constant contact area (pinned stage)
Figure 2.1: Evaporation modes of sessile droplets on a substrate: (a) evaporation at constant contact angle (de-pinned stage) and (b) evaporation at constant contact area (pinned stage)
Figure 2.2: A sessil droplet with its image can be profiled as the equiconvex lens formed by two intersecting spheres with radius of a.
Figure 2.2: A sessil droplet with its image can be profiled as the equiconvex lens formed by two intersecting spheres with radius of a.
Figure 2.3: The droplet life time for both evaporation modes derived from Equation 2.2.
Figure 2.3: The droplet life time for both evaporation modes derived from Equation 2.2.
Figure 2.4: A probability of escape for vapor molecules at two different sites of the surface of the droplet for diffusion controlled evaporation. The random walk path initiated from a vapor molecule is more likely to result in a return to the surface if the starting point is further away from the edge of the droplet.
Figure 2.4: A probability of escape for vapor molecules at two different sites of the surface of the droplet for diffusion controlled evaporation. The random walk path initiated from a vapor molecule is more likely to result in a return to the surface if the starting point is further away from the edge of the droplet.
Figure 2.5: Schematic of the sessile droplet on a substrate
Figure 2.5: Schematic of the sessile droplet on a substrate. The evaporation rate at the surface of the droplet is enhanced toward the edge of the droplet.
Figure 2.6: The domain mesh (a) and the solution of the Laplace equation for diffusion of the water vapor molecule with the concentration of Cv = 1.9×10−8 g/mm3 at the surface of the droplet into the ambient air with the relative humidity of 55%, i.e. φ = 0.55 (b).
Figure 2.6: The domain mesh (a) and the solution of the Laplace equation for diffusion of the water vapor molecule with the concentration of Cv = 1.9×10−8 g/mm3 at the surface of the droplet into the ambient air with the relative humidity of 55%, i.e. φ = 0.55 (b).
Figure 3.1: The portable micro printing setup. A motorized linear stage from Zaber Technologies Inc. was used to control the place and speed of the micro nozzle.
Figure 3.1: The portable micro printing setup. A motorized linear stage from Zaber Technologies Inc. was used to control the place and speed of the micro nozzle.
Figure 4.6: Temperature contours inside the substrate adjacent to the droplet
Figure 4.6: Temperature contours inside the substrate adjacent to the droplet
Figure 4.7: The effect of substrate cooling on the evaporation rate, the basic model shows the same value for all substrates.
Figure 4.7: The effect of substrate cooling on the evaporation rate, the basic model shows the same value for all substrates.

Bibliography

[1] R. G. Picknett and R. Bexon, “The evaporation of sessile or pendant drops in still air,” Journal of Colloid and Interface Science, vol. 61, pp. 336–350, Sept. 1977. → pages viii, 8, 9, 18, 42
[2] H. Y. Erbil, “Evaporation of pure liquid sessile and spherical suspended drops: A review,” Advances in Colloid and Interface Science, vol. 170, pp. 67–86, Jan. 2012. → pages 1
[3] R. Sharma, C. Y. Lee, J. H. Choi, K. Chen, and M. S. Strano, “Nanometer positioning, parallel alignment, and placement of single anisotropic nanoparticles using hydrodynamic forces in cylindrical droplets,” Nano Lett., vol. 7, no. 9, pp. 2693–2700, 2007. → pages 1, 54, 71
[4] S. Tokonami, H. Shiigi, and T. Nagaoka, “Review: Micro- and nanosized molecularly imprinted polymers for high-throughput analytical applications,” Analytica Chimica Acta, vol. 641, pp. 7–13, May 2009. →pages 71
[5] A. A. Sagade and R. Sharma, “Copper sulphide (CuxS) as an ammonia gas sensor working at room temperature,” Sensors and Actuators B: Chemical, vol. 133, pp. 135–143, July 2008. → pages
[6] W. R. Small, C. D. Walton, J. Loos, and M. in het Panhuis, “Carbon nanotube network formation from evaporating sessile drops,” The Journal of Physical Chemistry B, vol. 110, pp. 13029–13036, July 2006. → pages 71
[7] S. H. Ko, H. Lee, and K. H. Kang, “Hydrodynamic flows in electrowetting,” Langmuir, vol. 24, pp. 1094–1101, Feb. 2008. → pages 42
[8] T. T. Nellimoottil, P. N. Rao, S. S. Ghosh, and A. Chattopadhyay, “Evaporation-induced patterns from droplets containing motile and nonmotile bacteria,” Langmuir, vol. 23, pp. 8655–8658, Aug. 2007. → pages 1
[9] R. Sharma and M. S. Strano, “Centerline placement and alignment of anisotropic nanotubes in high aspect ratio cylindrical droplets of nanometer diameter,” Advanced Materials, vol. 21, no. 1, p. 6065, 2009. → pages 1, 54, 71
[10] V. Dugas, J. Broutin, and E. Souteyrand, “Droplet evaporation study applied to DNA chip manufacturing,” Langmuir, vol. 21, pp. 9130–9136, Sept. → pages 2, 71
[11] Y.-C. Hu, Q. Zhou, Y.-F. Wang, Y.-Y. Song, and L.-S. Cui, “Formation mechanism of micro-flows in aqueous poly(ethylene oxide) droplets on a substrate at different temperatures,” Petroleum Science, vol. 10, pp. 262–268, June 2013. → pages 2, 34, 54
[12] T.-S. Wong, T.-H. Chen, X. Shen, and C.-M. Ho, “Nanochromatography driven by the coffee ring effect,” Analytical Chemistry, vol. 83, pp. 1871–1873, Mar. 2011. → pages 71
[13] J.-H. Kim, S.-B. Park, J. H. Kim, and W.-C. Zin, “Polymer transports inside evaporating water droplets at various substrate temperatures,” The Journal of Physical Chemistry C, vol. 115, pp. 15375–15383, Aug. 2011. → pages 54
[14] S. Choi, S. Stassi, A. P. Pisano, and T. I. Zohdi, “Coffee-ring effect-based three dimensional patterning of Micro/Nanoparticle assembly with a single droplet,” Langmuir, vol. 26, pp. 11690–11698, July 2010. → pages
[15] D. Wang, S. Liu, B. J. Trummer, C. Deng, and A. Wang, “Carbohydrate microarrays for the recognition of cross-reactive molecular markers of microbes and host cells,” Nature biotechnology, vol. 20, pp. 275–281, Mar. PMID: 11875429. → pages 2, 54, 71
[16] H. K. Cammenga, “Evaporation mechanisms of liquids,” Current topics in materials science, vol. 5, pp. 335–446, 1980. → pages 3
[17] C. Snow, “Potential problems and capacitance for a conductor bounded by two intersecting spheres,” Journal of Research of the National Bureau of Standards, vol. 43, p. 337, 1949. → pages 9
[18] R. D. Deegan, O. Bakajin, T. F. Dupont, G. Huber, S. R. Nagel, and T. A. Witten, “Contact line deposits in an evaporating drop,” Physical Review E, vol. 62, p. 756, July 2000. → pages 10, 14, 18, 27, 53, 54, 71, 84
[19] H. Hu and R. G. Larson, “Evaporation of a sessile droplet on a substrate,” The Journal of Physical Chemistry B, vol. 106, pp. 1334–1344, Feb. 2002. → pages 12, 18, 29, 43, 44, 48, 49, 53, 61, 71, 84
[20] Y. O. Popov, “Evaporative deposition patterns: Spatial dimensions of the deposit,” Physical Review E, vol. 71, p. 036313, Mar. 2005. → pages 14, 27, 43, 44, 45, 54
[21] H. Gelderblom, A. G. Marin, H. Nair, A. van Houselt, L. Lefferts, J. H. Snoeijer, and D. Lohse, “How water droplets evaporate on a superhydrophobic substrate,” Physical Review E, vol. 83, no. 2, p. 026306,→ pages
[22] F. Girard, M. Antoni, S. Faure, and A. Steinchen, “Influence of heating temperature and relative humidity in the evaporation of pinned droplets,” Colloids and Surfaces A: Physicochemical and Engineering Aspects, vol. 323, pp. 36–49, June 2008. → pages 18
[23] Y. Y. Tarasevich, “Simple analytical model of capillary flow in an evaporating sessile drop,” Physical Review E, vol. 71, p. 027301, Feb. 2005. → pages 19, 54, 62, 72
[24] A. J. Petsi and V. N. Burganos, “Potential flow inside an evaporating cylindrical line,” Physical Review E, vol. 72, p. 047301, Oct. 2005. → pages 22, 55, 62, 68, 71
[25] A. J. Petsi and V. N. Burganos, “Evaporation-induced flow in an inviscid liquid line at any contact angle,” Physical Review E, vol. 73, p. 041201, Apr.→ pages 23, 53, 55, 72
[26] H. Masoud and J. D. Felske, “Analytical solution for stokes flow inside an evaporating sessile drop: Spherical and cylindrical cap shapes,” Physics of Fluids, vol. 21, pp. 042102–042102–11, Apr. 2009. → pages 23, 55, 62, 71, 72
[27] H. Hu and R. G. Larson, “Analysis of the effects of marangoni stresses on the microflow in an evaporating sessile droplet,” Langmuir, vol. 21, pp. 3972–3980, Apr. 2005. → pages 24, 28, 53, 54, 56, 62, 68, 71, 72, 74, 84
[28] R. Bhardwaj, X. Fang, and D. Attinger, “Pattern formation during the evaporation of a colloidal nanoliter drop: a numerical and experimental study,” New Journal of Physics, vol. 11, p. 075020, July 2009. → pages 28
[29] A. Petsi, A. Kalarakis, and V. Burganos, “Deposition of brownian particles during evaporation of two-dimensional sessile droplets,” Chemical Engineering Science, vol. 65, pp. 2978–2989, May 2010. → pages 28
[30] J. Park and J. Moon, “Control of colloidal particle deposit patterns within picoliter droplets ejected by ink-jet printing,” Langmuir, vol. 22, pp. 3506–3513, Apr. 2006. → pages 28
[31] H. Hu and R. G. Larson, “Marangoni effect reverses coffee-ring depositions,” The Journal of Physical Chemistry B, vol. 110, pp. 7090–7094, Apr. 2006. → pages 29, 74
[32] K. H. Kang, S. J. Lee, C. M. Lee, and I. S. Kang, “Quantitative visualization of flow inside an evaporating droplet using the ray tracing method,” Measurement Science and Technology, vol. 15, pp. 1104–1112, June 2004. → pages 34
[33] S. T. Beyer and K. Walus, “Controlled orientation and alignment in films of single-walled carbon nanotubes using inkjet printing,” Langmuir, vol. 28, pp. 8753–8759, June 2012. → pages 42, 71
[34] G. McHale, “Surface free energy and microarray deposition technology,” Analyst, vol. 132, pp. 192–195, Feb. 2007. → pages 42
[35] R. Bhardwaj, X. Fang, P. Somasundaran, and D. Attinger, “Self-assembly of colloidal particles from evaporating droplets: Role of DLVO interactions and proposition of a phase diagram,” Langmuir, vol. 26, pp. 7833–7842, June→ pages 42
[36] G. J. Dunn, S. K. Wilson, B. R. Duffy, S. David, and K. Sefiane, “The strong influence of substrate conductivity on droplet evaporation,” Journal of Fluid Mechanics, vol. 623, no. 1, p. 329351, 2009. → pages 44
[37] M. S. Plesset and A. Prosperetti, “Flow of vapour in a liquid enclosure,” Journal of Fluid Mechanics, vol. 78, pp. 433–444, 1976. → pages 44
[38] S. Das, P. R. Waghmare, M. Fan, N. S. K. Gunda, S. S. Roy, and S. K. Mitra, “Dynamics of liquid droplets in an evaporating drop: liquid droplet coffee stain? effect,” RSC Advances, vol. 2, pp. 8390–8401, Aug. 2012. → pages 53
[39] B. J. Fischer, “Particle convection in an evaporating colloidal droplet,” Langmuir, vol. 18, pp. 60–67, Jan. 2002. → pages 54
[40] J. L. Wilbur, A. Kumar, H. A. Biebuyck, E. Kim, and G. M. Whitesides, “Microcontact printing of self-assembled monolayers: applications in microfabrication,” Nanotechnology, vol. 7, p. 452, Dec. 1996. → pages 54
[41] T. Kawase, H. Sirringhaus, R. H. Friend, and T. Shimoda, “Inkjet printed via-hole interconnections and resistors for all-polymer transistor circuits,” Advanced Materials, vol. 13, no. 21, p. 16011605, 2001. → pages 71
[42] B.-J. de Gans, P. C. Duineveld, and U. S. Schubert, “Inkjet printing of polymers: State of the art and future developments,” Advanced Materials, vol. 16, no. 3, p. 203213, 2004. → pages 71
[43] H. Sirringhaus, T. Kawase, R. H. Friend, T. Shimoda, M. Inbasekaran, W. Wu, and E. P. Woo, “High-resolution inkjet printing of all-polymer transistor circuits,” Science, vol. 290, pp. 2123–2126, Dec. 2000. PMID:→ pages
[44] D. Soltman and V. Subramanian, “Inkjet-printed line morphologies and temperature control of the coffee ring effect,” Langmuir, vol. 24, pp. 2224–2231, Mar. 2008. → pages 54
[45] R. Tadmor and P. S. Yadav, “As-placed contact angles for sessile drops,” Journal of Colloid and Interface Science, vol. 317, pp. 241–246, Jan. 2008. → pages 56
[46] J. Drelich, “The significance and magnitude of the line tension in three-phase (solid-liquid-fluid) systems,” Colloids and Surfaces A: Physicochemical and Engineering Aspects, vol. 116, pp. 43–54, Sept. 1996. → pages 56
[47] R. Tadmor, “Line energy, line tension and drop size,” Surface Science, vol. 602, pp. L108–L111, July 2008. → pages 69
[48] C.-H. Choi and C.-J. C. Kim, “Droplet evaporation of pure water and protein solution on nanostructured superhydrophobic surfaces of varying heights,” Langmuir, vol. 25, pp. 7561–7567, July 2009. → pages 71
[49] K. F. Baughman, R. M. Maier, T. A. Norris, B. M. Beam, A. Mudalige, J. E. Pemberton, and J. E. Curry, “Evaporative deposition patterns of bacteria from a sessile drop: Effect of changes in surface wettability due to exposure to a laboratory atmosphere,” Langmuir, vol. 26, pp. 7293–7298, May 2010.
[50] D. Brutin, B. Sobac, and C. Nicloux, “Influence of substrate nature on the evaporation of a sessile drop of blood,” Journal of Heat Transfer, vol. 134, pp. 061101–061101, May 2012. → pages 71
[51] D. Pech, M. Brunet, P.-L. Taberna, P. Simon, N. Fabre, F. Mesnilgrente, V. Condra, and H. Durou, “Elaboration of a microstructured inkjet-printed carbon electrochemical capacitor,” Journal of Power Sources, vol. 195, pp. 1266–1269, Feb. 2010. → pages 71
[52] J. Bachmann, A. Ellies, and K. Hartge, “Development and application of a new sessile drop contact angle method to assess soil water repellency,” Journal of Hydrology, vol. 231232, pp. 66–75, May 2000. → pages 71
[53] H. Y. Erbil, G. McHale, and M. I. Newton, “Drop evaporation on solid surfaces: constant contact angle mode,” Langmuir, vol. 18, no. 7, pp. 2636–2641, 2002. → pages
[54] X. Fang, B. Li, J. C. Sokolov, M. H. Rafailovich, and D. Gewaily, “Hildebrand solubility parameters measurement via sessile drops evaporation,” Applied Physics Letters, vol. 87, pp. 094103–094103–3, Aug.→ pages
[55] Y. C. Jung and B. Bhushan, “Wetting behaviour during evaporation and condensation of water microdroplets on superhydrophobic patterned surfaces,” Journal of Microscopy, vol. 229, no. 1, p. 127140, 2008. → pages 71
[56] J. Drelich, J. D. Miller, and R. J. Good, “The effect of drop (bubble) size on advancing and receding contact angles for heterogeneous and rough solid surfaces as observed with sessile-drop and captive-bubble techniques,”
Journal of Colloid and Interface Science, vol. 179, pp. 37–50, Apr. 1996. →pages 72, 75
[57] D. Bargeman and F. Van Voorst Vader, “Effect of surfactants on contact angles at nonpolar solids,” Journal of Colloid and Interface Science, vol. 42, pp. 467–472, Mar. 1973. → pages 73
[58] J. Menezes, J. Yan, and M. Sharma, “The mechanism of alteration of macroscopic contact angles by the adsorption of surfactants,” Colloids and Surfaces, vol. 38, no. 2, pp. 365–390, 1989. → pages
[59] T. Okubo, “Surface tension of structured colloidal suspensions of polystyrene and silica spheres at the air-water interface,” Journal of Colloid and Interface Science, vol. 171, pp. 55–62, Apr. 1995. → pages 73, 76
[60] R. Pyter, G. Zografi, and P. Mukerjee, “Wetting of solids by surface-active agents: The effects of unequal adsorption to vapor-liquid and solid-liquid interfaces,” Journal of Colloid and Interface Science, vol. 89, pp. 144–153, Sept. 1982. → pages 73
[61] T. Mitsui, S. Nakamura, F. Harusawa, and Y. Machida, “Changes in the interfacial tension with temperature and their effects on the particle size and stability of emulsions,” Kolloid-Zeitschrift und Zeitschrift fr Polymere, vol. 250, pp. 227–230, Mar. 1972. → pages 73
[62] S. Phongikaroon, R. Hoffmaster, K. P. Judd, G. B. Smith, and R. A. Handler, “Effect of temperature on the surface tension of soluble and insoluble surfactants of hydrodynamical importance,” Journal of Chemical & Engineering Data, vol. 50, pp. 1602–1607, Sept. 2005. → pages 73, 80
[63] V. S. Vesselovsky and V. N. Pertzov, “Adhesion of air bubbles to the solid surface,” Zh. Fiz. Khim, vol. 8, pp. 245–259, 1936. → pages 75
[64] Hideo Nakae, Ryuichi Inui, Yosuke Hirata, and Hiroyuki Saito, “Effects of surface roughness on wettability,” Acta Materialia, vol. 46, pp. 2313–2318, Apr. 1998. → pages
[65] R. J. Good and M. Koo, “The effect of drop size on contact angle,” Journal of Colloid and Interface Science, vol. 71, pp. 283–292, Sept. 1979. → pages

Damascene templates

High-Rate Nanoscale Offset Printing Process Using Directed Assembly and Transfer of Nanomaterials

지난 10 년 동안 나노 크기의 재료와 공정을 제품에 통합하는 데 제한적인 성공을 거두면서 나노 기술에 상당한 투자와 발전이 있었습니다.

잉크젯, 그라비아, 스크린 프린팅과 같은 접근 방식은 나노 물질을 사용하여 구조와 장치를 만드는 데 사용됩니다. [1–7] 그러나 상당히 느리고 µm 스케일 분해능 만 제공 할 수 있습니다. 다양한 모양과 크기의 100nm 미만의 특징을 달성하기 위해 딥펜 리소그래피 (DPN) [8-11] 및 소프트 리소그래피 [12-16]와 같은 다양한 기술이 개발되고 광범위하게 연구되었습니다.

DPN은 직접 쓰기 기술로, atomic force microscopy 현미경 팁을 사용하여 다양한 기판에 여러 패턴을 생성합니다. DPN을 사용한 확장 성을 해결하기 위해 단일 AFM 팁 대신 2D 형식으로 배포 된 AFM (Atomic Force Microscopy) 팁 [17,18]이 사용되었습니다. 소프트 리소그래피에서는 나노 물질을 포함하는 잉크로 적셔진 원하는 릴리프 패턴을 가진 경화된 엘라스토머가 기판과 컨 포멀 접촉하게 되며, 여기서 패턴 화 된 나노 물질이 전달되어 기판에서 원하는 특징을 달성합니다.

이 논문에서는 작거나 큰 영역에서 몇 분 만에 나노, 마이크로 또는 거시적 구조를 인쇄 할 수 있는 다중 스케일 오프셋 인쇄 접근 방식을 제시합니다. 이 프로세스는 나노 입자 (NP), 탄소 나노 튜브 (CNT) 또는 용해 된 폴리머를 포함하는 서스펜션 (잉크)에서 나노 물질의 전기 영동 방향 조립을 사용하여 특별히 제작 된 재사용 가능한 Damascene 템플릿에 패턴을 “inking” 하는 것으로 시작됩니다. 이 잉크 프로세스는 실온과 압력에서 수행됩니다.

두 번째 단계는 템플릿에 조립된 나노 물질이 다른 기판으로 전송되는 “printing”로 구성됩니다. 전송 프로세스가 끝나면 템플릿은 다음 조립 및 전송주기에서 즉시 재사용 할 수 있습니다. 이 오프셋 인쇄 프로세스를 통해 NP (폴리스티렌 라텍스 (PSL), 실리카,은) 및 CNT (다중 벽 및 단일 벽)를 100μm에서 500nm까지의 크기 범위를 가진 패턴에 조립하고 유동성 기판에 성공적으로 옮깁니다.

다양한 나노 물질을 다양한 아키텍처로 조립하기 위해 템플릿 유도 유동, 대류, 유전 영동 (DEP) 및 전기 영동 조립과 같은 몇 가지 직접 조립 프로세스가 조사되었습니다. 모세관력이 지배적인 조립 메커니즘인 유체 조립 공정은 다양한 나노 물질에 적용 할 수 있습니다.

대류 조립 공정은 현탁 메니 스커 스와 증발을 활용하여 단일 나노 입자 분해능으로 정밀 조립을 가능하게 합니다. 이러한 조립 공정 중 많은 부분이 트렌치와 같은 마이크로 및 나노 스케일 기능으로 고해상도의 직접 조립을 보여 주었지만, 확장성 부족, 느린 공정 속도 및 반복성과 같은 많은 단점이 있습니다.

DEP 어셈블리는 NP와 전극 사이에 고배향 탄소 나노 튜브 어셈블리를 사용하여 나노 와이어 및 구조를 만드는 데 사용되었습니다. 조립 효율은 전기장과 전기장 구배에 상당한 영향을 미치는 전극의 기하학적 구조와 간격에 크게 좌우됩니다. 전기 영동 기반 조립 공정은 유체 조립에 비해 훨씬 짧은 시간에 전도성 표면에 표면 전하를 가진 나노 물질을 조립하는 것을 포함합니다. [34–37]

그러나 전기 영동 조립은 조립이 전도성 표면에 발생해야 하므로 다양한 장치를 만드는 데 실용적이지 않습니다. 한 가지 해결책은 원하는 나노 스케일 구조를 기반으로 전도성 패턴이 있는 템플릿을 만들고, 전기 영동 공정을 사용하여 패턴 위에 나노 물질을 조립 한 다음 조립 된 구조를 수용 기판에 옮기는 것입니다.

그림 1a와 같이 절연 필름에 전도성 와이어와 같은 패턴 구조가있는 기존 템플릿을 사용하면 나노 스케일 와이어의 잠재적 인 큰 강하로 인해 어셈블리가 불균일 해지며 대부분의 입자는 그림 1에 표시된 마이크로 와이어 b. 또한 NP는 3D 와이어의 측벽에도 조립되므로 바람직하지 않습니다. 또한 나노 스케일 와이어와 템플릿 사이의 작은 접촉 면적으로 인해 나노 스케일 와이어는 이송 과정에서 쉽게 벗겨집니다.

Damascene templates
Figure 1. Damascene templates: a) A schematic of a conventional wire template used for electrophoretic assembly. In these templates nanowire are connected to a micrometer scale electrodes, which are in turn connected, to a large metal pad through which the potential is applied. b) SEM images of a typical nanoparticle assembly result obtained for confi guration shown in (a). c) A schematic of a Damascene template where all of the wires (nano- or micrometer scale) and the metal pad are connected to a conductive fi lm underneath the insulating fi lm. d) A schematic of Damascene template fabrication. Inset is artifi cially colored cross-sectional SEM image showing the metal nanowires to be at the same height as that of the SiO 2 and showing the conductive fi lm underneath the insulator. e) An optical image of a 3 inch Damascene template.
Offset printing
Figure 2. Offset printing: a) A schematic of the nanoscale offset printing approach. The insulating (SiO 2 ) surface of the Damascene template is selectively coated with a hydrophobic SAM (OTS). Using electrophoresis, nanomaterials are assembled on the conductive patterns of the Damascene template (“inking”), which are then transferred to a recipient substrate (“printing”). After the transfer, the template is ready for the next assembly and transfer cycle. b) SEM image of 50 nm PSL particles assembly with high density on 1 µm wide electrodes. c) Silica particles (20 nm) assembly on crossbar 2D patterns demonstrating the versatility of the Damascene template. Inset fi gure is a high-resolution image of assembled silica particles. d) SEM image of assembled SWNTs on micrometer scale patterns. e) MWNTs assembled on 100 µm features. f) Cellulose assembled on 2 µm electrodes. g) SWNTs assembled in cross bar architecture patterns. h) Flexible devices with array of transferred SWNTs and metal electrodes (printed on PEN). Inset is the microscopy image of two electropads and transferred SWNTs on PEN fi lm.
Analysis of nanomaterial assembly on electrodes
Figure 3. Analysis of nanomaterial assembly on electrodes

이것은 또한 그림 3b에 표시된대로 유한 체적 모델링 (Flow 3D)을 사용하는 전기장 윤곽 시뮬레이션 결과에 의해 확인됩니다. 전기장 강도의 윤곽은 전도성 패턴의 가장자리에있는 전기장이 중앙에있는 것보다 더 강하다는 것을 나타냅니다. 그러나 적용된 전위가 2.5V로 증가하면 그림 3c에 표시된대로 100nm 실리카 입자가 Damascene 템플릿을 가로 질러 전도성 패턴의 표면에 완전히 조립되어 조립을위한 임계 전기장 강도에 도달했음을 나타냅니다. 정렬 된 SWNT는 여과 전달 경로를 피하고 나노 튜브 사이의 접합 저항을 최소화하여 소자 성능의 최소 변화를 가져 오기 때문에 많은 응용 분야에서 고도로 조직화 된 SWNT가 필요합니다.

References

[1] M.Abulikemu, E.H.Da’as, H.Haverinen, D.Cha, M.A.Malik, G.E.Jabbour, Angew.Chem.Int.Ed.2014, 53, 599.
[2] a) Z.Lu, M.Layani, X.Zhao, L.P.Tan, T.Sun, S.Fan, Q.Yan, S.Magdassi, H.H.Hng, Small 2014, 10, 3551; b) H.Ko, J.Lee, Y.Kim, B.Lee, C.H.Jung, J.H.Choi, O.S.Kwon, K.Shin, Adv.Mater.2014, 26, 2286.
[3] C.J.Hansen, R.Saksena, D.B.Kolesky, J.J.Vericella, S.J.Kranz, G.P.Muldowney, K.T.Christensen, J.A.Lewis, Adv.Mater.2013, 25, 2.
[4] F.C.Krebs, N.Espinosa, M.Hösel, R.R.Søndergaard, M.Jørgensen, Adv.Mater.2014, 26, 29.
[5] W.Honda, S.Harada, T.Arie, S.Akita, K.Takei, Adv.Funct.Mater. 2014, 24, 3298.
[6] R.Guo, Y.Yu, Z.Xie, X.Liu, X.Zhou, Y.Gao, Z.Liu, F.Zhou, Y.Yang, Z.Zheng, Adv.Mater.2013, 25, 3343.
[7] A.Dzwilewski, T.Wågberg, L.Edman, J.Am.Chem.Soc.2009, 131, 4006.
[8] R.D.Piner, J.Zhu, F.Xu, S.Hong, C.A.Mirkin, Science 1999, 283, 661.
[9] J.-H.Lim, C.A.Mirkin, Adv.Mater.2002, 14, 1474.
[10] X.Liu, L.Fu, S.Hong, V.P.Dravid, C.A.Mirkin, Adv.Mater.2002,14, 231.
[11] D.A.Weinberger, S.Hong, C.A.Mirkin, B.W.Wessels, T.B.Higgins, Adv.Mater.2000, 12, 1600.
[12] J.P.Rolland, E.C.Hagberg, G.M.Denison, K.R.Carter, J.M.DeSimone, Angew.Chem.2004, 116, 5920.
[13] T.Granlund, T.Nyberg, L.S.Roman, M.Svensson, O.Inganäs, Adv.Mater.2000, 12, 269.
[14] Y.Xia, G.M.Whitesides, Annu.Rev.Mater.Sci.1998, 28, 153.
[15] W.S.Beh, I.T.Kim, D.Qin, Y.Xia, G.M.Whitesides.Adv.Mater. 1999, 11, 1038.
[16] Y.Yin, B.Gates, Y.Xia.Adv.Mater.2000, 12, 1426.
[17] K.Salaita, Y.Wang, J.Fragala, R.A.Vega, C.Liu, C.A.Mirkin,Angew.Chem.2006, 118, 7378.
[18] D.Bullen, S.-W.Chung, X.Wang, J.Zou, C.A.Mirkin, C.Liu, Appl.Phys.Lett.2004, 84, 789.
[19] Y.L.Kim, H.Y.Jung, S.Park, B.Li, F.Liu, J.Hao, Y.-K.Kwon, Y.J.Jung, S.Kar, Nat.Photonics 2014, 8, 239.
[20] X.Xiong, L.Jaberansari, M.G.Hahm, A.Busnaina, Y.J.Jung, Small 2007, 3, 2006.
[21] A.B.Marciel, M.Tanyeri, B.D.Wall, J.D.Tovar, C.M.Schroeder, W.L.Wilson, Adv.Mater.2013, 25, 6398.
[22] J.T.Wang, J.Wang, J.J.Han, Small 2011, 7, 1728.
[23] S.Y.Lee, S.H.Kim, H.Hwang, J.Y.Sim, S.M.Yang, Adv.Mater. 2014, 26, 2391.
[24] J.Y.Oh, J.T.Park, H.J.Jang, W.J.Cho, M.S.Islam, Adv.Mater. 2014, 26, 1929.
[25] K.W.Song, R.Costi, V.Bulovi, Adv.Mater.2013, 25, 1420.
[26] P.Maury, M.Escalante, D.N.Reinhoudt, J.Huskens, Adv.Mater. 2005, 17, 2718.
[27] Y.Xia, Y.Yin, Y.Lu, J.McLellan, Adv.Funct.Mater.2003, 13, 907.
[28] L.Jaber-Ansari, M.G.Hahm, S.Somu, Y.E.Sanz, A.Busnaina, Y.J.Jung, J.Am.Chem.Soc.2008, 131, 804.
[29] T.Kraus, L.Malaquin, H.Schmid, W.Riess, N.D.Spencer, H.Wolf,Nat.Nanotechnol.2007, 2, 570.
[30] K.D.Hermanson, S.O.Lumsdon, J.P.Williams, E.W.Kaler, O.D.Velev, Science 2001, 294, 1082.
[31] H.-W.Seo, C.-S.Han, D.-G.Choi, K.-S.Kim, Y.-H.Lee, Microelectron.Eng.2005, 81, 83.
[32] E.M.Freer, O.Grachev, X.Duan, S.Martin, D.P.Stumbo, Nat.Nanotechnol.2010, 5, 525.
[33] D.Xu, A.Subramanian, L.Dong, B.J.Nelson, IEEE Trans.Nanotechnol.2009, 8, 449.
[34] X.Xiong, P.Makaram, A.Busnaina, K.Bakhtari, S.Somu, N.McGruer, J.Park, Appl.Phys.Lett.2006, 89, 193108.
[35] R.C.Bailey, K.J.Stevenson, J.T.Hupp, Adv.Mater.2000, 12, 1930.
[36] Q.Zhang, T.Xu, D.Butterfi eld, M.J.Misner, D.Y.Ryu, T.Emrick, T.P.Russell, Nano Lett.2005, 5, 357.
[37] E.Kumacheva, R.K.Golding, M.Allard, E.H.Sargent, Adv.Mater. 2002, 14, 221.
[38] M.Wei, Z.Tao, X.Xiong, M.Kim, J.Lee, S.Somu, S.Sengupta, A.Busnaina, C.Barry, J.Mead, Macromol.Rapid Commun.2006, 27, 1826.
[39] a) D.Schwartz, S.Steinberg, J.Israelachvili, J.Zasadzinski, Phys.Rev.Lett.1992, 69, 3354; b) W.Yang, P.Thordarson, J.J.Gooding, S.P.Ringer, F.Braet, Nanotechnology 2007, 18, 412001.
[40] S.Siavoshi, C.Yilmaz, S.Somu, T.Musacchio, J.R.Upponi, V.P.Torchilin, A.Busnaina, Langmuir 2011, 27, 7301.
[41] E.Artukovic, M.Kaempgen, D.Hecht, S.Roth, G.Grüner, NanoLett.2005, 5, 757.
[42] L.Hu, D.Hecht, G.Grüner, Nano Lett.2004, 4, 2513.
[43] M.Fuhrer, J.Nygård, L.Shih, M.Forero, Y.G.Yoon, H.J.Choi, J.Ihm, S.G.Louie, A.Zettl, P.L.McEuen, Science 2000, 288,
494.
[44] J.J.Gooding, A.Chou, J.Liu, D.Losic, J.G.Shapter, D.B.Hibbert,Electrochem.Commun.2007, 9, 1677.
[45] A.Chou, T.Böcking, N.K.Singh, J.J.Gooding, Chem.Commun. 2005, 7, 842.
[46] D.Hines, V.Ballarotto, E.Williams, Y.Shao, S.Solin, J.Appl.Phys. 2007, 101, 024503.
[47] H.Park, A.Afzali, S.-J.Han, G.S.Tulevski, A.D.Franklin, J.Tersoff, J.B.Hannon, W.Haensch, Nat.Nanotechnol.2012, 7, 787.
[48] S.Somu, H.Wang, Y.Kim, L.Jaberansari, M.G.Hahm, B.Li, T.Kim, X.Xiong, Y.J.Jung, M.Upmanyu, A.Busnaina, ACS Nano 2010, 4, 4142.
[49] L.Jaber-Ansari, M.G.Hahm, T.H.Kim, S.Somu, A.Busnaina, Y.J.Jung, Appl.Phys.A 2009, 96, 373.
[50] B.Li, M.G.Hahm, Y.L.Kim, H.Y.Jung, S.Kar, Y.J.Jung, ACS Nano 2011, 5, 4826.
[51] B.Li, H.Y.Jung, H.Wang, Y.L.Kim, T.Kim, M.G.Hahm, A.Busnaina, M.Upmanyu, Y.J.Jung, Adv.Funct.Mater.2011, 21, 1810.
[52] M.A.Meitl, Z.T.Zhu, V.Kumar, K.J.Lee, X.Feng, Y.Y.Huang, I.Adesida, R.G.Nuzzo, J.A.Rogers, Nat.Mater.2005, 5, 33.
[53] F.N.Ishikawa, H.Chang, K.Ryu, P.Chen, A.Badmaev, L.GomezDe Arco, G.Shen, C.Zhou, ACS Nano 2008, 3, 73.
[54] N.Inagaki, Plasma Surface Modifi cation and Plasma Polymerization, CRC, Boca Raton, FL, USA 1996.
[55] E.Liston, L.Martinu, M.Wertheimer, J.Adhes.Sci.Technol.1993, 7, 1091.
[56] T.Tsai, C.Lee, N.Tai, W.Tuan, Appl.Phys.Lett.2009, 95, 013107.
[57] J.G.Bai, Z.Z.Zhang, J.N.Calata, G.-Q.Lu, IEEE Trans.Compon.Packag.Technol.2006, 29, 589.
[58] J.G.Toffaletti, Crit.Rev.Clin.Lab.Sci.1991, 28, 253.
[59] J.-L.Vincent, P.Dufaye, J.Berré, M.Leeman, J.-P.Degaute, R.J.Kahn, Crit.Care Med.1983, 11, 449.
[60] R.Henning, M.Weil, F.Weiner, Circ.Shock 1982, 9, 307.

Micro/Bio/Nano Fluidics

Micro/Bio/Nano Fluidics

기계적, 유체적, 광학적 및 전자적 기능을 매우 작은 패키지에 통합한 현대적인 마이크로 유체 장치는 비용, 규모 및 대규모 시스템에 직접 통합하는 능력 면에서 기존 장치에 비해 중요한 장점을 가지고 있다. 3D모델링 및 시각화는 풍부한 기능을 제공하는 효율적인 도구이다. Ivy분석을 통해 연구 시간, 설계 및 생산 비용을 크게 절감할 수 있습니다. 마이크로, 바이오 및 나노 유체 역학은 FLOW-3D의 자유 표면 및 다중 유체 모델링 기능으로 쉽고 정확하게 시뮬레이션할 수 있습니다. 이 섹션의 시뮬레이션을 통해 보다 잘 이해할 수 있는 다양한 애플리케이션과 프로세스를 살펴보시기 바랍니다.

FLOW-3D는 시각적 관찰과 양호한 정량적 추세 예측을 바탕으로 우수한 정성적 합의를 제공했습니다. 마찬가지로 중요한 것은 소프트웨어가 설계 민감도를 정확하게 예측한다는 점이다. 그 결과, FLOW-3D는 Kodak의 고급 연구 개발 작업을 지원하는 데 유용한 통찰력을 제공했습니다.

FLOW-3D는 시각적 관찰과 양호한 정량적 추세 예측을 바탕으로 우수한 정성적 합의를 제공했습니다. 마찬가지로 중요한 것은 소프트웨어가 설계 민감도를 정확하게 예측한다는 점이다. 그 결과, FLOW-3D는 Kodak의 고급 연구 개발 작업을 지원하는 데 유용한 통찰력을 제공했습니다.

Christopher Delametter, Senior Research Scientist, Eastman Kodak Company

Acoustophoresis
Acoustophoresis
Microfluidics palette
Cell Behavior
Microfluidics particle sorting using hydrodynamics
Continuous Flow Microfluidics
Digital microfluidics
Digital Microfluidics
Droplet based microfluidics
Droplet Based Microfluidics
Optofluidics
Optofluidics
Phase change
Phase Change

Customer Case Studies

육안으로 볼 수 있는 것보다 더 작은 도전은 FLOW-3D를 사용하여 미세 유체 소자 응용 프로그램을 모델링하는 고객들이 매일 직면하는 과제입니다. FLOW-3D를 통해 이러한 엔지니어와 과학자들은 실험실에서 복제할 수 없는 것을 모델링하고, 생명을 구하는 의료 기기를 검증하고, 잉크젯 형성을 연구하며, 경우에 따라 육안 모델을 제작할 수 있습니다. 때로는 가장 작은 문제가 가장 큰 문제이기도 하지만, FLOW-3D가 도움이 될 수 있습니다.

CFD analysis of stem cell culture
Advances in Nanotechnology
Computational analysis drop formation low viscosity
Computational Analysis of Drop Formation and Detachment
Inkjet formations simulations
Inkjet Printhead Performance
Thermal bubble model
Kodak Develops New Printhead Design in 1/3rd the Time
Photonic switching platform
Microscopic Bubbles Switch Fiber-Optic Circuits
Blood volumetric fraction
Optimization of Magnetic Blood Cleansing Microdevices

관련 기술자료

Fig.1 Schematic diagram of the novel cytometric device

Fabrication and Experimental Investigation of a Novel 3D Hydrodynamic Focusing Micro Cytometric Device

Yongquan Wang*a , Jingyuan Wangb, Hualing Chenc School of Mechanical Engineering, Xi’an Jiaotong University, Xi’an, Shaanxi, 710049, P. R. Chinaa ...
더 보기
Figure 1. (a) Top view of the microfluidic-magnetophoretic device, (b) Schematic representation of the channel cross-sections studied in this work, and (c) the magnet position relative to the channel location (Sepy and Sepz are the magnet separation distances in y and z, respectively).

Continuous-Flow Separation of Magnetic Particles from Biofluids: How Does the Microdevice Geometry Determine the Separation Performance?

by  Cristina González Fernández1, Jenifer Gómez Pastora2, Arantza Basauri1, Marcos Fallanza1, Eugenio Bringas1, Jeffrey J. Chalmers2 and Inmaculada Ortiz1,* 1Department of Chemical and Biomolecular Engineering, ETSIIT, ...
더 보기
Fluid velocity magnitude including velocity vectors and blood volumetric fraction contours for scenario 3: (a,b) Magnet distance d = 0; (c,d) Magnet distance d = 1 mm.

Numerical Analysis of Bead Magnetophoresis from Flowing Blood in a Continuous-Flow Microchannel: Implications to the Bead-Fluid Interactions

Jenifer Gómez-Pastora,  Ioannis H. Karampelas,  Eugenio Bringas,  Edward P. Furlani &  Inmaculada Ortiz  Scientific Reports volume 9, Article number: 7265 (2019) Cite this article Abstract 이 연구에서는 ...
더 보기
Fig. 12. Comparison of simulation results with experimental data for a flow rate of water = Ql=15 ml/hr and a flow rate of air = Qg =3 ml/hr.

Simulation of Droplet Dynamics and Mixing in Microfluidic Devices using a VOF-Based Method

A. Chandorkar Published 2009 Abstract This paper demonstrates that the Volume of Fluid (TruVOF) method in FLOW-3D (a general purpose CFD ...
더 보기
Figure 1. Cross-sectional dimensions of a V-groove channel

Modeling Open Surface Microfluidics

개방형 표면 미세 유체 모델링 Open surface microfluidic systems are becoming increasingly popular in the fields of biology, biotechnology, medicine, ...
더 보기
Fig.4 Schematic of a package structure

Three-Dimensional Flow Analysis of a Thermosetting Compound during Mold Filling

Junichi Saeki and Tsutomu KonoProduction Engineering Research Laboratory, Hitachi Ltd.292, Y shida-cho, Totsuka-ku, Yokohama, 244-0817 Japan Abstract Thermosetting molding compounds ...
더 보기
The Simulation of Droplet Impact on the Super-Hydrophobic Surface with Micro-Pillar Arrays Fabricated by Laser Irradiation and Silanization Processes

The simulation of droplet impact on the super-hydrophobic surface with micro-pillar arrays fabricated by laser irradiation and silanization processes

레이저 조사 및 silanization 공정으로 제작된 micro-pillar arrays를 사용하여 초 소수성 표면에 대한 액적 영향 시뮬레이션 ZhenyanXiaa YangZhaoa ZhenYangabc ChengjuanYangab ...
더 보기
A new dynamic masking technique for time resolved PIV analysis

A new dynamic masking technique for time resolved PIV analysis

시간 분해 PIV 분석을위한 새로운 동적 마스킹 기술 물체 가시성을 허용하기 위해 형광 코팅과 결합 된 새로운 프리웨어 레이 캐스팅 ...
더 보기
On the role of the powder stream on the heat and fluid flow conditions during Directed Energy Deposition of maraging steel-Fig3

On the role of the powder stream on the heat and fluid flow conditions during Directed Energy Deposition of maraging steel—Multiphysics modeling and experimental validation

MohamadBayataVenkata K.NadimpalliaFrancesco G.BiondaniaSinaJafarzadehbJesperThorborgaNiels S.TiedjeaGiulianoBissaccoaDavid B.PedersenaJesper H.Hattela a Department of Mechanical Engineering, Technical University of Denmark, Building 425, Lyngby, Denmark b Department ...
더 보기
Fig. 2: Scheme of the LED photo-crosslinking and 3D-printing section of the microfluidic/3D-printing device. The droplet train is transferred from the chip microchannel into a microtubing in a straight section with nearly identical inner channel and inner microtubing diameter. Further downstream, the microtubing passes an LED-section for fast photo cross-linking to generate the microgels. This section is contained in an aluminum encasing to avoid premature crosslinking of polymer precursor in upstream channel sections by stray light. Subsequently, the microtubing is integrated into a 3D-printhead, where the microgels are jammed into a filament that is directly 3D-printed into the scaffold.

On-chip fabrication and in-flow 3D-printing of cellladen microgel constructs: From chip to scaffold materials in one integral process

cellladen 마이크로 겔 구조의 온칩 제작 및 인플 로우 3D 프린팅 : 하나의 통합 프로세스에서 칩에서 스캐폴드 재료까지 Benjamin Reineke ...
더 보기

Advances in Nanotechnology

Advances in Nanotechnology

This article was contributed by Prof. Edward Furlani and his students from the University at Buffalo, SUNY.

Microfluidics와 nanofluidics는 나노와 나노사이의 기능을 가진 재료와 시스템을 통한 유체 흐름의 과학과 기술을 포함하는 분야입니다. 최근 몇 년 사이에 이 분야의 연구는 재료 개발과 시스템의 급속한 발전된 유체공정의 독특한 이점으로 증가해 왔습니다. Microfluidic 및 nanofluidic 시스템은 화학 반응, 유체 가열, 혼합 및 감지와 같은 순차적 또는 다중화된 공정을 포함할 수 있는 응용 분야에서 마이크로 사이즈의 유체 유동은 매우 효율적이고 반복 가능하며 신속한 처리를 가능하게 합니다. 풀 라니 (Furlani) 교수 그룹의 연구는 새로운 공정 및 장치 개발에 대한 모델링 및 시뮬레이션을 보여줍니다. 이 연구의 대부분은 뉴턴 및 비 뉴턴 유체, 열 전달, 상변화 분석, 자유표면 및 다상분석, 유체와 관련된 유체 현상을 연구하기 위해 최첨단 전산 유체역학을 강조합니다. 매체 상호작용, 다공성 매체를 통한 유동, 완전히 결합된 유체구조 및 입자, 유체 상호작용에 대해 콜로이드. 국제 나노 기술 학술 대회에서 3 편의 논문이 발표될 예정입니다. 2014년 6월 15일부터 18 일까지 워싱턴 DC의 Gaylord National Hotel 및 Convention Center에서 개최됩니다. 이들은 버팔로 대학교 (University at Buffalo)에서 진행되는 획기적인 결과를 선보입니다. 여기에서는 이러한 작품의 미리 보기와 FLOW-3D로 생성된 시뮬레이션 결과 중 일부를 제시합니다.

Analysis of Stem Cell Culture Performance in a Microcarrier Bioreactor System

Koushik Ponnuru1, Jincheng Wu1, Preeti Ashok1, Emmanuel S. Tzanakakis1,3,4,5,6 and Edward P. Furlani1,2

1Dept. of Chemical and Biological Engineering, 2 Dept. of Electrical Engineering, 3Dept. of Biomedical Engineering, 4New York State Center of Excellence in Bioinformatics and Life Sciences, 5Western New York Stem Cell Culture and Analysis Center, 6Genetics, Genomics and Bioinformatics, University at Buffalo, SUNY

(left) Shear stress distribution along with velocity vectors in a cross sectional plane of the bioreactor running at 60 rpm; (right) Kolmogorov length scale distribution at the same plane under the same conditions.

CFD 기반 시뮬레이션과 실험결과의 조합으로 교반 탱크의 마이크로 캐리어 생물 반응기 시스템에서 세포 배양에 대한 난류 전단응력의 영향에 대한 분석을 제시합니다. Corning’s bench-scale spinner flask의 3D 계산 모델은 최첨단 CFD 소프트웨어 인 FLOW-3D를 사용하여 제작되었습니다. 임펠러 속도, 배양액 및 입자 크기와 같은 매개변수가 마이크로 캐리어 입자에 작용되는 전단응력에 미치는 영향을 CFD 분석을 사용하여 연구하였습니다. 이것은 세포가 겪는 정확한 전단 조건을 예측하고 세포의 손상을 방지하는 최적의 작동조건을 확인하는데 사용됩니다. 또한, 다원능 마커 Oct4, Sox2 및 Nanog를 운반하는 세포의 비율을 세포 계측법 및 정량적 PCR을 사용하여 측정함으로써 hPSCs의 다능성 전단효과를 연구합니다.

Numerical Analysis of Fully-Coupled Particle-Fluid Transport and Free-Flow Magnetophoretic Sorting in Microfluidic Systems

Chenxu Liu1, Xiaozheng Xue1 and Edward P. Furlani 1,2

1Dept. of Chemical and Biological Engineering, 2Dept. of Electrical Engineering, University at Buffalo, SUNY

Magnetic nanoparticle chaining and rotating following an external field and causing the mixing of two different molecular concentrations.

Magnetic 입자는 생체 의학 및 임상 진단 응용을 위해 생체 재료를 선택적으로 분리 및 분류하는 마이크로 유체시스템에 점점 더 많이 사용되고 있습니다. 그러한 시스템의 합리적인 설계에 사용될 수 있는 전산모델이 도입되었습니다. 이 모델은 자기 및 유체 역학적 힘, 완전 결합 입자 – 유체 상호 작용 및 입자의 자기 조립을 유도하는 자기 쌍극자와 쌍극자의 상호 작용을 비롯한 입자 수송에 대한 지배적 메커니즘을 고려합니다. 응용 프로그램을 통해 연속흐름 분리시스템 및 회전 조립 체인을 기반으로 하는 미세 유체 혼합프로세스로 시연됩니다.

Numerical Analysis of Laser Induced Photothermal Effects using Colloidal Plasmonic Nanostructures

Ioannis H. Karampelas1, Young Hwa Kim2 and Edward P. Furlani 1,2

1Dept. of Chemical and Biological Engineering, 2 Dept. of Electrical Engineering, University at Buffalo, SUNY

Photothermal heat cycle of a nanocage (a=50nm, t=5nm) (perspective 1/8 view): plot of nanocage temperature vs. time, pulse duration indicated by the red arrow and dashed line and inset plots showing various phases of the thermo -fluidic cycle: (a) nanobubble formation, (b) nanobubble (maximum size), (c) nanobubble collapse, (d) cooling.

Colloidal 귀금속 (plasmonic) 나노 구조는 나노 입자 합성에서부터 바이오 이미징 (bioimaging), 의학 요법 (medical therapy)에 이르기까지 다양한 광열 (photothermal) 분야에서 점점 더 많이 사용되고 있습니다. 많은 응용분야에서, 펄스 레이저는 plasmonic 공진 주파수에서 나노 구조를 사용하며, 이는 광자의 흡수 및 고도로 국부화된 파장필드의 향상을 가져옵니다. 원격 소스로부터 효율적인 나노 스케일 가열하는 것 외에도, 합성동안 나노 입자의 구조를 조정함으로써 근적외선 스펙트럼을 통한 공진 가열파장을 조정할 수 있습니다. 우리 그룹은 nanosecond-pulsed, laser-heated colloidal metallic nanoparticles 및 열 유체 거동을 예측하는 전산모델을 개발했습니다. 이 모델은 플라즈몬 공명, 입자에서 주변 유체로의 열 전달 및 균일한 기포 핵 형성을 유도하는 유체의 위상변화에서 나노 입자 내의 에너지 전환을 시뮬레이션 하는데 사용되었습니다. nanorods, nanotori, nanorings 및 nanocages 등 다양한 nanoparticle 형상이 연구되었습니다. 이 분석은 레이저 강도, 입사 파장, 편광, 펄스 지속 시간 및 나노 입자의 방향 및 모양과 같은 공정 매개 변수가 광열 공정을 최적화하도록 조정될 수 있음을 보여줍니다. Plasmonic nanoparticles는 악성 조직의 약물 치료, 약물 전달 및 생체치료에 사용됩니다.

Advances in Nanotechnology

Advances in Nanotechnology

This article was contributed by Prof. Edward Furlani and his students from the University at Buffalo, SUNY.

 

Microfluidics와 nanofluidics는 나노와 나노사이의 기능을 가진 재료와 시스템을 통한 유체 흐름의 과학과 기술을 포함하는 분야입니다. 최근 몇 년 사이에 이 분야의 연구는 재료 개발과 시스템의 급속한 발전된 유체공정의 독특한 이점으로 증가해 왔습니다. Microfluidic 및 nanofluidic 시스템은 화학 반응, 유체 가열, 혼합 및 감지와 같은 순차적 또는 다중화된 공정을 포함할 수 있는 응용 분야에서 마이크로 사이즈의 유체 유동은 매우 효율적이고 반복 가능하며 신속한 처리를 가능하게 합니다. 풀 라니 (Furlani) 교수 그룹의 연구는 새로운 공정 및 장치 개발에 대한 모델링 및 시뮬레이션을 보여줍니다. 이 연구의 대부분은 뉴턴 및 비 뉴턴 유체, 열 전달, 상변화 분석, 자유표면 및 다상분석, 유체와 관련된 유체 현상을 연구하기 위해 최첨단 전산 유체역학을 강조합니다. 매체 상호작용, 다공성 매체를 통한 유동, 완전히 결합된 유체구조 및 입자, 유체 상호작용에 대해 콜로이드. 국제 나노 기술 학술 대회에서 3 편의 논문이 발표될 예정입니다. 2014년 6월 15일부터 18 일까지 워싱턴 DC의 Gaylord National Hotel 및 Convention Center에서 개최됩니다. 이들은 버팔로 대학교 (University at Buffalo)에서 진행되는 획기적인 결과를 선보입니다. 여기에서는 이러한 작품의 미리 보기와 FLOW-3D로 생성된 시뮬레이션 결과 중 일부를 제시합니다.

Analysis of Stem Cell Culture Performance in a Microcarrier Bioreactor System

Koushik Ponnuru1, Jincheng Wu1, Preeti Ashok1, Emmanuel S. Tzanakakis1,3,4,5,6 and Edward P. Furlani1,2

1Dept. of Chemical and Biological Engineering, 2 Dept. of Electrical Engineering, 3Dept. of Biomedical Engineering, 4New York State Center of Excellence in Bioinformatics and Life Sciences, 5Western New York Stem Cell Culture and Analysis Center, 6Genetics, Genomics and Bioinformatics, University at Buffalo, SUNY

(left) Shear stress distribution along with velocity vectors in a cross sectional plane of the bioreactor running at 60 rpm; (right) Kolmogorov length scale distribution at the same plane under the same conditions.

CFD 기반 시뮬레이션과 실험결과의 조합으로 교반 탱크의 마이크로 캐리어 생물 반응기 시스템에서 세포 배양에 대한 난류 전단응력의 영향에 대한 분석을 제시합니다. Corning’s bench-scale spinner flask의 3D 계산 모델은 최첨단 CFD 소프트웨어 인 FLOW-3D를 사용하여 제작되었습니다. 임펠러 속도, 배양액 및 입자 크기와 같은 매개변수가 마이크로 캐리어 입자에 작용되는 전단응력에 미치는 영향을 CFD 분석을 사용하여 연구하였습니다. 이것은 세포가 겪는 정확한 전단 조건을 예측하고 세포의 손상을 방지하는 최적의 작동조건을 확인하는데 사용됩니다. 또한, 다원능 마커 Oct4, Sox2 및 Nanog를 운반하는 세포의 비율을 세포 계측법 및 정량적 PCR을 사용하여 측정함으로써 hPSCs의 다능성 전단효과를 연구합니다.

 

Numerical Analysis of Fully-Coupled Particle-Fluid Transport and Free-Flow Magnetophoretic Sorting in Microfluidic Systems

Chenxu Liu1, Xiaozheng Xue1 and Edward P. Furlani 1,2

1Dept. of Chemical and Biological Engineering, 2Dept. of Electrical Engineering, University at Buffalo, SUNY

Magnetic nanoparticle chaining and rotating following an external field and causing the mixing of two different molecular concentrations.

 

Magnetic 입자는 생체 의학 및 임상 진단 응용을 위해 생체 재료를 선택적으로 분리 및 분류하는 마이크로 유체시스템에 점점 더 많이 사용되고 있습니다. 그러한 시스템의 합리적인 설계에 사용될 수 있는 전산모델이 도입되었습니다. 이 모델은 자기 및 유체 역학적 힘, 완전 결합 입자 – 유체 상호 작용 및 입자의 자기 조립을 유도하는 자기 쌍극자와 쌍극자의 상호 작용을 비롯한 입자 수송에 대한 지배적 메커니즘을 고려합니다. 응용 프로그램을 통해 연속흐름 분리시스템 및 회전 조립 체인을 기반으로 하는 미세 유체 혼합프로세스로 시연됩니다.

 

Numerical Analysis of Laser Induced Photothermal Effects using Colloidal Plasmonic Nanostructures

Ioannis H. Karampelas1, Young Hwa Kim2 and Edward P. Furlani 1,2

1Dept. of Chemical and Biological Engineering, 2 Dept. of Electrical Engineering, University at Buffalo, SUNY

 

Photothermal heat cycle of a nanocage (a=50nm, t=5nm) (perspective 1/8 view): plot of nanocage temperature vs. time, pulse duration indicated by the red arrow and dashed line and inset plots showing various phases of the thermo -fluidic cycle: (a) nanobubble formation, (b) nanobubble (maximum size), (c) nanobubble collapse, (d) cooling.

Colloidal 귀금속 (plasmonic) 나노 구조는 나노 입자 합성에서부터 바이오 이미징 (bioimaging), 의학 요법 (medical therapy)에 이르기까지 다양한 광열 (photothermal) 분야에서 점점 더 많이 사용되고 있습니다. 많은 응용분야에서, 펄스 레이저는 plasmonic 공진 주파수에서 나노 구조를 사용하며, 이는 광자의 흡수 및 고도로 국부화된 파장필드의 향상을 가져옵니다. 원격 소스로부터 효율적인 나노 스케일 가열하는 것 외에도, 합성동안 나노 입자의 구조를 조정함으로써 근적외선 스펙트럼을 통한 공진 가열파장을 조정할 수 있습니다. 우리 그룹은 nanosecond-pulsed, laser-heated colloidal metallic nanoparticles 및 열 유체 거동을 예측하는 전산모델을 개발했습니다. 이 모델은 플라즈몬 공명, 입자에서 주변 유체로의 열 전달 및 균일한 기포 핵 형성을 유도하는 유체의 위상변화에서 나노 입자 내의 에너지 전환을 시뮬레이션 하는데 사용되었습니다. nanorods, nanotori, nanorings 및 nanocages 등 다양한 nanoparticle 형상이 연구되었습니다. 이 분석은 레이저 강도, 입사 파장, 편광, 펄스 지속 시간 및 나노 입자의 방향 및 모양과 같은 공정 매개 변수가 광열 공정을 최적화하도록 조정될 수 있음을 보여줍니다. Plasmonic nanoparticles는 악성 조직의 약물 치료, 약물 전달 및 생체치료에 사용됩니다.