“Sample‐in‐answer‐out” type integrated diagnostic devices have been widely recognized as the ultimate solution to simplify testing across healthcare systems. Such systems are equipped with advanced fluidic, mechanical, chemical, biological, and electronic components to handle patient samples without any manual steps therefore have the potential to accelerate intervention and improve patient outcomes. In this regard, the combination of integrated devices and non‐invasive sampling has gained a substantial interest to further improve the comfort and safety of patients. In this Review, the pioneering developments in integrated diagnostics are covered and their potential in non‐invasive sampling is discussed. The key properties of possible sample types are highlighted by addressing their relevance for the clinical practice. Last, the factors affecting the transition of integrated devices from academia to the market are identified by analyzing the technology readiness levels of selected examples and alternative remedies are explored to increase the rate of survival during this transition.

The topology of most membrane proteins is defined by the successive integration of α-helical transmembrane domains at the Sec61 translocon. The translocon provides a pore for the transfer of polypeptide segments across the membrane while giving them lateral access to the lipid. For each polypeptide segment of ∼20 residues, the combined hydrophobicities of its constituent amino acids were previously shown to define the extent of membrane integration. Here, we discovered that different sequences preceding a potential transmembrane domain substantially affect its hydrophobicity requirement for integration. Rapidly folding domains, sequences that are intrinsically disordered or very short or capable of binding chaperones with high affinity, allow for efficient transmembrane integration with low-hydrophobicity thresholds for both orientations in the membrane. In contrast, long protein fragments, folding-deficient mutant domains, and artificial sequences not binding chaperones interfered with membrane integration, requiring higher hydrophobicity. We propose that the latter sequences, as they compact on their hydrophobic residues, partially folded but unable to reach a native state, expose hydrophobic surfaces that compete with the translocon for the emerging transmembrane segment, reducing integration efficiency. The results suggest that rapid folding or strong chaperone binding is required for efficient transmembrane integration.

The rapid detection of pathogens in infected wounds can significantly improve the clinical outcome. Wound exudate, which can be collected in a non-invasive way, offers an attractive sample material for the detection of pathogens at the point-of-care (POC). Here, we report the development of a nucleic acid lateral flow immunoassay for direct detection of isothermally amplified DNA combined with fast sample preparation. The streamlined protocol was evaluated using human wound exudate spiked with the opportunistic pathogen Pseudomonas aeruginosa that cause severe health issues upon wound colonization. A detection limit of 2.1 × 105 CFU per mL of wound fluid was achieved, and no cross-reaction with other pathogens was observed. Furthermore, we integrated an internal amplification control that excludes false negative results and, in combination with the flow control, ensures the validity of the test result. The paper-based approach with only three simple hands-on steps has a turn-around time of less than 30 min and covers the complete analytical process chain from sample to answer. This newly developed workflow for wound fluid diagnostics has tremendous potential for reliable pathogen POC testing and subsequent target-oriented therapy.

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In article number 2010388, Can Dincer and co‐workers present integrated “sample‐to‐answer” diagnostic platforms including wearable, handheld, and tabletop devices for non‐invasive monitoring. Factors influencing the translation of these devices from the fundamental research phase through the commercialization and into our daily life are discussed via the technology readiness level concept. Image designed by Ceren Ates and created by Ella Maru Studio.