RESUMEN
A Point-of-Care system for molecular diagnosis (PoC-MD) is described, combining GaN and CMOS chips. The device is a micro-system for fluorescence measurements, capable of analyzing both intensity and lifetime. It consists of a hybrid micro-structure based on a 32 × 32 matrix addressable GaN microLED array, with square LEDs of 50 µm edge length and 100 µm pitch, with an underneath wire bonded custom chip integrating their drivers and placed face-to-face to an array of 16 × 16 single-photon avalanche diodes (SPADs) CMOS. This approach replaces instrumentation based on lasers, bulky optical components, and discrete electronics with a full hybrid micro-system, enabling measurements on 32 × 32 spots. The reported system is suitable for long lifetime (>10 ns) fluorophores with a limit of detection ~1/4 µM. Proof-of-concept measurements of streptavidin conjugate Qdot™ 605 and Amino PEG Qdot™ 705 are demonstrated, along with the device ability to detect both fluorophores in the same measurement.
Asunto(s)
Técnicas Biosensibles , Fluorescencia , Sistemas de Atención de Punto , Espectrometría de FluorescenciaRESUMEN
Recent research into miniaturized illumination sources has prompted the development of alternative microscopy techniques. Although they are still being explored, emerging nano-light-emitting-diode (nano-LED) technologies show promise in approaching the optical resolution limit in a more feasible manner. This work presents the exploration of their capabilities with two different prototypes. In the first version, a resolution of less than 1 µm was shown thanks to a prototype based on an optically downscaled LED using an LED scanning transmission optical microscopy (STOM) technique. This research demonstrates how this technique can be used to improve STOM images by oversampling the acquisition. The second STOM-based microscope was fabricated with a 200 nm GaN LED. This demonstrates the possibilities for the miniaturization of on-chip-based microscopes.
RESUMEN
The recent advances in chip-size microscopy based on optical scanning with spatially resolved nano-illumination light sources are presented. This new straightforward technique takes advantage of the currently achieved miniaturization of LEDs in fully addressable arrays. These nano-LEDs are used to scan the sample with a resolution comparable to the LED sizes, giving rise to chip-sized scanning optical microscopes without mechanical parts or optical accessories. The operation principle and the potential of this new kind of microscope are analyzed through three different implementations of decreasing LED dimensions from 20 µm down to 200 nm.
RESUMEN
In lensless microscopy, spatial resolution is usually provided by the pixel density of current digital cameras, which are reaching a hard-to-surpass pixel size / resolution limit over 1 µm. As an alternative, the dependence of the resolving power can be moved from the detector to the light sources, offering a new kind of lensless microscopy setups. The use of continuously scaled-down Light-Emitting Diode (LED) arrays to scan the sample allows resolutions on order of the LED size, giving rise to compact and low-cost microscopes without mechanical scanners or optical accessories. In this paper, we present the operation principle of this new approach to lensless microscopy, with simulations that demonstrate the possibility to use it for super-resolution, as well as a first prototype. This proof-of-concept setup integrates an 8 × 8 array of LEDs, each 5 × 5â µm2 pixel size and 10â µm pitch, and an optical detector. We characterize the system using Electron-Beam Lithography (EBL) pattern. Our prototype validates the imaging principle and opens the way to improve resolution by further miniaturizing the light sources.