Node-Pore Coded Coincidence Correction: Coulter Counters, Code Design, and Sparse Deconvolution

We present a novel method to perform individual particle (e.g., cells or viruses) coincidence correction through joint channel design and algorithmic methods. Inspired by multiple-user communication theory, we modulate the channel response, with node-pore sensing, to give each particle a binary Barker code signature. When processed with our modified successive interference cancellation method, this signature enables both the separation of coincidence particles and a high sensitivity to small particles. We identify several sources of modeling error and mitigate most effects using a data-driven self-calibration step and robust regression. Additionally, we provide simulation analysis to highlight our robustness, as well as our limitations, to these sources of stochastic system model error. Finally, we conduct experimental validation of our techniques using several encoded devices to screen a heterogeneous sample of several size particles.

[1]  Christian H. Reccius,et al.  Leukocyte analysis and differentiation using high speed microfluidic single cell impedance cytometry. , 2009, Lab on a chip.

[2]  Franklin D. Ohrtman,et al.  Wi-Fi Handbook: Building 802.11b Wireless Networks , 2003 .

[3]  Sam Emaminejad,et al.  Processing gain and noise in multi-electrode impedance cytometers: Comprehensive electrical design methodology and characterization , 2017 .

[4]  R. W. Davis,et al.  Coded Corrugated Microfluidic Sidewalls for Code Division Multiplexing , 2013, IEEE Sensors Journal.

[5]  Lydia L Sohn,et al.  High-throughput microfluidic device for rare cell isolation , 2015, Microtechnologies for the New Millennium.

[6]  L. W. Phipps,et al.  Determination of leucocyte concentrations in cow's milk with a Coulter counter , 1966, Journal of Dairy Research.

[7]  N. Levanon,et al.  Noncoherent pulse compression , 2006, IEEE Transactions on Aerospace and Electronic Systems.

[8]  A. F. Sarioglu,et al.  Microfluidic CODES: a scalable multiplexed electronic sensor for orthogonal detection of particles in microfluidic channels. , 2016, Lab on a chip.

[9]  Mehmet Toner,et al.  Clusters of circulating tumor cells traverse capillary-sized vessels , 2016, Proceedings of the National Academy of Sciences.

[10]  C. P. Bean,et al.  Electrokinetic measurements with submicron particles and pores by the resistive pulse technique , 1977 .

[11]  S. Blake.  OS-CFAR theory for multiple targets and nonuniform clutter , 1988 .

[12]  J. Mullin,et al.  Crystal Size Measurement: Comparison of the Techniques of Sieving and Coulter Counter , 1974 .

[13]  Joan Carletta,et al.  A microfluidic multichannel resistive pulse sensor using frequency division multiplexing for high throughput counting of micro particles , 2011 .

[14]  Sridhar Ramaswamy,et al.  A microfluidic device for label-free, physical capture of circulating tumor cell-clusters , 2015, Nature Methods.

[15]  Michael Lustig,et al.  Barker-Coded node-pore resistive pulse sensing with built-in coincidence correction , 2017, 2017 IEEE International Conference on Acoustics, Speech and Signal Processing (ICASSP).

[16]  M. Graham,et al.  The Coulter Principle: Foundation of an Industry , 2003 .

[17]  Robert Andersen.  Modern Methods for Robust Regression , 2007 .

[18]  Dongqing Li,et al.  Detection and sizing of nanoparticles and DNA on PDMS nanofluidic chips based on differential resistive pulse sensing. , 2017, Nanoscale.

[19]  Jeremy C. Whang,et al.  Node-Pore Sensing Enables Label-Free Surface-Marker Profiling of Single Cells , 2015, Analytical chemistry.

[20]  R. Bashir,et al.  Nanopore sensors for nucleic acid analysis. , 2011, Nature nanotechnology.

[21]  S. Lewis,et al.  Coincidence correction in red blood cell counting. , 1989, Physics in medicine and biology.

[22]  R. Gold,et al.  Optimal binary sequences for spread spectrum multiplexing (Corresp.) , 1967, IEEE Trans. Inf. Theory.

[23]  K. Kersting.  Specific problems using electronic particle counters , 1985, Hydrobiological Bulletin.

[24]  Joel A. Tropp,et al.  Signal Recovery From Random Measurements Via Orthogonal Matching Pursuit , 2007, IEEE Transactions on Information Theory.

[25]  A. F. Sarioglu,et al.  Design and modeling of electrode networks for code-division multiplexed resistive pulse sensing in microfluidic devices. , 2017, Lab on a chip.

[26]  Joan Carletta,et al.  A micromachined high throughput Coulter counter for bioparticle detection and counting , 2007 .

[27]  D. Branton,et al.  Characterization of individual polynucleotide molecules using a membrane channel. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[28]  L. H. Princen,et al.  Coincidence Corrections for Particle Size Determinations with the Coulter Counter , 1965 .

[29]  G. Brecher,et al.  Evaluation of electronic red blood cell counter. , 1956, American journal of clinical pathology.

[30]  Rashid Bashir,et al.  Electrical/electrochemical impedance for rapid detection of foodborne pathogenic bacteria. , 2008, Biotechnology advances.

[31]  F. S. Brackett,et al.  Determination of number and size of particles by electrical gating: blood cells. , 1957, Journal of applied physiology.

[32]  Michael R. Burcher,et al.  CODED ELECTRODES FOR LOW SIGNAL-NOISE RATIO SINGLE CELL DETECTION IN FLOW-THROUGH IMPEDANCE SPECTROSCOPY , 2010 .

[33]  Guang Gong,et al.  Signal Design for Good Correlation: For Wireless Communication, Cryptography, and Radar , 2005 .

[34]  Matt Trau,et al.  Advances in Resistive Pulse Sensors: Devices bridging the void between molecular and microscopic detection. , 2011, Nano today.

[35]  H. Amini,et al.  Inertial microfluidic physics. , 2014, Lab on a chip.

[36]  J. N. Wilson,et al.  Coincidence in Coulter Counters , 1962 .

[37]  A. Abate,et al.  SiC-Seq: Single-cell genome sequencing at ultra high-throughput with microfluidic droplet barcoding , 2017, Nature Biotechnology.

[38]  Christian H. Reccius,et al.  Conformation, length, and speed measurements of electrodynamically stretched DNA in nanochannels. , 2008, Biophysical journal.

[39]  L. Sohn,et al.  Label-free resistive-pulse cytometry. , 2011, Methods in cell biology.

[40]  I. Daubechies,et al.  Iteratively reweighted least squares minimization for sparse recovery , 2008, 0807.0575.

[41]  Jonathan Jedwab,et al.  Contemporary Mathematics What can be used instead of a Barker sequence ? , 2007 .

[42]  J. Patrick McGee,et al.  Count Loss with the Coulter Counter , 1965 .

[43]  J. N. Wilson,et al.  Theory of Coincidence in Coulter Particle Counters , 1961 .

[44]  L. Sohn,et al.  Correcting off-axis effects in an on-chip resistive-pulse analyzer , 2002 .

[45]  George Anwar,et al.  Node-pore sensing: a robust, high-dynamic range method for detecting biological species. , 2013, Lab on a chip.