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In this paper, we present a heterogeneous integration platform for bio-sensing applications, which seamlessly integrates low-power silicon-based circuits with cost-effective printed electronics. A prototype of wearable Bio-Sensing Node is fabricated to investigate the suitability of this integration approach. A 1.5 ×3.0 mm2 customized mixed-signal system-on-chip (SoC) with the size of is utilized to amplify, digitize, buffer, and transmit the sensed bio-signals. Inkjet printing technology is employed to print nano-particle silver ink on a flexible substrate to fabricate chip-on-ίex, electrodes as well as interconnections. This additive and digital fabrication technology enables fast prototype of the customized electrode pattern. Its high accuracy and fine resolution features allow the direct integration of the bare die (the pad size of 65 μm and pitch size of 90 μm) on the flexible substrate, which significantly miniaturizes the wearable system. The optimal size and layout of printed electrodes are investigated through the in vivo test for electrocardiogram recording applications. The total size of the implemented Bio-Sensing Node is 4.5 ×2.5 μm, which is comparable with a commercial electrode. This inkjet printed heterogeneous integration approach offers a promising solution for the next-generation cost-effective personalized wearable healthcare monitoring devices.