CONTENTSshould be inexpensive disposable chips or cartridges that include microfluidic features to provide or control sample preparation, flow rate, mixing with reagents, reaction time associated with binding events, filtration of nonanalytical components of the sample, separation of interfering agents and of multiple analytes, and an effective measurement capability. 4 POC diagnostics have been extensively reviewed in recent years, from the points of view of both use 5 and development. 6 The reviews have included coverage of micrototal analysis systems (μTAS), 7 miniaturized isothermal nucleic acid amplification 8 and molecular biological techniques for gene assay, 9 current and anticipated technology for POC infection diagnosis, 10 and microfluidic-based systems leading toward point-of-care detection of nucleic acids and proteins, 11 including multiplexing and labelfree methods. 12 Developments in this area include not only technology but also reliable measurement targets, which in some important areas remain elusive: progress toward viable point-ofcare protein biomarker measurements for cancer detection and diagnostics has been reviewed. 13 We review here the present status of POC diagnostics, emphasizing in particular the past 4 years, then extrapolate their progress into the future. Included are IVD tests for biochemical targets of all sorts relevant to human health, diagnosis, and therapy, as enumerated above. We begin with an overview of the different classes of bioanalytical targets. Then, after setting the context using the well-established glucose and pregnancy POC tests, recent progress in key enabling technologies is reviewed, including traditional and advanced lateral flow approaches, printing and laminating technologies, a range of microfluidic advances, progress in surface chemistry and the control of nonspecificbinding, and developments in labeled and label-free detection approaches. A number of specific innovative examples, in both commercial products and academic POC research, are presented, including assays based on binding to proteins, nucleic acids, and aptamers, with separate sections devoted to blood chemistry, coagulation, and whole cells. We close with trends and future perspectives.Why POC Diagnostics? Time POC measurements provide results rapidly, where needed, and often with major time savings: samples do not travel to a laboratory to await the attention of a skilled technician; results do not wait to be transmitted and collected. Rather, the doctor, nurse, care-giver, patient, or consumer initiates the test and receives the results on the spot. Inevitably this saves time, but speed must not be traded for accuracy or reliability. Figure 1. Idealized POC device. Adapted with permission from ref 6a.

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Direct, amplification-free detection of RNA has the potential to transform molecular diagnostics by enabling simple on-site analysis of human or environmental samples. CRISPR-Cas nucleases offer programmable RNA-guided RNA recognition that triggers cleavage and release of a fluorescent reporter molecule, but long reaction times hamper their detection sensitivity and speed. Here, we show that unrelated CRISPR nucleases can be deployed in tandem to provide both direct RNA sensing and rapid signal generation, thus enabling robust detection of ~30 molecules per µl of RNA in 20 min. Combining RNA-guided Cas13 and Csm6 with a chemically stabilized activator creates a one-step assay that can detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA extracted from respiratory swab samples with quantitative reverse transcriptase PCR (qRT-PCR)-derived cycle threshold (C t ) values up to 33, using a compact detector. This Fast Integrated Nuclease Detection In Tandem (FIND-IT) approach enables sensitive, direct RNA detection in a format that is amenable to point-of-care infection diagnosis as well as to a wide range of other diagnostic or research applications.

A series of ordered, periodic arrays of low barrier height n-Si/Ni nanometer-scale contacts interspersed among high barrier height n-Si/liquid contacts were prepared by evaporating Ni through bilayers of close-packed latex spheres deposited on n-Si. By varying the diameter of the spheres from 174 to 1530 nm, geometrically self-similar Si/Ni structures were produced having triangular Si/Ni features ranging from approximately 100 to 800 nm on a side. The resulting Si surfaces were used as electrodes in methanolic electrochemical cells containing LiClO4 and 1,1′-dimethylferrocene+/o. The dark current density–voltage properties of the resulting mixed barrier height contacts were strongly dependent on the size of the low barrier height contact regions even though the fraction of the Si surface covered by Ni remained constant.

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