On Chip Analysis of CNS Lymphoma in Cerebrospinal Fluid

Anna Turetsky^1*, Kyungheon Lee^1*, Jun Song^1,2*, Randy J. Giedt¹, Eunha Kim¹, Alexandra E. Kovach³, Ephraim P. Hochberg⁴, Cesar M. Castro^1,4, Hakho Lee¹, Ralph Weissleder^{1,5 ✉}

1. Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge St, CPZN 5206, Boston, MA 02114, USA
2. School of Engineering and Applied Sciences, Harvard University, Cambridge, MA
3. Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA
4. Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA
5. Department of Systems Biology, Harvard Medical School, 200 Longwood Ave, Boston, MA 02115, USA
* These authors equally contributed.

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Citation:
Turetsky A, Lee K, Song J, Giedt RJ, Kim E, Kovach AE, Hochberg EP, Castro CM, Lee H, Weissleder R. On Chip Analysis of CNS Lymphoma in Cerebrospinal Fluid. Theranostics 2015; 5(8):796-804. doi:10.7150/thno.11220. Available from https://www.thno.org/v05p0796.htm

Abstract

Molecular profiling of central nervous system lymphomas in cerebrospinal fluid (CSF) samples can be challenging due to the paucicellular and limited nature of the samples. Presented herein is a microfluidic platform for complete CSF lymphoid cell analysis, including single cell capture in sub-nanoliter traps, and molecular and chemotherapeutic response profiling via on-chip imaging, all in less than one hour. The system can detect scant lymphoma cells and quantitate their kappa/lambda immunoglobulin light chain restriction patterns. The approach can be further customized for measurement of additional biomarkers, such as those for differential diagnosis of lymphoma subtypes or for prognosis, as well as for imaging exposure to experimental drugs.

Keywords: lymphoma, microfluidics, point-of-care, cerebrospinal fluid, drug testing