This paper presents a novel hybrid microfluidic electronic sensing platform, featuring an electronic sensor incorporated with a microfluidic structure for life science applications. This sensor with a large sensing area of 0.7 mm2 is implemented through a foundry process called Open-Gate Junction FET (OG-JFET). The proposed OG-JFET sensor with a back gate enables the charge by directly introducing the biological and chemical samples on the top of the device. This paper puts forward the design and implementation of a PDMS microfluidic structure integrated with an OG-JFET chip to direct the samples toward the sensing site. At the same time, the sensor’s gain is controlled with a back gate electrical voltage. Herein, we demonstrate and discuss the functionality and applicability of the proposed sensing platform using a chemical solution with different pH values. Additionally, we introduce a mathematical model to describe the charge sensitivity of the OG-JFET sensor. Based on the results, the maximum value of transconductance gain of the sensor is ~1 mA/V at Vgs = 0, which is decreased to ~0.42 mA/V at Vgs = 1, all in Vds = 5. Furthermore, the variation of the back-gate voltage from 1.0 V to 0.0 V increases the sensitivity from ~40 mV/pH to ~55 mV/pH. As per the experimental and simulation results and discussions in this paper, the proposed hybrid microfluidic OG-JFET sensor is a reliable and high-precision measurement platform for various life science and industrial applications.