Automated CTC Analysis via Spectral Imaging and Antibody Enrichment
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Solution Overview
Problem
Current methods for analyzing circulating tumor cells (CTCs) are inefficient due to their rarity in blood samples, making it challenging to isolate and characterize them for cancer diagnosis and prognosis, particularly in prostate cancer.
Innovation Solution
An automated method using an instrument that enriches CTCs with capture antibodies specific for ERG, PSMA, or EpCAM proteins, followed by spectral imaging with labeled nucleic acid probes for ERG rearrangements, PTEN deletions, and CEN-10 detection, allowing for characterization of prostate cancer and prediction of treatment responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If manual methods are used to analyze circulating tumor cells, then operational flexibility is maintained, but analysis efficiency and productivity are insufficient due to the rarity of CTCs in blood samples
Solution Approach 1:
The automated instrument performs self-service by automatically enriching CTCs from blood samples through multiple sequential steps including initial enrichment, deposition on substrates, and characterization without requiring continuous manual intervention. The system autonomously handles the complex workflow from sample processing to spectral imaging and data analysis, resolving the contradiction between productivity improvement and device complexity.
2Measurement precision
If enrichment methods are used to increase CTC concentration, then detection sensitivity is improved, but the complexity of the isolation process increases
Solution Approach 1:
The enrichment process is segmented into distinct automated stages: initial CTC enrichment from blood, deposition onto specialized substrates, and subsequent spectral imaging for characterization. Each segment is handled by the automated instrument, which reduces the perceived complexity by breaking down the isolation process into manageable, automated steps while maintaining high detection sensitivity.
Solution Approach 2:
The automated instrument acts as an intermediary between the blood sample and the detection system, performing the complex enrichment and isolation tasks. This intermediary device manages the complexity of the isolation process internally while presenting a simplified interface to the user, thereby improving detection sensitivity without proportionally increasing user-facing complexity.
3Measurement precision
If multiple genetic markers are detected simultaneously, then diagnostic accuracy is improved, but the complexity of the characterization process increases
Solution Approach 1:
The automated instrument merges multiple detection functions into a single integrated system. It simultaneously performs spectral imaging to detect ERG rearrangements, PTEN deletions, and CEN-10 signals within the same CTC sample using quantum dot-labeled probes. This combining of multiple diagnostic functions into one automated workflow improves diagnostic accuracy while managing characterization process complexity through integration.
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
Enables accurate characterization of prostate cancer, predicting treatment responses, disease recurrence, progression, and metastasis by detecting ERG rearrangements and PTEN deletions in CTCs, improving diagnostic and prognostic capabilities.
Implementation Method 1
enriching the CTC content of the sample using a capture antibody specific for an ETS related gene (ERG) protein, a prostate specific membrane antigen (PSMA) protein, or an epithelial cell adhesion molecule (EpCAM) protein
Implementation Method 2
contacting the sample with CTC characterization reagents using the automated instrument... nucleic acid probes specific for ERG, PTEN, and CEN-10... under conditions sufficient for the nucleic acid probes to hybridize to their complementary sequence in the CTCs
Implementation Method 3
The nucleic acid probes are labeled, for example with one or more quantum dots... signals from the one or more quantum dots on the one or more nucleic acid probes are detected, for example by using spectral imaging
Data Source
AI summary
The disclosure provides methods for automated characterization of circulating tumor cells (CTCs), for example using automated tissue strainers. In specific examples, such methods permit characterizing a prostate cancer sample by simultaneously or contemporaneously detecting ERG rearrangements and PTEN deletions in the same CTC. Also provided are kits that can be used with such methods.