IP Library › Granted Patent US 12,630,857
Granted Patent B2
US 12,630,857 · App. 18/530,789 · Granted May 19, 2026

Biological indicator for determining the efficacy of a steam or heat sterilization process and its method of use

Inventors: Adrian Jesus Rovetto (Rosario, AR); Esteban Lombardia (Pueblo Esther, AR); Pablo Ravasi (Rosario, AR)
Assignee: Terragene LLC
C12Q1/22C12N1/20G01N21/6486
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Quick Facts
Patent No.
US 12,630,857
App. No.
18/530,789
Granted
May 19, 2026
Kind
B2
Abstract

The invention relates to a biological indicator for determining the efficacy of a steam or heat sterilization process, and its method. The biological indicator comprises microbial spores (a), at least one sensor protein exogenous to the microbial spores (b), one fluorophore (c), and a culture medium (d). The invention also refers to the method of use of this biological indicator. This method consists of (a) placing the biological indicator along with a target material to be steam or heat sterilized within a steam or heat sterilizer, (b) carrying out a steam or heat sterilization process, (c) placing the biological indicator in a an incubator, (d) screening the biological indicator for immediate detectable changes in fluorescence intensity, while incubating the biological indicator in the incubator, (e) determining the efficacy of the steam or heat sterilization process based on the screening carried out during step d), (f) extending the incubation of the biological indicator obtained in step d), (g) screening the incubated biological indicators obtained in step e) for an optically detectable color change, and (h) determining the efficacy of the steam or heat sterilization process, according to optically detectable changes obtained in step g).

Claims (29)

1 . An indicator for determining the efficacy of a steam or heat sterilization process, comprising:

a protein,

a fluorophore,

a colorimetric component,

microbial spores, and

a culture medium,

wherein the fluorophore interacts with a first region of the protein before the sterilization process providing a first fluorescence emission intensity and interacts with a second region of the protein after the sterilization process providing a second fluorescence emission intensity, and wherein exposing said protein to heat disrupts the interaction of the first region of the protein and the fluorophore to permit the interaction of the second region of the protein and fluorophore, yielding a different and immediate optically detectable signal;

and wherein the different and immediate optically detectable signal indicates the sterilization process was successful.

2 . The indicator of claim 1 , wherein the protein and the fluorophore are housed within a container.

3 . The indicator of claim 1 , wherein the protein is capable of differentially interacting with the fluorophore depending on the tridimensional structure of the protein.

4 . The indicator of claim 3 , wherein the tridimensional structure of the protein is related to the intensity of the immediate optically detectable signal.

5 . The indicator of claim 1 , wherein the protein is denatured by the heat sterilization process.

6 . The indicator of claim 1 , wherein the protein/fluorophore ratio is between 2:1 and 8:1.

7 . The indicator of claim 1 , wherein the immediate optically detectable signal is observed within 20 seconds after initiating a sterilization process.

8 . The indicator of claim 1 , wherein the protein comprises at least one of fibrin, elastin, casein, collagen, actin, keratin, albumin, lysozyme, amylase, pepsin, glucosidase, phosphatase, galactosidase, chymotrypsin and lipase.

9 . The indicator of claim 1 , wherein the protein comprises at least one of fibrin, elastin, casein, collagen, actin, keratin, and albumin.

10 . The indicator of claim 1 , wherein the protein comprises at least one of a lysozyme, amylase, pepsin, glucosidase, phosphatase, galactosidase, chymotrypsin and lipase.

11 . The indicator of claim 1 , wherein the fluorophore is selected from the group consisting of Nile red; coumarin 6H; coumarin 6; coumarin 30; coumarin 102; coumarin 153, 7-Amino-4-(trifluoromethyl) coumarin; 8-anilinonaphthalene-1-sulfonic acid; 7-hydroxy-4-(trifluoromethyl) coumarin; 4,4′-dianilino-1,1′-binaphthyl-5,5-disulfonic acid dipotassium salt; L-alanine-7-amido-4-methylcoumarin; L-proline-7-amido-4-methylcoumarin; L-tyrosine-7-amido-4-methylcoumarin; L-leucine-7-amido-4-methylcoumarin; and L-phenylalanine-7-amido-4-methylcoumarin.

12 . The indicator of claim 1 , wherein after the sterilization process the culture medium contacts the microbial spores and produces an optically detectable color shift in the presence of microbial growth.

13 . The indicator of claim 1 , wherein the colorimetric component comprises bromocresol purple, bromocresol green, phenol red, thymol blue, bromophenol blue, bromothymol blue, 6-chloro-3-indoxyl-alpha-D-glucopyranoside, 5-bromo-4-chloro-3-indolyl alpha-D-glucopyranoside, 6-chloro-3-indoxyl-beta-D-galactopyranoside, 5-bromo-4-chloro-3-indolyl beta-D-galactopyranoside, or 5-bromo-4-chloro-3-indoxyl phosphate.

14 . The indicator of claim 1 , wherein the colorimetric component is present in the culture medium.

15 . The indicator of claim 1 , wherein the protein is casein and the fluorophore is L-tyrosine-7-amido-4-methylcoumarin.

16 . The indicator of claim 1 , wherein the protein is albumin and the fluorophore is 8-anilinonaphthalene-1-sulfonic acid.

17 . The indicator of claim 1 , wherein the protein is casein and the fluorophore is 8-anilinonaphthalene-1-sulfonic acid.

18 . A method of sterilizing an object, the method comprising:

placing the indicator of claim 1 and an object within a sterilizer,

initiating a sterilization process,

determining that the sterilization process was effective by reviewing the fluorescent intensity of the indicator,

thereby sterilizing the object.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 1, 2025
From: TERRAGENE SA
To: TERRAGENE LLC
Reel/Frame 070699/0721 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 7, 2023
From: ROVETTO, ADRIAN JESUS; LOMBARDIA, ESTEBAN; RAVASI, PABLO
To: TERRAGENE SA; TERRAGENE LLC
Reel/Frame 065802/0550 →
Continuity (2)
Continuation 16543279 · Aug 16, 2019
Related Publication 20240110219A1 · Apr 4, 2024
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