Method and device for antibiotic susceptibility testing based on fluctuations of electrical resistance in a microchannel

Patent metadata

Field	Value
Publication number	US-10214763-B2
Application number	US-201815887787-A
Country	US
Kind code	B2
Filing date	Feb 2, 2018
Priority date	Aug 5, 2016
Publication date	Feb 26, 2019
Grant date	Feb 26, 2019

Abstract

A system and method for antibiotic susceptibility testing efficiently determines whether bacteria are alive or have been killed by antibiotic treatment. The antibiotic susceptibility testing device includes at least one reservoir into which a bacteria solution is introduced and a microfluidic channel connected to the reservoir, wherein the cross-sectional size of the microfluidic channel is selected to be comparable to the size of the bacterium to be tested. Furthermore, the electrical resistance or voltage signal across the microchannel is monitored as bacteria swim into and out of the channel. Alternatively, a small population of bacteria can be immobilized in the microchannel. The resistance or voltage signal fluctuates when the bacteria are alive and moving in and out of the channel or wiggling on the microchannel walls. If the bacteria are dead, they have limited motility and the signal fluctuations are significantly smaller. By monitoring the signal fluctuations, the antibiotic susceptibility testing device can determine whether or not bacteria are alive, thus enabling antibiotic susceptibility testing of bacteria.

First claim

What is claimed is:

1. A method for detecting live bacteria in a microchannel comprising
a) providing a constant current or constant voltage through the microchannel wherein the microchannel does not contain any bacteria and measuring baseline voltage or current fluctuations through the microchannel to determine a baseline voltage or current fluctuation signal;
b) providing a constant current or constant voltage through the microchannel wherein the microchannel contains at least one bacterium and measuring voltage or current fluctuations through the microchannel to determine a first voltage or current fluctuation signal; and
c) determining that the at least one bacterium is alive if the first voltage or current fluctuation signal is greater than the baseline voltage or current fluctuation signal by a predefined threshold amount.

2. The method according to claim 1 wherein the baseline voltage or current fluctuation signal is determined as a function of the measured baseline voltage or current fluctuations and the first voltage or current fluctuation signal is determined as a function of the measured voltage or current fluctuations.

3. The method according to claim 2 wherein the baseline voltage or current fluctuation signal includes an RMS signal level determined as a function of the measured baseline voltage or current fluctuations and the first voltage or current fluctuation signal includes an RMS signal level determined as a function of the measured voltage or current fluctuations.

4. The method according to claim 1 further comprising:
d) adding an antibiotic to the microchannel;
e) providing a constant current or constant voltage through the microchannel wherein the microchannel contains the at least one bacterium and the antibiotic, and measuring voltage or current fluctuations through the microchannel to determine a second voltage or current fluctuation signal; and
f) determining that the at least one bacterium is susceptible to the antibiotic if the second voltage or current fluctuation signal falls within a predefined threshold amount of the baseline voltage or current fluctuation signal after a predetermined period of time.

5. The method according to claim 4 wherein:
the baseline voltage or current fluctuation signal includes an RMS signal level determined as a function of the measured baseline voltage or current fluctuations;
the first voltage or current fluctuation signal includes an RMS signal level determined as a function of the measured voltage or current fluctuations; and
the second voltage or current fluctuation signal includes an RMS signal level determined as a function of the measured voltage or current fluctuations.

6. The method according to claim 4 wherein the at least one bacterium is determined to be susceptible to the antibiotic if the second voltage or current fluctuation signal falls within ten percent of the baseline voltage or current fluctuation signal after a predetermined period of time.

Assignees

• Univ Boston

Inventors

• Ekinci Kamil
• Li Le
• Duan Chuanhua
• Kara Vural
• Stearns-Kurosawa Deborah

Classifications

• G01N33/48735

  Investigating suspensions of cells, e.g. measuring microbe concentration (by chemical means C12Q1/04; colony counters C12M1/34; concentration of particle suspensions in general G01N15/06) · CPC title

• C12Q1/18 Primary

  Testing for antimicrobial activity of a material · CPC title

• B01L3/502761

  specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads or physically stretching molecules · CPC title

• G01N27/021

  before and after chemical transformation of the material · CPC title