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

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

The invention is directed to apparatus and methods for delivering multiple reagents to, and monitoring, a plurality of analytical reactions carried out on a large-scale array of electronic sensors underminimal noise conditions. In one aspect, the invention provides method of improving signal-to-noise ratios of output signals from the electronic sensors sensing analytes or reaction byproducts by subtracting an average of output signals measured from neighboring sensors where analyte or reaction byproducts are absent. In other aspects, the invention provides an array of electronic sensors integrated with a microwell array for confining analytes and/or particles for analytical reactions and a method for identifying microwells containing analytes and/or particles by passing a sensor-active reagent over the array and correlating sensor response times to the presence or absence of analytes or particles. Such detection of analyte- or particle-containing microwells may be used as a step in additional noise reduction methods.

Apparatus and methods for performing electrochemical reactions

The invention provides particle compositions having applications in nucleic acid analysis. Nucleic acid polymer particles of the invention allow polynucleotides to be attached throughout their volumes for higher loading capacities than those achievable solely with surface attachment. In one aspect, nucleic acid polymer particles of the invention comprise polyacrylamide particles with uniform size distributions having low coefficients of variations, which result in reduced particle-to-particle variation in analytical assays. Such particle compositions are used in various amplification reactions to make amplicon libraries from nucleic acid fragment libraries.

Scaffolded Nucleic Acid Polymer Particles and Methods of Making and Using

Specific ionic interactions with a sensing material that is electrically coupled with the floating gate of a floating gate-based ion sensitive field effect transistor (FGISFET) may be used to sense a target material. For example, an FGISFET can use (e.g., previously demonstrated) ionic interaction-based sensing techniques with the floating gate of floating gate field effect transistors. The floating gate can serves as a probe and an interface to convert chemical and/or biological signals to electrical signals, which can be measured by monitoring the change in the device's threshold voltage, V T .

Floating gate field effect transistors for chemical and/or biological sensing

This paper presents the use of Floating-Gate Ion Sensitive Field-Effect Transistor (FGISFET) as a real-time chemical and biological sensor. The structure of FGISFET is similar to that of an electrically erasable programmable read-only memory (EEPROM). The floating-gate of a FGISFET is connected to an exposed metallic structure, which serves as a probe for detecting ionic activities. By applying ion-sensitive chemical and biological materials to the floating gate, its threshold voltage can be modulated in the presence of selective chemical or biological targets. As a demonstration, FGISFETs have been fabricated in 1.2 µm process technology available through MOSIS [1]. Our preliminary measurements confirmed the basic design and operation of FGISFET, and using doped aniline trimer (TANI) as a sensing material, we were able to sense 70ppm of ammonium gas.

Floating-Gate Ion Sensitive Field-Effect Transistor for Chemical and Biological Sensing

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Floating gate field effect transistors for chemical and/or biological sensing

Floating-Gate Ion Sensitive Field-Effect Transistor for Chemical and Biological Sensing