Numerous approaches have been taken to miniaturizing fluorescence sensing, which is a key capability for micro-total-analysis systems. This critical, comprehensive review focuses on the optical hardware required to attenuate excitation light while transmitting fluorescence. It summarizes, evaluates, and compares the various technologies, including filtering approaches such as interference filters and absorption filters and filterless approaches such as multicolor sensors and light-guiding elements. It presents the physical principles behind the different architectures, the state-of-the-art micro-fluorometers and how they were microfabricated, and their performance metrics. Promising technologies that have not yet been integrated are also described. This information will permit the identification of methods that meet particular design requirements, from both performance and integration perspectives, and the recognition of the remaining technological challenges. Finally, a set of performance metrics are proposed for evaluating and reporting spectral discrimination characteristics of integrated devices in order to promote side-by-side comparisons among diverse technologies and, ultimately, to facilitate optimized designs of micro-fluorometers for specific applications.

Combining integrated circuitry with microfluidics enables lab-on-a-chip (LOC) devices to perform sensing, freeing them from benchtop equipment. However, this integration is challenging with small chips, as is briefly reviewed with reference to key metrics for package comparison. In this paper we present a simple packaging method for including mm-sized, foundry-fabricated dies containing complementary metal oxide semiconductor (CMOS) circuits within LOCs. The chip is embedded in an epoxy handle wafer to yield a level, large-area surface, allowing subsequent photolithographic post-processing and microfluidic integration. Electrical connection off-chip is provided by thin film metal traces passivated with parylene-C. The parylene is patterned to selectively expose the active sensing area of the chip, allowing direct interaction with a fluidic environment. The method accommodates any die size and automatically levels the die and handle wafer surfaces. Functionality was demonstrated by packaging two different types of CMOS sensor ICs, a bioamplifier chip with an array of surface electrodes connected to internal amplifiers for recording extracellular electrical signals and a capacitance sensor chip for monitoring cell adhesion and viability. Cells were cultured on the surface of both types of chips, and data were acquired using a PC. Long term culture (weeks) showed the packaging materials to be biocompatible. Package lifetime was demonstrated by exposure to fluids over a longer duration (months), and the package was robust enough to allow repeated sterilization and re-use. The ease of fabrication and good performance of this packaging method should allow wide adoption, thereby spurring advances in miniaturized sensing systems.

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We report simulated and experimental image quality for contact imaging, a method for imaging objects close to the sensor surface without intervening optics. This technique preserves microscale resolution for applications that can not tolerate the size or weight of conventional optical elements. In order to assess image quality, we investigated the spatial resolution of contact imaging, which depends on the sensor size as well as the distance between objects and the sensor surface. We studied how this distance affects image quality using a commercial optical simulator. Simulation results show that the image quality degrades as objects move away from the sensor surface. To experimentally validate these results, an image sensor was designed and fabricated in a commercially available three metal, two poly, 0.5 m CMOS technology. Experiments with the contact imager corroborate the simulation results. Two specific applications of contact imaging are demonstrated.Index Terms-CMOS analog integrated circuits, contact imaging, geometrical optics, image resolution, image sensors, mixed signal analog-digital integrated circuits.