<PAGE>

                                                                 EXHIBIT 10.34.1

CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS,
HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION PURSUANT TO RULE 24B-2 OF THE SECURITIES EXCHANGE ACT OF 1934, AS
AMENDED.

                                 FIRST AMENDMENT
                                       TO
                           LOAN AND SECURITY AGREEMENT

      This First Amendment to Loan and Security Agreement is entered into as of
May 13, 2003 (the "Amendment"), by and between COMERICA BANK - CALIFORNIA
("Bank") and LYNX THERAPEUTICS, INC. ("Borrower").

                                    RECITALS

      Borrower and Bank are parties to that certain Loan and Security Agreement
dated as of October 23, 2002, as amended (collectively, the "Agreement"). The
parties desire to amend the Agreement in accordance with the terms of this
Amendment.

      NOW, THEREFORE, the parties agree as follows:

      1.    Borrower shall not request nor receive any further Credit
Extensions.

      2.    The following defined term in Section 1.1 of the Agreement is hereby
amended in its entirety to read as follows:

                  "Collateral" means the property described on Exhibit A
attached hereto and the Cash Collateral (as defined in Section 13).

      3.    A new Section 13 is hereby added to the Agreement to read as
follows:

            13.   CASH COLLATERAL.

                  13.1  Pledge. Borrower shall maintain a money market account
      with Bank with a balance of at least 110% of the aggregate outstanding
      balance of all Indebtedness owing from Borrower to Bank (the "Required
      Balance") at all times. For purposes of clarity, Bank and Borrower agree
      that Borrower has no obligation to keep more than 110% of the aggregate
      outstanding balance of all Indebtedness owing from Borrower to Bank at
      Bank. Such money market account and all amounts held therein, together
      with all proceeds thereof, interest paid thereon, and substitutions
      therefor, including without limitation money market account # [ * ] at
      Bank, are the "Cash Collateral". Borrower grants and pledges to Bank a
      continuing security interest in all presently existing and hereafter
      acquired or arising Cash Collateral, in order to secure prompt repayment
      of any and all Obligations. Bank shall retain control over the Cash
      Collateral up to the Required Balance (as such Required Balance is
      adjusted downward from time to time as Borrower makes principal payments
      to Bank) to secure the Obligations until such Obligations have been
      satisfied in full. Borrower hereby authorizes Bank to place restrictions
      on Borrower's ability to withdraw amounts from accounts holding the Cash
      Collateral in order to ensure that such Required Balance is maintained.
      Borrower authorizes Bank to execute and/or file such documents, and take
      such actions, as Bank determines reasonable to perfect its security
      interest in the Cash Collateral. Such security interest constitutes a
      valid, first priority security interest in the Cash Collateral, and will
      constitute a valid, first priority security interest in Cash Collateral
      acquired after the date hereof. Notwithstanding termination of this
      Agreement, Bank's Lien on the Cash Collateral shall remain in effect for
      so long as any Obligations are outstanding.

                  13.2  Representations, Warranties and Covenants. Borrower
      represents and warrants to and covenants with Bank that:


                                       1
<PAGE>
                        (a)   Except for the Lien created hereunder, the Cash
      Collateral is owned by Borrower free and clear of any security interests,
      liens, encumbrances, options or other restrictions;

                        (b)   Borrower has full power and authority to create a
      first lien on the Cash Collateral in favor of Bank and no disability or
      contractual obligation exists that would prohibit Borrower from pledging
      the Cash Collateral pursuant to this Agreement, and, except for the Lien
      created hereunder, Borrower will not assign, create or permit to exist any
      other claim to, lien or encumbrance upon, or security interest in any of
      the Cash Collateral;

                        (c)   The Cash Collateral is not the subject of any
      present or threatened suit, action, arbitration, administrative or other
      proceeding, and Borrower knows of no reasonable grounds for the
      institution of any such proceedings; (d) Except for the Lien created
      hereunder, Borrower shall not transfer, encumber, dispose of, or otherwise
      direct the payment of any proceeds, interest, or amounts payable with
      respect to the Cash Collateral; and

                        (d)   Except for the Lien created hereunder, Borrower
      shall not transfer, encumber, dispose of, or otherwise direct the payment
      of any proceeds, interest, or amounts payable with respect to the Cash
      Collateral; and

                        (e)   Borrower shall execute and deliver such documents
      as Bank reasonably deems necessary to create, perfect and continue the
      security interest in the Cash Collateral contemplated hereby.

                  13.3  Bank's Remedies Upon Default. Upon the occurrence and
      during the continuance of an Event of Default, Bank shall have the right
      to exercise all such rights as a secured party under the Code as it, in
      its sole judgment, shall deem necessary or appropriate, including without
      limitation the right to apply the Cash Collateral to reduce the
      Obligations.

      4.    Provided that Borrower is in compliance with Section 13.1 of the
Agreement, any failure by Borrower to comply with Sections 6.8 and/or 6.9 of the
Agreement after the date hereof shall be automatically waived and such failure
shall not constitute an Event of Default. Bank does not waive any other failure
by Borrower to perform its Obligations under the Loan Documents. This waiver is
not a continuing waiver with respect to any failure to perform any other
Obligation after the date hereof.

      5.    Unless otherwise defined, all initially capitalized terms in this
Amendment shall be as defined in the Agreement. The Agreement, as amended
hereby, shall be and remain in full force and effect in accordance with its
respective terms and hereby is ratified and confirmed in all respects. Except as
expressly set forth herein, the execution, delivery, and performance of this
Amendment shall not operate as a waiver of, or as an amendment of, any right,
power, or remedy of Bank under the Agreement, as in effect prior to the date
hereof. Borrower ratifies and reaffirms the continuing effectiveness of all
promissory notes, guaranties, security agreements, mortgages, deeds of trust,
environmental agreements, and all other instruments, documents and agreements
entered into in connection with the Agreement.

      6.    Borrower represents and warrants that the representations and
warranties contained in the Agreement are true and correct in all material
respects as of the date of this Amendment (provided however, that those
representations and warranties expressly referring to another date shall be true
and correct in all material respects as of such date), and that no Event of
Default has occurred and is continuing.

      7.    This Amendment may be executed in two or more counterparts, each of
which shall be deemed an original, but all of which together shall constitute
one instrument.



[ * ] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION PURSUANT TO RULE 24B-2 OF THE SECURITIES EXCHANGE ACT OF 1934, AS
AMENDED.



                                       2
<PAGE>
      8.    As a condition to the effectiveness of this Amendment, Bank shall
have received, in form and substance satisfactory to Bank, the following:

                        (a)   this Amendment, duly executed by Borrower;

                        (b)   an amount equal to all Bank Expenses incurred in
      connection with this Amendment through the date of this Amendment; and

                        (c)   such other documents, and completion of such other
      matters, as Bank may reasonably deem necessary or appropriate.

            IN WITNESS WHEREOF, the undersigned have executed this Amendment as
of the first date above written.

                                      LYNX THERAPEUTICS, INC.


                                      By:  /s/ Edward C. Albini
                                           -------------------------------------

                                      Title:  Chief Financial Officer
                                             -----------------------------------


                                      COMERICA BANK - CALIFORNIA


                                      By:  /s/ Jonathan H. Norris
                                           -------------------------------------

                                      Title:  Vice President
                                             -----------------------------------





[ * ] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION PURSUANT TO RULE 24B-2 OF THE SECURITIES EXCHANGE ACT OF 1934, AS
AMENDED.



                                       3
<PAGE>
DEBTOR: LYNX THERAPEUTICS, INC.
SECURED PARTY: COMERICA BANK-CALIFORNIA

                                    EXHIBIT A

                        COLLATERAL DESCRIPTION ATTACHMENT
                         TO LOAN AND SECURITY AGREEMENT

            All equipment of Borrower (herein referred to as "Borrower" or
      "Debtor") financed by Bank, as listed on Appendix I attached hereto, and
      any additional equipment financed by Bank (which financings shall be
      supported by a UCC filing including an appendix listing such equipment),
      wherever located, and including all accessions and additions thereto, and
      any and all cash proceeds and/or noncash proceeds of any of the foregoing,
      including, without limitation, insurance proceeds, and all supporting
      obligations and the security therefor or for any right to payment.

All terms above have the meanings given to them in the California Uniform
Commercial Code, as amended or supplemented from time to time, including revised
Division 9 of the Uniform Commercial Code-Secured Transactions, added by Stats.
1999, c.991 (S.B. 45), Section 35, operative July 1, 2001.









[ * ] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION PURSUANT TO RULE 24B-2 OF THE SECURITIES EXCHANGE ACT OF 1934, AS
AMENDED.





                                       4