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An integrated acoustofluidic droplet-sorting platform for classification of lymphocyte activity and functional phenotyping at single cell level

Award Number: R01GM127714
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Abstract The outcome of many pathological diseases such as infection and cancer is determined by the interaction of diseased cells with various immune cell subsets, both of which are phenotypically and functionally diverse. Induced resistance to chemo- and immuno-therapeutic drugs remain one of the main challenges in modern medicine. Moreover, there exists significant inter-patient and even intra-patient variability in response to well- established drug regimens, making it difficult to predict a patient's response to applied treatments. Single-cell analysis techniques have great potential in revealing, and ultimately utilizing, patient-specific cellular information to devise a more personalized approach to therapeutic regimens. Thus, developing a rapid screening system for assessing target-immune cell interactions, which are modulated by immunogenic treatments, will allow clinicians to predict the patient's response to a treatment, streamline treatment protocols and improve the efficacy of immunotherapeutic strategies in patient-specific manner. Here, we propose to develop an integrated microfluidic droplet based platform that permits quantitative analysis of the efficiency of immune reactions (responsive vs. non-responsive and fast vs. slow kinetics) and subsequent sorting and recovery of functionally distinct subsets for molecular (transcriptomic) characterization. We propose to integrate large-scale droplet microfluidic arrays with dual acoustofluidic sorters that achieve a level of throughput (>18,000 events/sec) and controllability (four-channel sorting) that no microfluidic droplet sorter has been able to achieve. Collectively, the sorters and the droplet docking arrays will allow for selection, enrichment and visualization of droplets of interest containing effector immune and target cells at different cell ratios, thereby allowing dynamic analysis of cell-cell interaction to identify predictive phenotypic classifiers. The sorted cells will then be analyzed by global transcriptomic profiling and unbiased systems biology approaches to identify the correlation between key molecular signatures and functional heterogeneity. This multifunctional analytical platform will further enable screening and validation of targeted therapies at single-cell level by sequentially exposing the encapsulated effector/target cells to first and second generation drugs via an integrated droplet merging junction. This approach will greatly enhance the identification of drug candidates prior to therapeutic administration to assist in disease - and patient-specific treatment decisions. We will validate our platform by functionally classifying lymphoma-Natural Killer (NK) cell interaction in the presence of approved anti-CD20 immunotherapy to (1) determine optimal immune activity required to achieve highly effective response to anti-CD20 immunotherapy; and (2) obtain critical insights into the development of resistance to anti-CD20 therapy in cancer. We envision this platform ultimately being employed in a variety of single-cell analysis applications and being of high value to the biomedical, and pharmaceutical research communities.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = -$7,115 )
2024	2021	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	000	4	2/14/2024	NON-COMPETING CONTINUATION	-$7,115
														Subtotal = -$7,115

Issue Date FY: 2021 ( Subtotal = $270,187 )
2021	2021	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	000	4	4/28/2021	NON-COMPETING CONTINUATION	$270,187
														Subtotal = $270,187

Issue Date FY: 2020 ( Subtotal = $268,302 )
2020	2020	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	000	3	4/30/2020	NON-COMPETING CONTINUATION	$268,302
														Subtotal = $268,302

Issue Date FY: 2019 ( Subtotal = $294,609 )
2019	2019	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	000	2	4/18/2019	NON-COMPETING CONTINUATION	$294,609
														Subtotal = $294,609

Issue Date FY: 2018 ( Subtotal = $321,334 )
2018	2018	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	000	1	8/6/2018	NEW	$321,334
														Subtotal = $321,334

Grand Total All Awards = $1,147,317

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An integrated acoustofluidic droplet-sorting platform for classification of lymphocyte activity and functional phenotyping at single cell level

Award Number: R01GM127714

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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