The core requirements for point-of-care (POC) diagnostics necessitate low-cost, portability, easily integrated sample preparation, and quick measurement time. Frequency-shift based magnetic sensing is a measurement technique utilizing a complementary metal-oxide-semiconductor (CMOS) integrated- circuit (IC) chip for magnetic label detection. The sensing scheme leverages the low-cost manufacturing of IC chips while demonstrating the potential for multiplexing capabilities. In this article, we present modifications to this scheme for POC viability. We introduce a handheld reusable reader and a disposable open-well cartridge for the detection of nucleic acids and antigens. The diagnostic system utilizes a novel “magnetic freezing” technique to reduce measurement time, obviates baseline measurement before or during biological assay, and reduces sensor noise. We utilize these enhancements for the room temperature, amplification-free detection of a 31 base-pair DNA oligomer and the interferon-γ (IFN-γ) protein. We have demonstrated reliable measurements down to 100 pM for the DNA assay and 1 pM for the protein.