Digital Immunoassays for Sensitive Quantification of Blood Biomarkers Using Solid-State Nanopores.
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The authors' code
C · 265 lines · 9.6 KB · GPL-3.0
- /*
- bessel.c is a C port of select functions from the
- python library bessel filter implementation, scipy.signal.bessel.
- Copyright (c) 2001, 2002 Enthought, Inc.
- All rights reserved.
- Copyright (c) 2003-2016 SciPy Developers.
- All rights reserved.
- Redistribution and use in source and binary forms, with or without
- modification, are permitted provided that the following conditions are met:
- a. Redistributions of source code must retain the above copyright notice,
- this list of conditions and the following disclaimer.
- b. Redistributions in binary form must reproduce the above copyright
- notice, this list of conditions and the following disclaimer in the
- documentation and/or other materials provided with the distribution.
- c. Neither the name of Enthought nor the names of the SciPy Developers
- may be used to endorse or promote products derived from this software
- without specific prior written permission.
- THIS SOFTWARE IS PROVIDED BY THE COPYRIGHT HOLDERS AND CONTRIBUTORS "AS IS"
- AND ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING, BUT NOT LIMITED TO, THE
- IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE
- ARE DISCLAIMED. IN NO EVENT SHALL THE COPYRIGHT HOLDERS OR CONTRIBUTORS
- BE LIABLE FOR ANY DIRECT, INDIRECT, INCIDENTAL, SPECIAL, EXEMPLARY,
- OR CONSEQUENTIAL DAMAGES (INCLUDING, BUT NOT LIMITED TO, PROCUREMENT OF
- SUBSTITUTE GOODS OR SERVICES; LOSS OF USE, DATA, OR PROFITS; OR BUSINESS
- INTERRUPTION) HOWEVER CAUSED AND ON ANY THEORY OF LIABILITY, WHETHER IN
- CONTRACT, STRICT LIABILITY, OR TORT (INCLUDING NEGLIGENCE OR OTHERWISE)
- ARISING IN ANY WAY OUT OF THE USE OF THIS SOFTWARE, EVEN IF ADVISED OF
- THE POSSIBILITY OF SUCH DAMAGE.
- */
- #include"bessel.h"
- void filter_signal(double *signal, double *paddedsignal, bessel *lpfilter, int64_t length)
- {
- int64_t i;
- int64_t p;
- int64_t end;
- int64_t order = lpfilter->order;
- int64_t padding = lpfilter->padding;
- double *temp = lpfilter->temp;
- double *dcof = lpfilter->dcof;
- double *ccof = lpfilter->ccof;
- end = length+2*(order+padding);
- int64_t imax = order+padding;
- double start_padval = signal_average(signal,padding);
- double end_padval = signal_average(&signal[length - padding], padding);
- for (i=0; i<imax; i++)
- {
- temp[i] = start_padval;
- paddedsignal[i] = start_padval;
- paddedsignal[end-1-i] = end_padval;
- temp[end-1-i] = end_padval;
- }
- for (i=order; i<end; i++)
- {
- temp[i] = ccof[0]*paddedsignal[i];
- for (p=1; p<=order; p++)
- {
- temp[i] += ccof[p]*paddedsignal[i-p] - dcof[p]*temp[i-p];
- }
- }
- start_padval = signal_average(&temp[order],padding);
- end_padval = signal_average(&temp[length+imax],padding);
- for (i=0; i<imax; i++)
- {
- paddedsignal[end-1-i] = end_padval;
- paddedsignal[i] = start_padval;
- }
- for (i=order; i<end; i++)
- {
- paddedsignal[end-1-i] = ccof[0]*temp[end-1-i];
- for (p=1; p<=order; p++)
- {
- paddedsignal[end-1-i] += ccof[p]*temp[end-1-i+p] - dcof[p]*paddedsignal[end-1-i+p];
- }
- }
- }
- void besselap(int64_t N, double complex *poles, double complex *zeros)
- {
- switch(N)
- {
- case 2:
- poles[0] = -.8660254037844386467637229 + .4999999999999999999999996 * I;
- poles[1] = -.8660254037844386467637229 - .4999999999999999999999996 * I;
- zeros[0] = -1.0 + 0*I;
- zeros[1] = -1.0 + 0*I;
- break;
- case 4:
- poles[0] = -.6572111716718829545787781 - .8301614350048733772399715 * I;
- poles[1] = -.6572111716718829545787788 + .8301614350048733772399715 * I;
- poles[2] = -.9047587967882449459642637 - .2709187330038746636700923 * I;
- poles[3] = -.9047587967882449459642624 + .2709187330038746636700926 * I;
- zeros[0] = -1.0 + 0*I;
- zeros[1] = -1.0 + 0*I;
- zeros[2] = -1.0 + 0*I;
- zeros[3] = -1.0 + 0*I;
- break;
- case 6:
- poles[0] = -.9093906830472271808050953 - .1856964396793046769246397 * I;
- poles[1] = -.9093906830472271808050953 + .1856964396793046769246397 * I;
- poles[2] = -.7996541858328288520243325 - .5621717346937317988594118 * I;
- poles[3] = -.7996541858328288520243325 + .5621717346937317988594118 * I;
- poles[4] = -.5385526816693109683073792 - .9616876881954277199245657 * I;
- poles[5] = -.5385526816693109683073792 + .9616876881954277199245657 * I;
- zeros[0] = -1.0 + 0*I;
- zeros[1] = -1.0 + 0*I;
- zeros[2] = -1.0 + 0*I;
- zeros[3] = -1.0 + 0*I;
- zeros[4] = -1.0 + 0*I;
- zeros[5] = -1.0 + 0*I;
- break;
- case 8:
- poles[0] = -.9096831546652910216327629 - .1412437976671422927888150 * I;
- poles[1] = -.9096831546652910216327629 + .1412437976671422927888150 * I;
- poles[2] = -.8473250802359334320103023 - .4259017538272934994996429 * I;
- poles[3] = -.8473250802359334320103023 + .4259017538272934994996429 * I;
- poles[4] = -.7111381808485399250796172 - .7186517314108401705762571 * I;
- poles[5] = -.7111381808485399250796172 + .7186517314108401705762571 * I;
- poles[6] = -.4621740412532122027072175 - 1.034388681126901058116589 * I;
- poles[7] = -.4621740412532122027072175 + 1.034388681126901058116589 * I;
- zeros[0] = -1.0 + 0*I;
- zeros[1] = -1.0 + 0*I;
- zeros[2] = -1.0 + 0*I;
- zeros[3] = -1.0 + 0*I;
- zeros[4] = -1.0 + 0*I;
- zeros[5] = -1.0 + 0*I;
- zeros[6] = -1.0 + 0*I;
- zeros[7] = -1.0 + 0*I;
- break;
- case 10:
- poles[0] = -.9091347320900502436826431 - .1139583137335511169927714 * I;
- poles[1] = -.9091347320900502436826431 + .1139583137335511169927714 * I;
- poles[2] = -.8688459641284764527921864 - .3430008233766309973110589 * I;
- poles[3] = -.8688459641284764527921864 + .3430008233766309973110589 * I;
- poles[4] = -.7837694413101441082655890 - .5759147538499947070009852 * I;
- poles[5] = -.7837694413101441082655890 + .5759147538499947070009852 * I;
- poles[6] = -.6417513866988316136190854 - .8175836167191017226233947 * I;
- poles[7] = -.6417513866988316136190854 + .8175836167191017226233947 * I;
- poles[8] = -.4083220732868861566219785 - 1.081274842819124562037210 * I;
- poles[9] = -.4083220732868861566219785 + 1.081274842819124562037210 * I;
- zeros[0] = -1.0 + 0*I;
- zeros[1] = -1.0 + 0*I;
- zeros[2] = -1.0 + 0*I;
- zeros[3] = -1.0 + 0*I;
- zeros[4] = -1.0 + 0*I;
- zeros[5] = -1.0 + 0*I;
- zeros[6] = -1.0 + 0*I;
- zeros[7] = -1.0 + 0*I;
- zeros[8] = -1.0 + 0*I;
- zeros[9] = -1.0 + 0*I;
- break;
- }
- }
- void polymult(double complex *roots, int64_t N, double *rcoefs)
- {
- int64_t i, j;
- double complex *polycoefs;
- polycoefs = calloc_and_check(N+1, sizeof(double complex),"Cannot allocate polynomial coefficients");
- polycoefs[N]=1.0;
- for (i=0; i<N; i++)
- {
- for (j=0; j<N+1; j++)
- {
- polycoefs[j] = -roots[i]*polycoefs[j] + (j == N ? 0 : polycoefs[j+1]);
- }
- }
- for (i=0; i<N+1; i++)
- {
- rcoefs[i] = creal(polycoefs[i]);
- }
- free(polycoefs);
- }
- double scale_filter(double complex *poles, int64_t N, double warped, double scale)
- {
- int64_t i;
- for (i=0; i<N; i++)
- {
- poles[i] *= warped;
- }
- return scale * pow(warped, (double) N);
- }
- double bilinear(double complex *poles, int64_t N, double scale, double fs)
- {
- double fs2 = 2.0 * fs;
- double complex poleprod = 1;
- int64_t i;
- for (i=0; i<N; i++)
- {
- poleprod *= fs2 - poles[i];
- poles[i] = (fs2 + poles[i])/(fs2-poles[i]);
- }
- return scale * creal(1.0 / poleprod);
- }
- void transform_filter(double complex *poles, double complex *zeros, int64_t N, double scale, double *b, double *a)
- {
- int64_t i;
- polymult(zeros, N, b);
- polymult(poles, N, a);
- for (i=0; i<N+1; i++)
- {
- b[i] *= scale;
- }
- }
- bessel *initialize_filter(int usefilter, int eventfilter, int64_t order, double cutoff, int64_t length)
- {
- if (usefilter || eventfilter)
- {
- bessel *lpfilter;
- lpfilter = calloc_and_check(1,sizeof(bessel),"cannot allocate filter struct");
- lpfilter->order = order;
- lpfilter->cutoff = cutoff;
- lpfilter->padding = 100 * 2.0 / cutoff;;
- double complex *poles;
- double complex *zeros;
- poles = calloc_and_check(order,sizeof(double complex),"Cannot allocate Bessel poles");
- zeros = calloc_and_check(order,sizeof(double complex),"Cannot allocate Bessel zeros");
- lpfilter->ccof = calloc_and_check(order+1,sizeof(double complex),"Cannot allocate ccof");
- lpfilter->dcof = calloc_and_check(order+1,sizeof(double complex),"Cannot allocate dcof");
- double fs = 2.0;
- double warped = 2.0 * fs * tan(M_PI * cutoff / fs);
- double scale = 1;
- besselap(order, poles, zeros);
- scale = scale_filter(poles,order, warped, scale);
- scale = bilinear(poles, order, scale, fs);
- transform_filter(poles, zeros, order, scale, lpfilter->ccof, lpfilter->dcof);
- lpfilter->temp = NULL;
- lpfilter->temp = calloc_and_check(length+2*(order+lpfilter->padding), sizeof(double),"Cannot allocate filter temp");
- free(poles);
- free(zeros);
- return lpfilter;
- }
- return NULL;
- }
- void free_filter(bessel *lpfilter)
- {
- free(lpfilter->dcof);
- free(lpfilter->ccof);
- free(lpfilter->temp);
- free(lpfilter);
- }
bessel.c at commit 8bab778, under GPL-3.0 · at the source
Overview
- Department of Physics, University of Ottawa, Ottawa K1N 6N5, Canada
- Department of Urology, University of Rochester Medical Center, Rochester, New York 14620, United States
- Department of Biomedical Engineering, University of Rochester, Rochester, New York 14627, United States
Abstract
Digital immunoassays enable highly sensitive detection of biomolecules, offering absolute quantification rather than relying on bulk signal intensity. We adapt a digital immunoassay scheme for a nanopore sensor, a versatile platform for single-molecule counting. Current nanopore sensors have demonstrated great progress when counting nucleic acids but struggle with proteins due to variability in translocation behavior and limited recognition strategies. While recent advancements have highlighted the promise of nanopore platforms for protein studies, precise quantification remains a challenge. Here, building on previous work, we present a nanopore-based digital immunoassay that employs gold nanoparticle-mediated molecular amplification with a single-molecule readout. This approach translates protein recognition into quantifiable DNA, enabling a precise digital assay. This assay employs a DNA NanoLock probe combined with a paramagnetic bead-based immunocapture, where the target proteins trigger a structural transformation of the NanoLock, converting their presence into a binary DNA-based signal. By incorporating AuNPs carrying hundreds of DNA proxy reporters, we effectively amplify the detectable signal by 2 orders of magnitude, significantly improving sensitivity. We validate the performance of this system by detecting the glial fibrillary acidic protein, a biomarker for traumatic brain injury and neurodegenerative diseases, in plasma samples and demonstrate high femtomolar-level sensitivity (∼40 pg/
Reproduced under the paper's license (CC BY), from the paper cited above.
Repositories
Its files are read in the Code ↔ Paper reader above.
shadowk29/CUSUM
8bab778137a3caed2feedc28b213738d7028caa5, 24 June 2020Availability: 1 check, the latest on 30 September 2026: the link answers
- 30 September 2026: the link answers
16 files
- bessel.c, C, 265 lines
- bessel.h, C/C++, 66 lines
- detector.c, C, 1,126 lines
- detector.h, C/C++, 76 lines
- io.c, C, 998 lines
- io.h, C/C++, 69 lines
- lmmin_int64.c, C, 1,149 lines
- lmmin_int64.h, C/C++, 117 lines
- lmstruct_int64.h, C/C++, 120 lines
- main.c, C, 118 lines
- stepfit.c, C, 188 lines
- stepfit.h, C/C++, 52 lines
- utils.c, C, 666 lines
- utils.h, C/C++, 292 lines
- LICENSE, License, 225 lines
- README, Text, 5 lines
Zenodo 595675
Availability: 1 check, the latest on 30 September 2026: the link answers (HTTP 200)
- 30 September 2026: the link answers (HTTP 200)
16 files
- bessel.c, C, 265 lines
- bessel.h, C/C++, 66 lines
- detector.c, C, 1,126 lines
- detector.h, C/C++, 76 lines
- io.c, C, 996 lines
- io.h, C/C++, 69 lines
- lmmin_int64.c, C, 1,149 lines
- lmmin_int64.h, C/C++, 117 lines
- lmstruct_int64.h, C/C++, 120 lines
- main.c, C, 118 lines
- stepfit.c, C, 188 lines
- stepfit.h, C/C++, 52 lines
- utils.c, C, 660 lines
- utils.h, C/C++, 292 lines
- LICENSE, License, 225 lines
- README, Text, 5 lines
The paper's code and data availability statement is in the Data section.
Tracing map
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Data
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Data Availability Statement
The raw data included this study are available from the corresponding author upon reasonable request. Liqun He, Breeana Elliott, Philipp Mensing, Kyle Briggs, Michel Godin, Jonathan Flax, James McGrath and Vincent Tabard-Cossa. Digital Immunoassay for Sensitive Quantification of Blood Biomarkers using Solid-State Nanopores. 2025, ChemRxiv Preprint, DOI: 10.26434/
Reproduced under the paper's license (CC BY), from the paper cited above.
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Version 1, 30 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 8 authors, 7 keywords, 8 MeSH terms, 2 funders, 90 references.
Cite
This paper
He, L., Elliott, B., Mensing, P., Briggs, K., Godin, M., Flax, J., McGrath, J., & Tabard-Cossa, V. (2026). Digital Immunoassays for Sensitive Quantification of Blood Biomarkers Using Solid-State Nanopores. ACS nano, 20(13), 10308-10319. https://
BibTeX
@article{he2026digital,
author = {He, Liqun and Elliott, Breeana and Mensing, Philipp and Briggs, Kyle and Godin, Michel and Flax, Jonathan and McGrath, James and Tabard-Cossa, Vincent},
title = {{Digital Immunoassays for Sensitive Quantification of Blood Biomarkers Using Solid-State Nanopores}},
journal = {ACS nano},
year = {2026},
month = mar,
volume = {20},
number = {13},
pages = {10308--10319},
publisher = {American Chemical Society},
issn = {1936-0851},
doi = {10.1021/
url = {https://
pmid = {41873753},
pmcid = {PMC13063814}
}
RIS
TY - JOUR
AU - He, Liqun
AU - Elliott, Breeana
AU - Mensing, Philipp
AU - Briggs, Kyle
AU - Godin, Michel
AU - Flax, Jonathan
AU - McGrath, James
AU - Tabard-Cossa, Vincent
TI - Digital Immunoassays for Sensitive Quantification of Blood Biomarkers Using Solid-State Nanopores
T2 - ACS nano
J2 - ACS Nano
PY - 2026
DA - 2026/
VL - 20
IS - 13
SP - 10308
EP - 10319
SN - 1936-0851
PB - American Chemical Society
DO - 10.1021/
UR - https://
LA - en
ER -
CSL-JSON
{
"id": "10.1021/
"type": "article-journal",
"title": "Digital Immunoassays for Sensitive Quantification of Blood Biomarkers Using Solid-State Nanopores",
"container-title": "ACS nano",
"author": [
{
"family": "He",
"given": "Liqun"
},
{
"family": "Elliott",
"given": "Breeana"
},
{
"family": "Mensing",
"given": "Philipp"
},
{
"family": "Briggs",
"given": "Kyle"
},
{
"family": "Godin",
"given": "Michel"
},
{
"family": "Flax",
"given": "Jonathan"
},
{
"family": "McGrath",
"given": "James"
},
{
"family": "Tabard-Cossa",
"given": "Vincent"
}
],
"container-title-short":
"volume": "20",
"issue": "13",
"page": "10308-10319",
"DOI": "10.1021/
"PMID": "41873753",
"PMCID": "PMC13063814",
"ISSN": "1936-0851",
"publisher": "American Chemical Society",
"URL": "https://
"language": "en",
"issued": {
"date-parts": [
[
2026,
3,
24
]
]
}
}
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