Immunoassay for detailed analysis of immune−cancer intercellular interactions can achieve more promising diagnosis and treatment strategies for cancers including nasopharyngeal cancer (NPC). In this study, we report a microfluidic live−cell immunoassay integrated with a microtopographic environment to meet the rising demand for monitoring intercellular interactions in different tumor microenvironments. The developed assay allows: (1) coculture of immune cells and cancer cells on tunable (flat or micrograting) substrates, (2) simultaneous detection of different cytokines in a wide working range of 5–5000 pg/mL, and (3) investigation of migration behaviors of mono- and co-cultured cells on flat/grating platforms for revealing the topography-induced intercellular and cytokine responses. Cytokine monitoring was achieved on-chip by implementing a sensitive and selective microbead-based sandwich assay with an antibody on microbeads, target cytokines, and the matching fluorescent-conjugated detection antibody in an array of active peristaltic mixer-assisted cytokine detection microchambers. Moreover, this immunoassay requires a low sample volume down to 0.5 μL and short assay time (30 min) for on-chip cytokine quantifications. We validated the biocompatibility of the co-culture strategy between immune cells and NPC cells and compared the different immunological states of undifferentiated THP-1 monocytic cells or PMA-differentiated THP-1 macrophages co-culturing with NP460 and NPC43 on topographical and planar substrates, respectively. Hence, the integrated microfluidic platform provides an efficient, broad-range and precise on-chip cytokine detection approach, eliminates the manual sampling procedures and allows on-chip continuous cytokine monitoring without perturbing intercellular microenvironments on different topographical ECM substrates, which has the potential of providing clinical significance in early immune diagnosis, personalized immunotherapy, and precision medicine.

Intravenous injection is a rapid, low-cost, and direct method that is commonly used to deliver multifarious biotherapeutics and vaccines. However, intravenous injection often causes trauma or tissue injury that requires professional operation. Transdermal drug delivery overcomes the aforementioned defects, and the microneedles (MNs) array is one of the most promising transdermal drug delivery platforms. Timely, precise, and non-invasive monitoring and evaluation of the effects of MNs in transdermal administration is significant to the research of drug efficiency response to specific diseases. In this sense, photoacoustic computed tomography (PACT), which provides wavelength-selective and deep-penetrating optical contrast, could be a promising imaging tool for in situ evaluation of the treatment effects. In this work, we propose the use of PACT to non-invasively assess the effects of real-time drug delivery in glioma tumors through transdermal administration with degradable indocyanine green-loaded hyaluronic acid MNs (ICG-HA-MNs). The outcome is systematically and quantitatively compared with that via intravenous injection. It is found that the photoacoustic signals of ICG in the tumor site express a faster elevation and shorter duration time in the intravenous injection group; by contrast, the photoacoustic signals demonstrate a lower intensity but prolonged duration time in the MNs group. The observed phenomenon indicates faster response but shorter drug duration for intravenous injection, which is in contrast with the lower loading but prolonged performance for transdermal drug delivery with MNs. These results exhibit good consistency with the earlier, common-sense findings reported from other aspects, confirming that PACT can serve as a potential imaging tool to precisely, non-invasively, and quickly evaluate in situ drug delivery effects and provide constructive guidance for the design and fabrication of microneedles.

Hemodynamic status has been perceived as an important diagnostic value as fundamental physiological health conditions, including decisive signs of fatal diseases like arteriosclerosis, can be diagnosed by monitoring it. Currently, the conventional hemodynamic monitoring methods highly rely on imaging techniques requiring inconveniently large numbers of operation procedures and equipment for mapping and with a high risk of radiation exposure. Herein, an ultra-thin, noninvasive, and flexible electronic skin (e-skin) hemodynamic monitoring system based on the thermal properties of blood vessels underneath the epidermis that can be portably attached to the skin for operation is introduced. Through a series of thermal sensors, the temperatures of each subsection of the arrayed sensors are observed in real-time, and the measurements are transmitted and displayed on the screen of an external device wirelessly through a Bluetooth module using a graphical user interface (GUI). The degrees of the thermal property of subsections are indicated with a spectrum of colors that specify the hemodynamic status of the target vessel. In addition, as the sensors are installed on a soft substrate, they can operate under twisting and bending without any malfunction. These characteristics of e-skin sensors exhibit great potential in wearable and portable diagnostics including point-of-care (POC) devices.