Jose I Varillas | University of Florida (original) (raw)
Papers by Jose I Varillas
Scientific Reports, Aug 26, 2020
Journal of clinical and translational science, Sep 1, 2017
[Not an Abstract] The goal of this project is to develop and utilize a microfluidic device to iso... more [Not an Abstract] The goal of this project is to develop and utilize a microfluidic device to isolate and enrich tumor cells circulating in peripheral blood. Circulating tumor cells (CTCs) have been used as biomarkers for cancer diagnostics and prognosis. However, the rarity of these cells (roughly 1 in a billion) poses a technological challenge to sort and concentrate them. CTCs hold potential sources for early detection, characterization, monitoring of cancers, and development of personalized treatment. The project is currently funded by the US National Cancer Institute (NCI) of the National Institutes of Health (NIH).
Scientific Reports, 2020
The methods for isolating rare cells such as circulating tumor cells (CTCs) can be generally clas... more The methods for isolating rare cells such as circulating tumor cells (CTCs) can be generally classified into two categories: those based on physical properties (e.g., size) and methods based on biological properties (e.g., immunoaffinity). CellSearch, the only FDA-approved method for the CTC-based cancer prognosis, relies on immunoaffinity interactions between CTCs and antibodies immobilized on magnetic particles. Immunoaffinity-based CTC isolation has also been employed in microfluidic devices, which show higher capture efficiency than CellSearch. We report here our investigation of combining size-based microfiltration into a microfluidic device with immunoaffinity for enhanced capture efficiency of CTCs. The device consists of four serpentine main channels, and each channel contains an array of lateral filters that create a two-dimensional flow. The main flow is through the serpentine channel, allowing the majority of the sample to pass by while the secondary flow goes through the...
Canadian Journal of Chemistry, 2022
The analysis of circulating tumor cells (CTCs) is important for cancer diagnosis and prognosis. M... more The analysis of circulating tumor cells (CTCs) is important for cancer diagnosis and prognosis. Microfluidics has been employed for CTC analysis due to its scaling advantages and high performance. However, pre-analytical methods for CTC sample preparation are often combined with microfluidic platforms because a large sample volume is required to detect extremely rare CTCs. Among pre-analytical methods, Ficoll-Paque™, OncoQuick™, and RosetteSep™ are commonly used to separate cells of interest. To compare their performance, we spiked L3.6pl pancreatic cancer cells into healthy blood samples and then employed each technique to prepare blood samples, followed by using a microfluidic platform to capture and detect L3.6pl cells. We found these three methods have similar performance, though the slight edge of RosetteSep™ over Ficoll-Paque™ is statistically significant. We also studied the effects of the tumor cell concentrations on the performance of the frequently used Ficoll-Paque™ metho...
2017 IEEE 30th International Conference on Micro Electro Mechanical Systems (MEMS), 2017
This paper reports two microfluidic devices for isolating circulating tumor cells (CTCs) in blood... more This paper reports two microfluidic devices for isolating circulating tumor cells (CTCs) in blood samples of pancreatic cancer patients. These devices consist of micromixers or micropillars for enhancing the interactions between tumor cells and capture agents, which are immobilized onto the surfaces of microchannels and microfeatures. Both antibodies and aptamers, as well as their ensemble, have been explored for tumor cell isolation. The devices have been used for enumerating CTCs and we have correlated the CTC number with the anti-cancer treatment responses in a clinical trial.
Journal of Clinical Oncology
304 Background: Circulating tumor cells (CTCs) represent real time dissemination of solid tumors.... more 304 Background: Circulating tumor cells (CTCs) represent real time dissemination of solid tumors. Historically, CTC enumeration has been challenging to perform successfully in pancreatic cancer (PCa). Using a previously published microfluidic device designed to increase cell capture, we analyzed CTC characteristics in a cohort of newly diagnosed patients with metastatic PCa. Methods: After provision of informed consent, blood samples (7-10mL) were collected within 1 month of treatment initiation. Specimens were processed within 6 hours of collection. A UF developed microfluidic device was used to capture and identify EpCam+ CTCs. Isolated cells were verified as CTCs consistent with FDA-approved definitions (cytokeratin+, DAPI+, CD45-). Statistical analysis was performed using Scheffe’s method along with analysis of variance to test interactions between the clinical demographics and groups. The study was approved by the UF IRB. Results: A cohort of 27 patients had CTC determination a...
Journal of Clinical Oncology
318 Background: The collection and enumeration of circulating tumor cells (CTCs) are feasible in ... more 318 Background: The collection and enumeration of circulating tumor cells (CTCs) are feasible in metastatic breast, prostate and colorectal cancers. CTCs have diagnostic, prognostic and treatment monitoring implications, but have been challenging to detect in pancreatic cancer (PCa). We have proven feasibility of CTCs in PCa. This study is a pilot to assess use of CTCs as a surrogate for imaging response. Methods: Blood samples (7-10mL) from newly diagnosed metastatic PCa were collected within 1 month of treatment initiation (T0) and at repeat scan after 2mo of treatment (T1). Specimens were processed within 6 hours of collection. A UF developed microfluidic device was used to capture and identify EpCam+ CTCs. Isolated cells were verified as CTCs consistent with FDA-approved definitions (cytokeratin+, DAPI+, CD45-). CTC enumeration and changes were correlated with scan RECIST results at T0 and T1. The study was approved by the UF IRB. Results: A total of 16 patients had matched pair...
Biomicrofluidics, 2017
Circulating tumor cells (CTCs) have shown potential for cancer diagnosis and prognosis. Affinity-... more Circulating tumor cells (CTCs) have shown potential for cancer diagnosis and prognosis. Affinity-based CTC isolation methods have been proved to be efficient for CTC detection in clinical blood samples. One of the popular choices for affinity-based CTC isolation is to immobilize capture agents onto an array of microposts in microchannels, providing high CTC capture efficiency due to enhanced interactions between tumor cells and capture agents on the microposts. However, how the cells interact with microposts under different flow conditions and what kind of capture pattern results from the interactions have not been fully investigated; a full understanding of these interactions will help to design devices and choose experimental conditions for higher CTC capture effeciency. We report our study on their interaction and cell distribution patterns around microposts under different flow conditions. Human acute lymphoblastic leukemia cells (CCRF-CEM) were used as target cancer cells in th...
Methods in molecular biology (Clifton, N.J.), 2017
Enumeration of circulating tumor cells (CTCs) can provide valuable prognostic information to guid... more Enumeration of circulating tumor cells (CTCs) can provide valuable prognostic information to guide cancer treatment as well as help monitor disease progression. Analysis of these rare malignant cells has the potential to further our understanding of cancer metastasis by gaining insights into CTC characteristics and properties. Microfluidics presents a unique platform to isolate and study CTCs. In this chapter, we describe the detailed procedures for the fabrication and use of a microfluidic device to detect CTCs from the blood of pancreatic cancer patients.
Cell intrinsic motility and morphology are highly affected by its surrounding environmental condi... more Cell intrinsic motility and morphology are highly affected by its surrounding environmental conditions. Extracellular proteins have been thoroughly studied along with their effects on Rho GTPases, which been closely linked with cellular movement. Therefore, we investigated the contributing effects two ECM proteins, fibronectin and collagen, have on NIH-3T3 fibroblast motility. In this study, cell motility is characterized through a novel biophysical assay that uses the correlations of the cellular and nuclear centroid minutely displacements to precisely explain the subcellular activity of 3T3 fibroblasts on ECM and also quantify their migration capacity. The results suggest that a fibronectin-rich environment positively affects effective cell displacement and migration potential, compared to a collagen substrate which induced stagnant behavior associated with loss of cell polarity and increased cell sampling, or membrane ruffling. The student t-test was applied to indicate the statistical difference (p < 0.001). This provides us with an insight of the ECM effects on subcellular activity and on the cell-ECM interaction in general. Knowledge gained from these experiments could prove useful in cancer prognosis, diagnosis, or treatment.
Di-tert-butyl-peroxide (DTBP) is a clear organic compound and one of the most stable organic pero... more Di-tert-butyl-peroxide (DTBP) is a clear organic compound and one of the most stable organic peroxides, formed by the linkage of two flanking tert-butyl groups to a peroxide group. A versatile compound, DTBP is used as a radical initiator in polymer chemistry and organic synthesis, and is a cetane improver in diesel fuel, raising its ignition accelerations. It owes a great deal of its usefulness to the nature of its decomposition, or homolysis; it breaks down at temperatures greater than 100 degrees celsius, and because it can decompose both aerobically and anaerobically, it makes for a multifaceted fuel source. The following is a list of some of the many applications of DTBP: • An important initiator for high pressure, high temperature polymerizations of ethylene and halogenated ethylenes. • Cures resins of allyl acetate and allyl phthalate. • Applied in the making of polyketones from carbon and ethylene • Used as a finishing catalyst for polystyrene • Used as a polymerization cata...
Conference Proceedings by Jose I Varillas
The goal of this project is to develop and utilize a microfluidic device to isolate and enrich tu... more The goal of this project is to develop and utilize a microfluidic device to isolate and enrich tumor cells circulating in peripheral blood. Circulating tumor cells (CTCs) have been used as biomarkers for cancer diagnostics and prognosis. However, the rarity of these cells (roughly 1 in a billion) poses a technological challenge to sort and concentrate them. CTCs hold potential sources for early detection, characterization, monitoring of cancers, and development of personalized treatment. The project is currently funded by the US National Cancer Institute (NCI) of the National Institutes of Health (NIH).
Undergraduate by Jose I Varillas
Cell intrinsic motility and morphology are highly affected by its surrounding environmental condi... more Cell intrinsic motility and morphology are highly affected by its surrounding environmental conditions. Extracellular proteins have been thoroughly studied along with their effects on Rho GTPases, which been closely linked with cellular movement. Therefore, we investigated the contributing effects two ECM proteins, fibronectin and collagen, have on NIH-3T3 fibroblast motility. In this study, cell motility is characterized through a novel biophysical assay that uses the correlations of the cellular and nuclear centroid minutely displacements to precisely explain the subcellular activity of 3T3 fibroblasts on ECM and also quantify their migration capacity. The results suggest that a fibronectin-rich environment positively affects effective cell displacement and migration potential, compared to a collagen substrate which induced stagnant behavior associated with loss of cell polarity and increased cell sampling, or membrane ruffling. The student t-test was applied to indicate the statistical difference (p < 0.001). This provides us with an insight of the ECM effects on subcellular activity and on the cell-ECM interaction in general. Knowledge gained from these experiments could prove useful in cancer prognosis, diagnosis, or treatment.
As energy costs increase, it has become necessary to find a way to minimize the amount of money s... more As energy costs increase, it has become necessary to find a way to minimize the amount of money spent on energy in order to stay within ever-shrinking budgets. The original problem defined by the team was to reduce energy costs. But over time and through various problem-solving methods, it was refined to a more precise and practical goal: Optimization of energy consumption at Marston Science library in order to reduce energy costs...
Posters by Jose I Varillas
The goal of this project is to develop and utilize a microfluidic device to isolate and enrich tu... more The goal of this project is to develop and utilize a microfluidic device to isolate and enrich tumor cells circulating in peripheral blood. Circulating tumor cells (CTCs) have been used as biomarkers for cancer diagnostics and prognosis. However, the rarity of these cells (roughly 1 in a billion) poses a technological challenge to sort and concentrate them. CTCs hold potential sources for early detection, characterization, monitoring of cancers, and development of personalized treatment. The project is currently funded by the US National Cancer Institute (NCI) of the National Institutes of Health (NIH).
Scientific Reports, Aug 26, 2020
Journal of clinical and translational science, Sep 1, 2017
[Not an Abstract] The goal of this project is to develop and utilize a microfluidic device to iso... more [Not an Abstract] The goal of this project is to develop and utilize a microfluidic device to isolate and enrich tumor cells circulating in peripheral blood. Circulating tumor cells (CTCs) have been used as biomarkers for cancer diagnostics and prognosis. However, the rarity of these cells (roughly 1 in a billion) poses a technological challenge to sort and concentrate them. CTCs hold potential sources for early detection, characterization, monitoring of cancers, and development of personalized treatment. The project is currently funded by the US National Cancer Institute (NCI) of the National Institutes of Health (NIH).
Scientific Reports, 2020
The methods for isolating rare cells such as circulating tumor cells (CTCs) can be generally clas... more The methods for isolating rare cells such as circulating tumor cells (CTCs) can be generally classified into two categories: those based on physical properties (e.g., size) and methods based on biological properties (e.g., immunoaffinity). CellSearch, the only FDA-approved method for the CTC-based cancer prognosis, relies on immunoaffinity interactions between CTCs and antibodies immobilized on magnetic particles. Immunoaffinity-based CTC isolation has also been employed in microfluidic devices, which show higher capture efficiency than CellSearch. We report here our investigation of combining size-based microfiltration into a microfluidic device with immunoaffinity for enhanced capture efficiency of CTCs. The device consists of four serpentine main channels, and each channel contains an array of lateral filters that create a two-dimensional flow. The main flow is through the serpentine channel, allowing the majority of the sample to pass by while the secondary flow goes through the...
Canadian Journal of Chemistry, 2022
The analysis of circulating tumor cells (CTCs) is important for cancer diagnosis and prognosis. M... more The analysis of circulating tumor cells (CTCs) is important for cancer diagnosis and prognosis. Microfluidics has been employed for CTC analysis due to its scaling advantages and high performance. However, pre-analytical methods for CTC sample preparation are often combined with microfluidic platforms because a large sample volume is required to detect extremely rare CTCs. Among pre-analytical methods, Ficoll-Paque™, OncoQuick™, and RosetteSep™ are commonly used to separate cells of interest. To compare their performance, we spiked L3.6pl pancreatic cancer cells into healthy blood samples and then employed each technique to prepare blood samples, followed by using a microfluidic platform to capture and detect L3.6pl cells. We found these three methods have similar performance, though the slight edge of RosetteSep™ over Ficoll-Paque™ is statistically significant. We also studied the effects of the tumor cell concentrations on the performance of the frequently used Ficoll-Paque™ metho...
2017 IEEE 30th International Conference on Micro Electro Mechanical Systems (MEMS), 2017
This paper reports two microfluidic devices for isolating circulating tumor cells (CTCs) in blood... more This paper reports two microfluidic devices for isolating circulating tumor cells (CTCs) in blood samples of pancreatic cancer patients. These devices consist of micromixers or micropillars for enhancing the interactions between tumor cells and capture agents, which are immobilized onto the surfaces of microchannels and microfeatures. Both antibodies and aptamers, as well as their ensemble, have been explored for tumor cell isolation. The devices have been used for enumerating CTCs and we have correlated the CTC number with the anti-cancer treatment responses in a clinical trial.
Journal of Clinical Oncology
304 Background: Circulating tumor cells (CTCs) represent real time dissemination of solid tumors.... more 304 Background: Circulating tumor cells (CTCs) represent real time dissemination of solid tumors. Historically, CTC enumeration has been challenging to perform successfully in pancreatic cancer (PCa). Using a previously published microfluidic device designed to increase cell capture, we analyzed CTC characteristics in a cohort of newly diagnosed patients with metastatic PCa. Methods: After provision of informed consent, blood samples (7-10mL) were collected within 1 month of treatment initiation. Specimens were processed within 6 hours of collection. A UF developed microfluidic device was used to capture and identify EpCam+ CTCs. Isolated cells were verified as CTCs consistent with FDA-approved definitions (cytokeratin+, DAPI+, CD45-). Statistical analysis was performed using Scheffe’s method along with analysis of variance to test interactions between the clinical demographics and groups. The study was approved by the UF IRB. Results: A cohort of 27 patients had CTC determination a...
Journal of Clinical Oncology
318 Background: The collection and enumeration of circulating tumor cells (CTCs) are feasible in ... more 318 Background: The collection and enumeration of circulating tumor cells (CTCs) are feasible in metastatic breast, prostate and colorectal cancers. CTCs have diagnostic, prognostic and treatment monitoring implications, but have been challenging to detect in pancreatic cancer (PCa). We have proven feasibility of CTCs in PCa. This study is a pilot to assess use of CTCs as a surrogate for imaging response. Methods: Blood samples (7-10mL) from newly diagnosed metastatic PCa were collected within 1 month of treatment initiation (T0) and at repeat scan after 2mo of treatment (T1). Specimens were processed within 6 hours of collection. A UF developed microfluidic device was used to capture and identify EpCam+ CTCs. Isolated cells were verified as CTCs consistent with FDA-approved definitions (cytokeratin+, DAPI+, CD45-). CTC enumeration and changes were correlated with scan RECIST results at T0 and T1. The study was approved by the UF IRB. Results: A total of 16 patients had matched pair...
Biomicrofluidics, 2017
Circulating tumor cells (CTCs) have shown potential for cancer diagnosis and prognosis. Affinity-... more Circulating tumor cells (CTCs) have shown potential for cancer diagnosis and prognosis. Affinity-based CTC isolation methods have been proved to be efficient for CTC detection in clinical blood samples. One of the popular choices for affinity-based CTC isolation is to immobilize capture agents onto an array of microposts in microchannels, providing high CTC capture efficiency due to enhanced interactions between tumor cells and capture agents on the microposts. However, how the cells interact with microposts under different flow conditions and what kind of capture pattern results from the interactions have not been fully investigated; a full understanding of these interactions will help to design devices and choose experimental conditions for higher CTC capture effeciency. We report our study on their interaction and cell distribution patterns around microposts under different flow conditions. Human acute lymphoblastic leukemia cells (CCRF-CEM) were used as target cancer cells in th...
Methods in molecular biology (Clifton, N.J.), 2017
Enumeration of circulating tumor cells (CTCs) can provide valuable prognostic information to guid... more Enumeration of circulating tumor cells (CTCs) can provide valuable prognostic information to guide cancer treatment as well as help monitor disease progression. Analysis of these rare malignant cells has the potential to further our understanding of cancer metastasis by gaining insights into CTC characteristics and properties. Microfluidics presents a unique platform to isolate and study CTCs. In this chapter, we describe the detailed procedures for the fabrication and use of a microfluidic device to detect CTCs from the blood of pancreatic cancer patients.
Cell intrinsic motility and morphology are highly affected by its surrounding environmental condi... more Cell intrinsic motility and morphology are highly affected by its surrounding environmental conditions. Extracellular proteins have been thoroughly studied along with their effects on Rho GTPases, which been closely linked with cellular movement. Therefore, we investigated the contributing effects two ECM proteins, fibronectin and collagen, have on NIH-3T3 fibroblast motility. In this study, cell motility is characterized through a novel biophysical assay that uses the correlations of the cellular and nuclear centroid minutely displacements to precisely explain the subcellular activity of 3T3 fibroblasts on ECM and also quantify their migration capacity. The results suggest that a fibronectin-rich environment positively affects effective cell displacement and migration potential, compared to a collagen substrate which induced stagnant behavior associated with loss of cell polarity and increased cell sampling, or membrane ruffling. The student t-test was applied to indicate the statistical difference (p < 0.001). This provides us with an insight of the ECM effects on subcellular activity and on the cell-ECM interaction in general. Knowledge gained from these experiments could prove useful in cancer prognosis, diagnosis, or treatment.
Di-tert-butyl-peroxide (DTBP) is a clear organic compound and one of the most stable organic pero... more Di-tert-butyl-peroxide (DTBP) is a clear organic compound and one of the most stable organic peroxides, formed by the linkage of two flanking tert-butyl groups to a peroxide group. A versatile compound, DTBP is used as a radical initiator in polymer chemistry and organic synthesis, and is a cetane improver in diesel fuel, raising its ignition accelerations. It owes a great deal of its usefulness to the nature of its decomposition, or homolysis; it breaks down at temperatures greater than 100 degrees celsius, and because it can decompose both aerobically and anaerobically, it makes for a multifaceted fuel source. The following is a list of some of the many applications of DTBP: • An important initiator for high pressure, high temperature polymerizations of ethylene and halogenated ethylenes. • Cures resins of allyl acetate and allyl phthalate. • Applied in the making of polyketones from carbon and ethylene • Used as a finishing catalyst for polystyrene • Used as a polymerization cata...
The goal of this project is to develop and utilize a microfluidic device to isolate and enrich tu... more The goal of this project is to develop and utilize a microfluidic device to isolate and enrich tumor cells circulating in peripheral blood. Circulating tumor cells (CTCs) have been used as biomarkers for cancer diagnostics and prognosis. However, the rarity of these cells (roughly 1 in a billion) poses a technological challenge to sort and concentrate them. CTCs hold potential sources for early detection, characterization, monitoring of cancers, and development of personalized treatment. The project is currently funded by the US National Cancer Institute (NCI) of the National Institutes of Health (NIH).
Cell intrinsic motility and morphology are highly affected by its surrounding environmental condi... more Cell intrinsic motility and morphology are highly affected by its surrounding environmental conditions. Extracellular proteins have been thoroughly studied along with their effects on Rho GTPases, which been closely linked with cellular movement. Therefore, we investigated the contributing effects two ECM proteins, fibronectin and collagen, have on NIH-3T3 fibroblast motility. In this study, cell motility is characterized through a novel biophysical assay that uses the correlations of the cellular and nuclear centroid minutely displacements to precisely explain the subcellular activity of 3T3 fibroblasts on ECM and also quantify their migration capacity. The results suggest that a fibronectin-rich environment positively affects effective cell displacement and migration potential, compared to a collagen substrate which induced stagnant behavior associated with loss of cell polarity and increased cell sampling, or membrane ruffling. The student t-test was applied to indicate the statistical difference (p < 0.001). This provides us with an insight of the ECM effects on subcellular activity and on the cell-ECM interaction in general. Knowledge gained from these experiments could prove useful in cancer prognosis, diagnosis, or treatment.
As energy costs increase, it has become necessary to find a way to minimize the amount of money s... more As energy costs increase, it has become necessary to find a way to minimize the amount of money spent on energy in order to stay within ever-shrinking budgets. The original problem defined by the team was to reduce energy costs. But over time and through various problem-solving methods, it was refined to a more precise and practical goal: Optimization of energy consumption at Marston Science library in order to reduce energy costs...
The goal of this project is to develop and utilize a microfluidic device to isolate and enrich tu... more The goal of this project is to develop and utilize a microfluidic device to isolate and enrich tumor cells circulating in peripheral blood. Circulating tumor cells (CTCs) have been used as biomarkers for cancer diagnostics and prognosis. However, the rarity of these cells (roughly 1 in a billion) poses a technological challenge to sort and concentrate them. CTCs hold potential sources for early detection, characterization, monitoring of cancers, and development of personalized treatment. The project is currently funded by the US National Cancer Institute (NCI) of the National Institutes of Health (NIH).