Self-Powered Microfluidics for Point-of-Care Solutions: From Sampling to Detection of Proteins and Nucleic Acids.

Self-powered microfluidics presents a revolutionary approach to address the challenges of healthcare in decentralized and point-of-care settings where limited access to resources and infrastructure prevails or rapid clinical decision-making is critical. These microfluidic systems exploit physical and chemical phenomena, such as capillary forces and surface tension, to manipulate tiny volumes of fluids without the need for external power sources, making them cost-effective and highly portable. Recent technological advancements have demonstrated the ability to preprogram complex multistep liquid operations within the microfluidic circuit of these standalone systems, which enabled the integration of sensitive detection and readout principles. This chapter first addresses how the accessibility to in vitro diagnostics can be improved by shifting toward decentralized approaches like remote microsampling and point-of-care testing. Next, the crucial role of self-powered microfluidic technologies to enable this patient-centric healthcare transition is emphasized using various state-of-the-art examples, with a primary focus on applications related to biofluid collection and the detection of either proteins or nucleic acids. This chapter concludes with a summary of the main findings and our vision of the future perspectives in the field of self-powered microfluidic technologies and their use for in vitro diagnostics applications.

Innovative Fabrication of Hollow Microneedle Arrays Enabling Blood Sampling with a Self-Powered Microfluidic Patch.

Microneedles are gaining a lot of attention in the context of sampling cutaneous biofluids such as capillary blood. Their minimal invasiveness and user-friendliness make them a prominent substitute for venous puncture or finger-pricking. Although the latter is suitable for self-sampling, the impracticality of manual handling and the difficulty of obtaining enough qualitative sample is driving the search for better solutions. In this context, hollow microneedle arrays (HMNAs) are particularly interesting for completely integrating sample-to-answer solutions as they create a duct between the skin and the sampling device. However, the fabrication of sharp-tipped HMNAs with a high aspect ratio (AR) is challenging, especially since a length of ≥1500 µm is desired to reach the blood capillaries. In this paper, we first described a novel two-step fabrication protocol for HMNAs in stainless steel by percussion laser drilling and subsequent micro-milling. The HMNAs were then integrated into a self-powered microfluidic sampling patch, containing a capillary pump which was optimized to generate negative pressure differences up to 40.9 ± 1.8 kPa. The sampling patch was validated in vitro, showing the feasibility of sampling 40 µL of liquid. It is anticipated that our proof-of-concept is a starting point for more sophisticated all-in-one biofluid sampling and point-of-care testing systems.

Fabrication and characterization of porous tissue-mimicking optical phantoms as a tool for optical sensor validation.

This paper presents porous polydimethylsiloxane (PDMS) optical phantoms with tunable microstructural and optical properties to mimic porous biological tissues (e.g., fruit) during the design and optimization of novel optical setups. A well connected salt network formed using salt particles of various size distributions was used to obtain porous PDMS phantoms of different porous features including porosity, pore size distribution, pore number density and pore connectivity. These microstructural features are strongly related to the light scattering from the phantom where a higher reduced scattering coefficient ( µ s ' ) was observed from the porous PDMS phantom with a higher number of small pores compared to the optical phantom with a lower number of larger pores. The prepared phantoms were used to validate GASMAS (gas in scattering media absorption spectroscopy) H2 O and O2 sensors by quantifying the optical path length through the pores and the O2 concentration inside the pores.

Precise sample metering method by coordinated burst action of hydrophobic burst valves applied to dried blood spot collection.

Dried blood spot (DBS) sampling by finger-pricking has recently gained a lot of interest as an alternative sample collection method. The reduced invasiveness, requirement of lower sample volumes and suitability for long-term storage at room temperature make DBS ideal for use in home settings or low-resource environments. However, traditional protocols often suffer from biased analysis data due to variable and not exactly known blood volumes present in the samples. In this work, a novel device has been developed to split-off precisely metered volumes from a blood drop and load them on pre-cut filter paper. Hereto, hydrophobic burst valves (HBV) were developed to temporarily retain a fluid flow, configurable to burst at pressures within a range of 175-600 Pa. By combining HBVs with different burst pressures, a volume metering system was developed to allow parallel metering of multiple pre-defined sample volumes. The system was shown to be accurate and consistent for blood volumes between 5-15 µL and for hematocrit levels spanning the range of 25-70%. Finally, a point-of-care DBS sampling device was developed combining the self-powered microfluidic SIMPLE technology. To evaluate the system's practical applicability, a validation study in the context of therapeutic drug monitoring of biologicals was performed using adalimumab-spiked blood samples. Microfluidic DBS samples showed good performance compared to the traditional DBS method with improved recovery rates (86% over 62%). This innovative metering system, allowing for parallelization and integration with complex liquid manipulations, will greatly impact the field of robust sampling, sample preparation, storage and analysis at the point-of-care.