Alkylation of Substituted Benzoic Acids in a Continuous Flow Microfluidic Microreactor: Kinetics and Linear Free Energy Relationships

Alkylation of para-substituted benzoic acids by iodomethane using an organic superbase, 1,8-bis­(tetramethylguanidino)­naphthalene (TMGN) in DMF was chosen as a model reaction to test the quality of the control of experimental parameters in a continuous flow microfluidic reactor as it is expected to follow a perfect second order kinetics with a large dynamics by varying the substituents. These conditions may be directly used for the synthesis of natural product esters. Because TMGN reacts slowly with iodomethane, the three different mixing strategies between substrate, base and alkylating reagent were compared. The rate constants were determined for the reaction with a set of alkylating agents and in different solvents. In order to test the quality of the obtained data, temperature effect and free energy relationships, which are expected to follow predictable laws, were investigated. The kinetics vary over 6 orders of magnitude and follows a perfect Arrhenius law, allowing the determination of the energies, enthalpies, and entropies of activation. Finally, we established a Hammett linear relationship for a series of 16 substituted benzoic acids, leading to a reaction constant ρ of −0.65 for this reaction. The quality of the obtained kinetics allowed us to discuss the outliers. All kinetics were obtained with less than 0.5 mmol of substrate

High-Throughput Isolation of Circulating Tumor Cells Using Cascaded Inertial Focusing Microfluidic Channel

Circulating tumor cells (CTCs) are rare cells that detach from a primary or metastasis tumor and flow into the bloodstream. Intact and viable tumor cells are needed for genetic characterization of CTCs, new drug development, and other research. Although separation of CTCs using spiral channel with two outlets has been reported, few literature demonstrated simultaneous isolation of different types of CTCs from human blood using cascaded inertial focusing microfluidic channel. Herein, we introduce a cascaded microfluidic device consisting of two spiral channels and one zigzag channel designed with different fluid fields, including lift force, Dean drag force, and centrifugal force. Both red blood cells (RBCs)-lysed human blood spiked with CTCs and 1:50 diluted human whole blood spiked with CTCs were tested on the presented chip. This chip successfully separated RBCs, white blood cells (WBCs), and two different types of tumor cells (human lung cancer cells (A549) and human breast cancer cells (MCF-7)) simultaneously based on their physical properties. A total of 80.75% of A549 and 73.75% of MCF-7 were faithfully separated from human whole blood. Furthermore, CTCs gathered from outlets could propagate and remained intact. The cell viability of A549 and MCF-7 were 95% and 98%, respectively. The entire separating process for CTCs from blood cells could be finished within 20 min. The cascaded microfluidic device introduced in this study serves as a novel platform for simultaneous isolation of multiple types of CTCs from patient blood

High-Throughput Isolation of Circulating Tumor Cells Using Cascaded Inertial Focusing Microfluidic Channel

Circulating tumor cells (CTCs) are rare cells that detach from a primary or metastasis tumor and flow into the bloodstream. Intact and viable tumor cells are needed for genetic characterization of CTCs, new drug development, and other research. Although separation of CTCs using spiral channel with two outlets has been reported, few literature demonstrated simultaneous isolation of different types of CTCs from human blood using cascaded inertial focusing microfluidic channel. Herein, we introduce a cascaded microfluidic device consisting of two spiral channels and one zigzag channel designed with different fluid fields, including lift force, Dean drag force, and centrifugal force. Both red blood cells (RBCs)-lysed human blood spiked with CTCs and 1:50 diluted human whole blood spiked with CTCs were tested on the presented chip. This chip successfully separated RBCs, white blood cells (WBCs), and two different types of tumor cells (human lung cancer cells (A549) and human breast cancer cells (MCF-7)) simultaneously based on their physical properties. A total of 80.75% of A549 and 73.75% of MCF-7 were faithfully separated from human whole blood. Furthermore, CTCs gathered from outlets could propagate and remained intact. The cell viability of A549 and MCF-7 were 95% and 98%, respectively. The entire separating process for CTCs from blood cells could be finished within 20 min. The cascaded microfluidic device introduced in this study serves as a novel platform for simultaneous isolation of multiple types of CTCs from patient blood

High-Throughput Isolation of Circulating Tumor Cells Using Cascaded Inertial Focusing Microfluidic Channel

Circulating tumor cells (CTCs) are rare cells that detach from a primary or metastasis tumor and flow into the bloodstream. Intact and viable tumor cells are needed for genetic characterization of CTCs, new drug development, and other research. Although separation of CTCs using spiral channel with two outlets has been reported, few literature demonstrated simultaneous isolation of different types of CTCs from human blood using cascaded inertial focusing microfluidic channel. Herein, we introduce a cascaded microfluidic device consisting of two spiral channels and one zigzag channel designed with different fluid fields, including lift force, Dean drag force, and centrifugal force. Both red blood cells (RBCs)-lysed human blood spiked with CTCs and 1:50 diluted human whole blood spiked with CTCs were tested on the presented chip. This chip successfully separated RBCs, white blood cells (WBCs), and two different types of tumor cells (human lung cancer cells (A549) and human breast cancer cells (MCF-7)) simultaneously based on their physical properties. A total of 80.75% of A549 and 73.75% of MCF-7 were faithfully separated from human whole blood. Furthermore, CTCs gathered from outlets could propagate and remained intact. The cell viability of A549 and MCF-7 were 95% and 98%, respectively. The entire separating process for CTCs from blood cells could be finished within 20 min. The cascaded microfluidic device introduced in this study serves as a novel platform for simultaneous isolation of multiple types of CTCs from patient blood

High-Throughput Isolation of Circulating Tumor Cells Using Cascaded Inertial Focusing Microfluidic Channel

Circulating tumor cells (CTCs) are rare cells that detach from a primary or metastasis tumor and flow into the bloodstream. Intact and viable tumor cells are needed for genetic characterization of CTCs, new drug development, and other research. Although separation of CTCs using spiral channel with two outlets has been reported, few literature demonstrated simultaneous isolation of different types of CTCs from human blood using cascaded inertial focusing microfluidic channel. Herein, we introduce a cascaded microfluidic device consisting of two spiral channels and one zigzag channel designed with different fluid fields, including lift force, Dean drag force, and centrifugal force. Both red blood cells (RBCs)-lysed human blood spiked with CTCs and 1:50 diluted human whole blood spiked with CTCs were tested on the presented chip. This chip successfully separated RBCs, white blood cells (WBCs), and two different types of tumor cells (human lung cancer cells (A549) and human breast cancer cells (MCF-7)) simultaneously based on their physical properties. A total of 80.75% of A549 and 73.75% of MCF-7 were faithfully separated from human whole blood. Furthermore, CTCs gathered from outlets could propagate and remained intact. The cell viability of A549 and MCF-7 were 95% and 98%, respectively. The entire separating process for CTCs from blood cells could be finished within 20 min. The cascaded microfluidic device introduced in this study serves as a novel platform for simultaneous isolation of multiple types of CTCs from patient blood