<PAGE>   1
                                                                   Exhibit 10.22

                       PRINCIPALS' STOCKHOLDER AGREEMENT

                                       OF

                             THIRD WAVE AGBIO, INC.

      This PRINCIPALS' STOCKHOLDER AGREEMENT (this "Agreement") dated as of
October 16, 1998, by and among Third Wave Agbio, Inc., a Delaware corporation
(the "Company"), Third Wave Technologies, Inc., a Wisconsin corporation ("Third
Wave"), and The Burrill Agbio Capital Fund, L.P., a Delaware limited
partnership ("Burrill"). Third Wave and Burrill are collectively
referred to in this Agreement as the "Stockholders" and each individually is a
"Stockholder".

                                   RECITALS:

      Third Wave formed the Company and transferred certain rights in its
technology to the Company in return for One Thousand (1,000) shares of the
Company's Class A Common Stock (the "Class A Common") of the Company.

      The Company, Third Wave, Burrill, Venture Investors Early Stage Fund II
Limited Partnership, a Wisconsin limited partnership, Dr. Lance Fors, Dr. James
Dahlberg, and Dr. Lloyd Smith, have entered into an Investment Agreement, dated
as of October 16, 1998 (the "Investment Agreement"), providing, among other
things, for the purchase by Burrill of One Thousand (1,000) shares of Series A
Convertible Preferred Stock (the "Series A Preferred") of the Company. The
shares of the Class A Common and Series A Preferred are referred to in this
Agreement as "Shares" or "Stock".

      In consideration of the consummation of the transactions contemplated by
the Investment Agreement, and to maintain continuity in the control and
operations of the Company, to restrict the transfer of Stock, and for various
other matters as set forth herein, the parties enter into this Agreement.

      NOW, THEREFORE, in consideration of the mutual promises herein contained
and other good and valuable consideration, the receipt and sufficiency of which
is hereby acknowledged, the parties hereto agree as follows:



                                  Page 1 of 14
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                                   ARTICLE I

                            RESTRICTIONS ON TRANSFER


     1.1  General Restrictions on Transfer.

          (a)  Each Stockholder agrees that during the period commencing on the
date of this Agreement and ending on April 30, 2000, it will not, sell,
transfer, encumber or dispose of any shares of Stock (or interest therein) now
owned or hereafter acquired by the Stockholder or its successors, assigns, or
other legal representatives, whether by sale, assignment, exchange, gift,
pledge, encumbrance, or other transfer through merger or by operation of law or
any other means without first having received the prior written consent of the
other Stockholder. Thereafter, except as hereinafter provided, each Stockholder
agrees and covenants that neither it, nor its successors, assigns, or other
legal representatives may sell, transfer, encumber or dispose of any shares of
Stock (or interest therein) now owned or hereafter acquired by the Stockholder
or its successors, assigns or other legal representatives, whether by sale,
assignment, exchange, gift, pledge, encumbrance, or other transfer through
merger or by operation of law or any other means.

          (b)  For purposes of this Agreement, all references to Stock owned or
held by a Stockholder shall include, without limitation, all interests in Stock
now owned or hereafter acquired by the Stockholder or its successors, assigns,
or other legal representatives.

     1.2  Voluntary Transfer.

          (a)  First Refusal to Company. After the expiration of the period
delineate in Section 1.1(a) of this Agreement, and except as permitted under
Section 1.5 hereof, in the event a Stockholder ("Transferring Stockholder")
should decide to effect a voluntary transfer of any of its Stock, the
Transferring Stockholder shall first deliver written notice to the Company of
such intent to transfer ("Notice of Transfer"), which Notice of Transfer shall
specify (i) the number of shares of Stock proposed to be transferred ("Offered
Stock"), (ii) the date of the proposed transfer, which shall not be less than
thirty (30) days after the actual receipt of such Notice of Transfer to the
Company, (iii) the identity, including the complete name, address and telephone
number of the proposed transferee of the Offered Stock ("Proposed Transferee"),
and (iv) the proposed consideration to be received and terms of payment upon
such transfer (such consideration and the terms of payment being hereinafter
referred to collectively as the "Offer Price"). The Notice of Transfer shall be
accompanied by a copy of any bona fide written offer. Such Notice of Transfer
shall constitute an offer to sell and transfer the Offered Stock, in whole or
in part, to the Company at the Offer Price of the Offered Stock, and the date
of


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such offer ("Offer Date") shall be the date of actual receipt by the Company of
the Notice of Transfer. The Company shall promptly furnish a copy of the Notice
of Transfer to all members of its Board of Directors and to the other
Stockholders and schedule a special or regular meeting of the Board of
Directors to evaluate the Company's capacity to purchase the Offered Stock at
the Offer Price. For a period of thirty (30) days after the Offer Date, the
Company shall have the right and option to elect to purchase all, or any
portion, of the Offered Stock. In the event the Company shall exercise its
right and option to purchase in whole, or in part, the Offered Stock, the
Company shall signify such exercise and the number of shares of Offered Stock
to be purchased by giving written notice to the Transferring Stockholder
("Notice of Exercise") within thirty (30) days after the Offer Date. The Notice
of Exercise shall specify that the Company is exercising its right and option
to purchase the Offered Stock pursuant to this Section 1.2(a). In the event of
such exercise by the Company, the Transferring Stockholder shall sell and
transfer the Offered Stock to the Company on the terms and conditions identical
to those as set forth in the Notice of Transfer. Any Notice of Exercise that is
mailed in the manner provided herein shall be conclusively presumed to have
been duly given when mailed, whether or not the Transferring Stockholder shall
have actually received the Notice of Exercise.

          (b)  Second Refusal to Nontransferring Stockholders. Within ten (10)
days of the earlier of the Company's rejection, in whole or in part, of its
right of first refusal or the lapse of the offer by reason of the Company's
failure to exercise its right and option to purchase any or all of the Offered
Stock within the time permitted for exercise, the Transferring Stockholder
shall deliver to the other Stockholders (the "Nontransferring Stockholders") a
copy of the Notice of Transfer, together with a statement that the Company's
option to purchase the Offered Stock being transferred has lapsed. Such Notice
of Transfer shall constitute an offer to sell and transfer all (but not less
than all of) the Offered Stock not purchased by the Company under Section
1.2(a) to the Nontransferring Stockholders at the Offer Price. Upon actual
receipt of such written notice by the Nontransferring Stockholders, the
Nontransferring Stockholders shall have the right and option to purchase and
accept the shares of Offered Stock not purchased by the Company for a period of
thirty (30) days after actual receipt of such written notice, at a purchase
price equal to the Offer Price. In the event that one or more of the
Nontransferring Stockholders shall exercise the right and option to purchase
the shares of Offered Stock not purchased by the Company (the "Accepting
Stockholders"), each Accepting Stockholder shall signify such exercise by
mailing a written notice thereof to the Transferring Stockholder in the same
manner and form as the Notice of Exercise specified above. In the event of such
exercise by the Accepting Stockholders, the Transferring Stockholder shall sell
and transfer the Offered Stock to the Accepting Stockholders on the terms and
conditions as set forth in the Notice of Transfer. If the aggregate number of
shares of Offered Stock elected to be purchased by the


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Accepting Stockholders exceeds the Transferring Stockholder's shares of Offered
Stock not purchased by the Company, each of the Accepting Stockholders shall be
entitled to purchase a percentage of the shares of Offered Stock not purchased
by the Company in proportion to the existing Stock ownership of the Accepting
Stockholders, provided that no Accepting Stockholder shall be required to
purchase a number of shares of Offered Stock greater than the number set forth
in the Accepting Stockholder's Notice of Exercise. If any Accepting Stockholder
elected to purchase a number of shares of Offered Stock less than its pro rata
portion of Offered Stock not purchased by the Company, the Transferring
Stockholder shall make an additional offer to sell the remainder of the shares
of Offered Stock pro rata to the Accepting Stockholders. Such additional offer
shall be made within five (5) days after expiration of the original thirty
(30)-day period, and may be accepted, in whole or in part, by mailing a Notice
of Exercise specified above within five (5) days after receipt of such
additional offer. Notwithstanding the provisions of this Section 1.2(b), the
Nontransferring Stockholders may, in advance, agree to permit any
Nontransferring Stockholder to purchase more than its pro rata portion of such
Offered Stock.

        1.3 Failure to Exercise Refusal Right. In the event that neither the
Company nor the Nontransferring Stockholders exercise their right and option to
purchase the Offered Stock at the Offer Price within the time permitted under
Section 1.2 hereof, the Transferring Stockholder may transfer the Offered Stock
to the Proposed Transferee within a period of sixty (60) days thereafter;
provided, however, that such transfer must be made in strict compliance with
the terms and conditions of such transfer as set forth in the Notice of
Transfer, including, without limitation, the Offer Price. Such transfer shall
be made (a) pursuant to an effective registration statement under the
Securities Act of 1933, as amended (the "Securities Act") or an exemption from
the registration requirements thereof, and (b) in accordance with applicable
state law. The shares of Offered Stock transferred to the Proposed Transferee
shall continue to be subject to all of the terms and conditions of this
Agreement, and the Company shall have the right and option to require, as a
condition to such transfer to the Proposed Transferee, that the Proposed
Transferee execute an agreement substantially in the form of this Agreement and
to which the Proposed Transferee and all Stock then or thereafter acquired by
the Proposed Transferee shall be fully subject as though the Proposed
Transferee were a party hereto. In the event such transfer to the Proposed
Transferee is not consummated within such sixty (60)-day period, the
restrictions of this Agreement shall again apply.


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        1.4     Involuntary Transfer.

                (a) Whenever any Stockholder has any notice of knowledge of any
impending or consummated involuntary transfer of or lien, charge, security
interest, claim or encumbrance upon any of its Stock, whether by operation of
law or otherwise (collectively, "Involuntary Transfer"), such Stockholder shall
give immediate written notice thereof to the Company. Whenever the Company has
any other actual notice or actual knowledge of any such attempted, impending or
consummated Involuntary Transfer, it may give written notice thereof to the
applicable Stockholder. In either case, each Stockholder agrees to disclose in
writing immediately to the Company all pertinent information in its possession
relating to such Involuntary Transfer.

                (b) If any Stock is subject to any such Involuntary Transfer,
the Company for a period of ninety (90) days shall at all times have the
immediate and continuing right and option to purchase such Stock at a price
equal to the Fair Market Value of the Stock subject to the Involuntary Transfer
determined as set forth in Section 2.1 and upon the payment terms as provided
in Section 2.2 hereof upon the giving of written notice to such effect to the
applicable Stockholder.

                (c) If the Company fails to exercise such right and option in
full within such ninety (90)-day period, the remaining Stockholders shall have
the option to purchase the Stock not purchased by the Company within the sixty
(60)-day period following the expiration of the ninety (90)-day period
described in the preceding subparagraph by giving written notice to such effect
to the appropriate party. If the aggregate number of shares of Stock elected to
be purchased by such Stockholders exceeds the number of shares of Stock not
purchased by the Company, the Stock shall be sold to each such Stockholder in
proportion to its respective Stock ownership determined in the manner set forth
in Section 1.2(b).

        1.5     Permitted Transfers.

                (a)     After April 30, 2000, and notwithstanding any provision
of this Article I to the contrary, any Stockholder may transfer at any time any
or all of its Stock to any of its partners or to any entity that controls, is
controlled by, or is under common control with it, whether by direct transfer
or by operation of law, through merger or other any other form of asset
transfer, without first offering such shares first to the Company and second to
the other Stockholders as otherwise required herein.

                (b)     All provisions of this Agreement shall continue to
apply to Stock transferred pursuant to this Article I or otherwise. Following
any such


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transfer, the Company shall have the option to require the transferee to
execute an agreement substantially in the form of this Agreement.

                                   ARTICLE II

                         PURCHASE AND REDEMPTION PRICE

     2.1  Fair Market Value. For purposes of this Agreement, Fair Market Value
shall mean the value an informed and willing buyer and seller would agree upon
for the sale and purchase of One Hundred Percent (100%) of the issued and
outstanding Stock of the Company, giving a discount for lack of liquidity,
marketability or minority Stockholder status (if applicable). Fair Market Value
as of the end of the fiscal month of the Company immediately preceding the
event triggering the need to establish a Fair Market Value ("Triggering Event")
may be established by agreement of the parties without appraisal through the
good faith efforts of the parties to reach such an agreement. In the event the
parties are unable to agree upon Fair Market Value within sixty (60) days of
the Triggering Event, Fair Market Value shall be determined by a professional
appraiser mutually satisfactory to each of the parties based upon a valuation
by such appraiser of the Company as a going concern as of the end of the fiscal
month of the Company immediately preceding the Triggering Event. Each of the
parties shall pay one half (1/2) of the fees of any such appraiser. In the
event the parties are unable to agree upon a single appraiser within ninety
(90) days of the Triggering Event, the parties shall each select a professional
appraiser within twenty (20) days of the date the parties should have agreed
upon an appraiser. Each party so selecting an appraiser shall advise the other
party in writing of the name and address of such appraiser within such twenty
(20) day period. In the event either party fails to select an appraiser and
notify the other party in writing of the name and address of such appraiser
within the time period provided therefor, and in the further event that the
other party selects an appraiser and notifies the non-complying party in
writing of the name and address of such appraiser within the time period
provided therefor, then the determination made by the complying party's
appraiser shall be conclusive and binding upon the parties. Each party shall be
responsible for paying the fees of the appraiser selected by it. The two
appraisers so appointed shall be instructed to each prepare a written appraisal
that will show the Fair Market Value as of the end of the fiscal month of the
Company immediately preceding the Triggering Event. In determining the Fair
Market Value, the appraisers appointed under this Agreement shall submit all
relevant evidence submitted to them by the parties or otherwise obtained by
them, and shall set forth their determinations in writing together with data on
which their opinions are based, with a signed counterpart to be delivered to
each party within sixty (60) days of their appointment. Provided that the
difference, if any, in the Fair Market Value is less than or equal to ten
percent


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<PAGE>   7
(10%) of the Fair Market Value in the lower appraisal, then the arithmetic
average of the two appraisals shall be the Fair Market Value, and such
determination shall be conclusive and binding upon the parties. If the
difference between such two appraisals is more than such ten percent (10%)
amount, then within ten (10) days after the date that the parties are notified
of such appraisals, the two appraisers previously retained shall jointly appoint
a third professional appraiser and shall advise the parties in writing of the
name of said appraiser. If such two appraisers are unable to agree upon the
appointment of a third appraiser within such ten (10)-day period, they shall
give written notice of such failure to agree upon the selection of a third
appraiser within ten (10) additional days after they are so advised, then either
party may make application to the then acting senior judge of the Circuit Court
for Dane County, Wisconsin, to designate or appoint such a third appraiser. Each
of the parties hereto shall pay one-half (1/2) of the fees of any such third
appraiser. Such third appraiser shall then be instructed as the initial two
appraisers were previously instructed to prepare an appraisal showing the Fair
Market Value as of the end of the fiscal month of the Company immediately
preceding the Triggering Event. Such third appraiser shall notify both parties
simultaneously and in writing, of his determination as described herein within
thirty (30) days after his appointment, and the Fair Market Value set forth in
the appraisal that falls between the Fair Market Value set forth in the other
two appraisals shall be the Fair Market Value. It shall be a condition precedent
to the engagement of any appraiser hereunder that such appraiser shall agree in
writing to complete the appraisal called for and notify both parties in writing
of the determination of such appraiser within the time period herein provided
therefor.

     2.2  Payment. In the event of the redemption by the Company or the purchase
by Stockholders of shares of Stock, the Company and the Stockholders shall pay
the redemption or purchase price in cash and shall have the option to evidence
that amount of the redemption or purchase price that exceeds One Hundred
Thousand Dollars ($100,000) by a promissory note of the Company, or of each
purchasing Stockholder, dated the day of the redemption by the Company (the
"Company Note"), or purchased by a Stockholder (the "Stockholder Note") (the
"Company Note" and "Stockholder Note" are collectively referred to in this
Section 2.2 as "Promissory Notes" or, individually as "Promissory Note"). The
principal amount of the Promissory Note shall be payable in full on or prior to
their first anniversary. Interest at the announced rate of interest used by
Firstar Bank Madison, N.A. (the "Bank"), as its reference rate for interest rate
determinations as of the first business day of the calendar quarter in which the
Promissory Notes will be issued, shall be paid monthly. The Promissory Notes
shall be prepayable, in full or in part, without premium or penalty, at any time
and from time to time. Each Promissory Note shall be secured by such number of
shares of Stock redeemed or purchased that is equal in value to the principal
balance of the Promissory Note. Upon payment of each installment of a Promissory
Note, the number of shares of


                                  Page 7 of 14

<PAGE>   8
Stock that has the same proportion to the original number of shares of Stock
pledged to secure the Promissory Note as the amount of installment payment
bears to the original amount of the Promissory Note shall be released within
three (3) business days of receipt of the payment.


                                  ARTICLE III

                   VOTING AGREEMENT WITH RESPECT TO DIRECTORS

     3.1  Election of Directors. The Stockholders agree that the Company's
Board of Directors shall consist of five (5) directors. Each Stockholder may
select two (2) persons for election to the Board of Directors so long as such
Stockholder owns and/or retains voting control over at least seven and one-half
percent (7 1/2%) of the voting equity of the Company. One additional director
shall be selected by mutual agreement of the Stockholders. The director
selected by mutual agreement shall hold office until the expiration of his or
her one year term or until his or her earlier death, resignation, or removal.
Unless the Stockholders agree that such director shall continue for another one
year term, the position held by such director shall thereafter remain vacant
until it is again filled by a person mutually selected by the Stockholders.
The Stockholders agree to vote their shares and take all other actions
necessary from time to time such that the persons selected as described above
are elected annually to the Board of Directors of the Company.  Each
Stockholder shall retain the discretion to vote its shares for the election of
directors not selected by the other Stockholder or by mutual agreement as
described above.

     3.2  Compensation of Directors. The Company and the Stockholders agree
that the directors elected as described above shall receive the normal
director's fee and expense reimbursement customarily paid by the Company to its
outside directors, which shall be negotiated among the Stockholders and the
Company annually. If any of the Stockholders' representatives to the Company's
Board of Directors shall be members of the compensation or audit committees of
the Company's Board of Directors, such representatives shall receive the normal
fee and expense reimbursement customarily paid by the Company to members of
such committees, which shall be negotiated annually.


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<PAGE>   9
                                   ARTICLE IV

                        CO-SALE RIGHTS FOR STOCKHOLDERS

     Notwithstanding anything in this Agreement to the contrary and except for
permitted transfers as described in Section 1.5 of this Agreement, if any one
or more of the Stockholders proposes, in a single transaction or a series of
related transactions, to sell, dispose of or otherwise transfer (except by
operation of law and except a transfer to the Company) any shares of Stock,
such Stockholder(s) (the "Selling Stockholder(s)") shall refrain from effecting
such transaction unless, prior to the consummation thereof, the other
Stockholder(s) (the "Other Stockholder") shall have been afforded the
opportunity to join in such sale on a pro-rata basis, as hereinafter provided.

     Prior to the consummation of any transaction subject to this Article IV
(including those that may occur under Section 1.2 hereof), the person or group
that proposes to acquire shares of capital stock of the Company in such
transaction (the "Proposed Purchaser") shall offer (the "Purchaser Offer") in
writing to each Other Stockholder to purchase the same percentage of shares of
stock beneficially owned by each Other Stockholder as the Proposed Purchaser
purchases from the Selling Stockholder(s), at the highest price per share (the
"Offering Price") and on such other terms and conditions (the "Offering Terms")
as the Proposed Purchaser has offered to purchase shares to be sold by the
Selling Stockholder(s). If the Proposed Purchaser is acquiring shares of Stock
in a single transaction or a series of related transactions from one or more
Selling Stockholders, (a) the Offering Price shall be the highest of the
Offering Prices and the Offering Terms shall be those terms offered by the
Proposed Purchaser to any Selling Stockholder in any one of such transactions
which are most favorable to the offeree and (b) the percentage of each Other
Stockholder's shares which the Proposed Purchaser shall offer to acquire shall
be the highest percentage of shares owned by any one Selling Stockholder of
record which are acquired or to be acquired by the Proposed Purchaser from such
Selling Stockholder in the transaction or series of related transactions which
gave rise to the Other Stockholders' rights under this Article IV. Each Other
Stockholder shall have until the expiration of its rights to exercise its
second refusal under Section 1.2(b) to accept such Purchase Offer. In the event
that a sale or other transfer is subject to this Article IV, the Selling
Stockholder(s) shall so notify the Proposed Purchaser and shall ensure that no
sale or other transfer is consummated without the Proposed Purchaser first
complying with this Article IV.


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<PAGE>   10

                                   ARTICLE V

                                  STOCK LEGEND

      All certificates representing shares of Stock now owned or hereafter
acquired by a party to this Agreement or their transferee(s) shall bear a
legend in substantially the form set forth below:

      (a)   THE STOCK REPRESENTED BY THIS CERTIFICATE IS SUBJECT TO CERTAIN
            RESTRICTIONS UPON TRANSFER AND RIGHTS OF FIRST REFUSAL, CO-SALE,
            AND MANDATORY SALE UPON THE HAPPENING OF CERTAIN EVENTS AS SET
            FORTH IN AN AGREEMENT AMONG THE REGISTERED HOLDERS AND THE
            CORPORATION, A COPY OF WHICH IS ON FILE AT THE PRINCIPAL OFFICE OF
            THE CORPORATION.

      (b)   THE STOCK REPRESENTED BY THIS CERTIFICATE HAS BEEN ACQUIRED FOR
            INVESTMENT AND HAS NOT BEEN REGISTERED UNDER THE SECURITIES ACT OF
            1933 OR ANY APPLICABLE STATE SECURITIES LAW. SUCH STOCK MAY NOT BE
            PLEDGED, SOLD, TRANSFERRED OR HYPOTHECATED IN THE ABSENCE OF SUCH
            REGISTRATION OR UNLESS THE COMPANY RECEIVES AN OPINION OF COUNSEL
            REASONABLY ACCEPTABLE TO ITS STATING THAT SUCH PLEDGE, SALE,
            TRANSFER OR HYPOTHECATED IS EXEMPT FROM THE REGISTRATION
            REQUIREMENTS OF SAID ACT AND ANY APPLICABLE STATE SECURITIES LAW.


                                   ARTICLE VI

                                REPRESENTATIONS


      Each Stockholder who is a party to this Agreement represents that such
Stockholder is the record and beneficial owner of the number of issued and
outstanding shares of Stock appearing opposite such Stockholder's name in the
Schedule of Stockholders attached hereto as Exhibit A, free and clear of any
option, lien, encumbrance or charge of any kind whatsoever, except as created
by this Agreement.



                                 Page 10 of 14

<PAGE>   11
                                  ARTICLE VII

                                  TERMINATION

     This Agreement shall terminate and be of no further force or effect upon
the earlier of (a) the closing date of a sale of substantially all of the
assets of the Company; (b) merger of the Company pursuant to which Stockholders
of the Company receive securities of a buyer whose securities are publicly
traded, or (c) consummation by the Company of an offering of equity securities
of the Company pursuant to an effective registration statement under the
Securities Act of 1933, as amended, in the amount of not less than $7.5 million
by a nationally recognized underwriter pursuant to a firm underwriting
agreement. Upon termination of this Agreement, as herein provided, each
Stockholder may deliver the certificates of its Stock to the secretary of the
Company and have the certificates reissued, without the legend required under
this Agreement appearing on the certificates.

                                  ARTICLE VIII

                               GENERAL PROVISIONS

     8.1  Further Assurances. Subject to the terms and conditions herein
provided, each party hereto agrees to use its reasonable efforts to take, or
cause to be taken, all actions and to do, or cause to be done, all things
necessary, proper or advisable under applicable laws and regulations to
consummate and make effective, as soon as reasonably practicable, the
transactions contemplated by this Agreement. If at any time before or after the
date of this Agreement any further action is reasonably necessary, proper or
advisable to carry out the purposes of this Agreement, as soon as reasonably
practicable, each party hereto shall at the expense of the requesting party,
take all such reasonably necessary, proper or advisable action to effectuate
such purposes.

     8.2  Governing Law; Jurisdiction. The interpretation and construction of
this Agreement and the resolution of any disputes arising out of or in
connection with this Agreement or any breach hereof, shall, unless otherwise
expressly provided, be governed by and be construed in accordance with the
internal laws of the State of Wisconsin without regard to the conflicts of laws
principles thereof.

     8.3  Notices. All notices and other communications under this Agreement
shall be in writing and shall be deemed given or delivered when (a) delivered
by hand, (b) sent by certified mail, return receipt requested, or (c) received
by the


                                 Page 11 of 14

<PAGE>   12
addressee, if sent by Express Mail, Federal Express or other express delivery
service, to the addressee at the following addresses (or to such other address
as a party may specify by notice hereunder):

If to the Company:            Third Wave Agbio, Inc.
                              502 South Rosa Road
                              Madison, WI 53719
                              Fax No. (608) 273-6989

With a copy to:               Michael E. Skindrud, Esq.
                              LaFollette & Sinykin
                              One East Main Street Suite 500
                              Madison, WI 53703
                              Fax No. (608) 257-0609

If to Third Wave:             Third Wave Technologies, Inc.
                              502 South Rosa Road
                              Madison, WI 53719
                              Fax No. (608) 273-6989

With a copy to:               Michael E. Skindrud, Esq.
                              LaFollette & Sinykin
                              One East Main Street Suite 500
                              Madison, WI 53703
                              Fax No. (608) 257-0609

If to Burrill:                The Burrill Agbio Capital Fund, L.P.
                              c/o Burrill & Company
                              120 Montgomery Street, Suite 1370
                              San Francisco, CA 94104

With a copy to:               Richard A. Peers, Esq.
                              Heller Ehrman White & McAuliffe
                              525 University Avenue, Suite 1100
                              Palo Alto, CA 94301-1900
                              Fax No. (650) 324-0638





                                 Page 12 of 14
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     8.4  Entire Agreement; Amendments. This  Agreement together with the
Investment Agreement and any agreement executed pursuant thereto constitutes a
complete statement of all of the arrangements between the parties as of the
date hereof with respect to the transactions contemplated hereby, and thereby
supersedes all prior agreements and understandings between them with respect
thereto and cannot be changed or terminated orally.

     8.5  Headings and Defined Terms. The headings in this Agreement are
intended solely for convenience of reference and shall be given no effect in
the construction or interpretation of this Agreement. Any capitalized terms not
otherwise defined herein shall have the meanings ascribed to them in the
Investment Agreement.

     8.6  Successors. This Agreement shall inure to the benefit of, and be
binding upon, the parties hereto, successors and assigns.

     8.7  No Waiver. The failure of a party to insist upon strict adherence to
any term of this Agreement on any occasion shall not be considered a waiver or
deprive that party of the right thereafter to insist upon strict adherence to
that term or any other term of this Agreement. Any waiver must be in writing.

     8.8  Counterparts. This Agreement may be executed in two or more
counterparts, each of which shall be considered an original, but all of which
together shall constitute the same instrument.

     8.9  Severability. The invalidity of any provision in this Agreement shall
not affect the validity of any other provision.


                                 Page 13 of 14
<PAGE>   14
     IN WITNESS WHEREOF, the parties have executed this Agreement as of the day
and year first above written.


                              THIRD WAVE AGBIO, INC.
                              a Delaware corporation

                              By: /s/ DR. LANCE FORS
                                 -----------------------------------------
                              Name: Dr. Lance Fors
                              Title: President and Chief Executive Officer

                              THIRD WAVE TECHNOLOGIES, INC.
                              a Wisconsin corporation

                              By: /s/ DR. LANCE FORS
                                 ------------------------------------------
                              Name: Dr. Lance Fors
                              Title: President and Chief Executive Officer

                              THE BURRILL AGBIO CAPITAL FUND, L.P.,
                              a Delaware limited partnership


                              By:____________________________

                              Name:__________________________

                              Title:_________________________

[Signature Page of Principals' Shareholder Agreement of Third Wave Agbio, Inc.]




                                 Page 14 of 14
<PAGE>   15
     IN WITNESS WHEREOF, the parties have executed this Agreement as of the day
and year first above written.

                                        THIRD WAVE AGBIO, INC.
                                        a Delaware corporation


                                        By:
                                           -------------------------------------
                                        Name: Dr. Lance Fors
                                        Title: President and Chief Executive
                                               Officer


                                        THIRD WAVE TECHNOLOGIES, INC.
                                        a Wisconsin corporation


                                        By:
                                           -------------------------------------
                                        Name: Dr. Lance Fors
                                        Title: President and Chief Executive
                                               Officer


                                        THE BURRILL AGBIO CAPITAL FUND, L.P.,
                                        a Delaware limited partnership


                                        By: /s/ G. STEVEN BURRILL
                                           -------------------------------------
                                        Name: G. Steven Burrill
                                        Title: CEO



[Signature Page of Principals' Stockholder Agreement of Third Wave Agbio, Inc.]


                                 Page 14 of 14
<PAGE>   16
                                   EXHIBIT A

                            Schedule of Stockholders


<TABLE>
<CAPTION>
Name of and Address of Stockholder           Number of Shares
----------------------------------           ----------------
<S>                                          <C>
Third Wave Technologies, Inc.                1,000 Shares of Class A
502 South Rosa Road                          Common Stock
Madison, WI 53719

The Burrill Agbio Capital Fund, L.P.         1,000 Shares of Series A
c/o Burrill & Company                        Convertible Preferred Stock
120 Montgomery Street, Suite 1370
San Francisco, CA 94104
</TABLE>