The long term objective of this research is to diagnose cancer via a blood test at an earlier stage and thereby increase the cure rate. We will focus in this program on developing our two instruments to follow genetic changes associated with progressive carcinoma and thereby, eventually help to personalize therapy. It is known that malignant solid tumors shed tumor cells into the circulation at a relatively early stage in their growth. Therefore, if it were possible to capture these relatively rare cells (CTCs) and prove that they are malignant, earlier diagnosis would be expected. Microchips that capture CTCs with great sensitivity have been recently described. We have made such a microchip with proven sensitivity but have altered it using immunolablled nanomagnetic particles for capturing CTCs, which can then be released to an innovative hyperspectral imaging microscope (HMI) that can precisely quantify 10 tumor markers (TMs) in a single pass. The proposed CTC chip-HMI platform can find tumor markers in blood in less than an hour, and with 10-fold greater sensitivity and specificity then existing (commercial) devices such as Cell Tracks, an FDA approved instrument for determining prognosis and treatment effectiveness in breast cancer based on a very small number of captured CTCs. A major breakthrough is the demonstration that over expression of TMs by cancer breast cells allows them to be distinguished from normal breast cells which have consistently less over expression of TMs. Therefore, after capture of the CTCs, evaluation of their TM expression by the HMI and the pathologist's conclusion concerning malignancy, we can then allow for the development of criteria for the number and extent of TM over expression that minimizes false positives but not at the expense of increasing false negatives. The extent and patterns of over expression of particular TMs will also be of considerable value for prognosis and treatment decisions. We will study breast carcinoma as a prototype of other carcinomas, primarily due to that the malignant tumors can be precisely measured radiographically and we have a large supply of patients. We plan to focus on the ability of our instrumentation to find CTCs in patients with small breast carcinomas.

Public Health Relevance

A major goal in cancer research is to diagnose the disease earlier. There is substantial evidence that early diagnosis of cancer can improve the cure rate significantly. We are developing devices at a nanoscale level that will be very effective at capturing the circulating tumor cells and presenting them to a novel microscope. The new microscope will analyze these suspicious cells and determine whether or not they are cancer cells by their content of over expressed tumor markers. In addition to early diagnosis, expression of these tumor markers will help the physician to prognosticate and determine which treatments should be administered to the patient.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA139070-01A2
Application #
8042478
Study Section
Cancer Biomarkers Study Section (CBSS)
Program Officer
Ossandon, Miguel
Project Start
2011-04-01
Project End
2014-03-31
Budget Start
2011-04-01
Budget End
2012-03-31
Support Year
1
Fiscal Year
2011
Total Cost
$324,000
Indirect Cost
Name
University of Texas Austin
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
170230239
City
Austin
State
TX
Country
United States
Zip Code
78712
Hao, Nanjing; Nie, Yuan; Zhang, John X J (2018) Biomimetic hierarchical walnut kernel-like and erythrocyte-like mesoporous silica nanomaterials: controllable synthesis and versatile applications. Microporous Mesoporous Mater 261:144-149
Tadimety, Amogha; Closson, Andrew; Li, Cathy et al. (2018) Advances in liquid biopsy on-chip for cancer management: Technologies, biomarkers, and clinical analysis. Crit Rev Clin Lab Sci 55:140-162
Chorsi, Hamid T; Zhu, Ying; Zhang, John X J (2017) Patterned Plasmonic Surfaces-Theory, Fabrication, and Applications in Biosensing. J Microelectromech Syst 26:718-739
Wu, Jiao; Wei, Xiang; Gan, Jinrui et al. (2016) Multifunctional Magnetic Particles for Combined Circulating Tumor Cells Isolation and Cellular Metabolism Detection. Adv Funct Mater 26:4016-4025
Ng, Elaine; Chen, Kaina; Hang, Annie et al. (2016) Multi-Dimensional Nanostructures for Microfluidic Screening of Biomarkers: From Molecular Separation to Cancer Cell Detection. Ann Biomed Eng 44:847-62
Chen, Peng; Huang, Yu-Yen; Bhave, Gauri et al. (2016) Inkjet-Print Micromagnet Array on Glass Slides for Immunomagnetic Enrichment of Circulating Tumor Cells. Ann Biomed Eng 44:1710-20
Huang, Yu-Yen; Chen, Peng; Wu, Chun-Hsien et al. (2015) Screening and Molecular Analysis of Single Circulating Tumor Cells Using Micromagnet Array. Sci Rep 5:16047
Hoshino, Kazunori; Chung, HaeWon; Wu, Chun-Hsien et al. (2015) An Immunofluorescence-Assisted Microfluidic Single Cell Quantitative Reverse Transcription Polymerase Chain Reaction Analysis of Tumour Cells Separated from Blood. J Circ Biomark 4:11
Chen, Peng; Huang, Yu-Yen; Hoshino, Kazunori et al. (2015) Microscale magnetic field modulation for enhanced capture and distribution of rare circulating tumor cells. Sci Rep 5:8745
Hoshino, Kazunori; Joshi, Pratixa P; Bhave, Gauri et al. (2014) Use of colloidal quantum dots as a digitally switched swept light source for gold nanoparticle based hyperspectral microscopy. Biomed Opt Express 5:1610-5

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