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This paper deals with the design of a new hemofiltration system that consists of a blood transport device, a blood filtration device, a drug delivery device, flow sensors, blood pressure sensors, and the required control electronic circuits. The simulation and fabrication of microneedles and hemofilter have been performed. Silicon microneedles with length (L) = 200 μm, internal diameter (Di) = 60 μ m, and outer diameter (Do) = 150 μm have been successfully fabricated using inductive coupled plasma (ICP) etching technology for drug delivery. An aluminum (Al)-based hemofilter with hexagonal pores has been fabricated for blood filtration. Strength modeling and microfluidic analyses of the hemofilter have been conducted in finite element software to envisage structural properties and to model blood flow through the hexagonal pores. Simulation results show that a flow rate of 488.43 μL/min has been obtained at a driving pressure of 250 kPa through a hemofilter with hexagonal pores. Transient multifield analysis of the blood transport device (double lumen, side open, reservoir-based microneedles integrated with a piezoelectric actuator) has been conducted using the finite element method. The effects of actuator thickness, applied frequency and voltage on fluid flow rate have been investigated using the blood transport device. A maximum flow rate of 475 μL/min has been observed through 25 microneedles at an applied voltage of 125 V with a frequency of 250 Hz.