Microscale Immune and Cell Analysis (MICA)

Technology Summary

Researchers at Sandia National Laboratories have created a sophisticated, integrated platform for single-cell manipulation and interrogation.

Called Microscale Immune and Cell Analysis (MICA), this platform represents a revolutionary breakthrough in biological research. MICA offers experimenters the ability to understand cell behavior at the molecular and cellular levels with unprec­edented speed, resolution, sensitivity, and multiplexing.

Unlike other lab-on-a-chip platforms, MICA helps re­searchers target, sort, and measure samples as small as a single cell in a precise, automated system that incorporates flow cytometry. And because MICA is based on microfluid­ics, it enables biological measurements that are impossible at a conventional scale.

The promise of MICA is immense. MICA has already proven its value in a major Sandia research program that is investigating the responses of immune cells to pathogens. When fully developed as a research tool, the MICA platform may enable scientists to integrate experimentation on myriad cell types, thereby providing a systems understanding of mul­tiple cellular mechanisms that have long eluded researchers.

Description

MICA helps researchers unlock the secrets of cell functions by offering an integrated platform of tools that include dosing, cell preparation, imaging, flow cytometry, sorting, and single-cell arrays (SCAs). These tools can be used to perform comprehensive biology experiments and mea­surements on samples as small as a single cell.

MICA also offers high-sensitivity and high-throughput analyses that are both rapid and convenient. By using MICA, researchers can automate and integrate cellular experiments, thereby yielding rich—and sometimes previously unknown—findings.

Publications:

  • Srivastava N, Brennan JS, Renzi RF, Wu MY, Branda SS, Singh AK, Herr AE. Fully Integrated Microfluidic Platform Enabling Automated Phosphoprofiling of Macrophage Response. Analytical Chemistry 81, 3261-3269 (2009).
  • Boas, G. (2008). Sorting it all out: Optical forces enable cell sorting with infectious agents. Biophotonics Research [Online]. August 2008.
  • James, CD, N Reuel, ES Lee, RV Davalos, SS Mani, A Carroll-Portillo, R Rebeil, A Martino, C Apblett. (2008). Impedimetric and optical interrogation of single cells in a microfluidic device for real-time viability and chemical response assessment. Biosensors and Bioelectronics 23:845–861.
  • Patel, KD, TD Perroud. (in preparation). The microflow cytometer. Optical Sorters. Pan Stanford Publishing: Hackensack, NJ. To be published in May 2009.
  • Perroud, TD, JN Kaiser, JC Sy, TW Lane, CS Branda, AK Singh, KD Patel. (2008). Microfluidic-based cell sorting of Francisella tularensis infected macrophages using optical forces. Analytical Chemistry 80:6365–6372.
  • Perroud, TD; Meagher RJ; Kanouff, MP; Renzi, RF; Wu, M; Singh, AK; Patel, KD. Isotropically Etched Radial Micropore for Cell Concentration, Immobilization, and Picodroplet Generation. Lab on a Chip 9, 507-515 (2009). Featured on journal back cover.
  • Sinclair, MB, DM Haaland, JA Timlin, HDT Jones. (2006). Hyperspectral confocal microscope. Applied Optics 45:6283–6291.

Benefits

 MICA offers an array of benefits over conven­tional approaches:

New functionality. MICA offers the capa­bility to perform experimentation and mea­surement at single-cell resolution; this is not possible with commercial fluorescence-activated cell sorter (FACS) or proteomic techniques.

Systems understanding. MICA is a single, unified platform that can perform multiple measurements (e.g., translocation and pro­tein abundance measurements) on the same population of cells, enabling understanding of the entire system of cell responses.

Speed and efficiency. Researchers can use MICA to measure multiple components of cellular pathways simul­taneously and quickly—without requiring large quantities of cells and expensive reagents.

Enhanced control. MICA’s systems integration capability eliminates manual steps and provides scientists with com­plete control of the cell environment—enabling measure­ments of concentration and time events.

Convenient. MICA neatly fits on a typical microscope stage.

Versatility. MICA can handle many different cell types, and the MICA hardware adapts to many commercial microscopes.

MICA platforms have several key, differentiating features:

• Hands-free, automated operation

• Integrated valves and pumps

• Complete fluid control

• Multiple sample and reagent inlets

• Precise temperature control

• Reusability after following well-established cleaning protocols

• Automated, labview-based, user-friendly interface

• Completely contained platform for biological assays

• Minimal aerosol generation

• Improved biosafety

• Ideal for placement in Biosafety Level (BSL) 3 and 4 facilities

Applications and Industries

Within Sandia’s research of immune response, MICA has increased our understanding of exactly how immune cells counter viral or bacterial invasion. When fully developed, MICA could revolutionize the study of multiple cell mechanisms, engendering knowledge to advance biology, medicine, diag­nostics, and therapeutics. Potential applications of MICA include the following:

Drug discovery and therapeutics. High information-content screening, evaluating how drug candidates behave with spe­cific cell types in real time

Diagnostics. Observing and sorting abnormal cells, enriching rare cell types

Personalized medicine. Monitoring the behavior of individual patient cells

Immune and infectious disease. Observing the mechanisms of infection

Biomarker discovery. Identifying and quantifying specific proteins (e.g., cytokine profiling)

Intellectual Property

Title
ID Number
Patent Number
Date
Microfluidic devices and methods for integrated flow cytometry 11030.1 7,999,937 08/16/2011
Issued
Preconcentration and separation of analytes in microchannels 8604.1 7,828,948 11/09/2010
Issued
Particle sorter comprising a fluid displacer in a closed-loop fluid circuit 8,162,149 04/24/2012
Issued
Method for voltage-gated protein fractionation 8,163,154 04/24/2012
Issued
Method for forming polymerized microfluidic devices 8,047,829 11/01/2011
Issued
Methods and devices for immobilization of single particles in a virtual channel in a hydrodynamic trap 8,815,177 08/26/2014
Issued
Micropores and methods of making and using thereof 8,585,916 11/19/2013
Issued
Devices, systems, and methods for microscale isoelectric fractionation 9,005,417 04/14/2015
Issued
Devices, systems, and methods for microscale isoelectric fractionation 9,409,357 08/09/2016
Issued
Technology IDSD# 11030.1; SD# 10838.1; SD# 10740.2, SD# 10978.2, SD# 11149; SD# 11152; SD# 8604.1; SD# 11162.1: SD# 10745.1; SD# 10545.1Development StagePrototypeAvailabilityAvailablePublished11/16/2011Last Updated08/19/2016