The Experts below are selected from a list of 801 Experts worldwide ranked by ideXlab platform
Anthony Williams - One of the best experts on this subject based on the ideXlab platform.
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correction corrigendum separable bilayer microfiltration device for viable label free enrichment of circulating tumour cells
Scientific Reports, 2015Co-Authors: Mingda Zhou, Anthony Williams, Bo Lu, Ramdane Harouaka, Brett Schrand, Siddarth Rawal, Zheng Ao, Randall Brenneman, Eli Gilboa, Shuwen WangAbstract:The analysis of circulating tumour cells (CTCs) in cancer patients could provide important information for therapeutic management. Enrichment of viable CTCs could permit performance of functional analyses on CTCs to broaden understanding of metastatic disease. However, this has not been widely accomplished. Addressing this challenge, we present a separable bilayer (SB) Microfilter for viable size-based CTC capture. Unlike other single-layer CTC Microfilters, the precise gap between the two layers and the architecture of pore alignment result in drastic reduction in mechanical stress on CTCs, capturing them viably. Using multiple cancer cell lines spiked in healthy donor blood, the SB Microfilter demonstrated high capture efficiency (78–83%), high retention of cell viability (71–74%), high tumour cell enrichment against leukocytes (1.7–2 × 103), and widespread ability to establish cultures post-capture (100% of cell lines tested). In a metastatic mouse model, SB Microfilters successfully enriched viable mouse CTCs from 0.4–0.6 mL whole mouse blood samples and established in vitro cultures for further genetic and functional analysis. Our preliminary studies reflect the efficacy of the SB Microfilter device to efficiently and reliably enrich viable CTCs in animal model studies, constituting an exciting technology for new insights in cancer research.
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Fourier ptychographic microscopy for filtration-based circulating tumor cell enumeration and analysis
2014Co-Authors: Ram Datar, Siddarth Rawal, Jaebum Chung, Guoan Zheng, Changhuei Yang, Richard Cote, Anthony WilliamsAbstract:Abstract. Circulating tumor cells (CTCs) are recognized as a candidate biomarker with strong prognostic and predictive potential in metastatic disease. Filtration-based enrichment technologies have been used for CTC characterization, and our group has previously developed a membrane Microfilter device that demonstrates efficacy in model systems and clinical blood samples. However, uneven filtration surfaces make the use of standard microscopic techniques a difficult task, limiting the performance of automated imaging using commercially available technologies. Here, we report the use of Fourier ptychographic microscopy (FPM) to tackle this challenge. Employing this method, we were able to obtain high-resolution color images, including amplitude and phase, of the Microfilter samples over large areas. FPM's ability to perform digital refocusing on complex images is particularly useful in this setting as, in contrast to other imaging platforms, we can focus samples on multiple focal planes within the same frame despite surface unevenness. In model systems, FPM demonstrates high image quality, efficiency, and consistency in detection of tumor cells when comparing corresponding Microfilter samples to standard microscopy with high correlation (R 2 ¼ 0.99932). Based on these results, we believe that FPM will have important implications for improved, high throughput, filtration-based CTC analysis, and, more generally, image analysis of uneven surfaces. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI
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a novel precision engineered microfiltration device for capture and characterisation of bladder cancer cells in urine
European Journal of Cancer, 2013Co-Authors: Marc Birkhahn, Ram Datar, Anthony Williams, Anirban P Mitra, Nancy J Barr, Eila C Skinner, John P Stein, Donald G Skinner, Yuchong Tai, Richard J CoteAbstract:Background: Sensitivity of standard urine cytology for detecting urothelial carcinoma of the bladder (UCB) is low, attributable largely to its inability to process entire samples, paucicellularity and presence of background cells. Objective: Evaluate performance and practical applicability of a novel portable microfiltration device for capture, enumeration and characterisation of exfoliated tumour cells in urine, and compare it with standard urine cytology for UCB detection. Methods: A total of 54 urine and bladder wash samples from patients undergoing surveillance for UCB were prospectively evaluated by standard and Microfilter-based urine cytology. Head-to-head comparison of quality and performance metrics, and cost effectiveness was conducted for both methodologies. Results: Five samples were paucicellular by standard cytology; no samples processed by Microfilter cytology were paucicellular. Standard cytology had 33.3% more samples with background cells that limited evaluation (p < 0.001). Microfilter cytology was more concordant (κ = 50.4%) than standard cytology (κ = 33.5%) with true UCB diagnosis. Sensitivity, specificity and accuracy were higher for Microfilter cytology compared to standard cytology (53.3%/100%/79.2% versus 40%/95.8%/69.9%, respectively). Microfilter-captured cells were amenable to downstream on-chip molecular analyses. A 40 ml sample was processed in under 4 min by Microfilter cytology compared to 5.5 min by standard cytology. Median Microfilter cytology processing and set-up costs were approximately 63% cheaper and 80 times lower than standard cytology, respectively. Conclusions: The microfiltration device represents a novel non-invasive UCB detection system that is economical, rapid, versatile and has potentially better quality and performance metrics than routine urine cytology, the current standard-of-care.
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3D Microfilter device for viable circulating tumor cell (CTC) enrichment from blood
Biomedical Microdevices, 2011Co-Authors: Siyang Zheng, Henry K. Lin, Ram Datar, Anthony Williams, Bo Lu, Richard J CoteAbstract:Detection of circulating tumor cells has emerged as a promising minimally invasive diagnostic and prognostic tool for patients with metastatic cancers. We report a novel three dimensional Microfilter device that can enrich viable circulating tumor cells from blood. This device consists of two layers of parylene membrane with pores and gap precisely defined with photolithography. The positions of the pores are shifted between the top and bottom membranes. The bottom membrane supports captured cells and minimize the stress concentration on cell membrane and sustain cell viability during filtration. Viable cell capture on device was investigated with scanning electron microscopy, confocal microscopy, and immunofluorescent staining using model systems of cultured tumor cells spiked in blood or saline. The paper presents and validates this new 3D microfiltration concept for circulation tumor cell enrichment application. The device provides a highly valuable tool for assessing and characterizing viable enriched circulating tumor cells in both research and clinical settings.
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Portable Filter-Based Microdevice for Detection and Characterization of Circulating Tumor Cells
Clinical Cancer Research, 2010Co-Authors: Henry K. Lin, Ram Datar, Siyang Zheng, Anthony Williams, Marija Balic, Susan Groshen, Howard I. Scher, Martin Fleisher, Walter M. Stadler, Yuchong TaiAbstract:Purpose: Sensitive detection and characterization of circulating tumor cells (CTC) could revolutionize the approach to patients with early-stage and metastatic cancer. The current methodologies have significant limitations, including limited capture efficiency and ability to characterize captured cells. Here, we report the development of a novel parylene membrane filter-based portable microdevice for size-based isolation with high recovery rate and direct on-chip characterization of captured CTC from human peripheral blood. Experimental Design: We evaluated the sensitivity and efficiency of CTC capture in a model system using blood samples from healthy donors spiked with tumor cell lines. Fifty-nine model system samples were tested to determine the recovery rate of the microdevice. Moreover, 10 model system samples and 57 blood samples from cancer patients were subjected to both membrane Microfilter device and CellSearch platform enumeration for direct comparison. Results: Using the model system, the microdevice achieved >90% recovery with probability of 95% recovering at least one cell when five are seeded in 7.5 mL of blood. CTCs were identified in 51 of 57 patients using the microdevice, compared with only 26 patients with the CellSearch method. When CTCs were detected by both methods, greater numbers were recovered by the Microfilter device in all but five patients. Conclusions: This filter-based microdevice is both a capture and analysis platform, capable of multiplexed imaging and genetic analysis. The microdevice presented here has the potential to enable routine CTC analysis in the clinical setting for the effective management of cancer patients.
Ram Datar - One of the best experts on this subject based on the ideXlab platform.
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Fourier ptychographic microscopy for filtration-based circulating tumor cell enumeration and analysis
2014Co-Authors: Ram Datar, Siddarth Rawal, Jaebum Chung, Guoan Zheng, Changhuei Yang, Richard Cote, Anthony WilliamsAbstract:Abstract. Circulating tumor cells (CTCs) are recognized as a candidate biomarker with strong prognostic and predictive potential in metastatic disease. Filtration-based enrichment technologies have been used for CTC characterization, and our group has previously developed a membrane Microfilter device that demonstrates efficacy in model systems and clinical blood samples. However, uneven filtration surfaces make the use of standard microscopic techniques a difficult task, limiting the performance of automated imaging using commercially available technologies. Here, we report the use of Fourier ptychographic microscopy (FPM) to tackle this challenge. Employing this method, we were able to obtain high-resolution color images, including amplitude and phase, of the Microfilter samples over large areas. FPM's ability to perform digital refocusing on complex images is particularly useful in this setting as, in contrast to other imaging platforms, we can focus samples on multiple focal planes within the same frame despite surface unevenness. In model systems, FPM demonstrates high image quality, efficiency, and consistency in detection of tumor cells when comparing corresponding Microfilter samples to standard microscopy with high correlation (R 2 ¼ 0.99932). Based on these results, we believe that FPM will have important implications for improved, high throughput, filtration-based CTC analysis, and, more generally, image analysis of uneven surfaces. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI
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a novel precision engineered microfiltration device for capture and characterisation of bladder cancer cells in urine
European Journal of Cancer, 2013Co-Authors: Marc Birkhahn, Ram Datar, Anthony Williams, Anirban P Mitra, Nancy J Barr, Eila C Skinner, John P Stein, Donald G Skinner, Yuchong Tai, Richard J CoteAbstract:Background: Sensitivity of standard urine cytology for detecting urothelial carcinoma of the bladder (UCB) is low, attributable largely to its inability to process entire samples, paucicellularity and presence of background cells. Objective: Evaluate performance and practical applicability of a novel portable microfiltration device for capture, enumeration and characterisation of exfoliated tumour cells in urine, and compare it with standard urine cytology for UCB detection. Methods: A total of 54 urine and bladder wash samples from patients undergoing surveillance for UCB were prospectively evaluated by standard and Microfilter-based urine cytology. Head-to-head comparison of quality and performance metrics, and cost effectiveness was conducted for both methodologies. Results: Five samples were paucicellular by standard cytology; no samples processed by Microfilter cytology were paucicellular. Standard cytology had 33.3% more samples with background cells that limited evaluation (p < 0.001). Microfilter cytology was more concordant (κ = 50.4%) than standard cytology (κ = 33.5%) with true UCB diagnosis. Sensitivity, specificity and accuracy were higher for Microfilter cytology compared to standard cytology (53.3%/100%/79.2% versus 40%/95.8%/69.9%, respectively). Microfilter-captured cells were amenable to downstream on-chip molecular analyses. A 40 ml sample was processed in under 4 min by Microfilter cytology compared to 5.5 min by standard cytology. Median Microfilter cytology processing and set-up costs were approximately 63% cheaper and 80 times lower than standard cytology, respectively. Conclusions: The microfiltration device represents a novel non-invasive UCB detection system that is economical, rapid, versatile and has potentially better quality and performance metrics than routine urine cytology, the current standard-of-care.
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3D Microfilter device for viable circulating tumor cell (CTC) enrichment from blood
Biomedical Microdevices, 2011Co-Authors: Siyang Zheng, Henry K. Lin, Ram Datar, Anthony Williams, Bo Lu, Richard J CoteAbstract:Detection of circulating tumor cells has emerged as a promising minimally invasive diagnostic and prognostic tool for patients with metastatic cancers. We report a novel three dimensional Microfilter device that can enrich viable circulating tumor cells from blood. This device consists of two layers of parylene membrane with pores and gap precisely defined with photolithography. The positions of the pores are shifted between the top and bottom membranes. The bottom membrane supports captured cells and minimize the stress concentration on cell membrane and sustain cell viability during filtration. Viable cell capture on device was investigated with scanning electron microscopy, confocal microscopy, and immunofluorescent staining using model systems of cultured tumor cells spiked in blood or saline. The paper presents and validates this new 3D microfiltration concept for circulation tumor cell enrichment application. The device provides a highly valuable tool for assessing and characterizing viable enriched circulating tumor cells in both research and clinical settings.
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Portable Filter-Based Microdevice for Detection and Characterization of Circulating Tumor Cells
Clinical Cancer Research, 2010Co-Authors: Henry K. Lin, Ram Datar, Siyang Zheng, Anthony Williams, Marija Balic, Susan Groshen, Howard I. Scher, Martin Fleisher, Walter M. Stadler, Yuchong TaiAbstract:Purpose: Sensitive detection and characterization of circulating tumor cells (CTC) could revolutionize the approach to patients with early-stage and metastatic cancer. The current methodologies have significant limitations, including limited capture efficiency and ability to characterize captured cells. Here, we report the development of a novel parylene membrane filter-based portable microdevice for size-based isolation with high recovery rate and direct on-chip characterization of captured CTC from human peripheral blood. Experimental Design: We evaluated the sensitivity and efficiency of CTC capture in a model system using blood samples from healthy donors spiked with tumor cell lines. Fifty-nine model system samples were tested to determine the recovery rate of the microdevice. Moreover, 10 model system samples and 57 blood samples from cancer patients were subjected to both membrane Microfilter device and CellSearch platform enumeration for direct comparison. Results: Using the model system, the microdevice achieved >90% recovery with probability of 95% recovering at least one cell when five are seeded in 7.5 mL of blood. CTCs were identified in 51 of 57 patients using the microdevice, compared with only 26 patients with the CellSearch method. When CTCs were detected by both methods, greater numbers were recovered by the Microfilter device in all but five patients. Conclusions: This filter-based microdevice is both a capture and analysis platform, capable of multiplexed imaging and genetic analysis. The microdevice presented here has the potential to enable routine CTC analysis in the clinical setting for the effective management of cancer patients.
Richard J Cote - One of the best experts on this subject based on the ideXlab platform.
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a novel precision engineered microfiltration device for capture and characterisation of bladder cancer cells in urine
European Journal of Cancer, 2013Co-Authors: Marc Birkhahn, Ram Datar, Anthony Williams, Anirban P Mitra, Nancy J Barr, Eila C Skinner, John P Stein, Donald G Skinner, Yuchong Tai, Richard J CoteAbstract:Background: Sensitivity of standard urine cytology for detecting urothelial carcinoma of the bladder (UCB) is low, attributable largely to its inability to process entire samples, paucicellularity and presence of background cells. Objective: Evaluate performance and practical applicability of a novel portable microfiltration device for capture, enumeration and characterisation of exfoliated tumour cells in urine, and compare it with standard urine cytology for UCB detection. Methods: A total of 54 urine and bladder wash samples from patients undergoing surveillance for UCB were prospectively evaluated by standard and Microfilter-based urine cytology. Head-to-head comparison of quality and performance metrics, and cost effectiveness was conducted for both methodologies. Results: Five samples were paucicellular by standard cytology; no samples processed by Microfilter cytology were paucicellular. Standard cytology had 33.3% more samples with background cells that limited evaluation (p < 0.001). Microfilter cytology was more concordant (κ = 50.4%) than standard cytology (κ = 33.5%) with true UCB diagnosis. Sensitivity, specificity and accuracy were higher for Microfilter cytology compared to standard cytology (53.3%/100%/79.2% versus 40%/95.8%/69.9%, respectively). Microfilter-captured cells were amenable to downstream on-chip molecular analyses. A 40 ml sample was processed in under 4 min by Microfilter cytology compared to 5.5 min by standard cytology. Median Microfilter cytology processing and set-up costs were approximately 63% cheaper and 80 times lower than standard cytology, respectively. Conclusions: The microfiltration device represents a novel non-invasive UCB detection system that is economical, rapid, versatile and has potentially better quality and performance metrics than routine urine cytology, the current standard-of-care.
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3D Microfilter device for viable circulating tumor cell (CTC) enrichment from blood
Biomedical Microdevices, 2011Co-Authors: Siyang Zheng, Henry K. Lin, Ram Datar, Anthony Williams, Bo Lu, Richard J CoteAbstract:Detection of circulating tumor cells has emerged as a promising minimally invasive diagnostic and prognostic tool for patients with metastatic cancers. We report a novel three dimensional Microfilter device that can enrich viable circulating tumor cells from blood. This device consists of two layers of parylene membrane with pores and gap precisely defined with photolithography. The positions of the pores are shifted between the top and bottom membranes. The bottom membrane supports captured cells and minimize the stress concentration on cell membrane and sustain cell viability during filtration. Viable cell capture on device was investigated with scanning electron microscopy, confocal microscopy, and immunofluorescent staining using model systems of cultured tumor cells spiked in blood or saline. The paper presents and validates this new 3D microfiltration concept for circulation tumor cell enrichment application. The device provides a highly valuable tool for assessing and characterizing viable enriched circulating tumor cells in both research and clinical settings.
Jie Xu - One of the best experts on this subject based on the ideXlab platform.
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deformability based circulating tumor cell separation with conical shaped Microfilters concept optimization and design criteria
arXiv: Cell Behavior, 2016Co-Authors: Mohammad Aghaamoo, Zhifeng Zhang, Xiaolin Chen, Jie XuAbstract:The ability of detecting and separating CTCs can play a key role in early cancer detection and treatment. In recent years, there has been growing interest in using deformability-based CTC separation Microfilters due to their simplicity and low cost. Most of previous studies in this area are mainly based on experimental work. Although experimental research provides useful insights in designing CTC separation devices, there is still a lack of design guidelines based on fundamental understandings of the cell separation process in the filers. While experimental efforts face challenges especially microfabrication difficulties, we adopt numerical simulation here to study conical-shaped Microfilters using deformability difference between CTCs and blood cells for separation process. We use liquid drop model for modeling a CTC passing through such Microfilters. The accuracy of the model in predicting the pressure signature of the system is validated by comparing with previous experiments. Pressure-deformability analysis of the cell going through the channel is then carried out in detail in order to better understand how a CTC behaves throughout the filtration process. Different system design criteria such as system throughput and unclogging of the system are discussed. Specifically, pressure behavior under different system throughput is analyzed. Regarding the unclogging issue, we define pressure ratio as a key parameter representing the ability to overcome clogging in such CTC separation devices and investigate the effect of conical angle on the optimum pressure ratio. Finally, the effect of unclogging applied pressure on the system performance is examined. Our study provides detailed understandings of the cell separation process and its characteristics, which can be used for developing more efficient CTC separation devices.
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deformability based circulating tumor cell separation with conical shaped Microfilters concept optimization and design criteria
Biomicrofluidics, 2015Co-Authors: Mohammad Aghaamoo, Zhifeng Zhang, Xiaolin Chen, Jie XuAbstract:Circulating tumor cells (CTCs) separation technology has made positive impacts on cancer science in many aspects. The ability of detecting and separating CTCs can play a key role in early cancer detection and treatment. In recent years, there has been growing interest in using deformability-based CTC separation Microfilters due to their simplicity and low cost. Most of the previous studies in this area are mainly based on experimental work. Although experimental research provides useful insights in designing CTC separation devices, there is still a lack of design guidelines based on fundamental understandings of the cell separation process in the filters. While experimental efforts face challenges, especially microfabrication difficulties, we adopt numerical simulation here to study conical-shaped Microfilters using deformability difference between CTCs and blood cells for the separation process. We use the liquid drop model for modeling a CTC passing through such Microfilters. The accuracy of the model in predicting the pressure signature of the system is validated by comparing it with previous experiments. Pressure-deformability analysis of the cell going through the channel is then carried out in detail in order to better understand how a CTC behaves throughout the filtration process. Different system design criteria such as system throughput and unclogging of the system are discussed. Specifically, pressure behavior under different system throughput is analyzed. Regarding the unclogging issue, we define pressure ratio as a key parameter representing the ability to overcome clogging in such CTC separation devices and investigate the effect of conical angle on the optimum pressure ratio. Finally, the effect of unclogging applied pressure on the system performance is examined. Our study provides detailed understandings of the cell separation process and its characteristics, which can be used for developing more efficient CTC separation devices.
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the effects of 3d channel geometry on ctc passing pressure towards deformability based cancer cell separation
Lab on a Chip, 2014Co-Authors: Zhifeng Zhang, Jie Xu, Bin Hong, Xiaolin ChenAbstract:Various lab on a chip devices have been developed recently to detect and separate circulating tumour cells (CTCs) for early stage cancer detection. Because CTCs are extremely rare in the blood, next generation CTC Microfilters aim at significant improvement in both efficiency and throughput. CTC Microfilters based on cell deformability seem to be a promising direction. In the present research, we study a CTC passing event through a micro-filtering channel with various 3D geometries. The pressure signatures for different types of cells passing through different channels are characterized numerically. Specifically, five kinds of cross-sections, circular, square, triangular and two kinds of rectangular channels with aspect ratios of 2 and 5, are studied in this work. The total pressures for cells passing through the channels are calculated and reveal different behaviour from what is predicted by the static surface tension model. Among all five cross-sections studied, the circular cross-section features the highest critical pressure and thus is most suitable for high efficiency CTC separation. The square filtering channel provides the second largest critical pressure, and the triangular cross-section provides the least critical pressure among these three cross-sections. All these three cross-sections are better than the rectangular channels with aspect ratios of 2 and 5. For the rectangular channel, a high aspect ratio channel may lead to cell splitting at high speed, which will result in a periodic pressure signature. Our findings will provide valuable information for the design of next generation CTC Microfilters.
Yuchong Tai - One of the best experts on this subject based on the ideXlab platform.
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a novel precision engineered microfiltration device for capture and characterisation of bladder cancer cells in urine
European Journal of Cancer, 2013Co-Authors: Marc Birkhahn, Ram Datar, Anthony Williams, Anirban P Mitra, Nancy J Barr, Eila C Skinner, John P Stein, Donald G Skinner, Yuchong Tai, Richard J CoteAbstract:Background: Sensitivity of standard urine cytology for detecting urothelial carcinoma of the bladder (UCB) is low, attributable largely to its inability to process entire samples, paucicellularity and presence of background cells. Objective: Evaluate performance and practical applicability of a novel portable microfiltration device for capture, enumeration and characterisation of exfoliated tumour cells in urine, and compare it with standard urine cytology for UCB detection. Methods: A total of 54 urine and bladder wash samples from patients undergoing surveillance for UCB were prospectively evaluated by standard and Microfilter-based urine cytology. Head-to-head comparison of quality and performance metrics, and cost effectiveness was conducted for both methodologies. Results: Five samples were paucicellular by standard cytology; no samples processed by Microfilter cytology were paucicellular. Standard cytology had 33.3% more samples with background cells that limited evaluation (p < 0.001). Microfilter cytology was more concordant (κ = 50.4%) than standard cytology (κ = 33.5%) with true UCB diagnosis. Sensitivity, specificity and accuracy were higher for Microfilter cytology compared to standard cytology (53.3%/100%/79.2% versus 40%/95.8%/69.9%, respectively). Microfilter-captured cells were amenable to downstream on-chip molecular analyses. A 40 ml sample was processed in under 4 min by Microfilter cytology compared to 5.5 min by standard cytology. Median Microfilter cytology processing and set-up costs were approximately 63% cheaper and 80 times lower than standard cytology, respectively. Conclusions: The microfiltration device represents a novel non-invasive UCB detection system that is economical, rapid, versatile and has potentially better quality and performance metrics than routine urine cytology, the current standard-of-care.
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Portable Filter-Based Microdevice for Detection and Characterization of Circulating Tumor Cells
Clinical Cancer Research, 2010Co-Authors: Henry K. Lin, Ram Datar, Siyang Zheng, Anthony Williams, Marija Balic, Susan Groshen, Howard I. Scher, Martin Fleisher, Walter M. Stadler, Yuchong TaiAbstract:Purpose: Sensitive detection and characterization of circulating tumor cells (CTC) could revolutionize the approach to patients with early-stage and metastatic cancer. The current methodologies have significant limitations, including limited capture efficiency and ability to characterize captured cells. Here, we report the development of a novel parylene membrane filter-based portable microdevice for size-based isolation with high recovery rate and direct on-chip characterization of captured CTC from human peripheral blood. Experimental Design: We evaluated the sensitivity and efficiency of CTC capture in a model system using blood samples from healthy donors spiked with tumor cell lines. Fifty-nine model system samples were tested to determine the recovery rate of the microdevice. Moreover, 10 model system samples and 57 blood samples from cancer patients were subjected to both membrane Microfilter device and CellSearch platform enumeration for direct comparison. Results: Using the model system, the microdevice achieved >90% recovery with probability of 95% recovering at least one cell when five are seeded in 7.5 mL of blood. CTCs were identified in 51 of 57 patients using the microdevice, compared with only 26 patients with the CellSearch method. When CTCs were detected by both methods, greater numbers were recovered by the Microfilter device in all but five patients. Conclusions: This filter-based microdevice is both a capture and analysis platform, capable of multiplexed imaging and genetic analysis. The microdevice presented here has the potential to enable routine CTC analysis in the clinical setting for the effective management of cancer patients.
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a cancer detection platform which measures telomerase activity from live circulating tumor cells captured on a Microfilter
Cancer Research, 2010Co-Authors: Yuchong Tai, Amir GoldkornAbstract:Circulating tumor cells (CTC) quantified in cancer patients' blood can predict disease outcome and response to therapy. However, the CTC analysis platforms commonly used cannot capture live CTCs and only apply to tumors of epithelial origin. To address these limitations, we have developed a novel cancer detection platform which measures telomerase activity from live CTCs captured on a parylene-C slot Microfilter. Using a constant low-pressure delivery system, the new Microfilter platform was capable of cell capture from 1 mL of whole blood in less than 5 minutes, achieving 90% capture efficiency, 90% cell viability, and 200-fold sample enrichment. Importantly, the captured cells retained normal morphology by scanning electron microscopy and could be readily manipulated, further analyzed, or expanded on- or off-filter. Telomerase activity—a well-recognized universal cancer marker—was reliably detected by quantitative PCR from as few as 25 cancer cells added into 7.5 mL of whole blood and captured on the Microfilter. Moreover, significant telomerase activity elevation was also measured from patients' blood samples and from single cancer cells lifted off of the Microfilter. Live CTC capture and analysis is fast and simple yet highly quantitative, versatile, and applicable to nearly all solid tumor types, making this a highly promising new strategy for cancer detection and characterization.