An apparatus may include a semiconductor chip and a fluidics assembly. The semiconductor chip has an array of wells and an array of sensors and each sensor of the array of sensors is in fluid communication with a well of the array of wells. The fluidics assembly is located on top of the semiconductor chip and is configured to deliver fluids to the semiconductor chip. The fluidics assembly includes a flow expansion chamber configured to introduce the fluids, an outlet portion configured to pipe out the fluids, and a flow chamber portion. The flow chamber portion is configured to allow the fluids to flow from the flow expansion chamber to the outlet portion and to allow the fluids to interact along the way with material in the array of wells. The flow expansion chamber has a curved wall at the top or bottom so that the height of the flow expansion chamber at the center is less than at the walls that restrict the fluids to the left and right.

Methods and apparatus for measuring analytes using large scale fet arrays

Methods and apparatus relating to FET arrays including large FET arrays for monitoring chemical and/or biological reactions such as nucleic acid sequencing-by-synthesis reactions. Some methods provided herein relate to improving signal (and also signal to noise ratio) from released hydrogen ions during nucleic acid sequencing reactions.

Methods and apparatus for measuring analytes

Microelectrode arrays and microprobes have been widely utilized to measure neuronal activity, both in vitro and in vivo. The key advantage is the capability to record and stimulate neurons at multiple sites simultaneously. However, unlike the single-cell or single-channel resolution of intracellular recording, microelectrodes detect signals from all possible sources around the sensor. Here, we review the current understanding of microelectrode signals and the techniques for analyzing them. We introduce the ongoing advancements in microelectrode technology, with focus on achieving higher resolution and quality of recordings by means of monolithic integration with on-chip circuitry. We show how recent advanced microelectrode array measurement methods facilitate the understanding of single neurons as well as network function.

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Revealing neuronal function through microelectrode array recordings

Methods and apparatuses relating to large scale FET arrays for analyte detection and measurement are provided. ChemFET (e.g., ISFET) arrays may be fabricated using conventional CMOS processing techniques based on improved FET pixel and array designs that increase measurement sensitivity and accuracy, and at the same time facilitate significantly small pixel sizes and dense arrays. Improved array control techniques provide for rapid data acquisition from large and dense arrays. Such arrays may be employed to detect a presence and/or concentration changes of various analyte types in a wide variety of chemical and/or biological processes.

Methods and apparatus for detecting molecular interactions using FET arrays

We report a simple, yet effective method to disperse NaYF4 nanocrystals (NCs) doped with luminescent Ln3+ ions in water and physiological buffers using an amphiphilic polymer poly(ethylene glycol) ...

Two-Photon Upconversion Laser (Scanning and Wide-Field) Microscopy Using Ln3+-Doped NaYF4 Upconverting Nanocrystals: A Critical Evaluation of their Performance and Potential in Bioimaging

An optical and potential dual imaging CMOS sensor for bioscientific applications was proposed and fabricated The CMOS image sensor has the capability to simultaneously capture optical and on-chip potential images The sensor is designed with target applications of on-chip DNA (or protein) microarray analysis and on-chip neural imaging A potential imaging function was implemented onto a CMOS image sensor with a simple pixel circuitry that is compatible with optical image sensor pixels The basic properties of the potential-sensing pixel were characterized By choosing an appropriate operating sequence and off-chip configuration, the sensor can be operated in either a wide-range potential imaging mode (>5 V) or a high-resolution potential imaging mode (16 mV) The sensor is applicable for most of the target applications and is capable of detecting a pH change in the solution placed on the surface Two-dimensional optical and potential dual imaging was successfully demonstrated, and the profile of a potential spot smaller than 50 μm was clearly observed

A CMOS image sensor with optical and potential dual imaging function for on-chip bioscientific applications

We have developed an on-chip biofluorescence imaging device by packaging a dedicated CMOS image sensor using a simple technique. By using on-chip imaging configuration, we have verified in vivo fluorescence imaging inside a specially developed brain tissue phantom that closely resembles the mammalian brain. In order to implement on-chip imaging, an excitation light filter is applied onto the chip. A transmittance of −44 dB is achieved by multiple coating of the filter. On-chip measurement of the AMC fluorophore shows that detection of concentration of 1 μM is possible. The phantom medium has mechanical rigidity and optical property similar to the mouse brain. Feasibility of imaging the released fluorophore inside the phantom sample is demonstrated. It is shown that light scattering in the phantom medium does not reduce the image resolution considerably, if the imaging depth is kept below 500 μm. The fully packaged chip, specially designed with this technique is about 350 μm thick and 2.7 mm wide. The image sensor pixel size of 7.5 μm × 7.5 μm is close to the size of a single neuron cell. Although the device is designed specially for in vivo imaging of the mouse hippocampus to study its neuronal activity, a wide range of applications are foreseen in the biomedical and pharmaceutical field.

On-chip biofluorescence imaging inside a brain tissue phantom using a CMOS image sensor for in vivo brain imaging verification

Real time in vivo imaging and measurement of serine protease activity in the mouse hippocampus using a dedicated complementary metal-oxide semiconductor imaging device.

An optical/potential CMOS image sensor was designed and fabricated for bioimaging applications. The image sensor is capable to simultaneously sense an optical image and an on-chip potential image. Target applications of the sensor are on-chip (optical + potential) neural imaging and on-chip DNA microarray sensing. The sensor has a QCIF (176 times 144) pixel array with alternatively aligned optical/potential sensing pixels. The pixel size is 7.5 mum times 7.5 mum. The potential resolution is confirmed to be better than 10 mV. An on-chip fluorescence imaging of a mouse's hippocampus was performed to demonstrate that fluorescence imaging is possible with on-chip configuration

A CMOS optical/potential image sensor with 7.5&#956;m pixel size for on-chip neural and DNA spot sensing

A CMOS image sensor which is capable to simultaneously sense an optical and an op-chip potential image was designed and fabricated. The sensor was designed with target applications to sense neural activities and DNA spots in on-chip configuration. We designed compatibly configured light sensing pixel and potential sensing pixel. The pixel size is 7.5 /spl mu/m. A QCIF (176 /spl times/ 144) dual image sensor was fabricated and characterized. The basic characteristics of the potential sensing pixel are discussed and dual imaging functions are demonstrated.

Akio Yamamoto

Papers

A CMOS image sensor with optical and potential dual imaging function for on-chip bioscientific applications

On-chip biofluorescence imaging inside a brain tissue phantom using a CMOS image sensor for in vivo brain imaging verification

Real time in vivo imaging and measurement of serine protease activity in the mouse hippocampus using a dedicated complementary metal-oxide semiconductor imaging device.

A CMOS optical/potential image sensor with 7.5μm pixel size for on-chip neural and DNA spot sensing

An optical and potential dual-image CMOS sensor for on-chip neural and DNA imaging applications

Akio Yamamoto

Papers

A CMOS image sensor with optical and potential dual imaging function for on-chip bioscientific applications

On-chip biofluorescence imaging inside a brain tissue phantom using a CMOS image sensor for in vivo brain imaging verification

Real time in vivo imaging and measurement of serine protease activity in the mouse hippocampus using a dedicated complementary metal-oxide semiconductor imaging device.

A CMOS optical/potential image sensor with 7.5&#956;m pixel size for on-chip neural and DNA spot sensing

An optical and potential dual-image CMOS sensor for on-chip neural and DNA imaging applications

A CMOS optical/potential image sensor with 7.5μm pixel size for on-chip neural and DNA spot sensing