Advancements in miniaturization enable today the development of minimal invasive platforms. Small lancets and microneedles can operate on minimum fluid sample volumes <2μl without damaging the deeper layers of the patient’s skin. While less painful in daily use and more user-friendly, lightweight minimally-invasive biosensor devices offer the advantage of higher mobility levels to patients. The resulting higher acceptance by patients drives the transition from invasive to minimally invasive applications and for continuous application with patients bound at home or in care facilities. Therapeutic Drug Monitoring and Control of Immunogenicity In the case of many elderly or depressed patients, multimorbidity results in multi-medication. Medication effects, drug-drug interactions, and addictions in connection with alcohol abuse can be of great concern. The variety of drugs from different producers and for chemotherapy, antipsychotics, or analgesics is significant. Furthermore, overuse, underuse, or medication misuse can harm senior patients or cause unintended side effects. The use of invasive biosensing techniques today can be based on Surface Plasmon Resonance (SPR), which is still an established standard in drug monitoring. Used in many ICU/laboratories, the technology provides an optical detection method for real-time screening of drugs or serum antibody binding events on a molecular level. Minimally invasive biosensing techniques based on Reverse Iontophoresis are alternatives. Using an electrical detection method via enzymatic electrochemical electrodes beneath the microneedle array, analytes circulating within the convective flow of the ISF become measurable. These techniques provide less pain in daily use and offer continuous measurements at the home residence. A greater degree of freedom in the life of seniors becomes achievable. Monitoring Cardiovascular Diseases, Infections According to the World Health Organization (WHO), cardiovascular diseases are the most common cause of death over the last 20 years, followed by stroke. Chronic lung diseases and infections of the respiratory tract are also rising. Technologies such as Fluorescence Resonant Energy Transfer (FRET) can support patients effectively. Using a pair of fluorescent probes as biosensors underneath the patient skin, interactions between donor-acceptor molecules such as protein partners labeled with fluorophores become measurable based on their energy transfer efficiency. Minimally invasive FRET applications can deliver real-time insights on virus loads or the effectiveness of antivirals. Immune response, cell health, and intracellular processes of patients with cardiovascular diseases become visible.