PDMS with designer functionalities—Properties, modifications strategies, and applications

A hybrid CMOS/thin-film microsystem for fluorescence contact imaging is presented. The microsystem integrates a high-performance optical interference filter and a 128 × 128 pixel active pixel sensor fabricated in a standard 0.35-?m CMOS technology. The thin-film filter has an optical density greater than 6.0 at the wavelength of interest, providing adequate excitation rejection to the 532-nm solid-state laser. Microsystem performance is experimentally validated by imaging spots of Cyanine-3 fluorophore, conventionally used in DNA detection. The emission intensity as a function of fluorophore concentration is measured with an estimated sensitivity of 5000 fluorophore/?m2 . A human DNA microarray has been imaged with the sensor prototype.

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A CMOS/Thin-Film Fluorescence Contact Imaging Microsystem for DNA Analysis

A simple and versatile analytical device designed to perform, even simultaneously, different types of bioassays has been developed and optimized. A transparent microfluidics-based reaction chip, where analytes were quantitatively detected by means of biospecific reactions and chemiluminescence detection, was placed in contact with a thermoelectrically cooled CCD sensor through a fiber optic taper. Such a lensless contact imaging configuration combined adequate spatial resolution and high light collection efficiency within a small size portable device. The miniaturization of the reaction chamber ensured short analysis times (in the minutes range), while the use of chemiluminescence detection provided wide signal dynamic range and high detectability, down to attomole levels of protein and femtomole levels of nucleic acid analytes. A model hybrid panel test was realized by combining an enzyme assay for alkaline phosphatase activity, a nucleic acid hybridization assay for Parvovirus B19 DNA, and an immunoassa...

Portable Device Based on Chemiluminescence Lensless Imaging for Personalized Diagnostics through Multiplex Bioanalysis

Traditionally, charge-coupled device (CCD)-based image sensors have held sway over the field of biomedical imaging. Complementary metal-oxide semiconductor (CMOS)-based imagers so far lack sensitivity leading to poor low-light imaging. Certain applications including our work on animal-mountable systems for imaging in awake and unrestrained rodents require the high sensitivity and image quality of CCDs and the low power consumption, flexibility, and compactness of CMOS imagers. We present a 132 × 124 high sensitivity imager array with a 20.1-μ m pixel pitch fabricated in a standard 0.5- μm CMOS process. The chip incorporates n-well/p-sub photodiodes, capacitive transimpedance amplifier (CTIA)-based in-pixel amplification, pixel scanners, and delta differencing circuits. The 5-transistor all-nMOS pixel interfaces with peripheral pMOS transistors for column-parallel CTIA. At 70 frames/s, the array has a minimum detectable signal of 4 nW/cm2 at a wavelength of 450 nm while consuming 718 μA from a 3.3-V supply. The peak signal-to-noise ratio (SNR) was 44 dB at an incident intensity of 1 μW/cm2. Implementing 4 × 4 binning allowed the frame rate to be increased to 675 frames/s. Alternately, sensitivity could be increased to detect about 0.8 nW/cm2 while maintaining 70 frames/s. The chip was used to image single-cell fluorescence at 28 frames/s with an average SNR of 32 dB. For comparison, a cooled CCD camera imaged the same cell at 20 frames/s with an average SNR of 33.2 dB under the same illumination while consuming more than a watt.

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A CMOS In-Pixel CTIA High-Sensitivity Fluorescence Imager

Integrated optical system-on-chip in silicon operating in the visible range can have a tremendous impact on enabling new applications in sensing and imaging through the ultra-miniaturization of complex optical instrumentation. CMOS technology has allowed an integration of optical detection circuitry for image sensors with massively large number of pixels. In this paper, we focus on techniques to realize complex optical-field processing elements inside CMOS by exploiting optical interaction with sub-wavelength metal nanostructures realized in the electrical interconnects layers, whose feature sizes are now in the sub-100-nm range. In particular, we present a fully integrated fluorescence-based bio-molecular sensor in 65-nm CMOS with integrated nanoplasmonic waveguide-based filters capable of more than 50 dB of rejection ratio across a wide range of incident angles. Co-designed with the integrated photo-detection circuitry, capacitive TIAs, and correlated double-sampling circuitry, the sensor is capable of detecting 48 zeptomoles of quantum dots on the surface with 52 fA of photodetector current with a fluorescence/excitation ratio of nearly −62 dB without any post-fabrication, external optical filters, lenses, or collimators. The ability to integrate complex nanoplasmonic metal structures with unique optical properties in CMOS with no post-processing creates the opportunity to enable large multiplexed assays on a single chip and a wide variety of applications, from in vitro to in vivo .

Fully Integrated Fluorescence Biosensors On-Chip Employing Multi-Functional Nanoplasmonic Optical Structures in CMOS

In this paper, a fully functional low light 128 X 128 contact image sensor for cell detection in biosensing applications is presented. The imager, fabricated in 0.18 mum CMOS technology, provides low-noise operation by employing both a modified version of the active reset (AR) technique and a modified version of the active column sensor (ACS) readout method. High-sensitivity, low noise performance of the presented sensor is well-suited for fluorescence imaging. For this purpose, an emission filter was fabricated and integrated with the sensor. The filter was fabricated using PDMS and Sudan II Blue dye mix, spin-coated and deposited in a class 1000 clean room. The designed filter is suitable for excitation at wavelengths below 340 nm and emission at 450 nm and above. The fabricated imager architecture and operation are described, noise analysis is presented and measurements from a test chip are shown. Experimental results using live neurons from the pond snail, Lymnaea stagnalis, and fluorescence polystyrene micro-beads prove the functionality of the fabricated system and indicate its biocompatiblity.

A Low-Light CMOS Contact Imager With an Emission Filter for Biosensing Applications

In this work we present measurements from two generations of fully operational 128times128 CMOS image sensor arrays. In these imagers, we have modified two existing design techniques, the active reset (AR) technique and the active column sensor (ACS) readout technique, and combined them together to achieve low-noise reset and improved spatial gain fixed pattern noise (FPN). In addition, we have implemented three different types of pixels, employing nwell/psub photodiodes to examine the influence of the shallow trench isolation (STI) on dark currents of the photodiodes. While the first fabricated imager served as a basis for different pixels and techniques examination, the second sensor was designed based on the conclusions drawn from the measurements of the first imager. Measurements from both sensors are presented, showing that the proposed architecture achieves column-level FPN of 0.05%, pixel level FPN of 0.16% and SNR of 15 dB at illumination level as low as 4 nW/mm2, making it suitable for applications, where low light detection is required. Other imager attributes are also presented.

An advanced CMOS imager employing modified AR and ACS methods

This paper presents a 128x128 low noise CMOS image sensor with emission filter for fluorescence detection. The imager, fabricated in 0.18 mum CMOS technology, provides low- noise operation by employing both the active reset (AR) technique and the active column sensor (ACS) readout method. The emission filter was fabricated using PDMS and Sudan II Blue dye mixed, spin-coated and deposited in the class 1000 clean room. The designed filter is suitable for excitation at wavelengths below 340 nm and emission at 450nm and above. Filter properties, such as thickness, transmission and efficiency of utilization with the fabricated imager are discussed. Preliminary measurements of the system using microbeads are also presented.

A Low noise CMOS image sensor with an emission filter for fluorescence applications

Magnesium ion (Mg2+) is one of the most significant cations in living systems with involvement in many biochemical reactions and cellular processes and hence, sensitive and specific detection of Mg2+ is therefore essential for various applications. Here, we report the solvothermal synthesis of boron-doped carbon dots (BC10) with more oxygen surface states by using salicylaldehyde and naphthalene-1-boronic acid. The as-prepared BC10 showed greenish-white luminescence under 365 nm UV illumination with quantum yield (QY) of 5.5 % at optimum dilution with dimethyl sulfur oxide (DMSO) solvent. The BC10 in DMSO (DS-BC10) have shown high selectivity and sensitivity towards Mg2+ ion through the increased PL intensity due to chelation-enhanced photoluminescence (CHEP). The enhanced PL intensity was further supported by the increased QY by a factor of 12 after the addition of Mg2+ ions to 65.7 %. Moreover, the limit of detection of DS-BC10 is calculated to be 0.4 μM, which is 100 times better than the recently reported carbon dot-based Mg2+ sensor. Following that, DS-BC10 is also explored for detection of magnesium ions in lab tap water, seawater, and drinking mineral water with good precision. In addition, density functional theory (DFT) calculations using B3LYP/6-31G (d) method for the DS-BC10 and their Mg2+ complexes support the experimental observations. 

Boron‐doped Carbon Dots with Surface Oxygen Functional Groups as a Highly Sensitive and Label‐free Photoluminescence Probe for the Enhanced Detection of Mg
 2+
 Ions

M. Beiderman

Papers

A Low-Light CMOS Contact Imager With an Emission Filter for Biosensing Applications

An advanced CMOS imager employing modified AR and ACS methods

A Low noise CMOS image sensor with an emission filter for fluorescence applications

Boron‐doped Carbon Dots with Surface Oxygen Functional Groups as a Highly Sensitive and Label‐free Photoluminescence Probe for the Enhanced Detection of Mg 2+ Ions