Semiconductor Sequencing Biosensor with Multi-Well Pixel Detection

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Solution Overview

Problem

Conventional solid-state imaging systems for nucleic acid sequencing are limited by pixel density and require large footprints, leading to high costs and reduced throughput.

Innovation Solution

A biosensor device with a sample surface and array of sensors that generates multiple pixel signals per sensor, using illumination stages to classify nucleotide bases and account for uneven cluster distribution, enabling higher throughput and accuracy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional solid-state imaging systems are used for nucleic acid sequencing, then detection can be performed with compact size, but throughput is limited by pixel density and costs increase

Engineering Contradiction:

Improvesequencing throughputVSAvoidnumber of sensors required

Core Design Contradiction:

ProductivityVSQuantity of substance

Solution Approach 1:

The patent combines multiple pixel areas into a single sensor by using optical elements (lenses, mirrors) to direct light from multiple pixel areas to one sensor. This merging approach allows one sensor to detect signals from multiple clusters located at different pixel areas, thereby increasing the number of clusters that can be detected per sensor and improving sequencing throughput without proportionally increasing the number of sensors required

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The patent makes sensors multi-functional by enabling each sensor to perform detection for multiple pixel areas simultaneously. Through the optical system configuration, a single sensor serves multiple detection zones, allowing the system to achieve higher throughput with fewer sensors. This multi-functionality is achieved through illumination stages and optical routing that direct signals from different spatial locations to the same sensor

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Productivity

If pixel pitch is decreased to increase pixel density, then throughput may improve, but manufacturing complexity and costs increase significantly

Engineering Contradiction:

ImprovethroughputVSAvoidpixel pitch reduction complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

Instead of increasing pixel density by reducing pixel pitch in the same dimensional plane, the patent introduces an optical dimension by using lenses and mirrors to fold the optical path. This allows multiple pixel areas to be mapped to fewer sensors through three-dimensional optical routing, achieving increased effective pixel density without the manufacturing challenges of reducing actual pixel pitch

Inventive Principle:

Principle #17Another dimension (Dimensionality change)

3Measurement precision

If optical systems with lenses and filters are used for fluorescent detection, then detection accuracy is maintained, but system footprint and cost increase

Engineering Contradiction:

Improvefluorescent signal detection accuracyVSAvoidsystem footprint

Core Design Contradiction:

Measurement precisionVSArea of stationary object

Solution Approach 1:

The patent merges multiple optical functions (illumination, detection, signal routing) into a compact integrated system. By combining the illumination source, optical elements (lenses and mirrors), and sensor array into a tightly integrated configuration, the system achieves accurate fluorescent detection with a reduced footprint compared to conventional optical systems where these components are more dispersed

Inventive Principle:

Principle #5Merging (Combining)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

Enhances sequencing throughput and reduces costs by efficiently detecting nucleotide bases with fewer sensors, improving the efficiency of nucleic acid array detection.

Implementation Method 1

the solid-state imagers are limited to one cluster base call per sensor (or pixel) and their throughput is dependent on the pixel density of the sensors

Methodology Applied

Scientific EffectPhotodetection: Photoelectric Effect

Implementation Method 2

an optical system is used to direct an excitation light onto fluorescently-labeled analytes and to also detect the fluorescent signals that may emit from the analytes

Methodology Applied

Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS12498347B2Systems and devices for high-throughput sequencing with semiconductor-based detection

Publication Date: 2025.12.16 ILLUMINA INC

AI summary

In one embodiment, a sample surface of a biosensor includes pixel areas and holds a plurality of clusters during a sequence of sampling events such that the clusters are distributed unevenly over the pixel areas. In another embodiment, a biosensor has a sample surface that includes pixel areas and an array of wells overlying the pixel areas, the biosensor including two wells and two clusters per pixel area. The two wells per pixel area include a dominant well and a subordinate well. The dominant well has a larger cross section over the pixel area than the subordinate well. In yet another embodiment, an illumination system is coupled to a biosensor that illuminates the pixel areas with different angles of illumination during a sequence of sampling events, including, for a sampling event, illuminating each of the wells with off-axis illumination to produce asymmetrically illuminated well regions in each of the wells.