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NIH/NCI 439 - Advanced Sample Processing Platforms for Downstream Single-cell Multi-omic Analysis

Fast-Track proposals will NOT be accepted.

Direct Phase II proposal will be accepted

Number of anticipated awards: 3 - 5

Budget (total costs, per award):

Phase I: up to $400,000 for up to 12 months

Phase II: up to $2,000,000 for up to 2 years




Single cell multimodal omics (scMulti-omics) technologies by integrating different readouts, such as DNA, RNA and protein expression, can provide greater value than the sum of the parts making these technologies powerful to characterize the cell in-depth. Isolation of unique cell populations, and simultaneous and selective extraction of different macromolecules can enable further experimental analyses to answer critical questions in basic science and clinical research and empower observational and therapeutic studies. For example, in cancer, scMulti-omic technologies will enable us to identify rare cell types and their characteristics with unprecedented accuracy, to better understand the mechanisms related to tumorigenesis, metastasis, tumor heterogeneity, tumor immune response and immune evasion, and to improve the accuracy of tumor diagnosis, treatment, and prognosis. By 2025, the global scMulti-omics market is anticipated to be $5.32 billion, mainly driven by the increasing need for noninvasive or minimally invasive diagnosis and personalized medicine.

Recent advances have significantly improved multi-omic analysis; however, the sample processing technologies for tumors, in particular solid tumors for multi-omic analysis are lagging behind. The existing technologies are associated with low throughput, high cost, and sub-optimal processing affecting data quality, which hamper their widespread use in biology and ultimately in medicine. There is a need for robust sample processing technologies that are compatible with downstream analysis and can be easily integrated in the preanalytical workflow. In this contract topic, we will focus on improving the preanalytical workflow consisting of several steps to make the biomolecules ready for multi-omic analysis: cell isolation and enrichment for the population of interest followed by cell lysis to release biological materials and then processing of the materials, such as gDNA, mRNA, or expressed proteins, tailored for the downstream target analysis, since biomolecules from single cells are usually extremely low in quantity. Improving the preanalytical workflow may be done at different steps in the workflow such as processing of tissues to maintain integrity of biomolecules, isolation and enrichment of a cell population including unique/rare cell population, biomolecular isolation and enrichment, conversion of the molecular target species into a readable format, while ensuring reagent compatibility in the workflow for downstream analysis and also including quality control (QC) methods to assess capture, isolation and enrichment, QC tools that integrate cellular phenotypic information with the omics information to distinguish cell-to-cell variability from technical noise, and also tools that assess cell viability early on in the workflow to prevent processing of inadequate samples through costly multi-omic analysis.


Project Goals

The offerors are encouraged to integrate the preanalytical workflow from tumor cell dissociation/isolation, enrichment, tracking, cell lysis, to biomolecular isolation on a single platform to enable single cell multimodal-omic analysis. This approach should provide smoother transitions between functional components thereby leading to shorter analysis time and thus higher throughput. In addition, by omitting human intervention, workflow with higher degree of automation should ultimately translate into greater experimental reproducibility. Novel micropillar-based microfluidic platforms that are capable of providing high efficiency separation, isolation and enrichment of single cells and molecules instead of relying on a single-compartment design (e.g. droplet microfluidics, microwell technologies, valved and chambered microchannels, tube-based kits, etc.) for cell and biomolecular processing may be explored. Micropillar arrays within microfluidic channels may serve to physically size-separate genomic DNA from proteins and RNA during cell lysis in a manner compatible with the downstream target analysis.

Overall, at the end of the contract an offeror is expected to provide a robust sample processing platform that easily integrates with scMulti-omic analysis and allow better understanding of heterogeneity in solid tumors and the microenvironment, and also that enable analysis of rare and low-abundant cells such as circulating tumor cells and antigen presenting cells, to potentially open the door to new biomarker and therapeutic targets discoveries in cancer.

The activities that fall within the scope of this solicitation include development of technologies to improve single-cell multi-omic preanalytical microfluidic platforms that integrate steps of the preanalytical workflow such as sample processing, single-cell separation or isolation and enrichment, technologies for solid tumor dissociation/isolation, enrichment and tracking of cancer cells and/or biomolecules for scMulti-omics. Technology proposals focused on developing new or improved molecular analysis will be considered non-responsive to this contract topic.


Phase I Activities and Deliverables

Phase I activities should demonstrate the feasibility of a technology to improve single-cell multi-omic preanalytical platforms.

  • Develop an early/proof-of-principle prototype, single-cell multi-omic preanalytical device/platform or technology for at least one improved step of the scMulti-omic preanalytical workflow
  • If the technology developed is a novel technology for at least one step of the scMulti-omic preanalytical workflow, describe its capability for integration with other steps in the scMulti-omic workflow into a device/platform
  • Establish assays and/or metrics, especially functional comparability and quality attributes, and benchmark the approach against current methods used in single-cell analysis preanalytical workflows using at least two tumor types.
  • Define the target for analysis and demonstrate compatibility with the downstream analytical step (at least two downstream readouts for example DNA and RNA sequencing technologies)
  • Present assay performance and validation results and demonstrate the workflow of the technology during a potential NCI SBIR site visit.


Phase II Activities and Deliverables

Phase II activities should support establishing commercial prototype of the technology, including but not limited by the following activities:

  • Demonstrate system performance and functionality by adopting commercially relevant quantitative milestones:
    • Offerors should specify quantitative technical and commercially-relevant milestones that can be used to evaluate the success of the tool or technology being developed.
    • Offerors should also provide appropriate justification relevant to both the development and commercialization of these technologies.
    • Quantitative milestones may be relative metrics (e.g. comparison to benchmarks, alternative assays or minimization of the pitfalls of the experimental measurements described in phase I) or absolute metrics (e.g. minimum level of detection in a clinically meaningful indication).
  • Show potential/feasibility to scale up the technology at a throughput compatible with widespread adoption by the research and clinical community.
  • Develop a working, commercial prototype device/platform for the single-cell preanalytical workflow and perform pre-market evaluation at multiple sites.
  • Report throughput capacity and cost of the device/platform


Full PHS2022-1 Contract Solicitation

Receipt date: October 28, 2021, 5:00 p.m. Eastern Daylight Time

Apply for this topic on the Contract Proposal Submission (eCPS) website.

Inquiries: Cherie Wells (


Updated Date: 
August 2, 2021