A significant amount of noteworthy articles reviewing different label-free biosensors are being published in the last years. Most of the times, the comparison among the different biosensors is limited by the procedure used of calculating the limit of detection and the measurement uncertainty. This article clarifies and establishes a simple procedure to determine the calibration function and the uncertainty of the concentration measured at any point of the measuring interval of a generic label-free biosensor. The value of the limit of detection arises naturally from this model as the limit at which uncertainty tends when the concentration tends to zero. The need to provide additional information, such as the measurement interval and its linearity, among others, on the analytical systems and biosensor in addition to the detection limit is pointed out. Finally, the model is applied to curves that are typically obtained in immunoassays and a discussion is made on the application validity of the model and its limitations.

Despite the remarkable development related to Point-of-Care devices based on optical technology, their difficulties when used outside of research laboratories are notable. In this sense, it would be interesting to ask ourselves what the degree of transferability of the research work to the market is, for example, by analysing the relation between the scientific work developed and the registered one, through patent. In this work, we provide an overview of the state-of-the-art in the sector of optical Point-of-Care devices, not only in the research area but also regarding their transfer to market. To this end, we explored a methodology for searching articles and patents to obtain an indicator that relates to both. This figure of merit to estimate this transfer is based on classifying the relevant research articles in the area and the patents that have been generated from these ones. To delimit the scope of this study, we researched the results of a large enough number of publications in the period from 2015 to 2020, by using keywords “biosensor”, “optic”, and “device” to obtain the most representative articles from Web of Science and Scopus. Then, we classified them according to a particular classification of the optical PoC devices. Once we had this sampling frame, we defined a patent search strategy to cross-link the article with a registered patent (by surfing Google Patents) and classified them accordingly to the categories described. Finally, we proposed a relative figure called Index of Technology Transference (IoTT), which estimates to what extent our findings in science materialized in published articles are protected by patent.

A novel compact optical biochip based on a thin layer-sensing surface of nitrocellulose is used for in-situ label-free detection of metalloproteinase (MMP9) related to dry eye disease. In this article, a new integrated chip with different interferometric transducers layout with an optimal sensing surface is reported for the first time. We demonstrate that specific antibodies can be immobilized onto these transducers with a very low volume of sample and with good orientation. Many sensing transducers constitute the presented biochip in order to yield statistical data and stability in the acquired measurements. As a result, we report the recognition curve for pure recombinant MMP9, tests of model tears with MMP9, and real tear performance from patients, with a promising limit of detection.

In this work, we review the technology of vertically interrogated optical biosensors from the point of view of engineering. Vertical sensors present several advantages in the fabrication processes and in the light coupling systems, compared with other interferometric sensors. Four different interrelated aspects of the design are identified and described: sensing cell design, optical techniques used in the interrogation, fabrication processes, fluidics, and biofunctionalization of the sensing surface. The designer of a vertical sensor should decide carefully which solution to adopt on each aspect prior to finally integrating all the components in a single platform. Complexity, cost, and reliability of this platform will be determined by the decisions taken on each of the design process. We focus on the research and experience acquired by our group during last years in the field of optical biosensors.

This work describes a procedure to obtain the limit of detection (LoD) of a biosensor device from a set of measurements that we call immunoassays, which consists of testing the device’s response to different concentrations of the molecule, which has to be detected throughout its working range. The procedure, based on the recommendations of international organizations, provides general expressions to estimate the uncertainty throughout its working range and the LoD. In the metrological model, the contributions to the uncertainty, due to the determination of the parameters of the calibration curve, the resolution, the lack of repeatability and others are taken into account. The model is applied to experimental data from the calibration of a biosensor. Using iterative weighted least squares techniques, a general logistic function (6-parameters) has been fitted and used as a calibration curve. The example studied shows that the lack of repeatability is not always the most important contribution to the LoD. The final expression of the LoD is equivalent to that of the expanded uncertainty (for a coverage probability of 99.9%) assigned to the concentration when . This result permits seeing the LoD as the smallest concentration measured with the device, whereby uncertainty interval does not include negative values.